An official website of the United States government Here's how you know 

CDC Clinical Practice Guideline for Prescribing Opioids

for Pain — United States, 2022
Recommendations and Reports / November 4, 2022 / 71(3);1–95
Deborah Dowell, MD1; Kathleen R. Ragan, MSPH1; Christopher M. Jones, PharmD, DrPH2; Grant T. Baldwin, PhD1; Roger Chou,
MD3 (VIEW AUTHOR AFFILIATIONS)

View suggested citation

Summary Article Metrics

This guideline provides recommendations for clinicians providing pain care, including those
Altmetric:
prescribing opioids, for outpatients aged ≥18 years. It updates the CDC Guideline for
News (321)
Prescribing Opioids for Chronic Pain — United States, 2016 (MMWR Recomm Rep Blogs (15)
Policy
2016;65[No. RR-1]:1–49) and includes recommendations for managing acute (duration of <1
documents (9)
month), subacute (duration of 1–3 months), and chronic (duration of >3 months) pain. The X (341)
Facebook (9)
recommendations do not apply to pain related to sickle cell disease or cancer or to patients
Wikipedia (7)
receiving palliative or end-of-life care. The guideline addresses the following four areas: 1) Reddit (2)
Video (2)
determining whether or not to initiate opioids for pain, 2) selecting opioids and determining
Clinical
opioid dosages, 3) deciding duration of initial opioid prescription and conducting follow-up, guidelines (3)
and 4) assessing risk and addressing potential harms of opioid use. CDC developed the Mendeley (530)
guideline using the Grading of Recommendations Assessment, Development, and Evaluation
(GRADE) framework. Recommendations are based on systematic reviews of the scientific Citations: 634
evidence and reflect considerations of benefits and harms, patient and clinician values and
preferences, and resource allocation. CDC obtained input from the Board of Scientific Views: 1,308,916
Views equals page views plus
Counselors of the National Center for Injury Prevention and Control (a federally chartered PDF downloads
advisory committee), the public, and peer reviewers. CDC recommends that persons with pain Metric Details
receive appropriate pain treatment, with careful consideration of the benefits and risks of all
treatment options in the context of the patient’s circumstances. Recommendations should not
be applied as inflexible standards of care across patient populations. This clinical practice
Boxes
guideline is intended to improve communication between clinicians and patients about the
benefits and risks of pain treatments, including opioid therapy; improve the effectiveness and
Box 1
safety of pain treatment; mitigate pain; improve function and quality of life for patients with
pain; and reduce risks associated with opioid pain therapy, including opioid use disorder,
Box 2
overdose, and death.
Top Box 3
Introduction
Box 4
Background
Box 5
Pain is one of the most common reasons adults seek medical care in the United States (1). Acute
pain, a nearly universal experience, is a physiologic response to noxious stimuli that can become
pathologic. Acute pain is usually sudden in onset and time limited (defined in this clinical practice guideline as having a duration of

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 1 of 89
:
 <1 month) and often is caused by injury, trauma, or medical treatments such as surgery (2,3).
Table
Unresolved acute pain or subacute pain (defined in this clinical practice guideline as pain that has
been present for 1–3 months) can evolve into chronic pain (4). Chronic pain typically lasts >3
months (4) and can be the result of an underlying medical disease or condition, injury, medical Related Materials
treatment, inflammation, or unknown cause (2). Approximately one in five U.S. adults had chronic
pain in 2019 and approximately one in 14 adults experienced “high-impact” chronic pain, defined Prescribing Opioids for
as having pain on most days or every day during the past 3 months that limited life or work Pain — The New CDC
activities (5). Pain, especially chronic pain, can affect almost every aspect of a person’s life, Clinical Practice
leading to impaired physical functioning, poor mental health, and reduced quality of life, and Guideline 
contributes to substantial morbidity each year (6). In 2011, the economic costs of chronic pain
were estimated to range from $560 to $635 billion in annual direct medical costs, lost MMWR Article PDF
productivity, and disability (2).  [1 MB]

Pain is a complex phenomenon influenced by multiple factors, including biologic, psychological,

and social factors (7). This complexity means substantial heterogeneity exists in the effectiveness
of various pain treatments, depending on the type of underlying pain or condition being treated (7–11). Patients might experience
persistent pain that is not well controlled (6). Chronic pain often co-occurs with behavioral health conditions, including mental and
substance use disorders (12,13). Patients with chronic pain also are at increased risk for suicidal ideation and behaviors (14,15).
Data from death investigations in 18 states during 2003–2014 indicate that approximately 9% of suicide decedents had evidence
of having chronic pain at the time of death; however, this is likely an underestimate because of the limitations of the underlying
data sources used in the study (16). These factors and potentially harmful outcomes associated with chronic pain for some
persons add to the clinical complexity and underscore the importance of adequately treating and providing care to persons with
pain. Thus, prevention, assessment, and treatment of pain is a persistent challenge for clinicians. Pain might go unrecognized, and
some persons (e.g., members of marginalized racial and ethnic groups; women; older persons; persons with cognitive impairment;
persons with mental and substance use disorders, sickle cell disease, or cancer-related pain; and persons at the end of life) can be
at risk for inadequate pain treatment (2,6,17–23).

Although substantial opportunity exists for improved pain management broadly across the United States, data underscore
opportunities for addressing specific, long-standing health disparities (24–26) in the treatment of pain. For example, patients who
identify as Black or African American (Black), Hispanic or Latino (Hispanic), and Asian receive fewer postpartum pain assessments
relative to White patients (27). Black (28,29) and Hispanic (29) patients are less likely than White patients to receive analgesia for
acute pain. Among Black and White patients receiving opioids for pain, Black patients are less likely to be referred to a pain
specialist, and Black patients receive prescription opioids at lower dosages than White patients (24,30). Racial and ethnic
differences remain even after adjusting for access-related factors, the needs and preferences of patients, and the appropriateness
of the intervention (25). These disparities appear to be further magnified for Black and Hispanic patients who live in
socioeconomically disadvantaged neighborhoods (26). Women might be at higher risk for inadequate pain management (31),
although they have higher opioid prescription fill rates (32) than men at a population level. Geographic disparities contribute to
increased use of opioids for conditions for which nonopioid treatment options might be preferred but are less available. For
example, adults living in rural areas are more likely to be prescribed opioids for chronic nonmalignant pain than adults living in
nonrural areas (33). Although not Hispanic or Latino (non-Hispanic) American Indian or Alaska Native and non-Hispanic White
populations have experienced much higher rates of prescription opioid–related overdose deaths than non-Hispanic Black,
Hispanic, or non-Hispanic Asian or Pacific Islander populations (34), application of safeguards in opioid prescribing are
disproportionately applied to Black patients. In one study, Black patients were more likely than White patients to receive regular
office visits and have restricted early refills (35). In another study, clinicians were substantially more likely to discontinue opioids if
there was evidence of misuse for Black patients compared with White patients (36). Differentially untreated or undertreated pain
as a result of clinician biases persists and demands immediate and sustained attention and action (37–40).

Because of the clinical, psychological, and social consequences associated with pain, including limitations in activities, lost work
productivity, reduced quality of life, and pervasive stigma, it is essential that clinicians have the training, education, guidance, and
resources to provide appropriate, holistic, and compassionate care for patients with pain (2,6). An important aim of pain
management is the provision of person-centered care built on trust between patients and clinicians. Such care includes
appropriate evaluation to identify potentially reversible causes of pain and establish a diagnosis and measurable treatment

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 2 of 89
:
 outcomes that focus on optimizing function and quality of life (6). To achieve this aim, it is important that clinicians consider the full
range of pharmacologic and nonpharmacologic treatments for pain care, and that health systems, payers, and governmental
programs and entities make the full spectrum of evidence-based treatments accessible to patients with pain and their treating
clinicians.

The range of therapeutic options has historically been inaccessible to many patients because of factors such as inadequate
clinician education, training, and guidance; unconscious bias; a shortage of pain management specialists; insufficient access to
treatment modalities such as behavioral therapy; siloed health systems; insurance coverage and reimbursement policies; and lack
of clarity about the evidence supporting different pain treatments (6,17,41–46). Partly because of these factors affecting access to
a wide range of treatment modalities, for many years medications such as prescription opioids have been the mainstay to treat
pain, despite very limited evidence to support their long-term (>1 year) benefits; most placebo-controlled trials have been <6
weeks in duration (2,6,47,48).

Opioids can be essential medications for the management of pain; however, they carry considerable potential risk. A systematic
review published in 2014 by the Agency for Healthcare Research and Quality (AHRQ) found insufficient evidence to demonstrate
long-term benefits of prescription opioid treatment for chronic pain, and long-term prescription opioid use was found to be
associated with increased risk for overdose and opioid misuse, among other risks (47). Some risks, such as overdose, were dose
dependent (47). In 2014, on the basis of accumulating evidence of potential risks to patients, the Food and Drug Administration
(FDA) required new safety labeling changes for extended-release and long-acting opioids. Changes included a boxed warning on
the “risks of addiction, abuse, and misuse, which can lead to overdose and death” and, for patients receiving opioids during
pregnancy, the risk for neonatal abstinence syndrome (a group of conditions that can occur when newborns withdraw from certain
substances including opioids; withdrawal caused by in utero exposure to opioids also is called neonatal opioid withdrawal
syndrome) (49). In 2016, these warnings were added to the labels for immediate-release opioids (50).

In addition to the potential risks to patients, prescribed opioids have the potential for diversion and nonmedical use among
persons to whom they were not prescribed (51). In the United States, opioid prescribing increased fourfold during 1999–2010; this
increase was paralleled by an approximately fourfold increase in overdose deaths involving prescription opioids during the same
period (52) and increases in prescription opioid use disorder (53). In addition to the increased overall volume of opioid
prescriptions during this period, how opioids were prescribed also changed; opioids increasingly were prescribed at higher
dosages and for longer durations, prescribing behaviors associated with opioid use disorder and overdose (54,55). The limited
evidence of long-term effectiveness of opioids for chronic pain, coupled with risks to patients and to persons using prescription
opioids that were not prescribed to them, underscored the importance of reducing inappropriate opioid prescribing while
advancing evidence-based pain care to improve the lives of persons living with pain.

CDC recognized the need for a national guideline on pain management that could improve appropriate opioid prescribing while
minimizing opioid-related risks and released the CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016
(referred to as the 2016 CDC Opioid Prescribing Guideline hereafter). The 2016 CDC Opioid Prescribing Guideline included 12
recommendations for the prescribing of opioids for chronic pain by primary care clinicians in outpatient settings, excluding active
cancer treatment, palliative care, and end-of-life care (56). The recommendations in the 2016 CDC Opioid Prescribing Guideline
were based on a systematic review of the best-available evidence at the time, along with input from experts and the public and
review and deliberation by the Board of Scientific Counselors (BSC) of the National Center for Injury Prevention and Control
(NCIPC) (a federally chartered advisory committee). The goals of the guideline were to 1) ensure that clinicians and patients
considered safer and more effective pain treatment; 2) improve patient outcomes, such as reduced pain and improved function; and
3) reduce the number of persons who developed opioid use disorder, experienced overdose, or experienced other prescription
opioid–related adverse events (56). To facilitate uptake and implementation of the 2016 CDC Opioid Prescribing Guideline in
clinical practice, CDC used a broad-reaching strategy that included clinician education and training, partnerships with health
systems and payers, and multiple clinical tools and fact sheets (57).

The number of overall opioid prescriptions in the United States declined after 2012, and further declines have been observed after
the release of the 2016 CDC Opioid Prescribing Guideline (58). The timing of this release was associated with accelerated
decreases in overall opioid prescribing and declines in potentially high-risk prescribing (e.g., high-dosage opioid prescribing and
concurrent prescribing of opioid pain medication and benzodiazepines) (58,59). The release of the 2016 CDC Opioid Prescribing
Guideline also was temporally associated with modest increases in the prescribing of nonopioid pain medication (60). Although

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 3 of 89
:
 not the intent of the 2016 CDC Opioid Prescribing Guideline, design and implementation of new laws, regulations, and policies
also appeared to reflect its recommendations. For example, since 2016, consistent with SUPPORT Act requirements (61), some
state Medicaid programs have used the guideline and other resources to promote nonopioid options for chronic pain management
(62). Approximately half of all states have passed legislation limiting initial opioid prescriptions for acute pain to a ≤7-day supply
(63), and many insurers, pharmacy benefit managers, and pharmacies have enacted similar policies (64). At least 17 states have
passed laws requiring or recommending the coprescription of naloxone in the presence of overdose risk factors, such as high
dosages of opioids or concomitant opioid pain medications and benzodiazepines (65).

Although some laws, regulations, and policies that appear to support recommendations in the 2016 CDC Opioid Prescribing
Guideline might have had positive results for some patients, they are inconsistent with a central tenet of the guideline: that the
recommendations are voluntary and intended to be flexible to support, not supplant, individualized, patient-centered care. Of
particular concern, some policies purportedly drawn from the 2016 CDC Opioid Prescribing Guideline have been notably
inconsistent with it and have gone well beyond its clinical recommendations (6,66,67). Such misapplication includes extension to
patient populations not covered in the 2016 CDC Opioid Prescribing Guideline (e.g., cancer and palliative care patients), rapid
opioid tapers and abrupt discontinuation without collaboration with patients, rigid application of opioid dosage thresholds,
application of the guideline’s recommendations for opioid use for pain to medications for opioid use disorder treatment (previously
referred to as medication assisted treatment), duration limits by insurers and pharmacies, and patient dismissal and abandonment
(66–68). These actions are not consistent with the 2016 CDC Opioid Prescribing Guideline and have contributed to patient harm,
including untreated and undertreated pain, serious withdrawal symptoms, worsening pain outcomes, psychological distress,
overdose, and suicidal ideation and behavior (66–71).

Rationale
Since release of the 2016 CDC Opioid Prescribing Guideline, new evidence has emerged on the benefits and risks of prescription
opioids for both acute and chronic pain, comparisons with nonopioid pain treatments, dosing strategies, opioid dose-dependent
effects, risk mitigation strategies, and opioid tapering and discontinuation (7–11). This evidence includes studies on misapplication
of the 2016 CDC Opioid Prescribing Guideline (66), benefits and risks of different tapering strategies and rapid tapering
associated with patient harm (68,71–73), challenges in patient access to opioids (6), patient abandonment and abrupt
discontinuation of opioids (71), a seminal randomized clinical trial comparing prescription opioids to nonopioid medications on
long-term pain outcomes (74), the association of characteristics of initial opioid prescriptions with subsequent likelihood for long-
term opioid use (75,76), and the small proportion of opioids used by patients compared with the amount prescribed to them for
postoperative pain (77–79).

Opioid medications remain a common treatment for pain despite declines in the number of opioid prescriptions after 2012 (58).
During 2015–2018, approximately 6% of U.S. adults reported use of one or more prescription opioids during the past 30 days
(80), and in 2020, approximately 143 million opioid prescriptions were dispensed from pharmacies in the United States (81).
Rates of opioid prescribing continue to vary across states, medical specialties, patient demographics, and pain conditions in ways
that cannot be explained by the underlying health status of the population, and often are discordant with the 2016 CDC Opioid
Prescribing Guideline recommendations (25,77,82–84). The prevalence of prescription opioid misuse and prescription opioid use
disorder also has declined in recent years. In 2019, among persons aged ≥12 years in the United States, 9.7 million reported
misuse of prescription opioids during the past year (a decrease from 12.5 million in 2015), and 1.4 million met criteria for a past-
year prescription opioid use disorder (a decrease from 2.0 million in 2015) (85). However, in 2020, prescription opioids remained
the most commonly misused prescription drug in the United States (51). Also in 2020, among those reporting misuse during the
past year, 64.6% reported the main reason for their most recent misuse was to “relieve physical pain” compared with 11.3% to
“feel good or get high” and 2.3% “because I am hooked or have to have it” (51). Taken together, these factors underscore the need
for an updated clinical practice guideline on appropriate opioid prescribing for pain and pain management.

This clinical practice guideline expands and updates the 2016 CDC Opioid Prescribing Guideline to provide evidence-based
recommendations for prescribing opioid pain medication for acute, subacute, and chronic pain for outpatients aged ≥18 years,
excluding pain management related to sickle cell disease, cancer-related pain treatment, palliative care, and end-of-life care
(Boxes 1 and 2). Lessons learned from the development of the 2016 CDC Opioid Prescribing Guideline informed the process used
to generate this update. This update leverages new data to expand content on prescription opioids for acute and subacute pain

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 4 of 89
:
 throughout the recommendations. Importantly, the update also aims to clearly delineate recommendations that apply to patients
who are being considered for initial treatment with prescription opioids and patients who have been receiving opioids as part of
their ongoing pain management.

CDC developed a draft clinical practice guideline on the basis of five systematic reviews of the best-available evidence on the
benefits and risks of prescription opioids, nonopioid pharmacologic treatments, and nonpharmacologic treatments. The draft
clinical practice guideline was reviewed by an independent federal advisory committee (the Board of Scientific Counselors of the
National Center for Injury Prevention and Control), peer reviewers, and the public and was revised after feedback from these
reviews. Additional insights from patients, caregivers, and clinicians shared during virtual conversations held in 2020 were
incorporated in the update. Importantly, to discourage the misapplication of opioid pain medication dosage thresholds as inflexible
standards, revised recommendation statement language emphasizes principles such as avoiding increasing dosage above levels
likely to yield diminishing returns in benefits relative to risks to patients. More-specific considerations related to dosage have been
moved to implementation considerations that follow each recommendation statement, where more nuance is offered to inform
clinical decision-making and individualized patient care.

This clinical practice guideline provides recommendations but does not replace clinical judgment and individualized, patient-
centered decision-making. The recommendations are based on emerging evidence, including observational studies or randomized
clinical trials with notable limitations; thus, they should be considered in the context of the clinician-patient relationship built on
shared understanding and a whole-person approach that considers such factors as the patient’s physical and psychological
functioning, support needs, expected health outcomes and well-being, home environment, and home and work responsibilities.
Flexibility for clinicians and patients is paramount when making patient-centered clinical treatment decisions. The
recommendations aim to improve communication between clinicians and patients about the benefits and risks of prescription
opioids and other pain treatment strategies; improve the safety and effectiveness of pain treatment; improve pain, function, and
quality of life for persons with pain; and reduce the risks associated with opioid pain treatment (including opioid use disorder,
overdose, and death) and with other pain treatment.

This clinical practice guideline provides voluntary clinical practice recommendations for clinicians that should not be used as
inflexible standards of care. The recommendations are not intended to be implemented as absolute limits for policy or practice
across populations by organizations, health care systems, or government entities.

Scope and Audience

This clinical practice guideline is intended for clinicians who are treating outpatients aged ≥18 years with acute (duration of <1
month), subacute (duration of 1–3 months), or chronic (duration of >3 months) pain, and excludes pain management related to
sickle cell disease, cancer-related pain treatment, palliative care, and end-of-life care. The recommendations are most relevant to
clinicians whose scope of practice includes prescribing opioids (e.g., physicians, nurse practitioners and other advanced-practice
registered nurses, physician assistants, and oral health practitioners). Because clinicians might work within team-based care, this
clinical practice guideline also refers to and promotes integrated pain management and collaborative working relationships among
clinicians (e.g., behavioral health specialists such as social workers or psychologists, pharmacists, and registered nurses). This
guideline update includes recommendations for primary care clinicians (e.g., internists and family physicians) and other clinicians
managing pain in outpatient settings (e.g., surgeons, emergency medicine clinicians, occupational medicine clinicians, physical
medicine and rehabilitation clinicians, and neurologists). Applicable settings include clinician offices, clinics, and urgent care
centers. The recommendations do not apply to care provided to patients who are hospitalized or in an emergency department or
other observational setting from which they might be admitted to inpatient care. These recommendations do apply to prescribing
for pain management for patients when they are discharged from hospitals, emergency departments, or other facilities.

In addition to updating recommendations on the basis of new evidence regarding management of chronic pain, this clinical
practice guideline is intended to assist clinicians in weighing benefits and risks of prescribing opioid pain medication for painful
acute conditions (e.g., low back pain, neck pain, other musculoskeletal pain, neuropathic pain, dental pain, kidney stone pain, and
acute episodic migraine) and pain related to procedures (e.g., postoperative pain and pain from oral surgery). In 2020, several of
these indications were prioritized by an ad hoc committee of the National Academies of Sciences, Engineering, and Medicine (86)
as those for which evidence-based clinical practice guidelines would help inform prescribing practices, with the greatest potential
effect on public health. This update includes content on management of subacute painful conditions, when duration falls between

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 5 of 89
:
 that typically considered acute (defined as lasting <1 month) and chronic (defined as lasting >3 months). The durations used to
define acute, subacute, and chronic pain might imply more specificity than is found in real-life patient experience, when pain often
gradually transitions from acute to chronic. These time-bound definitions are not meant to be absolute but rather to be
approximate guides to facilitate the consideration and practical use of the recommendations by clinicians and patients.

The 2016 CDC Opioid Prescribing Guideline focused on recommendations for primary care physicians. This clinical practice
guideline expands the scope to additional clinicians. Although primary care physicians prescribe approximately 37% of all opioid
prescriptions, other clinicians, including pain medicine clinicians (8.9%) and dentists (8.6%), account for considerable proportions
of prescriptions. Pain medicine and physical medicine and rehabilitation clinicians prescribe opioids at the highest rates, followed
by orthopedic and family medicine clinicians (83). Thus, expanding the scope to outpatient opioid prescribing can provide
evidence-based advice for many additional clinicians, including dentists and other oral health providers, clinicians managing
postoperative pain in outpatients, and clinicians providing pain management for patients being discharged from emergency
departments.

Many principles of pain management are similar whether or not the treating clinician is a pain management specialist, and many of
the recommendations might be relevant for pain management specialists. Many pain management specialists already follow
principles outlined in this clinical practice guideline; however, use by pain management specialists is not the focus of this clinical
practice guideline. Pain management specialists often have extensive training and expertise in pain management modalities that
other clinicians do not, and they might treat patients with clinical situations that are more complex, less prevalent, and not well
addressed by the available evidence; therefore, the balance of benefits and risks to patients might differ when the treating clinician
is a pain management specialist.

The recommendations address the use of opioid pain medication in certain special populations (e.g., older adults and pregnant
persons) and in populations with conditions posing special risks (e.g., a history of a substance use disorder). The recommendations
do not address the use of opioid pain medication in children or adolescents aged <18 years. The available evidence concerning the
benefits and risks of long-term opioid therapy in children and adolescents remains limited, and few opioid medications provide
information in their labeling regarding safety and effectiveness in pediatric patients. Guidelines and recommendations are
available for pain management in children with sickle cell disease (87), for children undergoing surgical procedures (88), and for
palliative care in adolescent and young adult patients with cancer (89).

Although some principles in this clinical practice guideline might be helpful in the management of pain related to sickle cell
disease, cancer-related pain treatment, palliative care, and end-of-life care, some recommendations might not be relevant for pain
management in these contexts. Other guidelines more specifically address pain management in these situations (87,89–93);
therefore, this clinical practice guideline does not apply to patients experiencing pain associated with these conditions or types of
care. This does not imply that any other types of pain are more or less worthy of effective treatment, only that clinicians are
referred to existing clinical guidelines that more specifically address unique considerations for management of pain related to
sickle cell disease, cancer-related pain treatment, palliative care, and end-of-life care.

This clinical practice guideline follows the Institute of Medicine’s definition of palliative care as care that provides relief from pain
and other symptoms, supports quality of life, and is focused on patients with serious advanced illness (94). Palliative care can
begin early in the course of treatment for any serious illness that requires advanced management of pain or other distressing
symptoms (94). In this guideline, end-of-life care refers to care for persons in hospice care and others with a terminal illness or at
high risk for dying in the near future in hospitals, receiving long-term services and supports (including institutional care and home-
and community-based services), or at home. This clinical practice guideline does not apply to patients undergoing cancer-related
pain treatment, palliative care, or end-of-life care because of the unique therapeutic goals, ethical considerations, opportunities for
medical supervision, and balance of benefits and risks with opioid therapy in such care. For example, for many persons at the end
of life, serious potential long-term opioid-related harms such as opioid use disorder might not be relevant.

Recommendations on pain management for patients with cancer and patients who have survived cancer are available in the
National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology: Adult Cancer Pain (90), NCCN Clinical
Practice Guidelines in Oncology: Survivorship (91), and Management of Chronic Pain in Survivors of Adult Cancers: American
Society of Clinical Oncology (ASCO) Clinical Practice Guideline (92). Because of unique considerations in management of pain
related to sickle cell disease, which can change the balance of benefits and risks of the use of opioids, clinicians should refer to the

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 6 of 89
:
 American Society of Hematology (ASH) 2020 Guidelines for Sickle Cell Disease: Management of Acute and Chronic Pain (87). In
2018, NCCN and ASCO convened and led a meeting including representatives and guideline authors from NCNN, ASCO, ASH,
and CDC to review existing pain management guidelines and guidelines then in development from these organizations (56,87,90–
92). Meeting participants noted that these guidelines applied to different patient populations and target audiences but found no
disagreement among recommendations when applied to the appropriate patient and clinical situation (95).

Although this update includes content on pain management for patients with opioid use disorder and one recommendation on
management of opioid use disorder as a complication of opioid use, recommendations on opioids used specifically as medications
for opioid use disorder are not the focus of this clinical practice guideline. More detailed recommendations on management of
patients with opioid use disorder are available in the American Society of Addiction Medicine (ASAM) National Practice Guideline
for the Treatment of Opioid Use Disorder: 2020 Focused Update (96).
Top

Clinical Practice Guideline Development Methods

Systematic Reviews and Evidence Sources
The 2016 CDC Opioid Prescribing Guideline was based on a systematic clinical evidence review sponsored by AHRQ on the
effectiveness and risks of long-term opioid therapy for chronic pain (47,97), a CDC update to the AHRQ-sponsored review, and
additional contextual questions (56,98). The systematic review addressed the effectiveness of long-term opioid therapy for
outcomes related to pain, function, and quality of life; the comparative effectiveness of different methods for initiating and titrating
opioids; the harms and adverse events associated with opioids; and the accuracy of risk prediction instruments and effectiveness
of risk mitigation strategies on outcomes related to overdose, opioid use disorder, illicit drug use, and prescription opioid misuse.
The CDC update to the AHRQ-sponsored review included literature published during or after 2015 and an additional question on
the association between opioid therapy for acute pain and long-term use. The contextual evidence review addressed effectiveness
of nonpharmacologic and nonopioid pharmacologic treatments, clinician and patient values and preferences, and information
about resource allocation.

For this update to the 2016 CDC Opioid Prescribing Guideline, CDC funded AHRQ in 2018 and 2019 to conduct five systematic
reviews (7–11). AHRQ’s Evidence-based Practice Centers completed these reviews, which included new evidence related to the
treatment of chronic and acute pain. The AHRQ review of opioids for chronic pain updated and expanded the evidence for the
2016 CDC review; studies were included on short-term (1 to <6 months), intermediate-term (6 to <12 months) and long-term
(≥12 months) outcomes of therapy involving opioids, effects of opioid plus nonopioid combination therapy, effects of tramadol,
effects of naloxone coprescription, risks of coprescribed benzodiazepines, risks of coprescribed gabapentinoids, and effects of
concurrent use of cannabis (7). The systematic clinical evidence review on opioids for chronic pain (7) also included contextual
questions on clinician and patient values and preferences, costs and cost-effectiveness of opioid therapy, and risk mitigation
strategies. CDC considered four new complementary AHRQ reviews on the benefits and harms of nonpharmacologic treatments
for chronic pain (9), nonopioid pharmacologic treatments for chronic pain (8), treatments for acute episodic migraine (11), and
treatments for acute (nonmigraine) pain (10). A question on management of acute pain in the systematic clinical evidence review
for the 2016 CDC Opioid Prescribing Guideline was included in the new review on therapies for acute pain (10). CDC also
reviewed AHRQ-sponsored surveillance reports conducted in follow-up to the five systematic reviews for any new evidence that
could potentially change systematic review conclusions. To supplement the clinical evidence reviews, CDC sponsored a contextual
evidence review on clinician and patient values and preferences and resource allocation (costs) for the areas addressed in the four
new reviews (8–11).

AHRQ Method for Evaluating Quality of Evidence

The reviews used the AHRQ approach to synthesize and grade the strength of evidence (99). The AHRQ approach is based on a
systematic review of the evidence and provides an overall strength of evidence indicating the level of certainty (high, moderate,
low, or insufficient); similar factors are considered in the Advisory Committee on Immunization Practices (ACIP) adapted (100,101)
Grading of Recommendations Assessment, Development, and Evaluation (GRADE) (102) method. These factors include study
limitations and risk for bias, consistency, directness, precision, and reporting bias. Large strength of association, dose response,
and plausible confounders can strengthen observed findings. The primary clinical questions, detailed methods, and findings for
the systematic and contextual evidence reviews are presented (Appendix).

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 7 of 89
:
 ACIP Adapted GRADE Method for Evaluating Quality of Evidence
The GRADE method is predicated on a systematic review of scientific evidence and provides a transparent framework for grading
the quality of evidence and strength of recommendations. GRADE has been adapted by ACIP (100,101), and CDC used the ACIP
adaptation in this clinical practice guideline. Under the ACIP GRADE framework, each body of evidence is initially categorized
using a hierarchy that reflects the degree of confidence in the effect of a clinical action on health outcomes. The categories in the
hierarchy are type 1 evidence (randomized clinical trials or overwhelming evidence from observational studies), type 2 evidence
(randomized clinical trials with important limitations, or exceptionally strong evidence from observational studies), type 3 evidence
(observational studies or randomized clinical trials with notable limitations), and type 4 evidence (clinical experience and
observations, observational studies with important limitations, or randomized clinical trials with several major limitations) (Box 3).
The evidence is downgraded if issues are identified with regard to risk for bias, inconsistency, indirectness, imprecision, or
publication bias. Observational studies might be upgraded in certain situations (large strength of association, presence of dose
response, or plausible effects of confounding would strengthen findings; that is, if confounding would likely provide results
opposite to the observed findings, it strengthens the confidence that the observed association is present). A final evidence type is
assigned based on these considerations. Type 1 evidence indicates high confidence that the true effect is close to the estimate of
the effect; type 2 evidence means that the true effect is likely to be close to the estimate of the effect, but there is some
uncertainty; type 3 evidence means that confidence in the effect estimate is limited (moderate uncertainty), and the true effect
could differ substantially from the estimate of the effect; and type 4 evidence indicates very little confidence in the effect estimate
(high uncertainty), and the likelihood is high that the true effect differs from the estimate of the effect (100,103). When no studies
are available or the evidence is too limited to estimate effects, evidence is considered insufficient.

Categorizing the Evidence

The AHRQ approach uses a different method and terminology (high, moderate, low, or insufficient) to grade the strength of
evidence from the ACIP adapted GRADE method (evidence types 1, 2, 3, or 4) (99). However, the underlying principles are similar,
enabling translation from AHRQ to CDC grades. A methodologist translated the AHRQ strength of evidence grades to CDC
evidence types according to the information provided in the summary of evidence tables in the AHRQ reviews. Tables with GRADE
clinical evidence review ratings of the evidence for the key clinical questions are available (https://stacks.cdc.gov/view/cdc/121663).
Evidence was categorized into the following types: type 1 (randomized clinical trials or overwhelming evidence from observational
studies; equivalent to AHRQ high strength of evidence), type 2 (randomized clinical trials with important limitations, or
exceptionally strong evidence from observational studies; equivalent to AHRQ moderate strength of evidence), type 3
(observational studies, or randomized clinical trials with notable limitations; equivalent to most AHRQ low strength of evidence
ratings), or type 4 (clinical experience and observations, observational studies with important limitations, or randomized clinical
trials with several major limitations; equivalent to AHRQ low strength of evidence with serious limitations). When no studies were
available or the evidence was too limited to estimate effects, evidence was assessed as insufficient. Results from meta-analyses
conducted for the AHRQ reviews were reported when available; otherwise, the evidence was synthesized qualitatively.

Recommendation Development
CDC developed this clinical practice guideline using the method developed by the GRADE working group
(https://www.gradeworkinggroup.org  ). Recommendations are based on the reviewed evidence. In the ACIP adapted GRADE
framework, recommendations are assigned one of two categories (category A or B). Four major factors determine the category of
the recommendation: 1) the quality of evidence, 2) the balance between desirable and undesirable effects, 3) values and
preferences, and 4) resource allocation (e.g., costs to patients or health systems) (104). Other considerations include feasibility and
acceptability and effect on equity (105). Recommendations are more likely to be category A when the evidence is higher quality, a
balance of desirable relative to undesirable effects is greater, resources and costs are lower, and recommendations are less
sensitive to differences in values and preferences. Category A recommendations typically apply to all persons in the group
addressed in the recommendation and indicate a course of action that can be followed in most circumstances. Category B
recommendations indicate that the recommendation might not apply to all persons in the group addressed in the
recommendation; therefore, different choices will be appropriate for different patients, and decisions should be made based on the
patient’s circumstances. For category B recommendations, clinicians must help patients arrive at a decision consistent with patient
values and preferences and specific clinical situations (shared decision-making) (106). In the GRADE method, a particular quality
of evidence does not necessarily result in a particular strength of recommendation (102–104). Although it is desirable for category

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 8 of 89
:
 A recommendations to be based on type 1 or type 2 evidence, category A recommendations can be based on type 3 or type 4
evidence when the advantages of a clinical action clearly outweigh the disadvantages in terms of benefits and harms, values and
preferences, and costs, despite uncertainty in effect estimates (104). The GRADE working group has presented several
paradigmatic situations in which strong (category A) recommendations might be justified despite low-quality evidence (e.g., when
high-quality evidence suggests equivalence of two alternatives and low-quality evidence suggests harm in one alternative, or
when high-quality evidence suggests modest benefits and low- or very low–quality evidence suggests possibility of catastrophic
harm) (104). Category B recommendations are made when the advantages and disadvantages of a clinical action are more
balanced or when more uncertainty exists with regard to whether benefits clearly outweigh harms.

In accordance with the ACIP adapted GRADE method, CDC drafted evidence-based recommendations focused on determining
whether or not to initiate opioids for pain, selecting opioids and determining opioid dosages, deciding duration of initial opioid
prescription and conducting follow-up, and assessing risk and addressing potential harms of opioid use. To help assure the draft
guideline’s integrity and credibility, CDC then began a multistep review process.

Federal Advisory Committee Review and Recommendation

CDC sought recommendations on the draft clinical practice guideline from one of its federal advisory committees, the Board of
Scientific Counselors of the National Center for Injury Prevention and Control (BSC/NCIPC). BSC/NCIPC advises the U.S.
Department of Health and Human Services (HHS) Secretary, the CDC Director, and the NCIPC Director and makes
recommendations regarding scientific, programmatic, and research policies, strategies, objectives, projects, and priorities.
BSC/NCIPC also reviews progress toward injury and violence prevention. BSC/NCIPC members are special government
employees appointed by the HHS Secretary or their designee as CDC advisory committee members. Members are required to
complete the Office of Government Ethics Form 450 annually to disclose relevant interests and report on their disclosures during
meetings. Disclosures for BSC/NCIPC are reported in this clinical practice guideline. Meeting minutes and documents for public
BSC/NCIPC meetings are available on the BSC/NCIPC website (https://www.cdc.gov/injury/bsc/meetings.html).

On December 4–5, 2019, CDC held a public meeting of BSC/NCIPC (announced via Federal Register 84 FR 57021; 84 FR 65159)
and provided a presentation on the background for updating the clinical practice guideline. CDC then requested the formation of
an Opioid Workgroup (OWG), under the parent BSC, whose primary purpose would be to review a draft clinical practice guideline
and to develop a report of their observations for BSC/NCIPC (107). After considering CDC’s presentations, the proposed OWG
Terms of Reference, and public comments, BSC/NCIPC voted unanimously to establish an OWG that reports to BSC/NCIPC. CDC
then held a public nomination process for prospective OWG members (107).

To provide background to BSC/NCIPC for informing the creation of OWG with a balance of perspectives, CDC identified audiences
that would be 1) directly affected by the clinical practice guideline, 2) directly involved with implementing or integrating
recommendations into current practice, and 3) qualified to represent a specific discipline or expertise in alignment with the tasks of
the workgroup for consideration by BSC/NCIPC. Identified groups with perspectives that would support the workgroup’s capacity
included, but were not limited to, patients with pain, family members and caregivers, clinicians, public health practitioners, and
research scientists. CDC announced the call for nominations at the December 4–5, 2019, public meeting and heard
recommendations from the public during the public comment opportunities, as well as from BSC/NCIPC members, regarding
recommendations for nominations. Persons interested in being considered for the workgroup were encouraged to submit self-
nominations from December 4, 2019, through February 4, 2020. CDC’s BSC/NCIPC received 255 nominations for OWG.

After reviewing clinical expertise, professional credentials, and diversity in perspectives of all nominees (including diversity of
gender, race and ethnicity, geographic region, institutional affiliations, and personal experiences relevant to pain management and
providing care to patients with pain), OWG’s Designated Federal Officer (DFO) created a list of prospective workgroup members
and sent them invitations to participate, along with conflict of interest disclosure forms. OWG’s DFO and BSC/NCIPC’s DFO
reviewed conflict of interest disclosure forms. CDC’s Strategic Business Initiatives Unit (SBIU), which oversees the Federal
Advisory Committee Act program, also reviewed the OWG Terms of Reference, prospective OWG roster, curricula vitae, and
conflict of interest disclosure forms and determined all reported financial or other conflicts of interest were not present or
nonsignificant before finalizing selection.* OWG members disclosed any potential topical conflicts of interest related to OWG
meeting agenda items before each meeting. Disclosures of OWG are reported in the clinical practice guideline.

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 9 of 89
:
 OWG had 23 members (108) including four ex officio members representing federal partner agencies (see Federal Partner
Engagement). In accordance with CDC guidance (109,110) that at least two BSC/NCIPC members must serve on OWG and one of
the two members must serve as the workgroup chair, OWG included a total of three BSC/NCIPC members, with one BSC/NCIPC
member serving as the OWG chair. An NCIPC subject matter expert served as OWG’s DFO. OWG members included patients
with pain, caregivers, and family members of patients with pain. OWG also comprised clinicians and subject matter experts, with
the following perspectives represented: primary care, pain medicine, public health, behavioral health, pharmacy, emergency
medicine, medical toxicology, obstetrics/gynecology, bioethics, orthopedic surgery, plastic surgery, dentistry, sickle cell disease,
substance use disorder treatment, and research. OWG members were diverse in regard to gender, race and ethnicity, geographic
region, institutional affiliation, subject matter expertise, and personal experiences. The CDC NCIPC OWG DFO presented the
OWG roster and reviewed the Terms of Reference at the publicly held BSC/NCIPC meeting on July 22, 2020 (Federal Register 85
FR 30709; 85 FR 40290).

OWG had 11 meetings from October 2020 through June 2021. Before receiving the draft clinical practice guideline, OWG held
meetings to review and discuss the 2016 CDC Opioid Prescribing Guideline; CDC’s community engagement activities with
patients, caregivers, and clinicians; and GRADE methodology. CDC NCIPC staff provided OWG with evidence reviews, public
comments from BSC/NCIPC meetings, and summaries of community engagements for review before providing OWG with the
draft clinical practice guideline in March 2021. OWG held seven meetings to review and discuss the draft clinical practice
guideline and develop a report summarizing their expert observations and findings for BSC/NCIPC. The OWG report provided
overall observations on overarching themes and draft clinical practice guideline recommendations (111). In addition, many
members of OWG developed a document entitled OWG Guiding Principles that was included as an appendix in the OWG report;
this document outlines the “general process and principles by which OWG approached their assigned tasks.” These Guiding
Principles included minimizing bias, ensuring scientific integrity, enhancing inclusivity, being patient and clinician centered, and
considering historical context.

The OWG chair presented the OWG report at a public BSC/NCIPC meeting on July 16, 2021 (Federal Register 86 FR 30048).
After hearing additional CDC presentations on the process and progress of the draft clinical practice guideline, discussion of the
OWG report, and a 2-hour public comment period, BSC/NCIPC voted unanimously that CDC adopt the OWG report, while
considering ideas and suggestions raised by BSC/NCIPC and the public during the meeting, and that OWG’s work be considered
complete and that OWG be sunsetted. BSC/NCIPC provided their recommendations to HHS and CDC on July 20, 2021. CDC
considered OWG’s observations, BSC/NCIPC recommendations, and public comments during BSC/NCIPC meetings when revising
the draft clinical practice guideline (112,113). A list of BSC/NCIPC and of OWG members appears at the end of this report. The
recommendations and all statements included in this guideline are those of CDC and do not necessarily represent the official
position of any persons or organizations providing comments on this guideline.

Federal Partner Engagement

BSC/NCIPC invited federal partners to serve as ex officio members of OWG, including representatives from the National Institute
on Drug Abuse (NIDA) at the National Institutes of Health (NIH), the Substance Abuse and Mental Health Services Administration
(SAMHSA), FDA, and the Indian Health Service (IHS). BSC/NCIPC included ex officio members from the Administration for
Children and Families; the Administration on Aging in the Administration for Community Living; the National Institute for
Occupational Safety and Health and the National Center for Health Statistics at CDC; the Health Resources and Services
Administration; IHS; SAMHSA; and the National Institute on Aging, the National Institute of Child Health and Human
Development, NIDA, and the National Institute of Mental Health at NIH. Additional federal partners were engaged throughout the
clinical practice guideline update process. Federal partners reviewed the full draft clinical practice guideline as part of CDC’s
agency clearance process.

Public Comment and Community Engagement

CDC sought input through Federal Register notices to better understand community members’ experiences and perspectives
related to pain and pain management options before drafting the clinical practice guideline (113). Through the Federal Register
notice (85 FR 21441) posted from April 17, 2020, through June 16, 2020, CDC invited input specifically on topics focused on using
or prescribing opioid pain medications, nonopioid medications, or nonpharmacologic treatments and received 5,392 public
comments. Public comments were synthesized into common themes, using a CDC-funded analysis contract, and reviewed by CDC.

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 10 of 89
:
 In addition, the Lab at the U.S. Office of Personnel Management (OPM) (https://lab.opm.gov  ) worked with CDC to design and
implement community engagement opportunities. These opportunities were designed to gain additional insight into the values
and preferences of groups including patients with acute or chronic pain, patients’ family members or caregivers, and clinicians who
care for patients with pain or conditions that can complicate pain management (e.g., opioid use disorder or overdose).

CDC planned to have in-person individual conversations with patients, caregivers, and clinicians but pivoted to holding
conversations with persons in a virtual format because of the COVID-19 pandemic. CDC posted a companion Federal Register
notice (85 FR 44303) from July 22, 2020, through August 21, 2020, to solicit input from patients, caregivers, and clinicians
interested in participating in individual conversations. After the Federal Register notice closed, CDC and OPM randomly selected
participants within each group (i.e., patients, caregivers, and clinicians) from 973 respondents. CDC and OPM also developed a
randomly selected waiting list of participants to fill conversation appointments that were missed or canceled by participants. The
community engagement was authorized under the Generic Clearance for the Collection of Qualitative Feedback on Agency Service
Delivery (OMB Control Number 0920–1050) approval for the Paperwork Reduction Act. CDC and OPM conducted telephone and
video conversations throughout September 2020 and spoke with 106 persons, including 42 patients, 21 caregivers, and 43
clinicians. Participants lived and worked all over the United States and had diverse experiences with opioids. Participants provided
verbal consent for their conversations to be recorded. A transcription service reviewed the conversation recordings to develop
anonymized transcripts. CDC and OPM reviewed the anonymized transcripts to develop thematic summaries.

CDC and OPM also held two human-centered codesign workshops with staff from CDC and the Centers for Medicare & Medicaid
Services. Workshop topics included framing priority needs for public input; objectives for individual conversations; and
synthesizing engagement strategies on the basis of insights from public comments and conversations with patients, caregivers,
and clinicians. Workshop participants included HHS staff who were themselves patients, caregivers, clinicians, clinical practice
guideline authors, and other subject matter experts.

CDC also gathered input through oral and written public comment opportunities at and in conjunction with public BSC/NCIPC
meetings. These public comment opportunities were announced through Federal Register notices (Federal Register 84 FR 57021;
84 FR 65159; 85 FR 30709; 85 FR 40290; 86 FR 1502; 86 FR 30048) and NCIPC newsletters.

CDC reviewed thematic summaries of public comments, individual conversations, and workshops to learn more about values and
preferences of patients, caregivers, clinicians, and experts before drafting the clinical practice guideline (113). After incorporating
observations and comments on the draft clinical practice guideline from BSC/NCIPC and the agency clearance process, CDC
posted the revised full draft clinical practice guideline and supporting materials in the Federal Register for public comment
(Federal Register 87 FR 7838). The public comment period was open for 60 days (February 10–April 11, 2022). The Federal
Docket received approximately 5,500 unique comments (including one comment submitted with 28,322 additional signatories)
from the public, including patients with acute and chronic pain, caregivers, and clinicians, and organizational perspectives from
medical associations, professional organizations, academic institutions, state and local governments, and advocacy and industry
groups. CDC reviewed and considered all public comments when revising the clinical practice guideline.

Peer Review
This clinical practice guideline provides influential scientific information that could have a clear and substantial effect on public-
and private-sector decisions. Therefore, peer review of the draft clinical practice guideline was required per the final information
quality bulletin for peer review (https://www.whitehouse.gov/wp-content/uploads/2019/04/M-19-15.pdf   ).

CDC identified peer reviewers on the basis of multiple factors, including scientific and subject matter expertise, racial and ethnic
diversity, gender diversity, diversity of experiences and perspectives, independence from the clinical practice guideline
development process, and consideration of conflicts of interest. Specific effort was made to identify subject matter experts with
knowledge and experience in topics such as chronic and acute pain management, clinical practice, health equity, mental health and
well-being, opioids and opioid therapies, opioid tapering, opioid use disorder treatment, pharmacologic and nonpharmacologic
pain management, and surgical pain management. CDC assessed potential conflicts of interest before finalizing selection of peer
reviewers. The NCIPC Associate Director for Science reviewed conflict of interest disclosure forms and determined no conflicts of
interest were present. After the peer reviews were completed, CDC posted the names of peer reviewers on the NCIPC and
CDC/ATSDR Peer Review Agenda websites, which provide information about the peer review of influential government scientific

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 11 of 89
:
 documents (114,115). Peer reviewers independently reviewed the draft clinical practice guideline and evaluated its scientific merit
and practical implementation considerations, with the goal of maintaining high-quality science and providing evidence-based
recommendations to guide clinical practice and decision-making to help prevent opioid-related harms. CDC reviewed and
considered peer review comments when revising the clinical practice guideline.
Top

Recommendations
This clinical practice guideline includes 12 recommendations for clinicians who are prescribing opioids for outpatients aged ≥18
years with acute (duration of <1 month), subacute (duration of 1–3 months), or chronic (duration of >3 months) pain, excluding
pain management related to sickle cell disease, cancer-related pain treatment, palliative care, and end-of-life care (Box 3). The
recommendations are not intended to be implemented as absolute limits of policy or practice across populations by organizations,
health care systems, or government entities. In accordance with the ACIP adapted GRADE method, CDC based the
recommendations on consideration of clinical evidence, contextual evidence (e.g., benefits and harms, values and preferences, and
resource allocation), and expert opinion. Expert input is reflected within the recommendation rationales. For each recommendation
statement, CDC notes the recommendation category (A or B) and the type of evidence (1, 2, 3, or 4) supporting the statement
(Box 3).

Category A recommendations indicate that most patients should receive the recommended course of action; category B
recommendations indicate that different choices will be appropriate for different patients, requiring clinicians to help patients
arrive at a decision consistent with patient values and preferences and specific clinical situations. Consistent with the ACIP
(106,116) and GRADE method (103), category A recommendations were made, even with type 3 and 4 evidence, when there was
broad agreement that the advantages of a clinical action greatly outweighed the disadvantages. Category B recommendations
were made when there was broad agreement that the advantages and disadvantages of a clinical action were more balanced, but
advantages were significant enough to warrant a recommendation. Recommendations were associated with a range of evidence
types, from type 1 to type 4.

In summary, the categorization of recommendations was based on the following assessment:

A number of nonpharmacologic treatments and nonopioid medications are associated with improvements in pain, function, or
both that are reportedly comparable to improvements associated with opioid use (7–11).
Evidence exists that multiple noninvasive nonpharmacologic interventions improve chronic pain and function, with small to
moderate effects in specific pain conditions, and are not associated with serious harms. Compared with medication treatment,
for which benefits are anticipated while patients are taking the medication but are not usually expected to persist after
patients stop taking the medication, multiple noninvasive nonpharmacologic interventions are associated with improvements
in pain, function, or both that are sustained after completion of treatment (9).
Nonopioid drugs, including serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressants, pregabalin or gabapentin,
and nonsteroidal anti-inflammatory drugs (NSAIDs), are associated with small to moderate improvements in chronic pain and
function. Drug class–specific adverse events include serious cardiovascular, gastrointestinal, or renal effects with NSAIDs and
sedation with anticonvulsants (8).
Opioid therapy is associated with similar or decreased effectiveness for pain and function versus NSAIDs across multiple
common acute pain conditions (10). Opioid therapy is associated with small improvements in short-term (duration of 1 to <6
months) pain and function compared with placebo, with increased short-term harms compared with placebo, and with
evidence of attenuated pain reduction over time (between 3 and 6 months versus between 1 and 3 months) (10). Evidence
exists from observational studies of an association between opioid use for acute pain and long-term opioid use (10). Evidence
on long-term effectiveness of opioids remains very limited (7); a long-term (12 months) randomized trial of stepped therapy
for chronic musculoskeletal pain found no difference in function and higher pain intensity after starting with opioid therapy
compared with starting with nonopioid therapy (74). Evidence exists of increased risk for serious harms (including opioid use
disorder and overdose) with long-term opioid therapy that appears to rise with increase in opioid dosage, without a clear
threshold below which there is no risk (7).
No validated, reliable way exists to predict which patients will experience serious harm from opioid therapy and which
patients will benefit from opioid therapy (7).

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 12 of 89
:
 Discontinuing opioids after extended periods of continuous opioid use can be challenging for clinicians and patients. Tapering
or discontinuing opioids in patients who have taken them long term can be associated with clinically significant risks (68),
particularly if opioids are tapered rapidly or patients do not receive effective support.
Patients, caregivers, and clinicians responded to CDC with invited input about their experiences and perspectives related to
pain and pain management options. Themes included strained patient-clinician relationships and the need for patients and
clinicians to make shared decisions, the effects of misapplication of the 2016 CDC Opioid Prescribing Guideline, inconsistent
access to effective pain management solutions, and achieving reduced prescription opioid use through diverse approaches.
Members of the public responded to CDC with invited comments. Themes included experiences with pain or experiences in
the aftermath of the overdose of a friend, family member, or significant other; barriers and access to pain care and to
evidence-based treatment; concerns about the level of specificity of recommendations; and overall communication and
implementation of the clinical practice guideline.

Each of the 12 recommendation statements is followed by considerations for implementation and a rationale for the
recommendation. The implementation considerations offer practical insights, context, and specific examples meant to further
inform clinician-patient decision-making for the respective recommendation and are not meant to be rigidly or inflexibly followed.

The recommendations are grouped into four areas:

1. Determining whether or not to initiate opioids for pain

2. Selecting opioids and determining dosages
3. Deciding duration of initial opioid prescription and conducting follow-up
4. Assessing risk and addressing potential harms of opioid use

In addition, these five guiding principles should broadly inform implementation across recommendations (Box 4):

1. Acute, subacute, and chronic pain needs to be appropriately assessed and treated independent of whether opioids are part of
a treatment regimen.
2. Recommendations are voluntary and are intended to support, not supplant, individualized, person-centered care. Flexibility to
meet the care needs and the clinical circumstances of a specific patient is paramount.
3. A multimodal and multidisciplinary approach to pain management attending to the physical health, behavioral health, long-
term services and supports, and expected health outcomes and well-being of each person is critical.
4. Special attention should be given to avoid misapplying this clinical practice guideline beyond its intended use or
implementing policies purportedly derived from it that might lead to unintended and potentially harmful consequences for
patients.
5. Clinicians, practices, health systems, and payers should vigilantly attend to health inequities; provide culturally and
linguistically appropriate communication (117), including communication that is accessible to persons with disabilities; and
ensure access to an appropriate, affordable, diversified, coordinated, and effective nonpharmacologic and pharmacologic pain
management regimen for all persons.

Determining Whether or Not to Initiate Opioids for Pain

All patients with pain should receive treatment that provides the greatest benefits relative to risks. (See Recommendation 1 for
determining whether or not to initiate opioids for acute pain [i.e., pain lasting <1 month] and Recommendation 2 for determining
whether or not to initiate opioids for subacute pain [i.e., pain lasting 1–3 months] or chronic pain [i.e., pain lasting >3 months].)

Recommendation 1
Nonopioid therapies are at least as effective as opioids for many common types of acute pain. Clinicians should maximize use
of nonpharmacologic and nonopioid pharmacologic therapies as appropriate for the specific condition and patient and only
consider opioid therapy for acute pain if benefits are anticipated to outweigh risks to the patient. Before prescribing opioid

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 13 of 89
:
 therapy for acute pain, clinicians should discuss with patients the realistic benefits and known risks of opioid therapy
(recommendation category: B; evidence type: 3).

Implementation Considerations
Nonopioid therapies are at least as effective as opioids for many common acute pain conditions, including low back pain, neck
pain, pain related to other musculoskeletal injuries (e.g., sprains, strains, tendonitis, and bursitis), pain related to minor
surgeries typically associated with minimal tissue injury and mild postoperative pain (e.g., simple dental extraction), dental
pain, kidney stone pain, and headaches including episodic migraine.
Clinicians should maximize use of nonopioid pharmacologic (e.g., topical or oral NSAIDs, acetaminophen) and
nonpharmacologic (e.g., ice, heat, elevation, rest, immobilization, or exercise) therapies as appropriate for the specific
condition.
Opioid therapy has an important role for acute pain related to severe traumatic injuries (including crush injuries and burns),
invasive surgeries typically associated with moderate to severe postoperative pain, and other severe acute pain when
NSAIDs and other therapies are contraindicated or likely to be ineffective.
When diagnosis and severity of acute pain warrant the use of opioids, clinicians should prescribe immediate-release opioids
(see Recommendation 3) at the lowest effective dose (see Recommendation 4) and for no longer than the expected duration
of pain severe enough to require opioids (see Recommendation 6).
Clinicians should prescribe and advise opioid use only as needed (e.g., hydrocodone 5 mg/acetaminophen 325 mg, one tablet
not more frequently than every 4 hours as needed for moderate to severe pain) rather than on a scheduled basis (e.g., one
tablet every 4 hours) and encourage and recommend an opioid taper if opioids are taken around the clock for more than a few
days (see Recommendation 6).
If patients already receiving opioids long term require additional medication for acute pain, nonopioid medications should be
used when possible and, if additional opioids are required (e.g., for superimposed severe acute pain), they should be
continued only for the duration of pain severe enough to require additional opioids, returning to the patient’s baseline opioid
dosage as soon as possible, including a taper to baseline dosage if additional opioids were used around the clock for more
than a few days (see Recommendation 6).
Clinicians should ensure that patients are aware of expected benefits of, common risks of, serious risks of, and alternatives to
opioids before starting or continuing opioid therapy and should involve patients meaningfully in decisions about whether to
start opioid therapy.

Supporting Rationale
Evaluation of the patient is critical to appropriate management. Evaluation can identify reversible causes of pain and underlying
etiologies with potentially serious sequelae that require urgent action. To guide patient-specific selection of therapy, clinicians
should evaluate patients and establish or confirm the diagnosis. Diagnosis can help identify interventions to reverse, ameliorate, or
prevent worsening of pain and improve function (e.g., surgical intervention to repair structure and function after certain traumatic
injuries, bracing to prevent recurrence of acute ankle sprain, fracture immobilization, ice or elevation to reduce swelling, and early
mobilization to maintain function) (118).

Noninvasive Nonpharmacologic Approaches to Acute Pain

Noninvasive nonpharmacologic approaches to acute pain have the potential to improve pain and function without risk for serious
harms (10). Clinical evidence reviews found that some nonpharmacologic treatments were likely effective for acute pain, such as
heat therapy for acute low back pain; several others might be effective for specific acute pain conditions, such as spinal
manipulation for acute back pain with radiculopathy, a cervical collar or exercise for acute neck pain with radiculopathy,
acupressure for acute musculoskeletal pain, massage for postoperative pain (10), and remote electrical neuromodulation for acute
pain related to episodic migraine (11).

The American College of Physicians (ACP) recommends nonpharmacologic treatment with superficial heat, massage, acupuncture,
or spinal manipulation as a cornerstone of treatment for acute low back pain (119). ACP and the American Academy of Family
Physicians (AAFP) suggest acupressure to improve pain and function and transcutaneous electrical nerve stimulation to reduce
pain in patients with acute musculoskeletal injuries (120).

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 14 of 89
:
 Despite evidence supporting their use, noninvasive nonpharmacologic therapies are not always or fully covered by insurance (43),
and access and cost can be barriers, particularly for persons who are uninsured, have limited income, have transportation
challenges, or live in rural areas where treatments are not available (121). Experts from OWG expressed concern about limited
access to nonopioid pain management modalities, in part because of lack of availability or lack of coverage by payers, and
emphasized improving access to nonopioid pain management modalities as a priority. Health insurers and health systems can
contribute to improved pain management and reduced medication use by increasing access to noninvasive nonpharmacologic
therapies with evidence of effectiveness (9,43). Noninvasive nonpharmacologic approaches should be used as appropriate to
alleviate acute pain, including ice and elevation to reduce swelling and discomfort from musculoskeletal injuries, heat to alleviate
low back pain, and other modalities depending on the cause of the acute pain.

Nonopioid Medications for Acute Pain

Many acute pain conditions often can be managed most effectively with nonopioid medications (10,122). A systematic review
found that for musculoskeletal injuries such as sprains, whiplash, and muscle strains, topical NSAIDs provided the greatest
benefit-harm ratio, followed by oral NSAIDs or acetaminophen with or without diclofenac (122). NSAIDs have been found to be
more effective than opioids for surgical dental pain and kidney stone pain and similarly effective to opioids for low back pain (10).
Evidence is limited on comparative effectiveness of therapies for acute neuropathic pain, neck pain, and postoperative pain (10).
For episodic migraine, triptans, NSAIDs, antiemetics, dihydroergotamine, calcitonin gene-related peptide antagonists (gepants),
and lasmiditan are associated with improved pain and function with usually mild and transient adverse events (11).

ACP recommends NSAIDs or skeletal muscle relaxants if pharmacologic treatment is desired to treat low back pain (119). For
acute musculoskeletal injuries other than low back pain, ACP and AAFP recommend topical NSAIDs with or without menthol gel
as first-line therapy and suggest oral NSAIDs to relieve pain or improve function or oral acetaminophen to reduce pain (120). The
American Dental Association (ADA) recommends NSAIDs as first-line treatment for acute dental pain management (123). For
acute kidney stone pain, NSAIDs are at least as effective as opioids (124–127), can decrease the ureteral smooth muscle tone and
ureteral spasm (128) causing kidney stone pain, and are preferred for kidney stone pain if not contraindicated. Triptans, NSAIDs,
combined triptans with NSAIDs, antiemetics, dihydroergotamine, and acetaminophen are established acute treatments for
migraine (11). Lasmiditan, an 5-HT1F receptor agonist, and ubrogepant, a gepant, were approved by FDA in 2019 for the
treatment of migraine (129); another gepant, rimegepant, was approved in 2020. Lasmiditan and the gepants were more effective
than placebo in providing pain relief at 2 hours, 1 day, and 1 week (11). Adverse events related to these newer medications
require further study; however, their mechanisms of action are believed to be nonvasoconstrictive (130) and potentially carry
lower risks than vasoactive medications in patients with cardiovascular risk factors (11).

When not contraindicated, NSAIDs should be used for low back pain, painful musculoskeletal injuries (including minor pain
related to fractures), dental pain, postoperative pain, and kidney stone pain; triptans, NSAIDs, or their combinations should be
used along with antiemetics as needed for acute pain related to episodic migraine. NSAID use has been associated with serious
gastrointestinal events and major coronary events (8), particularly in patients with cardiovascular or gastrointestinal comorbidities,
and clinicians should weigh risks and benefits of use, dose, and duration of NSAIDs when treating older adults as well as patients
with hypertension, renal insufficiency, heart failure, or those with risk for peptic ulcer disease or cardiovascular disease. Vasoactive
effects of triptans and ergot alkaloids might preclude their use in patients with migraine who also have cardiovascular risk factors
(11,131,132). Clinicians should review FDA-approved labeling, including boxed warnings, before initiating treatment with any
pharmacologic therapy.

Pain Management for Pregnant and Postpartum Persons

For pain management in the postpartum period, the American College of Obstetricians and Gynecologists (ACOG) recommends
stepwise, multimodal, shared decision-making, incorporating pharmacologic treatments that might include opioids. After vaginal
delivery, ACOG recommends acetaminophen or NSAIDs, and if needed, adding an opioid. After cesarean delivery, ACOG
recommends standard oral and parenteral medications such as acetaminophen, NSAIDs, or low-dose, low-potency, short-acting
opioids with duration of opioid use limited to the shortest reasonable course expected for treating acute pain (133). ACOG
recommends counseling persons who are prescribed opioids about the risk for central nervous system depression in the
postpartum person and in the breastfed infant (133), noting that if a codeine-containing medication is selected, duration of therapy
and neonatal signs of toxicity should be reviewed with patients and their families (133).

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 15 of 89
:
 Opioid Medication for Acute Pain
A systematic review found that for musculoskeletal injuries such as sprains, whiplash, and muscle strains, no opioid provided
better benefit than NSAIDs, and opioid use caused the most harms (122). The evidence review (10) found that opioids might not
be more effective than nonopioid therapies for some acute pain conditions (134–138), and use of opioids might negatively affect
recovery and function (139,140). The review found that opioids were probably less effective than NSAIDs for surgical dental pain
and kidney stone pain, less effective than acetaminophen for kidney stone pain, and similarly effective as NSAIDs for low back
pain (10). For postoperative pain, effects of opioids on pain intensity were inconsistent, and opioids were associated with increased
likelihood of repeat or rescue analgesic use (10). Evidence was insufficient for opioids in treatment of episodic migraine (11).
Compared with NSAIDs or acetaminophen, opioids were associated with increased risk for short-term adverse events, including
any adverse event, nausea, dizziness, and somnolence (10). Observational studies found that opioid use for acute low back pain or
postoperative pain was associated with increased likelihood of long-term opioid use (10). Proportions of adults with new long-
term opioid use at follow-up after initiation for short-term use for postoperative pain have ranged from <1% to 13% (141–146).
Odds of long-term opioid use at follow-up after initiation for short-term use for acute pain might be greater with higher dosage
and longer initial duration of exposure. For example, one study found that, compared with no early opioid use for acute low back
pain, the adjusted odds ratio was 2.08 (95% CI: 1.55–2.78) for an early prescription totaling 1–140 MME and increased to 6.14
(95% CI: 4.92–7.66) for an early prescription totaling ≥450 MME (140). In episodic migraine, opioids as well as butalbital-
containing medications were associated with a twofold higher risk for development of medication overuse headache compared
with simple analgesics and triptans (11,147). Serious adverse events were uncommon for opioids and other medications; however,
studies were not designed to assess risk for overdose, opioid use disorder, or long-term harms (10).

For acute low back pain, ACP found insufficient evidence for effectiveness of opioids and recommends nonopioid medications (see
Nonopioid Medications for Acute Pain) if choosing pharmacologic treatment (119). ACP and AAFP suggest against treating
patients with acute pain from musculoskeletal injuries with opioids, including tramadol (120). ADA recommends NSAIDs as the
first-line therapy for acute pain management (see Nonopioid Medications for Acute Pain) (123). Multiple guidelines that address
prescribing for postoperative pain include both nonopioid and opioid treatment options and have emphasized multimodal
analgesia, incorporating around-the-clock nonopioid analgesics and nonpharmacologic therapies and noting that systemic opioids
often are needed postoperatively but are not required in all patients (148–151). The American Headache Society recommends
against prescribing opioid or butalbital-containing medications as first-line treatment for recurrent headache disorders (152), and
the American Academy of Neurology also recommends against use of both of these classes of medications for treatment of
migraine, except as a last resort (153).

Because of equivalent or lesser effectiveness for pain relief compared with NSAIDs and risks for long-term opioid use after using
opioids for acute pain, opioids are not recommended as first-line therapy for many common acute pain conditions, including low
back pain, neck pain, pain related to other musculoskeletal injuries (e.g., sprains, strains, tendonitis, and bursitis), pain related to
minor surgeries typically associated with minimal tissue injury and only mild postoperative pain (e.g., simple dental extraction),
dental pain, kidney stone pain, and headaches including episodic migraine. Opioid therapy has an important role for acute pain
related to severe traumatic injuries (including crush injuries and burns), invasive surgeries typically associated with moderate to
severe postoperative pain, and other severe acute pain when NSAIDs and other therapies are contraindicated or likely to be
ineffective.

When diagnosis and severity of acute pain warrant the use of opioids, clinicians should prescribe immediate-release opioids (see
Recommendation 3) at the lowest effective dose (see Recommendation 4) and for no longer than the expected duration of pain
severe enough to require opioids (see Recommendation 6) to minimize unintentional initiation of long-term opioid use. Clinicians
should maximize use of nonopioid pharmacologic (e.g., NSAIDs, acetaminophen, or both) and nonpharmacologic (e.g., ice, heat,
elevation, rest, immobilization, or exercise) therapies as appropriate for the specific condition and continue these therapies as
needed after opioids are discontinued. Clinicians should work with patients to prevent prolonged opioid use, prescribe and advise
opioid use only as needed (e.g., hydrocodone 5 mg/acetaminophen 325 mg, one tablet not more frequently than every 4 hours as
needed for moderate to severe pain) rather than on a scheduled basis (e.g., one tablet every 4 hours), and encourage and include
an opioid taper if opioids will be taken around the clock for more than a few days (see Recommendation 6). Clinicians should
consider concurrent medical conditions, including sleep apnea, pregnancy, renal or hepatic insufficiency, mental health conditions,
and substance use disorders, in assessing risks of opioid therapy (see Recommendation 8); offer naloxone, particularly if the
patient or a household member has risk factors for opioid overdose (see Recommendation 8); use particular caution when

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 16 of 89
:
 prescribing benzodiazepines or other sedating medications with opioid pain medication (see Recommendation 11); and check the
prescription drug monitoring program (PDMP) database to ensure a new opioid prescription will not contribute to cumulative
opioid dosages or medication combinations that put the patient at risk for overdose (see Recommendation 9). If signs of opioid use
disorder are present, clinicians should address concerns with the patient, offer or arrange medication treatment for patients who
meet criteria for opioid use disorder, and use nonpharmacologic and pharmacologic treatments as appropriate to manage the
patient’s pain (see Recommendation 12 and the ASAM National Practice Guideline for the Treatment of Opioid Use Disorder: 2020
Focused Update) (96).

Although findings regarding risks for new long-term opioid use after use for acute pain (10) relate specifically to patients who
were previously opioid naïve, risks also might be associated with dosage escalation (see Recommendation 4) if patients already
treated with long-term opioids are prescribed additional opioid medication for new acute pain superimposed on chronic pain.
Therefore, strategies that minimize opioid use should be implemented for both opioid-naïve and opioid-tolerant patients with
acute pain when possible. If patients receiving long-term opioid therapy require additional medication for acute pain, nonopioid
medications should be used when possible. If additional opioids are required (e.g., for superimposed severe acute pain), they
should be continued only for the duration of pain severe enough to require additional opioids, returning to the patient’s baseline
opioid dosage as soon as possible, including an appropriate taper to baseline dosage if additional opioids were used around the
clock for more than a few days (see Recommendation 6).

Patient education and discussion before starting outpatient opioid therapy are critical so that patient preferences and values can
be understood and used to inform clinical decisions. Clinicians should ensure that patients are aware of expected benefits of,
common risks of, serious risks of, and alternatives to opioids before starting or continuing opioid therapy and should involve
patients in decisions about whether to start opioid therapy. Essential elements for communication and discussion with patients
before prescribing outpatient opioid therapy for acute pain include the following:

Advise patients that short-term opioid use can lead to unintended long-term opioid use and of the importance of working
toward planned discontinuation of opioid use as soon as feasible, including a plan to appropriately taper opioids as pain
resolves if opioids have been used around the clock for more than a few days (see Recommendation 6).
Review communication mechanisms and protocols patients can use to tell clinicians of severe or uncontrolled pain and to
arrange for timely reassessment and management.
Advise patients about serious adverse effects of opioids, including potentially fatal respiratory depression and development
of a potentially serious opioid use disorder (see Recommendation 12) that can cause distress and inability to fulfill major role
obligations at work, school, or home.
Advise patients about common effects of opioids, such as constipation, dry mouth, nausea, vomiting, drowsiness, confusion,
tolerance, physical dependence, and withdrawal symptoms when stopping opioids. To prevent constipation associated with
opioid use, advise patients to increase hydration and fiber intake and to maintain or increase physical activity as they are able.
Prophylactic pharmacologic therapy (e.g., a stimulant laxative such as senna, with or without a stool softener) might be
needed to ensure regular bowel movements if opioids are used for more than a few days. Stool softeners or fiber laxatives
without another laxative should be avoided. To minimize withdrawal symptoms, clinicians should provide and discuss an
opioid tapering plan when opioids will be used around the clock for more than a few days (see Recommendation 6). Limiting
opioid use to the minimum needed to manage pain (e.g., taking the opioid only when needed if needed less frequently than
every 4 hours and the prescription is written for every 4 hours as needed for pain) can help limit development of tolerance
and therefore withdrawal after opioids are discontinued.
If formulations are prescribed that combine opioids with acetaminophen, advise patients of the risks of taking additional over-
the-counter products containing acetaminophen.
To help patients assess when a dose of opioids is needed, explain that the goal is to reduce pain to make it manageable
rather than to eliminate pain.
Discuss effects that opioids might have on a person’s ability to safely operate a vehicle or other machinery, particularly when
opioids are initiated or when other central nervous system depressants (e.g., benzodiazepines or alcohol) are used
concurrently.
Discuss the potential for workplace toxicology testing programs to detect therapeutic opioid use.

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 17 of 89
:
 Discuss increased risks for opioid use disorder, respiratory depression, and death at higher dosages, along with the
importance of taking only the amount of opioids prescribed (i.e., not taking more opioids than prescribed or taking them more
often).
Review increased risks for respiratory depression when opioids are taken with benzodiazepines, other sedatives, alcohol,
nonprescribed or illicit drugs (e.g., heroin), or other opioids (see Recommendations 8 and 11).
Discuss risks to household members and other persons if opioids are intentionally or unintentionally shared with others for
whom they are not prescribed, including the possibility that others might experience overdose at the same or lower dosage
than prescribed for the patient and that young children and pets are susceptible to unintentional ingestion. Discuss storage of
opioids in a secure and preferably locked location, options for safe disposal of unused opioids (154), and the value of having
naloxone available.
Discuss planned use of precautions to reduce risks, including naloxone for overdose reversal (see Recommendation 8) and
clinician use of PDMP information (see Recommendation 9).

Recommendation 2
Nonopioid therapies are preferred for subacute and chronic pain. Clinicians should maximize use of nonpharmacologic and
nonopioid pharmacologic therapies as appropriate for the specific condition and patient and only consider initiating opioid
therapy if expected benefits for pain and function are anticipated to outweigh risks to the patient. Before starting opioid
therapy for subacute or chronic pain, clinicians should discuss with patients the realistic benefits and known risks of opioid
therapy, should work with patients to establish treatment goals for pain and function, and should consider how opioid
therapy will be discontinued if benefits do not outweigh risks (recommendation category: A; evidence type: 2).

Implementation Considerations
To guide patient-specific selection of therapy, clinicians should evaluate patients and establish or confirm the diagnosis.
Clinicians should recommend appropriate noninvasive nonpharmacologic approaches to help manage chronic pain, such as
exercise (e.g., aerobic, aquatic, or resistance exercises) or exercise therapy (a prominent modality in physical therapy) for back
pain, fibromyalgia, and hip or knee osteoarthritis; weight loss for knee osteoarthritis; manual therapies for hip osteoarthritis;
psychological therapy, spinal manipulation, low-level laser therapy, massage, mindfulness-based stress reduction, yoga,
acupuncture, and multidisciplinary rehabilitation for low back pain; mind-body practices (e.g., yoga, tai chi, or qigong),
massage, and acupuncture for neck pain; cognitive behavioral therapy, myofascial release massage, mindfulness practices, tai
chi, qigong, acupuncture, and multidisciplinary rehabilitation for fibromyalgia; and spinal manipulation for tension headache.
Low-cost options to integrate exercise include walking in public spaces or use of public recreation facilities for group exercise.
Physical therapy can be helpful, particularly for patients who have limited access to safe public spaces or public recreation
facilities for exercise or whose pain has not improved with low-intensity physical exercise.
Health insurers and health systems can improve pain management and reduce medication use and associated risks by
increasing reimbursement for and access to noninvasive nonpharmacologic therapies with evidence for effectiveness.
Clinicians should review FDA-approved labeling, including boxed warnings, and weigh benefits and risks before initiating
treatment with any pharmacologic therapy.
When patients affected by osteoarthritis have an insufficient response to nonpharmacologic interventions such as exercise
for arthritis pain, topical NSAIDs can be used in patients with pain in a single or few joints near the surface of the skin (e.g.,
knee). For patients with osteoarthritis pain in multiple joints or incompletely controlled with topical NSAIDs, duloxetine or
systemic NSAIDs can be considered.
NSAIDs should be used at the lowest effective dose and shortest duration needed and should be used with caution,
particularly in older adults and in patients with cardiovascular comorbidities, chronic renal failure, or previous gastrointestinal
bleeding.
When patients with chronic low back pain have had an insufficient response to nonpharmacologic approaches such as
exercise, clinicians can consider NSAIDs or duloxetine for patients without contraindications.
Tricyclic, tetracyclic, and SNRI antidepressants; selected anticonvulsants (e.g., pregabalin, gabapentin enacarbil,
oxcarbazepine); and capsaicin and lidocaine patches can be considered for neuropathic pain. In older adults, decisions to use
tricyclic antidepressants should be made judiciously on a case-by-case basis because of risks for confusion and falls.

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 18 of 89
:
 Duloxetine and pregabalin are FDA-approved for the treatment of diabetic peripheral neuropathy, and pregabalin and
gabapentin are FDA-approved for treatment of postherpetic neuralgia.
In patients with fibromyalgia, tricyclic (e.g., amitriptyline) and SNRI antidepressants (e.g., duloxetine, milnacipran), NSAIDs
(e.g., topical diclofenac), and specific anticonvulsants (i.e., pregabalin and gabapentin) are used to improve pain, function, and
quality of life. Duloxetine, milnacipran, and pregabalin are FDA-approved for the treatment of fibromyalgia. In older adults,
decisions to use tricyclic antidepressants should be made judiciously on a case-by-case basis because of risks for confusion
and falls.
Patients with co-occurring pain and depression might be especially likely to benefit from antidepressant medication (see
Recommendation 8).
Opioids should not be considered first-line or routine therapy for subacute or chronic pain. This does not mean that patients
should be required to sequentially fail nonpharmacologic and nonopioid pharmacologic therapy or be required to use any
specific treatment before proceeding to opioid therapy. Rather, expected benefits specific to the clinical context should be
weighed against risks before initiating therapy. In some clinical contexts (e.g., serious illness in a patient with poor prognosis
for return to previous level of function, contraindications to other therapies, and clinician and patient agreement that the
overriding goal is patient comfort), opioids might be appropriate regardless of previous therapies used. In other situations
(e.g., headache or fibromyalgia), expected benefits of initiating opioids are unlikely to outweigh risks regardless of previous
nonpharmacologic and nonopioid pharmacologic therapies used.
Opioid therapy should not be initiated without consideration by the clinician and patient of an exit strategy to be used if
opioid therapy is unsuccessful.
Before opioid therapy is initiated for subacute or chronic pain, clinicians should determine jointly with patients how functional
benefit will be evaluated and establish specific, measurable treatment goals.
For patients with subacute pain who started opioid therapy for acute pain and have been treated with opioid therapy for ≥30
days, clinicians should ensure that potentially reversible causes of chronic pain are addressed and that opioid prescribing for
acute pain does not unintentionally become long-term opioid therapy simply because medications are continued without
reassessment. Continuation of opioid therapy at this point might represent initiation of long-term opioid therapy, which
should occur only as an intentional decision that benefits are likely to outweigh risks after informed discussion between the
clinician and patient and as part of a comprehensive pain management approach.
Clinicians seeing new patients already receiving opioids should establish treatment goals, including functional goals, for
continued opioid therapy. Clinicians should avoid rapid tapering or abrupt discontinuation of opioids (see Recommendation 5).
Patient education and discussion before starting opioid therapy are critical so that patient preferences and values can be
understood and used to inform clinical decisions.
Clinicians should review available low-cost options for pain management for all patients and particularly for patients who
have low incomes, do not have health insurance, or have inadequate insurance.
Clinicians should ensure that patients are aware of expected benefits of, common risks of, serious risks of, and alternatives to
opioids before starting or continuing opioid therapy and should involve patients in decisions about whether to start opioid
therapy.

Supporting Rationale
To guide patient-specific selection of therapy, clinicians should evaluate patients and establish or confirm the diagnosis (155).
Detailed recommendations on diagnosis are provided in other guidelines (156–159). Evaluation should include a focused history,
including history and characteristics of pain and potential contributing factors (e.g., function, work history and current work
demands, psychosocial stressors, and sleep), and physical examination, with imaging or other diagnostic testing only if indicated
(e.g., if severe or progressive neurologic deficits are present or if serious underlying conditions are suspected) (158,159). For
complex pain syndromes, consultation with a pain specialist can be considered to assist with diagnosis and management.

Diagnosis can help identify disease-specific interventions to reverse, ameliorate, or prevent worsening of pain and improve
function (e.g., improving glucose control to prevent progression of diabetic neuropathy; immune-modulating agents for rheumatoid
arthritis; physical or occupational therapy to address posture, muscle weakness, or repetitive occupational motions that contribute
to musculoskeletal pain; or surgical intervention to relieve severe mechanical or compressive pain) (159). The underlying
mechanism for most pain syndromes has traditionally been categorized as neuropathic (e.g., diabetic neuropathy and postherpetic

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 19 of 89
:
 neuralgia) or nociceptive (e.g., osteoarthritis and muscular back pain). More recently, nociplastic pain has been suggested as a
third, distinct category of pain with augmented central nervous system pain and sensory processing and altered pain modulation
as experienced in conditions such as fibromyalgia (160). The diagnosis and pathophysiologic mechanism of pain have implications
for symptomatic pain treatment with medication. For example, evidence is limited for improved pain or function, or evidence exists
of worse outcomes, with long-term use of opioids for several chronic pain conditions for which opioids are commonly prescribed,
such as osteoarthritis (161), nonspecific low back pain (119,162), headache (152), and fibromyalgia (163,164). For moderate to
severe chronic back pain or hip or knee osteoarthritis pain, a nonopioid strategy starting with acetaminophen or NSAIDs results in
improved pain intensity with fewer side effects compared with a strategy starting with opioids (74). Tricyclic antidepressants,
SNRI antidepressants, selected anticonvulsants, or transdermal lidocaine are recommended for neuropathic pain syndromes (e.g.,
diabetic neuropathy or postherpetic neuralgia) (156).

Review of the patient’s history and context beyond the presenting pain syndrome is helpful in selection of pain treatments. In
particular, medications should be used only after assessment and determination that expected benefits outweigh risks,
considering patient-specific factors. For example, clinicians should consider fall risk when selecting and dosing potentially
sedating medications (e.g., tricyclic antidepressants, anticonvulsants, and opioids) and should weigh benefits and risks of use,
dosage, and duration of NSAIDs when treating older adults and patients with hypertension, renal insufficiency, heart failure, or
those with risk for peptic ulcer disease or cardiovascular disease. NSAIDs are potentially inappropriate for use in older adults with
chronic pain because of higher risk for adverse effects with prolonged use (165). Some guidelines recommend topical NSAIDs for
localized osteoarthritis (e.g., knee osteoarthritis) over oral NSAIDs in patients aged ≥75 years to minimize systemic effects (166).
(See Recommendation 8 for additional considerations for assessing risks of opioid therapy.)

Noninvasive Nonpharmacologic Approaches to Subacute and Chronic Pain

Many noninvasive nonpharmacologic approaches, including physical therapy, weight loss for knee osteoarthritis, and behavioral
therapies (e.g., cognitive behavioral therapy and mindfulness-based stress reduction), can improve pain and function without risk
for serious harms (9). High-quality evidence exists that exercise therapy (a prominent modality in physical therapy) for back pain,
fibromyalgia, and hip or knee osteoarthritis reduces pain and improves function immediately after treatment and that the
improvements are sustained for at least 2–6 months (9,167–170). Previous guidelines have recommended aerobic, aquatic, or
resistance exercises for persons with chronic pain, including osteoarthritis of the knee or hip, back pain, and fibromyalgia
(119,156,166,171). Other noninvasive nonpharmacologic therapies that improve pain, function, or both for at least 1 month after
delivery without apparent risk for serious harm include cognitive behavioral therapy for knee osteoarthritis; manual therapies for
hip osteoarthritis; psychological therapy, spinal manipulation, low-level laser therapy, massage, mindfulness-based stress
reduction, yoga, acupuncture, and multidisciplinary rehabilitation for low back pain; mind-body practices (e.g., yoga, tai chi, and
qigong), massage, and acupuncture for neck pain; cognitive behavioral therapy, myofascial release massage, mindfulness
practices, tai chi, qigong, acupuncture, and multidisciplinary rehabilitation for fibromyalgia; and spinal manipulation for tension
headache (9). For temporomandibular disorder pain, patient education and self-care can be effective, as can occlusal splints for
some patients and biobehavioral therapy for prevention of disabling symptoms (172,173). Exercise, mind-body interventions, and
behavioral treatments (including cognitive behavioral therapy and mindfulness practices) can encourage active patient
participation in the care plan and help address the effects of pain in the patient’s life; these active therapies have somewhat more
robust evidence for sustained improvements in pain and function than more passive treatments (e.g., massage), particularly at
longer-term follow-up (9). In addition, physical activity can provide additional health benefits, such as preventing or reducing
symptoms of depression (174). Active approaches that engage the patient should be used when possible, with a supplementary
role for more passive approaches, to reduce pain and improve function.

Despite their favorable benefit-to-risk profile, noninvasive nonpharmacologic therapies are not always covered or fully covered by
insurance (43). Access and cost can be barriers for patients, particularly persons who have low incomes, do not have health
insurance or have inadequate insurance, have transportation challenges, or live in rural areas where services might not be
available (121). Health insurers and health systems can improve pain management and reduce medication use and associated
risks by increasing reimbursement for and access to noninvasive nonpharmacologic therapies with evidence for effectiveness
(9,43). In addition, for many patients, aspects of these approaches can be used even when access to specialty care is limited. For
example, previous guidelines have strongly recommended aerobic, aquatic, or resistance exercises for patients with osteoarthritis
of the knee or hip (166) and maintenance of physical activity, including normal daily activities, for patients with low back pain
(158). A randomized trial found no difference in reduced chronic low back pain intensity, frequency, or disability between patients

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 20 of 89
:
 assigned to relatively low-cost group aerobics and those assigned to individual physiotherapy or muscle reconditioning sessions
(175). Low-cost options to integrate exercise include walking in public spaces or use of public recreation facilities for group
exercise. Physical therapy can be helpful, particularly for patients who have limited access to safe public spaces or public
recreation facilities for exercise or whose pain has not improved with low-intensity physical exercise. A randomized trial found a
stepped exercise program, in which patients were initially offered an Internet-based exercise program and progressively advanced
to biweekly coaching calls and then to in-person physical therapy if not improved at previous steps, successfully improved
symptomatic knee osteoarthritis, with 35% of patients ultimately requiring in-person physical therapy (176). In addition, primary
care clinicians can integrate elements of psychosocial therapies such as cognitive behavioral therapy, which addresses
psychosocial contributors to pain and improves function (177), by encouraging patients to take an active role in the care plan,
supporting patients in engaging in activities such as exercise that are typically beneficial but that might initially be associated with
fear of exacerbating pain (159), or providing education in relaxation techniques and coping strategies. In many locations, free or
low-cost patient support, self-help, and educational community-based or employer-sponsored programs are available that can
provide stress reduction and other mental health benefits. Clinicians should become familiar with such options within their
communities so they can refer patients to low-cost services. Patients with higher levels of anxiety or fear related to pain or other
clinically significant psychological distress can be referred for treatment with a mental health specialist (e.g., psychologist,
psychiatrist, or clinical social worker).

Nonopioid Medications for Subacute and Chronic Pain

Several nonopioid pharmacologic therapies (including acetaminophen, NSAIDs, and selected antidepressants and anticonvulsants)
are used for painful symptoms in chronic pain conditions. Nonopioid pharmacologic therapies are associated with risks, particularly
in older adults, pregnant patients, and patients with certain comorbidities such as cardiovascular, renal, gastrointestinal, and liver
disease. For example, NSAID use has been associated with serious gastrointestinal events and major coronary events (8).
Increases in nonserious adverse events have been found with anticonvulsants pregabalin (blurred vision, cognitive effects,
sedation, weight gain, dizziness, and peripheral edema) and gabapentin (blurred vision, cognitive effects, sedation, and weight
gain), cannabis (nausea and dizziness), and SNRI antidepressants duloxetine (nausea and sedation) and milnacipran (nausea);
dosage reductions reduced the risk for some adverse events with SNRI antidepressants (8). Clinicians should review FDA-
approved labeling, including boxed warnings, before initiating treatment with any pharmacologic therapy.

For osteoarthritis, NSAIDs including topical NSAIDs and SNRI antidepressant duloxetine have small to moderate benefits for pain
and function at short-term assessment (3–6 months), with intermediate-term (6–12 months) evidence for certain medications
(celecoxib and duloxetine) and evidence that duloxetine is more effective in older (>65 years) than younger patients and in
patients with knee osteoarthritis (8). Acetaminophen has limited evidence for effectiveness (8) and is no longer considered a first-
line treatment for osteoarthritis (161). When patients have an insufficient response to nonpharmacologic interventions (e.g.,
exercise for arthritis pain), and if a single or a few joints near the surface of the skin (e.g., knee) are affected by osteoarthritis, use
of topical NSAIDs is recommended (161). In patients with osteoarthritis pain in multiple joints or incompletely controlled pain with
topical NSAIDs, systemic NSAIDs or duloxetine can be used. However, systemic NSAIDs should be used at the lowest effective
dosage and shortest duration needed because risks might increase with longer use and at higher dosages (178).

Oral NSAIDs should be used with caution, particularly in older persons and in patients with cardiovascular comorbidities, chronic
renal failure, or previous gastrointestinal bleeding. In patients with gastrointestinal comorbidities but without current or previous
gastrointestinal bleeding, cyclooxygenase-2 inhibitors or NSAIDs with proton pump inhibitors can be used to minimize risk
compared with risk with use of NSAIDs alone (161).

Moderate-quality evidence demonstrates small improvements in chronic low back pain with NSAIDs (119) and with duloxetine
(8). When patients with low back pain have had an insufficient response to nonpharmacologic approaches such as exercise,
clinicians can consider NSAIDs or duloxetine (119) for patients without contraindications.

For temporomandibular disorder pain that is not sufficiently improved with nonpharmacologic interventions, NSAIDs can be
effective (179,180). Tricyclic, tetracyclic, and SNRI antidepressants; selected anticonvulsants; and capsaicin and lidocaine patches
are recommended for neuropathic pain (156). However, evidence on topical lidocaine and capsaicin is limited (8). SNRI
antidepressant duloxetine and anticonvulsants pregabalin, gabapentin, enacarbil, and oxcarbazepine are associated with small

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 21 of 89
:
 improvements in neuropathic pain (mainly diabetic neuropathy and postherpetic neuralgia) (8). Duloxetine and pregabalin are
FDA-approved for the treatment of diabetic neuropathy, and pregabalin and gabapentin are FDA-approved for treatment of
postherpetic neuralgia.

In patients with fibromyalgia, multiple medications are associated with small to moderate improvements in pain, function, and
quality of life, including SNRI antidepressants (duloxetine and milnacipran), NSAIDs (topical diclofenac), and specific
anticonvulsants (pregabalin and gabapentin) (8). Tricyclic and SNRI antidepressants also can relieve fibromyalgia symptoms.
Duloxetine, milnacipran, and pregabalin are FDA-approved for and are recommended for the treatment of fibromyalgia (156).
Tricyclic antidepressant amitriptyline often is used and recommended for patients with fibromyalgia (156), although evidence for
its effectiveness is limited (8). Because patients with chronic pain might experience concurrent depression (181) and depression
can exacerbate physical symptoms including pain (182), patients with co-occurring pain and depression might be especially likely
to benefit from antidepressant medication (see Recommendation 8).

Tricyclic antidepressants are potentially inappropriate for older adults (aged ≥65 years) because of their anticholinergic effects
(165). Evidence on effectiveness of cannabis for painful conditions is limited and inconsistent across studies, and some studies
have reported adverse events such as dizziness, nausea, and sedation (8,183).

Opioid Medication for Subacute and Chronic Pain

Clinical evidence reviews found insufficient evidence to determine long-term benefits of opioid therapy for chronic pain and found
an increased risk for serious harms related to long-term opioid therapy that appears to be dose dependent (7). Compared with no
opioid use, opioid use was associated with increased risk for opioid use disorder, overdose, all-cause deaths, fractures, falls, and
myocardial infarction (7). Opioids also were associated with increased risk for discontinuation because of gastrointestinal adverse
events, somnolence, dizziness, and pruritus (7). Compared with placebo, at short-term follow-up (1 to <6 months), opioids were
associated with small mean improvements in pain intensity (mean difference: −0.79 on a 0–10 scale; 95% CI: −0.93 to −0.67;
I2: 71%) and function (7). Some evidence indicates that improvement in pain is reduced with longer duration of opioid therapy,
from a mean improvement of 1 on a 0–10 scale at 1–3 months to approximately 0.5 at 3–6 months (7). No placebo-controlled trial
evaluated effectiveness of opioids at intermediate (6 to <12 months) or long-term (≥12 months) follow-up (7). Compared with
nonopioid treatments at short-term follow-up, there were no differences in mean pain improvement (mean difference: −0.29 on a
0–10 scale; 95% CI: −0.61 to 0.03) or functional improvement. No trials were identified that compared opioids with nonopioid
therapies at intermediate- or long-term follow-up, with the exception of one trial that found stepped therapy starting with opioids
to be associated with higher pain intensity than stepped therapy starting with nonopioids (4.0 versus 3.5; mean difference: 0.5;
95% CI: 0–1.0) at 12 months (7,74).

Clinical evidence reviews identified an observational study (54) finding long-term (>90 days’ supply) opioid prescription to be
associated with considerably increased risk for a new opioid use disorder diagnosis for all dosages of long-term (>90 days’ supply)
opioids prescribed compared with no opioids prescribed, with adjusted odds ratios of 15, 29, and 122 at low (1–36 MME/day),
medium (36–120 MME/day), and high (≥120 MME/day) opioid dosages, respectively. Compared with no opioid use, opioid use was
associated with increased risk for opioid use disorder, overdose, all-cause deaths, fractures, falls, and myocardial infarction (7).

Multiple experts from OWG stated that they appreciated this recommendation because of the importance of highlighting both
pain and function, sharing realistic expectations with patients before initiating treatment, and paying attention to tapering and exit
strategies. Although some experts reasoned the recommendation statement could state nonopioid therapies “may be preferred”
or “may be effective” for chronic pain, others agreed with language that nonopioid therapies “are preferred” for chronic pain
because opioid therapies are associated with small short-term benefits compared with placebo, comparable or reduced short-term
benefits compared with nonopioid therapies, uncertain long-term benefits, and potential for serious harms.

Opioids should not be considered first-line or routine therapy for subacute or chronic pain. Although evidence on long-term
benefits of nonopioid therapies also is limited, these therapies also are associated with short-term benefits, no evidence exists for
attenuated benefit over time or difficulty stopping therapy when benefits do not outweigh risks, and risks for serious harms are
usually lower. This does not mean that patients should be required to sequentially fail nonpharmacologic and nonopioid
pharmacologic therapy or be required to use any specific treatment before proceeding to opioid therapy. Rather, expected benefits
specific to the clinical context should be weighed against risks before initiating therapy. In some clinical contexts (e.g., serious

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 22 of 89
:
 illness in a patient with poor prognosis for return to previous level of function, contraindications to other therapies, and clinician
and patient agreement that the overriding goal is patient comfort), opioids might be appropriate regardless of previous therapies
used. In other situations (e.g., headache or fibromyalgia), expected benefits of initiating opioids are unlikely to outweigh risks
regardless of previous nonpharmacologic and nonopioid pharmacologic therapies used.

Clinical evidence reviews found no instrument with high accuracy for predicting opioid-related harms, such as overdose or opioid
use disorder (7). For clinicians, predicting whether benefits of opioids for chronic pain will outweigh risks of ongoing opioid
treatment for individual patients can be challenging. Therefore, opioid therapy should only be initiated with consideration by the
clinician and patient of an exit strategy that could be used if opioid therapy is unsuccessful in improving pain and pain-related
function.

Before opioid therapy is initiated for subacute or chronic pain, clinicians should determine with patients how functional benefit will
be evaluated and establish treatment goals. Some patients have reported treatment goals are effective in increasing motivation
and functioning (7). Goals ideally include improvement in function (including social, emotional, and physical dimensions), pain, and
quality of life. Goals can be tailored to specific patient and clinical circumstances. For example, for some patients with diseases
typically associated with progressive functional impairment or catastrophic injuries such as spinal cord trauma, reductions in pain
without improvement in physical function might be more realistic. Clinicians can assess and then follow function, pain severity,
and quality of life using tools such as the three-item PEG (Pain average, interference with Enjoyment of life, and interference with
General activity) assessment scale (184) (see Recommendation 7). Clinically meaningful improvement has been defined as a 30%
improvement in scores for both pain and function (185). Clinicians can ask patients about functional goals that have meaning for
them (e.g., walking the dog or walking around the block, returning to part-time work, and attending family events or recreational
activities), and then use these goals in assessing benefits of opioid therapy and weighing benefits against risks of continued opioid
therapy for individual patients (see Recommendation 7).

Patients with subacute pain might be at a particularly critical point, both for potential transition to chronic pain and potential
transition to long-term opioid therapy. Clinicians should reevaluate patients with subacute pain and their treatment course, ensure
that potentially reversible causes of ongoing pain are addressed, and optimize pain management as needed. For patients with
subacute pain who started opioid therapy for acute pain and have been treated with opioid therapy for ≥30 days, clinicians should
ensure that opioid prescribing for acute pain does not unintentionally become long-term opioid prescribing simply because
medications are continued without reassessment. Continuation of opioid therapy at this point might represent initiation of long-
term opioid therapy, which should occur only as an intentional decision that benefits are likely to outweigh risks after informed
discussion between the clinician and patient and as part of a comprehensive pain management approach.

Clinicians seeing new patients already using opioid medication should establish treatment goals, including functional goals, for
continued opioid therapy. Clinicians should avoid rapid tapering or abrupt discontinuation of opioids (see Recommendation 5).
Although the clinical evidence reviews did not find studies evaluating the effectiveness of written agreements or treatment plans
(7), clinicians and patients who clearly document a treatment plan including specific functional goals in advance of prescribing will
clarify expectations about how opioids will be prescribed and monitored with an aim to improve patient safety, health, and well-
being.

Patient education and discussion before starting opioid therapy are critical so that patient preferences and values can be
understood and used to inform clinical decisions. Clinicians should ensure that patients are aware of expected benefits of, common
risks of, serious risks of, and alternatives to opioids before starting or continuing opioid therapy and should involve patients in
decisions about whether to start opioid therapy. Many patients rank pain relief, nausea, vomiting, and constipation as important
effects (7). The following elements are essential for communication and discussion with patients before starting opioid therapy:

Review available low-cost options for pain management for all patients, and particularly for patients who have low incomes,
do not have health insurance, or have inadequate insurance. Review considerations related to access to care because of the
clinical oversight needed to initiate and continue opioid therapy and other treatments for pain.
Be explicit and realistic about expected benefits of opioids, explaining that there is not robust evidence that opioids improve
pain or function with long-term use and that complete elimination of pain is unlikely.
Emphasize improvement in function as a primary goal and that function can improve even when pain is not eliminated.

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 23 of 89
:
 Advise patients about serious adverse effects of opioids, including potentially fatal respiratory depression and development
of a potentially serious opioid use disorder that can cause distress and inability to fulfill major obligations at work, school, or
home.
Advise patients about common effects of opioids, such as constipation, dry mouth, nausea, vomiting, drowsiness, confusion,
tolerance, physical dependence, and withdrawal symptoms when stopping opioids. To prevent constipation associated with
opioid use, advise patients to increase hydration and fiber intake and to maintain or increase physical activity. Prophylactic
pharmacologic therapy (e.g., a stimulant laxative such as senna, with or without a stool softener) is usually needed to ensure
regular bowel movements if opioids are taken regularly. Stool softeners or fiber laxatives without another laxative should be
avoided.
If formulations are prescribed that combine opioids with acetaminophen, advise patients of the risks for taking additional
over-the-counter products containing acetaminophen.
Discuss effects that opioids might have on ability to safely operate a vehicle or other machinery, particularly when opioids are
initiated, when dosages are increased, or when other central nervous system depressants, such as benzodiazepines or
alcohol, are used concurrently.
Discuss the potential for workplace toxicology testing programs to detect therapeutic opioid use.
Discuss increased risks for opioid use disorder, respiratory depression, and death at higher dosages, along with the
importance of taking only the amount of opioids prescribed (i.e., not taking more opioids than prescribed or taking them more
often).
Review increased risks for respiratory depression when opioids are taken with benzodiazepines, other sedatives, alcohol,
nonprescribed drugs such as heroin, or other opioids.
Discuss risks for household members and other persons if opioids are intentionally or unintentionally shared with others for
whom they are not prescribed, including the possibility that others might experience overdose at the same or at lower
dosage than prescribed for the patient and that young children are susceptible to unintentional ingestion. Discuss storage of
opioids in a secure, preferably locked location and options for safe disposal of unused opioids (154).
Discuss the importance of periodic reassessment to ensure that opioids are helping to meet patient goals and, if opioids are
not effective or are harmful, to allow opportunities for consideration of opioid tapering and dosage reduction or
discontinuation and of additional nonpharmacologic or nonopioid pharmacologic treatment options.
Discuss expectations for clinician and patient responsibilities to mitigate risks of opioid therapy and planned use of
precautions to reduce risks, including naloxone for overdose reversal (see Recommendation 8) and clinician use of PDMP
information (see Recommendation 9) and toxicology screening (see Recommendation 10).
Consider whether cognitive status might interfere with management of opioid therapy and, if so, determine whether a
caregiver can responsibly comanage medication therapy. Discuss the importance of reassessing medication use over time
with both the patient and caregiver, as appropriate.

Because of the possibility that benefits of opioid therapy might diminish or that risks might become more prominent over time,
clinicians should elicit patients’ experiences and preferences and review expected benefits and risks of continued opioid therapy
with patients periodically (see Recommendation 7).

Interventional Approaches to Subacute and Chronic Pain

Office-based interventional approaches, such as arthrocentesis and intra-articular glucocorticoid injection for pain associated with
rheumatoid arthritis (186) or osteoarthritis (187) and subacromial corticosteroid injection for rotator cuff disease (188), can provide
short-term improvement in pain and function to supplement or facilitate exercise, physical therapy, and other conservative
approaches. Evidence is insufficient to determine the extent to which repeated glucocorticoid injection increases potential risks
such as articular cartilage changes (in osteoarthritis) and sepsis (187).

Interventional pain management specialists offer additional interventions that can alleviate pain as part of a comprehensive pain
management approach (6) for patients with indications including back pain, persistent pain after spinal surgery, neuropathic pain,
and complex regional pain syndrome. Certain more common procedures include epidural steroid injections (for lumbar
radiculopathy with herniated disc), nerve ablation procedures (e.g., radiofrequency denervation for low back pain), and
neurostimulation procedures (e.g., peripheral nerve stimulation and spinal cord stimulation). Descriptions of common

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 24 of 89
:
 interventional procedures are available (6). Level of evidence for effectiveness and risks varies by procedure, and additional
research is needed to establish the clinical benefits as well as risks of specific interventional procedures for specific pain conditions
(6,189) compared with risks of opioid pain medications and other pharmacologic therapies. Rare, serious adverse events have
been reported with epidural injection (190). Interventional procedures should be performed by properly trained clinicians
following meticulous infection control protocols. Clinicians can consult with a qualified pain management specialist who is well
versed in benefits and risks of diagnostic and therapeutic options to determine potential appropriateness of specific interventional
procedures for their patients’ indications and clinical circumstances.

Multimodal Therapy for Subacute and Chronic Pain

Integrated pain management requires coordination of medical, psychological, and social aspects of health care and includes
primary care, mental and behavioral health care, and specialist services when needed (191). Multimodal therapies and
multidisciplinary biopsychosocial rehabilitation (e.g., combining psychological therapies with exercise) can reduce long-term pain
and disability compared with usual care and compared with physical treatments (e.g., exercise) alone. Nonpharmacologic therapies
also can provide synergistic benefits when nonopioid or opioid pain medications are used (6). When needed, medications should
ideally be combined with nonpharmacologic therapy to provide greater benefits to patients in improving pain and function.
Multimodal therapies are not always available or reimbursed by insurance and can be time consuming and costly for patients, and
disparities in abilities to access multimodal care exist (6). Evidence exists that less-intensive multidisciplinary rehabilitation can be
similarly effective to high-intensity multidisciplinary rehabilitation (9). Multimodal therapies should be considered for patients not
responding to single-modality therapy, and combinations should be tailored depending on patient needs, cost, convenience, and
other individual factors.

Depending on patient comorbidities and benefit-to-risk ratios in individual patients, combinations of medications (e.g., two
nonopioid medications with different mechanisms of action or a nonopioid with an opioid medication) also might be used. In some
cases, medication combinations might provide complementary or synergistic benefits and facilitate lower dosing of individual
medications, as has been demonstrated in trials of patients with neuropathic pain (7). However, this approach should be used with
caution to avoid synergistic risks of medications. For example, combinations of medications that depress the central nervous
system and cause sedation (see Recommendation 11), such as an opioid with gabapentin, have been associated with increased
risk for overdose compared with either medication alone (7).

Selecting Opioids and Determining Opioid Dosages

Recommendation 3
When starting opioid therapy for acute, subacute, or chronic pain, clinicians should prescribe immediate-release opioids
instead of extended-release and long-acting (ER/LA) opioids (recommendation category: A; evidence type: 4).

Implementation Considerations
Clinicians should not treat acute pain with ER/LA opioids or initiate opioid treatment for subacute or chronic pain with ER/LA
opioids, and clinicians should not prescribe ER/LA opioids for intermittent or as-needed use.
ER/LA opioids should be reserved for severe, continuous pain. FDA has noted that some ER/LA opioids should be considered
only for patients who have received certain dosages of opioids of immediate-release opioids daily for at least 1 week.
When changing to an ER/LA opioid for a patient previously receiving a different immediate-release opioid, clinicians should
consult product labeling and reduce total daily dosage to account for incomplete opioid cross-tolerance.
Clinicians should use additional caution with ER/LA opioids and consider a longer dosing interval when prescribing to
patients with renal or hepatic dysfunction because decreased clearance of medications among these patients can lead to
accumulation of drugs to toxic levels and persistence in the body for longer durations.
Methadone should not be the first choice for an ER/LA opioid. Only clinicians who are familiar with methadone’s unique risk
profile and who are prepared to educate and closely monitor their patients, including assessing risk for QT prolongation and
considering electrocardiographic monitoring, should consider prescribing methadone for pain.
Only clinicians who are familiar with the dosing and absorption properties of the ER/LA opioid transdermal fentanyl and are
prepared to educate their patients about its use should consider prescribing it.

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 25 of 89
:
 Supporting Rationale
ER/LA opioids include methadone, transdermal fentanyl, and extended-release versions of opioids such as oxycodone,
hydromorphone, hydrocodone, and morphine. Clinical evidence reviews found that effects of opioids on short-term pain and
function were generally consistent across duration of action (short- or long-acting) and opioid type (opioid agonist, partial agonist,
or mixed mechanism [with mixed opioid and nonopioid mechanisms of action] agent), although five trials directly comparing
different types of opioids found a mixed mechanism agent associated with greater pain relief versus a pure opioid agonist, with
fewer nonserious adverse events (7). A fair-quality study demonstrated a higher risk for overdose among patients treated with
ER/LA opioids than among those treated with immediate-release opioids, especially within the first 2 weeks of therapy, with
relative risk decreasing with longer duration of exposure (7,192). Clinical evidence reviews did not find evidence that continuous,
time-scheduled use of ER/LA opioids is more effective or safer than intermittent use of immediate-release opioids or that time-
scheduled use of ER/ LA opioids reduces risk for opioid use disorder (7).

In 2014, FDA modified the labeling for ER/LA opioid pain medications, noting serious risks and recommending that ER/LA opioids
be reserved for management of pain severe enough to require daily, around-the-clock, long-term opioid treatment when
alternative treatment options (e.g., nonopioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be
otherwise inadequate to provide sufficient management of pain and not used as as-needed pain relievers (49). FDA also noted
that some ER/LA opioids are only appropriate for opioid-tolerant patients, defined as patients who have received certain dosages
of opioids (e.g., 60 mg daily of oral morphine, 30 mg daily of oral oxycodone, or equianalgesic dosages of other opioids) for at least
1 week (193). Time-scheduled opioid use can be associated with greater total average daily opioid dosage compared with
intermittent, as-needed opioid use (194). Technologies have been used to prevent manipulation intended to defeat extended-
release properties of ER/LA opioids and to prevent opioid use by unintended routes of administration, such as intravenous injection
of oral opioids. FDA guidance for industry on evaluation and labeling of these “abuse-deterrent” opioids (195) indicates that these
technologies, although they are expected to make manipulation of opioids more difficult or reduce the potent effects of
manipulation, do not prevent opioid misuse or overdose through oral intake (the most common route of opioid misuse) and can still
be misused by nonoral routes. The “abuse-deterrent” label does not indicate that there is no risk for misuse or opioid use disorder.
No studies were found in the clinical evidence reviews assessing the effectiveness of “abuse-deterrent” technologies as a risk
mitigation strategy for deterring or preventing opioid misuse, opioid use disorder, or overdose (7). Experts from OWG agreed with
the recommendation for clinicians to initiate opioid treatment with immediate-release opioids instead of with ER/LA opioids and
said they appreciated discussion of the lack of evidence for “abuse-deterrent” formulations.

In comparing different ER/LA formulations, clinical evidence reviews found inconsistent results for overdose risk with methadone
versus other ER/LA opioids used for chronic pain, with two cohort studies of Medicaid beneficiaries finding methadone associated
with increased risk for overdose or all-cause deaths versus morphine and one cohort study of U.S. Department of Veterans Affairs
patients finding methadone to be associated with decreased risk (7). Methadone has been associated with disproportionate
numbers of overdose deaths relative to the frequency with which it is prescribed for pain (196). In addition, methadone is
associated with cardiac arrhythmias along with QT prolongation on the electrocardiogram, and it has complicated
pharmacokinetics and pharmacodynamics, including a long and variable half-life and peak respiratory depressant effect occurring
later and lasting longer than peak analgesic effect (197–199). In regard to other ER/LA opioid formulations, the absorption and
pharmacodynamics of transdermal fentanyl are complex, with gradually increasing serum concentration during the first part of the
72-hour dosing interval, and variable absorption affected by factors such as external heat. In addition, the dosing of transdermal
fentanyl is in mcg/hour, which is not typical for a drug used by outpatients and can be confusing. These complexities might
increase the risk for fatal overdose when methadone or transdermal fentanyl is prescribed.

Clinicians should not treat acute pain with ER/LA opioids or initiate opioid treatment for subacute or chronic pain with ER/LA
opioids, and clinicians should not prescribe ER/LA opioids for intermittent use. Because of the longer half-life and longer duration
of effects (e.g., respiratory depression) of ER/LA opioids (e.g., methadone, fentanyl patches, or extended-release versions of
oxycodone, hydromorphone, hydrocodone, or morphine), clinicians should not prescribe ER/LA opioids for the treatment of acute
pain. ER/LA opioids should be reserved for severe, continuous pain and should be considered only for patients who have received
certain dosages of immediate-release opioids daily (e.g., 60 mg daily of oral morphine, 30 mg daily of oral oxycodone, or
equianalgesic dosages of other opioids) for at least 1 week (193). When changing to an ER/LA opioid for a patient previously
receiving a different immediate-release opioid, clinicians should consult product labeling and reduce total daily dosage to account
for incomplete opioid cross-tolerance. Clinicians should use additional caution with ER/LA opioids and consider a longer dosing

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 26 of 89
:
 interval when prescribing to patients with renal or hepatic dysfunction because decreased clearance of medications among these
patients can lead to accumulation of medications to toxic levels and persistence in the body for longer durations. Although in
certain situations clinicians might need to prescribe immediate-release and ER/LA opioids together (e.g., when transitioning
patients from ER/LA opioids to immediate-release opioids by temporarily using lower dosages of both, for temporary
postoperative use of short-term opioids in a patient already receiving ER/LA opioids, or in patients with opioid use disorder treated
and stabilized on methadone who need short-acting opioids for acute pain), clinicians should consider the potential for increased
overdose risk and use caution when prescribing immediate-release opioids in combination with ER/LA opioids.

When an ER/LA opioid is prescribed, using one with predictable pharmacokinetics and pharmacodynamics is preferred to minimize
unintentional overdose risk. In particular, unique characteristics of methadone and transdermal fentanyl make safe prescribing of
these medications for pain especially challenging. Methadone should not be the first choice for an ER/LA opioid. Only clinicians
who are familiar with methadone’s unique risk profile and who are prepared to educate and closely monitor their patients,
including risk assessment for QT prolongation and consideration of electrocardiographic monitoring, should consider prescribing
methadone for pain. A clinical practice guideline regarding methadone prescribing for pain has been published previously (200).
Because dosing effects of transdermal fentanyl often are misunderstood by both clinicians and patients, only clinicians who are
familiar with its dosing and absorption properties of and are prepared to educate their patients about its use should consider
prescribing transdermal fentanyl.

Recommendation 4
When opioids are initiated for opioid-naïve patients with acute, subacute, or chronic pain, clinicians should prescribe the
lowest effective dosage. If opioids are continued for subacute or chronic pain, clinicians should use caution when prescribing
opioids at any dosage, should carefully evaluate individual benefits and risks when considering increasing dosage, and should
avoid increasing dosage above levels likely to yield diminishing returns in benefits relative to risks to patients
(recommendation category: A; evidence type: 3).

Implementation Considerations
The recommendations related to opioid dosages are not intended to be used as an inflexible, rigid standard of care; rather,
they are intended to be guideposts to help inform clinician-patient decision-making. Risks of opioid use, including risk for
overdose and overdose death, increase continuously with dosage, and there is no single dosage threshold below which risks
are eliminated. Therefore, the recommendation language emphasizes that clinicians should avoid increasing dosage above
levels likely to yield diminishing returns in benefits relative to risks to patients rather than emphasizing a single specific
numeric threshold. Further, these recommendations apply specifically to starting opioids or to increasing opioid dosages, and
a different set of benefits and risks applies to reducing opioid dosages (see Recommendation 5).
When opioids are initiated for opioid-naïve patients with acute, subacute, or chronic pain, clinicians should prescribe the
lowest effective dosage.
For patients not already taking opioids, the lowest effective dose can be determined using product labeling as a starting point
with calibration as needed based on the severity of pain and other clinical factors such as renal or hepatic insufficiency (see
Recommendation 8).
The lowest starting dose for opioid-naïve patients is often equivalent to a single dose of approximately 5–10 MME or a daily
dosage of 20–30 MME/day. A listing of common opioid medications and their doses in MME equivalents is provided (Table).
If opioids are continued for subacute or chronic pain, clinicians should use caution when prescribing opioids at any dosage
and should generally avoid dosage increases when possible.
Many patients do not experience benefit in pain or function from increasing opioid dosages to ≥50 MME/day but are exposed
to progressive increases in risk as dosage increases. Therefore, before increasing total opioid dosage to ≥50 MME/day,
clinicians should pause and carefully reassess evidence of individual benefits and risks. If a decision is made to increase
dosage, clinicians should use caution and increase dosage by the smallest practical amount. The recommendations related to
opioid dosages are not intended to be used as an inflexible, rigid standard of care; rather, they are intended to be guideposts
to help inform clinician-patient decision-making.
Additional dosage increases beyond 50 MME/day are progressively more likely to yield diminishing returns in benefits for
pain and function relative to risks to patients as dosage increases further. Clinicians should carefully evaluate a decision to

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 27 of 89
:
 further increase dosage on the basis of individualized assessment of benefits and risks and weighing factors such as
diagnosis, incremental benefits for pain and function relative to risks with previous dosage increases, other treatments and
effectiveness, and patient values and preferences. The recommendations related to opioid dosages are not intended to be
used as an inflexible, rigid standard of care; rather, they are intended to be guideposts to help inform clinician-patient
decision-making.

Supporting Rationale
Benefits of high-dose opioids for pain are not well established. Few trials evaluated opioid dosages of ≥90 MME/day (7). Opioid
dosages of 50–90 MME/day were associated with a minimally greater (below the threshold for small) improvement in mean pain
intensity compared with dosages of <50 MME/day (mean difference: −0.26; 95% CI: −0.57 to −0.02); there was no difference in
mean improvement in function (7). Analyses of placebo-controlled trials also found some evidence of a plateauing effect at ≥50
mg MME/day (7). One trial of more liberal dose escalation compared with maintenance of current dosage found no difference in
outcomes related to pain or function (7).

At the same time, risks for serious harms related to opioid therapy, including opioid misuse, overdose, and death, increase at
higher opioid dosage, without a single point below which there is no risk (201). One cohort study from the clinical evidence
reviews found higher dosages of opioids were associated with increased risk for all-cause deaths; one cohort study found modest
associations between higher dose of long-term opioid and increased risk for falls and major trauma; one case-control study found
opioid dosages of >20 MME/day were associated with increased odds of road trauma injury when the analysis was restricted to
drivers, with no dose-dependent association at dosages of >20 MME/day; and cohort studies found association between higher
opioid dose and risk for various endocrinological adverse events (7). Patients on higher doses reported reliance on opioids despite
ambivalence about their benefits (7).

Four observational studies identified in the clinical evidence reviews consistently found an association between higher doses of
long-term opioids and risk for overdose or overdose death (7). Opioid dosages for chronic pain of 50 to <100 MME/day in
observational studies have been associated with increased risks for opioid overdose by factors of 1.9–4.6 compared with dosages
of 1 to <20 MME/day, and dosages of ≥100 MME/day were found to be associated with increased risks for overdose 2.0–8.9 times
the risk at 1 to <20 MME/day, after adjusting for confounders on the basis of demographics, comorbidities, concomitant
medications, and other factors (55,202,203). When opioids are prescribed for acute pain, similar associations have been found,
with dosages of 50 to <100 MME/day associated with 4.73 times the risk for overdose and dosages of ≥100 MME/day associated
with 6.64 times the risk, compared with dosages of 1 to <20 MME/day (55). The MME cut points in these studies (e.g., 20 MME, 50
MME, and 100 MME) were selected by the authors for research purposes, and whereas their findings are consistent with
progressive increases in overdose risk being associated with increases in prescribed opioid dosages, they do not demonstrate a
specific dosage threshold below which opioids are never associated with overdose. In a national sample of Veterans Health
Administration patients with chronic pain who were prescribed opioids, mean prescribed daily opioid dosage among patients who
died from opioid overdose was 98 MME (median: 60 MME), compared with mean prescribed daily opioid dosage of 48 MME
(median: 25 MME) among patients not experiencing fatal overdose (204). A narrative review conducted by FDA staff concluded
that, although there is not a single dosage threshold below which overdose risk is eliminated (201), the studies included in the
review indicated an increasing risk for serious adverse health outcomes, including misuse, overdose, and death associated with
increasing opioid dose. These studies examined dose-response risk for overdose for full agonist opioids and not for partial agonist
opioids such as buprenorphine, which is unlikely to have the same continuous association between dosage and overdose risk
because respiratory depressant effects of buprenorphine reach a plateau (205).

Multiple experts from OWG expressed concern that including specific dosage thresholds in a main recommendation statement
would emphasize them as authoritative absolutes and would lead to noncollaborative tapers or other potentially harmful
consequences. Experts also noted the lack of a single standard formula for calculating MMEs (206). However, experts agreed
there is a need for thresholds as benchmarks and suggested including them in the supporting text after the main recommendation
statement. Experts also agreed with separating recommendations on dosage into a recommendation applying to patients starting
opioids and patients already receiving opioids.

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 28 of 89
:
 When opioids are used for acute, subacute, or chronic pain, clinicians should start opioids at the lowest possible effective dosage.
For patients not already taking opioids, the lowest effective dose can be determined using product labeling as a starting point with
calibration as needed on the basis of the severity of pain and other clinical factors, such as renal or hepatic insufficiency (see
Recommendation 8). The lowest starting dose for opioid-naïve patients is often equivalent to a single dose of approximately 5–10
MME or a daily dosage of 20–30 MME/day. A listing of common opioid medications and their doses in MME equivalents is provided
(Table). For example, a label for hydrocodone bitartrate (5 mg) and acetaminophen (300 mg) (207) states that the usual adult
dosage is one or two tablets every 4–6 hours as needed for pain, and the total daily dosage should not exceed eight tablets.
Clinicians should use additional caution when initiating opioids for patients aged ≥65 years and patients with renal or hepatic
insufficiency because of a potentially smaller therapeutic window between safe dosages and dosages associated with respiratory
depression and overdose (see Recommendation 8). Formulations with lower opioid doses (e.g., hydrocodone bitartrate 2.5
mg/acetaminophen 325 mg) are available and can facilitate dosing when additional caution is needed. Product labeling regarding
tolerance includes guidance for patients already taking opioids. In addition to opioids, clinicians should consider cumulative
dosages of other medications, such as acetaminophen, that are combined with opioids in many formulations and for which
decreased clearance of medications might result in accumulation of medications to toxic levels.

Clinicians should generally avoid unnecessary dosage increases, use caution when increasing opioid dosages, and increase dosage
by the smallest practical amount because overdose risk increases with increases in opioid dosage. Although evidence to
recommend specific intervals for dosage titration is limited, rapid dosage increases put patients at greater risk for sedation,
respiratory depression, and overdose. For opioid-naïve outpatients with acute pain treated with an opioid for a few days or less,
dosage increases are usually unnecessary and should not be attempted without close monitoring because of the risks for
respiratory depression. In the context of long-term opioid use, when dosage is increased, clinicians should reevaluate patients
after increasing dosage for changes in pain, function, and risk for harm (see Recommendation 7).

Before increasing total opioid dosage to ≥50 MME/day, clinicians should pause, considering that dosage increases to >50 MME/day
are unlikely to provide substantially improved pain control for most patients while overdose risk increases with dosage, and
carefully reassess evidence of benefits and risks. If a patient’s opioid dosage for all sources of opioids combined reaches or
exceeds 50 MME/day, clinicians should implement additional precautions, including increased frequency of follow-up (see
Recommendation 7), and offer naloxone and overdose prevention education to both the patient and the patient’s household
members (see Recommendation 8).

Additional dosage increases beyond 50 MME/day are progressively more likely to yield diminishing returns in benefits for pain and
function relative to risks to patients. Clinicians should carefully evaluate a decision to increase dosage after an individualized
assessment of benefits and risks and weighing factors such as diagnosis, incremental benefits for pain and function relative to
risks with previous dosage increases, other treatments and effectiveness, and patient values and preferences.

Certain states require clinicians to implement clinical protocols at specific dosage levels. For example, before increasing long-term
opioid therapy dosage to >120 MME/day, clinicians in Washington state must obtain consultation from a pain specialist who
agrees that the increase is indicated and appropriate (208). Clinicians should be aware of policies related to MME thresholds and
associated clinical protocols established by their states.

Recommendation 5
For patients already receiving opioid therapy, clinicians should carefully weigh benefits and risks and exercise care when
changing opioid dosage. If benefits outweigh risks of continued opioid therapy, clinicians should work closely with patients to
optimize nonopioid therapies while continuing opioid therapy. If benefits do not outweigh risks of continued opioid therapy,
clinicians should optimize other therapies and work closely with patients to gradually taper to lower dosages or, if warranted
based on the individual circumstances of the patient, appropriately taper and discontinue opioids. Unless there are
indications of a life-threatening issue such as warning signs of impending overdose (e.g., confusion, sedation, or slurred
speech), opioid therapy should not be discontinued abruptly, and clinicians should not rapidly reduce opioid dosages from
higher dosages (recommendation category: B; evidence type: 4).

Implementation Considerations
Clinicians should carefully weigh both the benefits and risks of continuing opioid medications and the benefits and risks of

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 29 of 89
:
 tapering opioids.
If benefits outweigh risks of continued opioid therapy, clinicians should work closely with patients to optimize nonopioid
therapies while continuing opioid therapy.
When benefits (including avoiding risks of tapering) do not outweigh risks of continued opioid therapy, clinicians should
optimize other therapies and work closely with patients to gradually taper to a reduced opioid dosage or, if warranted based
on the individual clinical circumstances of the patient, appropriately taper and discontinue opioid therapy.
In situations where benefits and risks of continuing opioids are considered to be close or unclear, shared decision-making
with patients is particularly important.
At times, clinicians and patients might not be able to agree on whether or not tapering is necessary. When patients and
clinicians are unable to arrive at a consensus on the assessment of benefits and risks, clinicians should acknowledge this
discordance, express empathy, and seek to implement treatment changes in a patient-centered manner while avoiding
patient abandonment.
Patient agreement and interest in tapering is likely to be a key component of successful tapers.
For patients agreeing to taper to lower opioid dosages and for those remaining on higher opioid dosages, clinicians should
establish goals with the patient for continued opioid therapy (see Recommendations 2 and 7) and maximize pain treatment
with nonpharmacologic and nonopioid pharmacologic treatments as appropriate (see Recommendation 2).
Clinicians should collaborate with the patient on the tapering plan, including patients in decisions such as how quickly
tapering will occur and when pauses in the taper might be warranted.
Clinicians should follow up frequently (at least monthly) with patients engaging in opioid tapering. Team members (e.g.,
nurses, pharmacists, and behavioral health professionals) can support the clinician and patient during the ongoing taper
process through telephone contact, telehealth visits, or face-to-face visits.
When opioids are reduced or discontinued, a taper slow enough to minimize symptoms and signs of opioid withdrawal (e.g.,
anxiety, insomnia, abdominal pain, vomiting, diarrhea, diaphoresis, mydriasis, tremor, tachycardia, or piloerection) should be
used.
Longer duration of previous opioid therapy might require a longer taper. For patients who have taken opioids long-term (e.g.,
for ≥1 year), tapers can be completed over several months to years depending on the opioid dosage and should be
individualized based on patient goals and concerns.
When patients have been taking opioids for longer durations (e.g., for ≥1 year), tapers of 10% per month or slower are likely
to be better tolerated than more rapid tapers.
For patients struggling to tolerate a taper, clinicians should maximize nonopioid treatments for pain and should address
behavioral distress.
Clinically significant opioid withdrawal symptoms can signal the need to further slow the taper rate.
At times, tapers might have to be paused and restarted again when the patient is ready and might have to be slowed as
patients reach low dosages.
Before reversing a taper, clinicians should carefully assess and discuss with the patient the benefits and risks of increasing
opioid dosage.
Goals of the taper might vary (e.g., some patients might achieve discontinuation whereas others might attain a reduced
dosage at which functional benefits outweigh risks). If the clinician has determined with the patient that the ultimate goal of
tapering is discontinuing opioids, after the smallest available dose is reached the interval between doses can be extended
and opioids can be stopped when taken less frequently than once a day.
Clinicians should access appropriate expertise if considering tapering opioids during pregnancy because of possible risks to
the pregnant patient and the fetus if the patient goes into withdrawal.
Clinicians should advise patients of an increased risk for overdose on abrupt return to a previously prescribed higher dose
because of loss of opioid tolerance, provide opioid overdose education, and offer naloxone.
Clinicians should remain alert to signs of and screen for anxiety, depression, and opioid misuse or opioid use disorder (see
Recommendations 8 and 12) that might be revealed by an opioid taper and provide treatment or arrange for management of
these comorbidities.

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 30 of 89
:
 Clinicians should closely monitor patients who are unable to taper and who continue on high-dose or otherwise high-risk
opioid regimens (e.g., opioids prescribed concurrently with benzodiazepines) and should work with patients to mitigate
overdose risk (e.g., by providing overdose education and naloxone) (see Recommendation 8).
Clinicians can use periodic and strategic motivational questions and statements to encourage movement toward appropriate
therapeutic changes and functional goals.
Clinicians have a responsibility to provide or arrange for coordinated management of patients’ pain and opioid-related
problems, including opioid use disorder.
Payers, health systems, and state medical boards should not use this clinical practice guideline to set rigid standards or
performance incentives related to dose or duration of opioid therapy; should ensure that policies based on cautionary dosage
thresholds do not result in rapid tapers or abrupt discontinuation of opioids; and should ensure that policies do not penalize
clinicians for accepting new patients who are using prescribed opioids for chronic pain, including those receiving high
dosages of opioids, or for refraining from rapidly tapering patients prescribed long-term opioid medications.
Although Recommendation 5 specifically refers to patients using long-term opioid therapy for subacute or chronic pain, many
of the principles in these implementation considerations and supporting rationale, including communication with patients,
pain management, behavioral support, and slower taper rates, also are relevant when discontinuing opioids in patients who
have received them for shorter durations (see Recommendations 6 and 7).

Supporting Rationale
Patients receiving long-term, high-dosage opioid therapy for chronic pain are at increased risk for adverse events including
overdose death (55,72,202,203,209). However, discontinuation of long-term, high-dosage opioid therapy has been associated
with adverse events including mental health crisis, overdose events, and overdose death (71–73,210,211). In addition, opioid
tapering has been found to be associated with subsequent termination of care (212). One study found that whereas sustained
opioid therapy discontinuation (i.e., opioid discontinuation for at least 3 months) was associated with an approximately 50%
reduction in risk for overdose, dose variability was a risk factor for opioid overdose (213). In another study, discontinuation of long-
term, high-dosage opioid therapy was associated with increased risk for suicide but with reduced risk for overdose when
compared with stable or increasing dosage (211). Both starting and stopping opioids were associated with overdose or suicide
risk in another study; risk associated with stopping opioids was increased when patients had received opioids for longer durations.
Death rates for overdose or suicide in one study increased immediately after starting or stopping treatment with opioids, with the
incidence decreasing over approximately 3–12 months (214) in one study and persisting over 2 years in another study (215). In
observational studies evaluating outcomes related to heroin use after discontinuation of prescription opioids, one study found that
heroin use was associated with discontinuation of long-term opioid use (216); another study found that among persons
experiencing heroin overdose, prescription opioid use in the past 12 months was common but discontinuation of long-term opioid
use was uncommon (217).

Discontinuation of opioids has been associated with greater risks when it occurs over shorter periods. FDA has advised that risks
of rapid tapering or sudden discontinuation of opioids in physically dependent patients include acute withdrawal symptoms,
exacerbation of pain, serious psychological distress, and thoughts of suicide (68). One observational study found that, among
adults prescribed stable higher opioid dosages (mean: ≥50 MME/day) long-term, increasing maximum monthly dose reduction rate
by 10% was associated with an adjusted incidence rate ratio of 1.09 for overdose (95% CI: 1.07–1.11) and 1.18 for mental health
crisis (95% CI: 1.14–1.21) (210). Another study of patients on long-term, high-dosage (≥120 MME/day) opioid therapy found that
each additional week of tapering time before opioid discontinuation was associated with a 7% relative reduction in the risk for
opioid-related emergency department visits or hospitalizations (71). The clinical evidence reviews did not find studies comparing
different rates of opioid tapering; however, a taper support intervention (psychiatric consultation, opioid dosage tapering, and 18
weekly meetings with a physician assistant to explore motivation for tapering and learn pain self-management skills) was
associated with better functional outcomes (specifically, improvement in pain interference) compared with usual care, with effects
persisting at 34-week follow-up (7). A systematic review (218) found that, among studies rated as good or fair quality, when
opioids were tapered after discussion with patients who agreed to taper, opioid dose reduction was associated with improved
pain, function, and quality of life. These results suggest that involving patients in decisions regarding continuation or
discontinuation of opioid medications as well as practices including behavioral support, integration of nonpharmacologic pain
management, and slower tapers might improve outcomes.

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 31 of 89
:
 Experts from OWG said they appreciated the complexity of managing patients already receiving higher dosages of opioids long-
term. Although some experts indicated there should be more consideration of obtaining informed consent before tapering opioids,
others believed that informed discussion is more appropriate than informed consent when considering tapering opioids because of
clinicians’ overriding responsibility to avoid providing treatment that harms patients. Some experts were concerned that
overemphasizing risks of tapering could increase harm from continued high-dosage opioid use.

Determining Whether, When, and How to Taper Opioids

The benefits and risks of opioid therapy change over time and should be reevaluated periodically (see Recommendations 6 and 7).
Opioid therapy should be limited to circumstances where benefits of therapy outweigh risks. Because tapering opioids can be
harmful in some circumstances, benefits of continuing opioids in patients who have already received them long-term might include
avoiding risks of tapering and discontinuing opioids. In situations where benefits and risks of continuing opioids are considered to
be close or unclear, shared decision-making with patients is particularly important. At times, clinicians and patients might not be
able to agree on whether tapering is necessary. When patients and clinicians are unable to arrive at a consensus on the
assessment of benefits and risks, clinicians should acknowledge this discordance, express empathy, and seek to implement
treatment changes in a patient-centered manner while avoiding patient abandonment. Unless there is a life-threatening issue
such as warning signs of an imminent overdose, the benefits of rapidly tapering or abruptly discontinuing opioids are unlikely to
outweigh the substantial risks of these practices (71,219). However, after slow, voluntary reduction of long-term opioid dosages,
patients might experience improvements in function, quality of life, anxiety, and mood without worsening pain or with decreased
pain levels (218). Clinicians and patients should consider whether opioids continue to meet treatment goals, including functional
goals; whether opioids are exposing the patient to an increased risk for serious adverse events or opioid use disorder; and whether
benefits continue to outweigh risks of opioids. Clinicians should not insist on opioid tapering or discontinuation when opioid use
might be warranted (i.e., when benefits of opioids outweigh risks) (66,219). Clinicians should access appropriate expertise if
considering tapering opioids during pregnancy because of possible risk to the pregnant patient and the fetus if the patient goes
into withdrawal. For pregnant persons with opioid use disorder, medications for opioid use disorder are preferred over withdrawal
management (i.e., discontinuation of opioids through either short- or medium-term tapering) (220,221).

Some patients using more than one respiratory depressant (e.g., benzodiazepines and opioids) might require tapering one or more
medications to reduce risk for respiratory depression. Tapering decisions and plans should be coordinated with prescribers of all
respiratory depressant medications (see Recommendation 11). Benzodiazepines should be tapered gradually because of risks
(anxiety, hallucinations, seizures, delirium tremens, and, rarely, death) of benzodiazepine withdrawal (222,223). Patients who are
not taking prescribed opioids (e.g., patients who are diverting all opioids they obtain) do not require tapers.

Consistent with the HHS Guide for Clinicians on the Appropriate Dosage Reduction or Discontinuation of Long-Term Opioid
Analgesics (219), clinicians should consider tapering to a reduced opioid dosage or tapering and discontinuing opioid therapy and
discuss these approaches with patients before initiating changes when

the patient requests dosage reduction or discontinuation,

pain improves and might indicate resolution of an underlying cause,
opioid therapy has not meaningfully reduced pain or improved function,
the patient has been treated with opioids for a prolonged period (e.g., years) and the benefit-risk balance is unclear (e.g.,
decreased positive effects because of tolerance and symptoms such as reduced focus or memory that might be due to
opioids),
the patient is receiving higher opioid dosages without evidence of benefit from the higher dosage,
the patient experiences side effects that diminish quality of life or impair function,
evidence of opioid misuse exists,
the patient experiences an overdose or other serious event (e.g., an event leading to hospitalization or injury) or has warning
signs for an impending event (e.g., confusion, sedation, or slurred speech), or
the patient is receiving medications (e.g., benzodiazepines) or has medical conditions (e.g., sleep apnea, liver disease, kidney
disease, or fall risk) that increase risk for adverse outcomes.

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 32 of 89
:
 For patients already taking opioids long term (both established patients and patients transferring from other clinicians), the
possibility of opioid dosage reduction might provoke substantial anxiety. In addition, tapering opioids after years of taking them
can be especially challenging because of physical and psychological dependence. However, patients should be offered the
opportunity to reevaluate their continued use of opioids. Clinicians should review benefits and risks of continued opioid therapy
with empathy.

Whenever possible, clinicians should collaborate with patients and share decision-making about whether and how to taper
opioids. Clinicians should review benefits and risks of opioid therapy with the patient and decide whether tapering is appropriate
for the patient. If the existing opioid regimen does not put the patient at imminent risk for overdose or other injury, tapering does
not need to occur immediately, and clinicians can take time to reach agreement with patients (224). For patients who agree to
taper opioids to lower dosages, clinicians should collaborate with the patient on a tapering plan. Open discussion between the
clinician and patient should take place, whether the goal of the taper is stopping opioids or reducing opioids to a point where
benefits outweigh risks; the goal will depend on the patient’s circumstances and an individualized assessment of benefits and
risks. Tapering is more likely to be successful when patients collaborate in the taper (224). Clinicians can discuss with patients the
patient’s perceptions of benefits, risks, and adverse effects of continued opioid therapy; include patient concerns in taper planning;
and include patients in making decisions such as which medication will be decreased first (e.g., in patients prescribed more than
one opioid) and how quickly tapering will occur.

Providing Advice to Patients Before Tapering

Clinicians should advise patients that overall, after voluntary reduction of long-term opioid dosages, most patients report stable or
improved function, anxiety, and mood without worsening pain or with decreased pain levels (66,218,225–228). However, other
patients report insomnia, anxiety, depression, and increased pain, particularly in the short term (66,225,227,229,230). Increased
pain might be related to hyperalgesia or opioid withdrawal and can be prolonged in some patients (229). Patients can be
counseled that worsening of pain is a frequent symptom of opioid withdrawal that tends to diminish over time (219). Clinicians
should advise patients about the increased risk for overdose with abrupt return to a previously prescribed higher dosage because
of loss of opioid tolerance and warn of a risk for overdose if the patient returns to their original dosage (219). Clinicians should
provide opioid overdose education and offer naloxone.

Pain Management During Tapering

Clinicians should commit to working with patients to improve function and decrease pain, whether or not opioids are tapered.
Nonpharmacologic and nonopioid treatments should be integrated into patients’ pain management plans after an individualized
assessment of benefits and risks that considers the patient’s diagnosis, circumstances, and unique needs (see Recommendation 2).
Integrating behavioral and nonopioid pain therapies before and during a taper can help manage pain (218) and strengthen the
therapeutic relationship between the clinician and patient. Whether patients are agreeing to taper to lower opioid dosages or
remaining on higher opioid dosages, clinicians should work with them to establish functional goals for continued opioid therapy
(see Recommendations 2 and 7) and maximize pain treatment with nonpharmacologic and nonopioid pharmacologic treatments as
appropriate (see Recommendation 2).

Behavioral Health Support During Tapering

Integrating behavioral and nonopioid pain therapies and treatment for comorbid mental health conditions before and during a
taper can help manage pain (218), strengthen the therapeutic relationship between the clinician and patient, and improve the
likelihood of positive tapering outcomes (228). Mental health comorbidities including depression and anxiety are common in
patients with painful conditions, especially those receiving long-term opioid therapy (231). Depressive symptoms predict taper
dropout (225,226). Primary care clinicians should collaborate with mental health specialists and with other specialty clinicians as
needed to optimize nonopioid pain management (see Recommendation 2) and provide psychosocial support for patients who have
anxiety related to the taper. Clinicians should consider arranging for consultation with a behavioral health specialist before
initiating a taper in patients with serious mental illness who are at high risk for suicide or with suicidal ideation (219). Clinicians
should remain alert to signs of and screen for anxiety, depression, and opioid misuse or opioid use disorder (see Recommendations
8 and 12) that might be revealed by an opioid taper and provide treatment or arrange for management of these comorbidities.
Successful tapering studies have used at least weekly follow-up (218), and clinicians should follow up frequently (at least
monthly) with patients engaging in opioid tapering. Team members (e.g., nurses, pharmacists, and behavioral health professionals)
can support the clinician and patient during the ongoing taper process through telephone contact, telehealth visits, or face-to-face

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 33 of 89
:
 visits. Clinicians can acknowledge patient fears about tapering (232), ask how they can support the patient (232), and make sure
patients receive appropriate and accessible psychosocial support (228). Many patients fear withdrawal symptoms, pain, or
abandonment (233), and clinicians can help patients by telling them what to expect (e.g., the rate will be kept slow to minimize
withdrawal symptoms and pain might worsen at first but usually improves over time) and that they will be supporting them
through the process.

Tapering Rate
Evidence to support specific tapering rates is limited. The rate of tapering should be individualized based on the patient’s clinical
situation. When opioids are reduced or discontinued, a taper slow enough to minimize symptoms and signs of opioid withdrawal
(e.g., anxiety, insomnia, abdominal pain, vomiting, diarrhea, diaphoresis, mydriasis, tremor, tachycardia, or piloerection) should be
used. Tapers can be completed over several months to years depending on the opioid dosage and should be individualized based
on patient goals and concerns. Longer durations of previous opioid therapy might require longer tapers. Evidence on optimal taper
rate is emerging. Tapers of approximately 10% per month or slower are likely to be better tolerated than more rapid tapers when
patients have been taking opioids for longer durations (e.g., ≥1 year) (219). When patients have taken opioids for shorter
durations (e.g., weeks to months rather than years), a decrease of 10% of the original dose per week or slower (until
approximately 30% of the original dose is reached, followed by a weekly decrease of approximately 10% of the remaining dose) is
less likely to trigger withdrawal (225) and can be successful for some patients. For patients struggling to tolerate a taper,
clinicians should maximize nonopioid treatments for pain and should address behavioral distress (234). Clinically significant opioid
withdrawal symptoms can signal the need to further slow the taper rate. At times, tapers might have to be paused and restarted
again when the patient is ready and might have to be slowed as patients reach low dosages to allow gradual accommodation to
lower opioid dosages and development of new skills for nonopioid management of pain and emotional distress. Before reversing a
taper, clinicians should carefully assess and discuss with patients benefits and risks of increasing opioid dosage. If the clinician and
patient have determined that the goal is discontinuing opioids, after the smallest available dose is reached, the interval between
doses can be extended and opioids can be stopped when taken less frequently than once a day.

More rapid tapers might be needed for patient safety under certain circumstances (e.g., for patients who have experienced
overdose on their current dosage) (219). However, unless there are indications of a life-threatening issue, such as warning signs of
impending overdose, opioid therapy should not be discontinued abruptly, and clinicians should not rapidly reduce opioid dosages
from higher dosages. Sudden discontinuation might precipitate substantial opioid withdrawal (71). Rapid tapering or sudden
discontinuation of opioids in physically dependent patients also can increase risks for psychological distress and opioid-related
emergency department visits and hospitalizations (68,71). Ultrarapid detoxification under anesthesia is associated with
substantial risks, including death, and should not be used (235).

Management of Opioid Withdrawal During Tapering

The first approach to withdrawal symptoms and signs should generally be consideration of slowing or pausing the taper rate. If
needed, short-term oral medications might also help manage withdrawal symptoms (232). These include alpha-2 agonists for the
management of autonomic signs and symptoms (e.g., sweating and tachycardia). Alpha-2 agonists clonidine and lofexidine are
more effective than placebo in reducing severity of withdrawal (236) from heroin or methadone in the context of abrupt (not
gradual) discontinuation. Similar research could not be found on clonidine and lofexidine in patients tapering from long-term
opioid treatment for pain (225); however, alpha-2 agonist tizanidine has been used to help taper patients from long-term, high-
dosage opioids for chronic pain (230). Other medications addressing specific symptoms (NSAIDs, acetaminophen, or topical
menthol or methyl salicylate for muscle aches; trazodone for sleep disturbance; prochlorperazine, promethazine, or ondansetron
for nausea; dicyclomine for abdominal cramping; and loperamide or bismuth subsalicylate for diarrhea) also have been used (232).

Challenges to Tapering
Some patients with unanticipated challenges to tapering, such as inability to make progress in tapering despite opioid-related
harm, might have undiagnosed opioid use disorder. Therefore, patients experiencing such challenges should be assessed for
opioid use disorder using Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria and, if criteria for
opioid use disorder are met, offered evidence-based medication treatment (see Recommendation 12) and naloxone for opioid
overdose reversal (see Recommendation 8).

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 34 of 89
:
 Emerging evidence suggests that patients for whom risks of continued high-dose opioid use outweigh benefits but who are
unable to taper and who do not meet criteria for opioid use disorder might benefit from transition to buprenorphine (219,237,238).
Buprenorphine is a partial agonist opioid that can treat pain and opioid use disorder (239) and has other properties that might be
helpful (155), including less respiratory depression (205) and overdose risk than other opioids (155,237). Although overdose is
less likely with buprenorphine than with full agonist opioids, overdose is still possible, particularly if buprenorphine is taken
concurrently with other respiratory depressants (e.g., full agonist opioids, benzodiazepines, or alcohol) (240). A specialty clinic
offering opioid tapering services for patients receiving high-dosage opioids (defined in this study as ≥90 MME/day) for chronic pain
found that 44.6% of patients referred for opioid taper were able to successfully taper to <90 MME/day, and an additional 18.8%
who were unable to taper were able to successfully transition to sublingual buprenorphine (230). Different buprenorphine
products, available at different formulations and doses, are approved for the treatment of pain and for the treatment of opioid use
disorder. Although prescription of buprenorphine for treatment of opioid use disorder requires the clinician to have a waiver from
SAMHSA (see Recommendation 12), prescription of buprenorphine for treatment of chronic pain does not require a waiver (237).

To avoid precipitating withdrawal, transitioning any patient taking full agonist opioids to buprenorphine requires specific timing of
the initial buprenorphine dose (219) (see Recommendation 12 for application to patients with opioid use disorder). Patients should
be in mild to moderate withdrawal from full agonist opioids before the first buprenorphine dose (219). To do this, experts have
advised that clinicians and patients should wait at least 8–12 hours after the last dose of short-acting full agonist opioids and
longer after the last dose of long-acting full agonist opioids (e.g., at least 12–24 hours after the last dose of an ER/LA full agonist
opioid, and longer for methadone) before the first dose of buprenorphine is administered (229). As an alternative for patients not
yet in opioid withdrawal, certain studies have described low dose initiation of buprenorphine to allow for initiation of
buprenorphine in patients receiving full agonist opioids for acute or chronic pain (241). SAMHSA’s Providers Clinical Support
System (https://pcssnow.org  ) offers training, technical assistance, and mentors to assist clinicians who are unfamiliar with
initiation of buprenorphine and have additional questions about the diagnosis and treatment of opioid use disorder. Because the
duration of action for analgesia is shorter than the duration of action for suppression of opioid withdrawal and stabilization of
opioid use disorder (242), dosing of buprenorphine for pain is typically multiple times daily rather than once-a-day dosing as done
for the treatment of opioid use disorder (229).

Continuing High-Dosage Opioids

Clinicians should closely monitor patients who are unable to taper and who continue on high-dosage or otherwise high-risk opioid
regimens (e.g., opioids prescribed concurrently with benzodiazepines) and should work with patients to mitigate overdose risk
(e.g., by providing overdose education and naloxone) (see Recommendation 8). Clinicians can use periodic and strategic
motivational questions and statements to encourage movement toward appropriate therapeutic changes (224).

Management of chronic pain with opioids can be challenging, as can management of opioid discontinuation (67). However,
clinicians have a responsibility to provide or arrange for coordinated management of patients’ pain and opioid-related challenges.
Payers and health systems should not use this clinical practice guideline to set rigid standards related to dosage or duration of
opioid therapy and should ensure that policies based on cautionary dosage thresholds do not result in rapid tapers or abrupt
discontinuation of opioids, do not penalize clinicians for accepting new patients who are receiving opioids for chronic pain, and do
not provide incentives to clinicians to implement rapid tapering. Patients prescribed opioids but unable to access ongoing care
(243) might be at risk for abrupt opioid discontinuation and might miss opportunities to receive life-saving interventions, including
monitoring for and management of mental health and substance use comorbidities.

Deciding Duration of Initial Opioid Prescription and Conducting Follow-Up

Recommendation 6
When opioids are needed for acute pain, clinicians should prescribe no greater quantity than needed for the expected
duration of pain severe enough to require opioids (recommendation category: A; evidence type: 4).

Implementation Considerations
Nontraumatic, nonsurgical acute pain can often be managed without opioids (see Recommendation 1).
Opioids are sometimes needed for treatment of acute pain (see Recommendation 1). When the diagnosis and severity of

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 35 of 89
:
 acute pain warrant use of opioids, clinicians should prescribe no greater quantity than needed for the expected duration of
pain severe enough to require opioids. For many common causes of nontraumatic, nonsurgical pain, when opioids are needed,
a few days or less are often sufficient, and shorter courses can minimize the need to taper opioids to prevent withdrawal
symptoms at the end of a course of opioids. However, durations should be individualized to the patient’s clinical
circumstances.
Clinicians should generally avoid prescribing additional opioids to patients just in case pain continues longer than expected.
For postoperative pain related to major surgery, procedure-specific opioid prescribing recommendations are available with
ranges for amounts of opioids needed (on the basis of actual use and refills and on consensus).
To minimize unintended effects on patients, clinicians, practices, and health systems should have mechanisms in place for the
subset of patients who experience severe acute pain that continues longer than the expected duration. These mechanisms
should allow for timely reevaluation to confirm or revise the initial diagnosis and adjust pain management accordingly.
Clinicians, practices, and health systems can help minimize disparities in access to and affordability of care and refills by
ensuring all patients can obtain and afford additional evaluation and treatment, as needed.
Longer durations of opioid therapy are more likely to be needed when the mechanism of injury is expected to result in
prolonged severe pain (e.g., severe traumatic injuries).
Patients should be evaluated at least every 2 weeks if they continue to receive opioids for acute pain.
If opioids are continued for ≥1 month, clinicians should ensure that potentially reversible causes of chronic pain are addressed
and that opioid prescribing for acute pain does not unintentionally become long-term opioid therapy simply because
medications are continued without reassessment. Continuation of opioid therapy at this point might represent initiation of
long-term opioid therapy, which should occur only as an intentional decision that benefits are likely to outweigh risks after
discussion between the clinician and patient and as part of a comprehensive pain management approach. Clinicians should
refer to recommendations on subacute and chronic pain for initiation (Recommendation 2), follow-up (Recommendation 7),
and tapering (Recommendation 5) of ongoing opioid therapy.
If patients already receiving long-term opioid therapy require additional opioids for superimposed severe acute pain (e.g.,
major surgery), opioids should be continued only for the duration of pain severe enough to require additional opioids,
returning to the patient’s baseline opioid dosage as soon as possible, including a taper to baseline dosage if additional
opioids were used around the clock for more than a few days.
If opioids are used continuously (around the clock) for more than a few days for acute pain, clinicians should prescribe a brief
taper to minimize withdrawal symptoms on discontinuation of opioids.
If a taper is needed, taper durations might need to be adjusted depending on the duration of the initial opioid prescription
(see Supporting Rationale for this recommendation for additional details).
Tapering plans should be discussed with the patient before hospital discharge and with clinicians coordinating the patient’s
care as an outpatient. (See Recommendation 5 for tapering considerations when patients have taken opioids continuously for
>1 month.)

Supporting Rationale
Data suggest that pain improves within days for many patients with common types of acute pain in primary care or emergency
department settings. Analysis of nationwide U.S. commercial insurance claims in 2014 found median durations of initial opioid
analgesic prescriptions for acute pain indications in primary care settings were 4–7 days (244), suggesting that in most cases,
clinicians considered an initial opioid prescription of 4–7 days’ duration sufficient. Some patients (17.8%; range: 11.7%–30.0%
depending on the acute pain condition) obtained at least one refill within 30 days after their initial opioid prescription, suggesting
that although these durations might have been sufficient or more than necessary for most patients, variation across diagnoses and
among patients in time to recovery is likely. In an older study of the course of acute low back pain (not associated with
malignancies, infections, spondyloarthropathies, fractures, or neurologic signs) in a primary care setting, a large decrease in pain
occurred until the fourth day after treatment with paracetamol, with smaller decreases thereafter (245). A more recent single-
center survey of patients prescribed opioids for acute pain on emergency department discharge (246) found that patients taking
opioids continued them for a median of 4 days (IQR: 2–7 days), including on the day of discharge, with variation across patients
and diagnoses. Median numbers of days that patients continued taking prescribed opioids were 6 days (IQR: 4–8 days) for back
pain and fractures, 2 days (IQR: 1–5 days) for renal colic, 5.5 days (IQR: 4–7 days) for musculoskeletal injury, and 3 days (IQR: 2–6)
for other diagnoses. Most patients (92.5%) reported having leftover pills, with 52.2% of pills unused overall. A Canadian study

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 36 of 89
:
 following patients for 14 days after discharge from the emergency department with opioid prescriptions for acute pain similarly
found most (68%) total prescribed opioids were unused, and the quantity of 5-mg morphine tablets to prescribe to adequately
supply 80% of the patients with the amount of opioids they used was 20 tablets for musculoskeletal pain, 30 for fracture, 15 for
renal colic or abdominal pain, and 20 for other pain conditions (247).

Since 2017, multiple studies have found that many patients do not use all prescribed opioids after surgery and that prescribing a
lower quantity of opioids postoperatively is associated with less opioid use without increases in pain score or in requests for refills
of pain medication and without reductions in satisfaction with pain management (77–79). One study found that, after five common
surgical procedures, median opioid consumption was three 5-mg oxycodone pills or less, and that following consensus
recommendations intended to reduce unnecessary postoperative opioid prescribing published in 2018 and 2019 would still result
in 47%–56% of pills prescribed remaining unused (248). Evidence exists of variation in opioid needs across patients undergoing
the same procedures attributable to factors including pain at discharge and previous opioid use (249). One study found that,
although a majority of patients used no or few (>0 to <50 MME during their entire postoperative course) opioids, some patients
required opioids for up to 15 days after surgery (250).

Clinical evidence reviews found observational evidence that opioid use for acute pain is associated with long-term opioid use and
that a greater amount of early opioid exposure is associated with greater likelihood of long-term use, noting recent evidence for a
dose- and duration-dependent effects (63,75,141,244,251,252). Opioids prescribed for surgery and other acute pain conditions
that go unused are a potential source for misuse and diversion (249,253–255). In addition, sudden discontinuation of opioids
might result in clinically significant opioid withdrawal (71). Therefore, limiting duration of opioids prescribed can minimize the
need for a taper to prevent distressing or unpleasant withdrawal symptoms.

Many common causes of nonsurgical, nontraumatic acute pain can often be managed without opioids (see Recommendation 1).
When the diagnosis and severity of acute pain warrant the use of opioids, clinicians should prescribe no greater quantity than
needed for the expected duration of pain severe enough to require opioids. A few days or less are often sufficient when opioids are
needed for many common causes of nonsurgical acute pain, and limiting the duration of opioid therapy can minimize the need to
taper to prevent withdrawal symptoms at the end of the course of opioids and limit unused opioids. Certain circumstances (e.g.,
severe traumatic injuries) might require use of opioids for durations of >7 days. Durations should be individualized based on the
patient’s clinical circumstances.

When patients are discharged from the hospital after surgery, the course and dosage of any opioid medications administered
during hospitalization and before discharge can help predict ongoing pain management needs (150,256,257). For postoperative
pain, procedure-specific opioid prescribing recommendations are available with ranges for amounts of opioids needed (on the
basis of use and refills and on consensus) (149,151,250).

Clinicians should generally not prescribe additional opioids to patients just in case pain continues longer than expected. However,
if pain continues longer than expected, some patients might face challenges in successfully navigating the health care system
(e.g., clinician and pharmacy contact, transportation, and need for assistance) to obtain additional medication as needed, leading to
potential disparities in treatment. Clinicians, practices, and health systems should have mechanisms in place for the subset of
patients who experience severe acute pain that continues longer than the expected duration. These mechanisms should allow for
timely reevaluation to confirm or revise the initial diagnosis and adjust pain management accordingly. In particular, clinicians,
practices, and health systems should ensure all patients can obtain and afford additional evaluation and treatment as needed to
minimize disparities in access to and affordability of care and refills.

Patients should be evaluated at least every 2 weeks if they continue to receive opioids for acute pain. If opioids are continued for
≥1 month, clinicians should ensure that potentially reversible causes of chronic pain are addressed and that opioid prescribing for
acute pain does not unintentionally become long-term opioid therapy simply because medications are continued without
reassessment. Continuation of opioid therapy at this point might represent initiation of long-term opioid therapy, which should
occur only as an intentional decision that benefits are likely to outweigh risks after discussion between the clinician and patient
and as part of a comprehensive pain management approach. Clinicians should refer to recommendations on subacute and chronic
pain for initiation (Recommendation 2), follow-up (Recommendation 7), and tapering (Recommendation 5) of ongoing opioid
therapy. If patients already receiving long-term opioids require additional opioids for superimposed severe acute pain (e.g., major

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 37 of 89
:
 surgery), opioids should be continued only for the duration of pain severe enough to require additional opioids, returning to the
patient’s baseline opioid dosage as soon as possible, including a taper to baseline dosage if additional opioids were used around
the clock for more than a few days.

If opioids are used continuously (around the clock) for more than a few days for acute pain, clinicians should prescribe a brief taper
to minimize withdrawal symptoms on discontinuation of opioids. Taper durations might need to be adjusted depending on the
duration of the initial opioid prescription. For example, if opioids are used continuously for >3 days but for <1 week, clinicians can
consider reducing the daily dosage to 50% for 2 days to ameliorate withdrawal symptoms when discontinuing opioids. When
patients have taken opioids continuously for ≥1 week but <1 month, clinicians might consider a slower taper (e.g., reducing the
daily dosage by approximately 20% every 2 days, a range consistent with tapering rates successfully used in studies of
postoperative opioid prescribing) (256,257). When patients are discharged from the hospital after surgery, opioid dosages needed
during hospitalization and before discharge can help predict tapering needs to prevent withdrawal symptoms (150,256,257).
Tapering plans should be discussed with the patient before discharge and with clinicians coordinating the patient’s care as an
outpatient. (See Recommendation 5 for tapering considerations when patients have taken opioids continuously for >1 month.)

Recommendation 7
Clinicians should evaluate benefits and risks with patients within 1–4 weeks of starting opioid therapy for subacute or
chronic pain or of dosage escalation. Clinicians should regularly reevaluate benefits and risks of continued opioid therapy
with patients (recommendation category: A; evidence type: 4).

Implementation Considerations
In addition to evaluating benefits and risks of opioids before starting opioid therapy (see Recommendation 2), clinicians
should evaluate patients to assess benefits and risks of opioids within 1–4 weeks of starting long-term opioid therapy or of
dosage escalation.
Clinicians should consider follow-up intervals within the lower end of this range when ER/LA opioids are started or
increased, because of the increased risk for overdose within the first 2 weeks of treatment, or when total daily opioid dosage
is ≥50 MME/day. (Overdose risk is doubled across multiple studies for dosages of 50 to <100 MME/day relative to <20
MME/day.) (See Recommendation 4.)
Shorter follow-up intervals (every 2–3 days for the first week) should be strongly considered when starting or increasing the
dosage of methadone, because of the variable half-life of this drug (see Recommendation 3) and the potential for drug
accumulation during initiation and during upward titration of dosage.
An initial follow-up interval closer to 4 weeks can be considered when starting immediate-release opioids at a dosage of <50
MME/day.
Clinicians should follow up with and evaluate patients with subacute pain who started opioid therapy for acute pain and have
been treated with opioid therapy for 30 days to reassess the patient’s pain, function, and treatment course; ensure that
potentially reversible causes of chronic pain are addressed; and prevent unintentional initiation of long-term opioid therapy.
Continuation of opioid therapy at this point might represent initiation of long-term opioid therapy, which should occur only as
an intentional decision that benefits are likely to outweigh risks after discussion between the clinician and patient and as part
of a comprehensive pain management approach (see Recommendation 2).
Clinicians should regularly reassess all patients receiving long-term opioid therapy, including patients who are new to the
clinician but on long-term opioid therapy, with a suggested interval of every 3 months or more frequently for most patients.
Clinicians seeing new patients already receiving opioids should establish treatment goals, including functional goals, for
continued opioid therapy (see Recommendation 2).
Clinicians should reevaluate patients who are at higher risk for opioid use disorder or overdose (e.g., patients with depression
or other mental health conditions, a history of substance use disorder, a history of overdose, taking ≥50 MME/day, or taking
other central nervous system depressants with opioids) more frequently than every 3 months. Clinicians should regularly
screen all patients for these conditions, which can change during the course of treatment (see Recommendation 8).
Clinicians, practices, and health systems can help minimize unintended effects on patients by ensuring all patients can access
and afford follow-up evaluation.
In practice contexts where virtual visits are part of standard care (e.g., in remote areas where distance or other context makes

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 38 of 89
:
 follow-up visits challenging), or for patients for whom in-person follow-up visits are challenging (e.g., frail patients), follow-
up assessments that allow the clinician to communicate with and observe the patient through telehealth modalities might be
conducted.
At follow-up, clinicians should review patient perspectives and goals, determine whether opioids continue to meet treatment
goals, including sustained improvement in pain and function, and determine whether the patient has experienced common or
serious adverse events or early warning signs of serious adverse events or has signs of opioid use disorder.
Clinicians should ensure that treatment for depression, anxiety, or other psychological comorbidities is optimized.
Clinicians should ask patients about their preferences for continuing opioids, considering their effects on pain and function
relative to any adverse effects experienced. If risks outweigh benefits of continued opioid therapy (e.g., if patients do not
experience meaningful, sustained improvements in pain and function compared with before initiation of opioid therapy; if
patients are taking higher-risk regimens [e.g., dosages of ≥50 MME/day or opioids combined with benzodiazepines] without
evidence of benefit; if patients believe benefits no longer outweigh risks; if patients request dosage reduction or
discontinuation; or if patients experience overdose or other serious adverse events), clinicians should work with patients to
taper and reduce opioid dosage or taper and discontinue opioids when possible (see from Recommendation 5).
Clinicians should maximize pain treatment with nonpharmacologic and nonopioid pharmacologic treatments as appropriate
(see Recommendation 2).

Supporting Rationale
Although clinical evidence reviews did not find studies evaluating the effectiveness of more frequent monitoring intervals (7), they
identified an observational study (54) that found risk for opioid use disorder was associated with continuing opioid therapy for ≥3
months. The reviews also identified a study that found risk for overdose associated with ER/LA opioids might be particularly high
during the first 2 weeks of treatment (192). Another study found the first 3 months after opioid initiation to be a period of higher
risk for opioid overdose (214). Patients who do not have pain relief with opioids at 1 month are unlikely to experience pain relief
with opioids at 6 months (258). Although evidence is insufficient to determine at what point within the first 3 months of opioid
therapy the risks for opioid use disorder increase, reassessment of pain and function within 1 month of initiating opioids provides
an opportunity to modify the treatment plan to achieve pain treatment goals, including functional goals, and minimize risks of
long-term opioid use by tapering and discontinuing opioids among patients not receiving a clear benefit from these medications. In
addition, evaluation within the first 3 months might provide opportunities to identify and mitigate risks for opioid use disorder and
overdose.

Experts from OWG noted that although little evidence exists for specific follow-up time frames, the recommendation was
reasonable and reflects common practice and therefore supported the recommendation. Experts further noted that social
determinants of health affecting ability to return frequently for care (e.g., role as unpaid caregiver or work at a job with minimal
paid time off) or payer issues (e.g., copays) could have consequences when recommending frequent visits and should be
considered.

Clinicians should evaluate patients to assess benefits and risks of opioids within 1–4 weeks of starting long-term opioid therapy or
of dosage escalation. Clinicians should consider follow-up intervals within the lower end of this range when ER/LA opioids are
started or increased, because of the increased risk for overdose within the first 2 weeks of treatment (192), or when total daily
opioid dosage is ≥50 MME/day, because the overdose risk is doubled across multiple studies for dosages of 50 to <100 MME/day
relative to <20 MME/day (see Recommendation 4). Shorter follow-up intervals (every 2–3 days for the first week) should be
strongly considered when starting or increasing the dosage of methadone because of the variable half-life of this drug (see
Recommendation 3) and the potential for drug accumulation during initiation and during upward titration of dosage. An initial
follow-up interval closer to 4 weeks can be considered when starting immediate-release opioids at a dosage of <50 MME/day.

Patients who started opioid therapy for acute pain and are continuing to receive opioids for subacute pain might be at a
particularly critical point for potential transition to chronic pain and potential transition to long-term opioid therapy. Clinicians
should follow up with and evaluate patients with subacute pain who have been treated with opioid therapy for 30 days. Clinicians
should ensure that opioid prescribing for acute pain does not unintentionally become long-term opioid therapy simply because
medications are continued without reassessment, but only as an intentional decision that benefits are likely to outweigh risks after

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 39 of 89
:
 discussion between the clinician and patient. Clinicians should reassess the patient’s pain, function, and treatment course; ensure
that potentially reversible causes of chronic pain are addressed; and optimize pain management as needed (see Recommendation
2).

In analyses of placebo-controlled trials, the clinical evidence reviews found that effects of opioids on mean improvement in pain
and in function were greater at 1–3 months than at 3–6 months (7). A cohort study found an association between longer duration
of therapy and increased risk for new-onset depression (7). Because of potential changes in the balance of benefits and risks of
opioid therapy over time, clinicians should regularly reassess all patients receiving long-term opioid therapy, including patients
who are new to the clinician but on long-term opioid therapy, with a suggested interval of every 3 months or more frequently.
Clinicians seeing new patients already receiving opioids should establish treatment goals, including functional goals, for continued
opioid therapy (see Recommendation 2). Clinicians should reevaluate patients who are at greater risk for opioid use disorder or
overdose (e.g., patients with depression or other mental health conditions, a history of substance use disorder, a history of
overdose, taking ≥50 MME/day, or taking other central nervous system depressants with opioids) more frequently than every 3
months. Clinicians should regularly screen all patients for these conditions, which can change during the course of treatment (see
Recommendation 8). Clinicians, practices, and health systems can help minimize unintended effects on patients by ensuring all
patients can access and afford follow-up evaluation (86). In addition, policymakers can consider evidence-based methods of
minimizing barriers to care (e.g., paid sick leave) (259). In practice contexts where virtual visits are part of standard care (e.g., in
remote areas where distance or other context makes follow-up visits challenging), or for patients for whom in-person follow-up
visits are challenging (e.g., frail patients), follow-up assessments that allow the clinician to communicate with and observe the
patient through telehealth modalities might be conducted when available.

At follow-up, clinicians should review patient perspectives on progress and challenges in moving toward treatment goals;
determine whether opioids continue to meet treatment goals, including sustained improvement in pain and function; determine
whether the patient has experienced common or serious adverse events or early warning signs of serious adverse events or has
signs of opioid misuse or opioid use disorder (e.g., difficulty controlling use, cravings, work, and social or family problems related
to opioid use); determine whether benefits of opioids continue to outweigh risks; and determine whether there is a need for opioid
dosage reduction or discontinuation. Clinicians should assess benefits in function, pain control, and quality of life by asking
patients about progress toward person-centered functional goals that have meaning for them (see Recommendation 2) or by
using tools such as the three-item PEG assessment scale (184); clinically meaningful improvement has been defined as a 30%
improvement in scores for both pain and function (185). Clinicians also should ask patients about common adverse effects such as
constipation and drowsiness (see Recommendation 2) and should ask about and assess for effects that might be early warning
signs for more serious problems such as overdose (e.g., sedation or slurred speech) or opioid use disorder (e.g., craving, wanting to
take opioids in greater quantities or more frequently than prescribed, difficulty controlling use, or work, social, or family problems
related to opioid use). Clinicians can use validated screening tools such as the Drug Abuse Screening Test (DAST) (260), the
Tobacco, Alcohol, Prescription medication, and other Substance use Tool (TAPS) (261), and the three-question version of the
Alcohol Use Disorders Identification Test (AUDIT-C) (262,263) (see Recommendations 8 and 12). Because depression, anxiety,
and other psychological comorbidities often coexist with and can interfere with resolution of pain, clinicians should use validated
instruments to assess for these conditions (see Recommendation 8) and ensure that treatment for these conditions is optimized.
Clinicians should ask patients about their preferences for continuing opioids considering their effects on pain and function relative
to any adverse effects experienced.

If risks outweigh benefits of continued opioid therapy (e.g., if patients do not experience meaningful, sustained improvements in
pain and function compared with before initiation of opioid therapy; if patients are taking higher-risk regimens [e.g., dosages of
≥50 MME/day or opioids combined with benzodiazepines] without evidence of benefit; if patients believe benefits no longer
outweigh risks; if patients request dosage reduction or discontinuation; or if patients experience overdose or other serious adverse
events), clinicians should work with patients to taper and reduce opioid dosage or to taper and discontinue opioids when possible
(see Recommendation 5). Clinicians should maximize pain treatment with nonpharmacologic and nonopioid pharmacologic
treatments as appropriate (see Recommendation 2).

Assessing Risk and Addressing Potential Harms of Opioid Use

Recommendation 8

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 40 of 89
:
 Before starting and periodically during continuation of opioid therapy, clinicians should evaluate risk for opioid-related harms
and discuss risk with patients. Clinicians should work with patients to incorporate into the management plan strategies to
mitigate risk, including offering naloxone (recommendation category: A; evidence type: 4).

Implementation Considerations
Clinicians should ask patients about their drug and alcohol use and use validated tools or consult with behavioral specialists
to screen for and assess mental health and substance use disorders.
When considering initiating long-term opioid therapy, clinicians should ensure that treatment for depression and other
mental health conditions is optimized, consulting with behavioral health specialists when needed.
Clinicians should offer naloxone when prescribing opioids, particularly to patients at increased risk for overdose, including
patients with a history of overdose, patients with a history of substance use disorder, patients with sleep-disordered
breathing, patients taking higher dosages of opioids (e.g., ≥50 MME/day), patients taking benzodiazepines with opioids (see
Recommendation 11), and patients at risk for returning to a high dose to which they have lost tolerance (e.g., patients
undergoing tapering or recently released from prison).
Practices should educate patients on overdose prevention and naloxone use and offer to provide education to members of
their households.
Naloxone coprescribing can be facilitated by clinics or practices with resources to provide naloxone training, by collaborative
practice models with pharmacists, or through statewide protocols or standing orders for naloxone at pharmacies.
Resources for prescribing naloxone in primary care and emergency department settings can be found through Prescribe to
Prevent at https://prescribetoprevent.org  . Additional resources are at https://www.samhsa.gov  .
In part because of concerns about cost of naloxone and access for some patients and reports that purchasing of naloxone has
in some cases been required to fill opioid prescriptions, including for patients without a way to afford naloxone, this
recommendation specifies that naloxone should be offered to patients. To that end, clinicians, health systems, and payers can
work to ensure patients can obtain naloxone, a potentially lifesaving treatment.
Clinicians should avoid prescribing opioids to patients with moderate or severe sleep-disordered breathing when possible to
minimize risk for respiratory depression.
When making decisions about whether to initiate opioid therapy for pain during pregnancy, clinicians and patients together
should carefully weigh benefits and risks. For pregnant persons already receiving opioids, clinicians should access
appropriate expertise if tapering is being considered because of possible risks to the pregnant patient and the fetus if the
patient goes into withdrawal (see Recommendation 5).
For pregnant persons with opioid use disorder, medication for opioid use disorder (buprenorphine or methadone) is the
recommended therapy and should be offered as early as possible in pregnancy to prevent harms to both the patient and the
fetus (see Recommendation 12).
Clinicians should use additional caution and increased monitoring (see Recommendation 7) to minimize risks of opioids
prescribed for patients with renal or hepatic insufficiency and for patients aged ≥65 years. Clinicians should implement
interventions to mitigate common risks of opioid therapy among older adults, such as exercise or bowel regimens to prevent
constipation, risk assessment for falls, and patient monitoring for cognitive impairment.
For patients with jobs that involve potentially hazardous tasks and who are receiving opioids or other medications that can
negatively affect sleep, cognition, balance, or coordination, clinicians should assess patients’ abilities to safely perform the
potentially hazardous tasks (e.g., driving, use of heavy equipment, climbing ladders, working at heights or around moving
machinery, or working with high-voltage equipment).
Clinicians should use PDMP data (see Recommendation 9) and toxicology screening (see Recommendation 10) as
appropriate to assess for concurrent substance use that might place patients at higher risk for opioid use disorder and
overdose.
Clinicians should provide specific counseling on increased risks for overdose when opioids are combined with other drugs or
alcohol (see Recommendation 2) and ensure that patients are provided or receive effective treatment for substance use
disorders when needed (see Recommendation 12).
Although substance use disorders can alter the expected benefits and risks of opioid therapy for pain, patients with co-
occurring pain and substance use disorder require ongoing pain management that maximizes benefits relative to risks. (See

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 41 of 89
:
 Recommendation 12, Pain Management for Patients with Opioid Use Disorder for additional considerations specific to these
patients.)
If clinicians consider opioid therapy for chronic pain for patients with substance use disorder, they should discuss increased
risks for opioid use disorder and overdose with patients, carefully consider whether benefits of opioids outweigh increased
risks, and incorporate strategies to mitigate risk into the management plan (e.g., offering naloxone [see Offering Naloxone to
Patients] and increasing frequency of monitoring [see Recommendation 7]).
If patients experience nonfatal opioid overdose, clinicians should evaluate for opioid use disorder and treat or arrange
treatment if needed. Clinicians should work with patients to reduce opioid dosage and to discontinue opioids when indicated
(see Recommendation 5) and should ensure continued close monitoring and support for patients prescribed or not prescribed
opioids.
If clinicians continue opioid therapy in patients with previous opioid overdose, they should discuss increased risks for
overdose with patients, carefully consider whether benefits of opioids outweigh substantial risks, and incorporate strategies
to mitigate risk into the management plan (e.g., offering naloxone and increasing frequency of monitoring [see
Recommendation 7]).

Supporting Rationale
The clinical evidence reviews found evidence too limited to determine effects of patient demographics and comorbidities on risk for
opioid-related harms (7). However, on the basis of observational studies (181,264–273) and expert opinion, certain risk factors are
likely to increase susceptibility to opioid-related harms and warrant incorporation of additional strategies into the management
plan to mitigate risk. Clinicians should assess these risk factors periodically, with frequency individualized to patient comorbidities
and other risk factors. For example, factors that vary over time, such as alcohol use, require more frequent assessment. Clinicians
should offer naloxone and reevaluate patients more frequently (see Recommendation 7) when factors are present that increase
risk for harm, such as sleep-disordered breathing, history of overdose, history of substance use disorder, higher dosages of opioids
(e.g., ≥50 MME/day), and concurrent use of benzodiazepines with opioids. Experts from OWG had concerns about the cost of
purchasing naloxone for patients with limited means and reported that purchasing of naloxone has in some cases been required to
fill opioid prescriptions. In part because of these concerns and because in certain settings naloxone is directly provided by a
practice or health system to patients, “offering” naloxone (which can be done by offering a prescription or by offering naloxone
directly) is recommended rather than specifying “prescribing” naloxone. Clinicians, health systems, and payers should work to
ensure patients can obtain naloxone, a potentially lifesaving treatment.

Patients with Sleep-Disordered Breathing, Including Sleep Apnea

A case-control analysis among veterans prescribed opioids found that sleep apnea was associated with increased risk for life-
threatening respiratory/central nervous system depression or overdose (264). Careful monitoring and cautious dose titration
should be used if opioids are prescribed for patients with mild sleep-disordered breathing. Clinicians should avoid prescribing
opioids to patients with moderate or severe sleep-disordered breathing, whenever possible, to minimize risks for respiratory
depression.

Pregnant Persons
Pregnant, postpartum, and parenting persons should receive compassionate, evidence-based care for pain or opioid use disorder.
ACOG has noted that a cautious approach to prescribing opioids should be balanced with the need to address pain, and
pregnancy should not be a reason to avoid treating acute pain (274). At the same time, opioid use during pregnancy might be
associated with risks to both the pregnant person and the fetus. Certain observational studies have shown an association of opioid
use in pregnancy with stillbirth, poor fetal growth, and preterm delivery (265–268,275). In some cases, opioid use during
pregnancy leads to neonatal abstinence syndrome/neonatal opioid withdrawal syndrome (269). ACOG has emphasized that
pregnancy should not be a reason to avoid treating acute pain because of concern for opioid misuse or neonatal abstinence
syndrome and that neonatal abstinence syndrome is an expected and treatable condition that can follow prenatal exposure to
opioid agonists.

Clinicians and patients together should carefully weigh benefits and risks when making decisions about whether to initiate opioid
therapy for pain during pregnancy. In addition, before initiating opioid therapy for persons who can become pregnant, clinicians
and patients should discuss family planning and potential effects of long-term opioid use on any future pregnancy. For all persons

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 42 of 89
:
 with reproductive potential, discussing future pregnancy intentions and engaging in shared decision-making regarding
contraception, if appropriate, is a core component of care. A review of all prescription and nonprescription medications is
recommended during prepregnancy and interpregnancy care (276,277). Intentional application of a patient-centered reproductive
justice framework and use of a shared decision-making model is the recommended approach for providing supportive
contraceptive counseling and care to help patients to achieve their reproductive goals (278). Counseling should be noncoercive
and include a discussion of all contraceptive options (276–278). When opioids are needed for treatment of acute pain in pregnant
persons, the lowest effective dose (see Recommendation 4) should be used for no longer than the expected duration of pain
severe enough to require opioids (see Recommendation 6). For pregnant persons with chronic pain, ACOG recommends that
practice goals include strategies to avoid or minimize the use of opioids for pain management, highlighting alternative pain
therapies such as nonpharmacologic (e.g., exercise, physical therapy, and behavioral approaches), and nonopioid pharmacologic
treatments (274). Pharmacokinetic and physiologic changes occur during pregnancy, especially in the third trimester, and these
changes might require dose adjustments (274). For pregnant persons already receiving opioids, clinicians should access
appropriate expertise if considering tapering opioids because of possible risk to the pregnant patient and the fetus if the patient
goes into withdrawal (see Recommendation 5).

ACOG has noted that early universal screening, brief intervention (e.g., engaging in a short conversation and providing feedback
and advice), and referral for treatment of pregnant persons with opioid use disorder improve both maternal and infant outcomes
(274). For pregnant persons with opioid use disorder, medication for opioid use disorder (buprenorphine or methadone) is the
recommended therapy, has been associated with improved maternal outcomes, and should be offered as early as possible in
pregnancy to prevent harms to both the patient and the fetus (274) (see Recommendation 12). In contrast, criminalization or
otherwise punishing (e.g., through threatened loss of child custody) the use of opioids, including for opioid use disorder,
discourages pregnant, postpartum, and parenting persons from seeking care; nonpunitive public health approaches to treatment
result in better outcomes (274,279).

The American Academy of Pediatrics (AAP) has published recommendations for the care of infants with neonatal opioid
withdrawal syndrome, including that pregnant persons with opioid use disorder should receive antenatal counseling to provide
education on the clinical signs of withdrawal and on postnatal treatment for neonatal opioid withdrawal syndrome (e.g.,
nonpharmacologic treatment, including breastfeeding, and pharmacotherapy) (280). In addition, all infants with long-term opioid
exposure should be observed for at least 72 hours (4–7 days if exposed to buprenorphine or ER/LA opioids and 5–7 days if
exposed to methadone) to monitor for the development of withdrawal (280). Clinicians caring for pregnant persons receiving
prescribed or using nonprescribed opioids should arrange for delivery at a facility prepared to monitor, evaluate for, and treat
neonatal opioid withdrawal syndrome. In instances when travel to such a facility would present an undue burden on the pregnant
person, it is appropriate for the clinician to arrange delivery locally, monitor and evaluate the newborn for neonatal opioid
withdrawal syndrome, and transfer the newborn for additional treatment if needed. Previous consensus recommendations have
advised that if a codeine-containing medication is selected for postpartum management, clinicians should review duration of
therapy and neonatal signs of toxicity with patients and their families (133).

Patients with Renal or Hepatic Insufficiency

A case-control study of risk for life-threatening respiratory/central nervous system depression or overdose among veterans
prescribed opioids found that renal disease and moderate or severe liver disease were associated with increased risk for these
events (264). Clinicians should use additional caution and increased monitoring (see Recommendation 7) to minimize risks of
opioids prescribed for patients with renal or hepatic insufficiency because of their decreased ability to process and excrete
medications, susceptibility to accumulation of opioids, and reduced therapeutic window between safe dosages and dosages
associated with respiratory depression and overdose (281) (see Recommendations 3, 4, and 7).

Patients Aged ≥65 Years

Older adults are a heterogenous group comprising a wide span of ages and functional abilities, ranging from healthy, active older
adults to frail older adults. Frail older adults in particular can be at risk for changes in function that might be exacerbated by pain
and contribute to deterioration in overall health and independence. Functional assessment is especially important in patients aged
≥65 years to better assess effects of pain on function and independence. Persons aged ≥65 years can be at risk for inadequate

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 43 of 89
:
 pain treatment (2,6,17,282). For certain older adults (e.g., older adults with serious illness that requires advanced management of
pain or other distressing symptoms) (94), palliative care, which is beyond the scope of this guideline but addressed in other
guidelines (93), is appropriate.

Pain management for older patients can be challenging because of increased risks of both nonopioid pharmacologic therapies (see
Recommendation 2) and opioid therapy in this population. Because of reduced renal function and medication clearance even in the
absence of renal disease, patients aged ≥65 years might have increased susceptibility to accumulation of all medications,
increased risk for drug-drug interactions, and a smaller therapeutic window between safe dosages and dosages associated with
adverse effects. These adverse effects include renal, cardiovascular, and gastrointestinal effects with oral NSAIDs (see
Recommendation 2) and respiratory depression and overdose with opioids. A case-control analysis among veterans prescribed
opioids found that age ≥55 years was associated with increased risk for life-threatening respiratory/central nervous system
depression or overdose (264). Some older adults might have a cognitive impairment, such as dementia, that can increase risk for
medication errors and make opioid-related confusion riskier. In addition, older adults are more likely than younger adults to
experience comorbid medical conditions and are more likely to receive multiple medications, some of which might interact with
opioids.

Clinicians should review all current medications, over-the-counter drugs, and natural remedies before prescribing any new drugs.
Clinicians should use additional caution and increased monitoring (see Recommendation 7) for patients aged ≥65 years to ensure
pain is addressed and minimize risks of opioids prescribed. Clinicians should educate older adults receiving opioids to avoid
medication-related behaviors that increase risk, such as saving unused medications. Caregivers can have an important role in
management of opioid therapy for older persons with cognitive impairment. Clinicians also should implement interventions to
mitigate common risks of opioid therapy among older adults, such as monitoring for cognitive impairment, risk assessment for
falls, and exercise and bowel regimens to prevent constipation.

Patients in Safety Critical Jobs

A safety critical job involves work or an occupational environment where limitations in physical or mental performance, or both,
involve dangers to self, coworkers, or the public. According to the American College Occupational Environmental Medicine, for
occupations with higher risks (especially public transportation), prescription of an opioid might be incompatible with continued
employment in a safety critical job (270,283). For patients with safety critical jobs who are receiving opioids or other medications
that can negatively affect sleep, cognition, balance, or coordination, clinicians should assess patients’ abilities to perform jobs that
involve driving, using heavy equipment, climbing ladders, working at heights or around moving machinery, or working with high-
voltage equipment.

Patients with Mental Health Conditions

Psychological distress frequently interferes with improvement of pain and function in patients with chronic pain; therefore, using
validated instruments such as the Generalized Anxiety Disorder (GAD)-7 and the Patient Health Questionnaire (PHQ-9 or PHQ-4)
to support assessment for anxiety, posttraumatic stress disorder (PTSD), and depression (284) might help clinicians improve
overall pain treatment outcomes. Patients with mental health conditions including depression might be at higher risk than other
patients for opioid use disorder (181,271) and drug overdose (272). Additional caution and increased monitoring (see
Recommendation 7) might lessen the increased risk for overdose among patients with depression (264,272). In addition, patients
with anxiety disorders and other mental health conditions are more likely to receive benzodiazepines, which can exacerbate
opioid-induced respiratory depression and increase risk for overdose (see Recommendation 11). Clinicians should ensure that
treatment for depression and other mental health conditions as well as treatment for pain is optimized, consulting with behavioral
health specialists when needed. Treatment for depression can improve pain symptoms and depression and might decrease
overdose risk (272). For treatment of chronic pain in patients with depression, clinicians should consider using tricyclic or SNRI
antidepressants for analgesic as well as antidepressant effects if these medications are not otherwise contraindicated (see
Recommendation 2).

Patients with Substance Use Disorders

Patients with substance use disorders are likely to experience greater risks for opioid use disorder and overdose (55,202,264) than
persons without these conditions. Despite increased risk for opioid misuse and opioid use disorder when prescribed opioid
analgesics (271,285), patients with histories of substance use disorders are more likely than other patients to receive long-term

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 44 of 89
:
 opioid treatment for chronic pain (286). Previous guidelines have recommended screening or risk assessment tools to identify
patients at higher risk for opioid misuse or opioid use disorder. However, the clinical evidence reviews found that available risk
stratification tools (e.g., Opioid Risk Tool, Screener and Opioid Assessment for Patients with Pain [SOAPP] Version 1, SOAPP-R,
and Brief Risk Interview) demonstrate limited and variable accuracy for classification of patients as at low or high risk for opioid
use disorder or misuse (7). If these tools are used, they should be supplemented with other assessments, such as discussions with
patients, family, and caregivers; clinical records; PDMP data (see Recommendation 9); and toxicology screening data (see
Recommendation 10). Clinicians should always use caution when considering or prescribing opioids and should not overestimate
the ability of available risk stratification tools to rule out risks of long-term opioid therapy.

Nonprescribed drugs (e.g., heroin, illicitly manufactured fentanyl, cocaine, and methamphetamine) (287) and alcohol (288) are
listed as contributory factors on a substantial proportion of death certificates for prescription opioid–involved overdose deaths.
Clinicians should ask patients about their drug (289) and alcohol use. Single screening questions can be used (290). For example,
the question “How many times in the past year have you used an illegal drug or used a prescription medication for nonmedical
reasons?” (with an answer of one or more considered positive) was found in a primary care setting to be 100% sensitive and
73.5% specific for the detection of a drug use disorder compared with a standardized diagnostic interview (291). Validated
screening tools, such as the Drug Abuse Screening Test (DAST) (260); the Tobacco, Alcohol, Prescription medication, and other
Substance use Tool (TAPS) (261); and the three-question version of the Alcohol Use Disorders Identification Test (AUDIT-C)
(262,263), also can be used. Clinicians should use PDMP data (see Recommendation 9) and toxicology screening (see
Recommendation 10) as appropriate to assess for concurrent substance use that might place patients at higher risk for opioid use
disorder and overdose. Clinicians should also provide specific counseling on increased risks for overdose when opioids are
combined with other drugs or alcohol (see Recommendation 2) and ensure that patients receive effective treatment for substance
use disorders when needed (see Recommendation 12).

If clinicians consider prescribing opioid therapy for chronic pain to patients with substance use disorders, they should discuss
increased risks for opioid use disorder and overdose with patients; carefully consider whether benefits of opioids outweigh
increased risks; and incorporate strategies to mitigate risk into the management plan, such as offering naloxone (see Offering
Naloxone to Patients) and increasing frequency of monitoring (see Recommendation 7) when opioids are prescribed. Clinicians
should communicate with patients’ substance use disorder treatment providers if opioids are prescribed. Although substance use
disorders can alter the expected benefits and risks of opioid therapy for pain, patients with co-occurring pain and substance use
disorder require ongoing pain management that maximizes benefits relative to risks. (See Recommendation 12, Pain Management
for Patients with Opioid Use Disorder for additional considerations.)

Patients with Previous Overdose

Previous opioid overdose is associated with substantially increased risk for future nonfatal or fatal opioid overdose (273). Yet, a
cohort study of commercially insured patients found that opioids were dispensed to 91% of patients who had a previous overdose;
a substantial percentage experienced a repeated opioid overdose, with a cumulative incidence at 2 years of 17% among patients
receiving ≥100 MME/day, 15% among those prescribed 50–100 MME/day, 9% among those prescribed <50 MME/day, and 8%
among those prescribed no opioids (273).

If patients experience nonfatal opioid overdose, clinicians should evaluate them for opioid use disorder and provide or arrange
treatment if needed. Treatment with buprenorphine or methadone for opioid use disorder after overdose is associated with
reduced all-cause and opioid-related deaths (292). Clinicians should work with patients to reduce opioid dosage and discontinue
opioids when indicated (see Recommendation 5) and should ensure continued close monitoring and support for patients
prescribed or not prescribed opioids. If clinicians continue opioid therapy in patients with previous opioid overdose, they should
discuss increased risks for overdose with patients; carefully consider whether benefits of opioids outweigh substantial risks; and
incorporate strategies to mitigate risk into the management plan, such as offering naloxone (see Offering Naloxone to Patients),
involving patient-identified trusted family members, and increasing frequency of monitoring combined with shorter prescription
durations (see Recommendation 7).

Offering Naloxone to Patients

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 45 of 89
:
 Naloxone is an opioid antagonist that can reverse severe respiratory depression; its administration by laypersons, such as friends,
family, and caregivers of persons who experience opioid overdose, can save lives (293). Naloxone precipitates acute withdrawal
among patients physically dependent on opioids. Serious adverse effects (e.g., pulmonary edema, cardiovascular instability, and
seizures) have been reported but are rare at doses consistent with labeled use for opioid overdose (294). The clinical evidence
reviews identified one observational study (295) that found provision of naloxone to patients prescribed opioids in primary care
clinics was associated with decreased likelihood of opioid-related emergency department visits (7).

Clinicians should offer naloxone when prescribing opioids, particularly to patients at increased risk for overdose, including patients
with a history of overdose, patients with a history of substance use disorder, patients taking benzodiazepines with opioids (see
Recommendation 11), patients at risk for returning to a high dose to which they have lost tolerance (e.g., patients undergoing
tapering or recently released from prison), and patients taking higher dosages of opioids (≥50 MME/day). Practices should provide
education on overdose prevention and naloxone use to patients receiving naloxone prescriptions and members of their
households. Naloxone coprescribing can be facilitated by clinics or practices with resources to provide naloxone training and by
collaborative practice models with pharmacists. Resources for prescribing naloxone in primary care settings can be found through
Prescribe to Prevent at https://prescribetoprevent.org  .

Recommendation 9
When prescribing initial opioid therapy for acute, subacute, or chronic pain, and periodically during opioid therapy for chronic
pain, clinicians should review the patient’s history of controlled substance prescriptions using state prescription drug
monitoring program (PDMP) data to determine whether the patient is receiving opioid dosages or combinations that put the
patient at high risk for overdose (recommendation category: B; evidence type: 4).

Implementation Considerations
Ideally, PDMP data should be reviewed before every opioid prescription for acute, subacute, or chronic pain. This practice is
recommended in all jurisdictions where PDMP availability and access policies, as well as clinical practice settings, make it
practicable (e.g., clinician and delegate access permitted).
At a minimum, during long-term opioid therapy, PDMP data should be reviewed before an initial opioid prescription and then
every 3 months or more frequently. Recommendation category B acknowledges variation in PDMP availability and
circumstances. However, because PDMP information can be most helpful when results are unexpected and, to minimize bias
in application, clinicians should apply this recommendation when feasible to all patients rather than differentially on the basis
of assumptions about what they will learn about specific patients.
Clinicians should use specific PDMP information about medications prescribed to their patient in the context of other clinical
information, including their patient’s history, physical findings, and other relevant testing, to help them communicate with and
protect their patient.
Clinicians should review PDMP data specifically for prescription opioids and other controlled medications patients have
received from additional prescribers to determine whether a patient is receiving total opioid dosages or combinations (e.g.,
opioids combined with benzodiazepines) that put the patient at risk for overdose.
PDMP-generated risk scores have not been validated against clinical outcomes such as overdose and should not take the
place of clinical judgment.
Clinicians should not dismiss patients from their practice on the basis of PDMP information. Doing so can adversely affect
patient safety and could result in missed opportunities to provide potentially lifesaving information (e.g., about risks of
prescription opioids and about overdose prevention) and interventions (e.g., safer prescriptions, nonopioid pain treatment [see
Recommendations 1 and 2], naloxone [see Recommendation 8], and effective treatment for substance use disorders [see
Recommendations 8 and 12]).
Clinicians should take actions to improve patient safety:
Discuss information from the PDMP with the patient and confirm that the patient is aware of any additional
prescriptions. Because clinicians often work as part of teams, prescriptions might appropriately be written by more than
one clinician coordinating the patient’s care. Occasionally, PDMP information can be incorrect (e.g., if the wrong name or
birthdate has been entered, the patient uses a nickname or maiden name, or another person has used the patient’s
identity to obtain prescriptions).

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 46 of 89
:
 Discuss safety concerns, including increased risk for respiratory depression and overdose, with patients found to be
receiving overlapping prescription opioids from multiple clinicians who are not coordinating the patient’s care or patients
who are receiving medications that increase risk when combined with opioids (e.g., benzodiazepines) (see
Recommendation 11), and offer naloxone (see Recommendation 8).
Use particular caution when prescribing opioid pain medication and benzodiazepines concurrently, understanding that
some patient circumstances warrant prescribing of these medications concomitantly. Clinicians should communicate
with others managing the patient to discuss the patient’s needs, prioritize patient goals, weigh risks of concurrent
benzodiazepine and opioid exposure, and coordinate care (see Recommendation 11).
Consider the total MME/day for concurrent opioid prescriptions to help assess the patient’s overdose risk (see
Recommendation 4). Buprenorphine should not be counted in the total MME/day in calculations because of its partial
agonist properties at opioid receptors that confer a ceiling effect on respiratory depression. If a patient is found to be
receiving total daily dosages of opioids that put them at risk for overdose, discuss safety concerns with the patient,
consider in collaboration with the patient whether or not benefits of tapering outweigh risks of tapering (see
Recommendation 5), and offer naloxone (see Recommendation 8).
Discuss safety concerns with other clinicians who are prescribing controlled substances for the patient. Ideally, clinicians
should first discuss concerns with the patient and inform them that they plan to coordinate care with their other
clinicians to improve the patient’s safety.
Screen for substance use and discuss concerns with the patient in a nonjudgmental manner (see Recommendations 8
and 12).
When diverting (sharing or selling prescription opioids and not taking them) might be likely, consider toxicology testing
to assist in determining whether prescription opioids can be discontinued without causing withdrawal (see
Recommendations 5 and 10). A negative toxicology test for prescribed opioids might indicate the patient is not taking
prescribed opioids, although clinicians should consider other possible reasons for this test result (e.g., false-negative
results or misinterpretation of results) (see Recommendation 10).

Supporting Rationale
PDMPs are databases overseen by states, territories, counties, and the District of Columbia that collect information on controlled
prescription drugs dispensed by pharmacies and, in selected jurisdictions, by dispensing clinicians. PDMPs do not report
nonprescribed opioid use. A clinical evidence review did not find studies evaluating the effectiveness of PDMPs for risk mitigation
(7). However, among patients receiving concurrent treatment with opioids and benzodiazepines, overdose risk is further increased
among patients receiving these treatments from multiple prescribers rather than one prescriber, highlighting potential room for
improvement in care coordination (296). PDMP data also can be helpful when patient medication history is not otherwise available
(e.g., when patients transition care to a new clinician). A contextual evidence review (7) identified a survey of physicians in
Maryland (297) finding that although barriers to PDMP review were noted (e.g., not knowing about the program, registration
difficulties, and difficulty accessing data), most participants felt that PDMPs improved opioid prescribing by decreasing opioid
prescription amounts and increasing comfort with prescribing opioids (7). Integration of PDMPs with electronic health records
(EHRs) can reduce burden on clinicians compared with having to access a separate system (298,299).

Special attention should be paid to ensure that PDMP information is not used in a way that is harmful to patients. For example,
PDMP information has been used to dismiss patients from clinician practices (300), which might adversely affect patient safety
and result in untreated or undertreated pain. Many state laws require PDMP use under specific circumstances (301). Experts from
OWG had concerns about PDMP risk scores or other algorithmic interpretations from software platforms that can lead to distrust
between clinicians and patients and stigmatization, particularly for patients with conditions such as opioid use disorder. Risk
scores are reportedly generated by applying proprietary algorithms that are not publicly available to information from patient
EHRs and other sources such as court records and criminal and sexual trauma histories; these algorithms might disparately affect
women, persons of color, and persons who live in poverty (302). Importantly, whereas one PDMP-generated risk measure has
shown fair concurrence with the WHO Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST), these scores have
not been externally validated against clinical outcomes (302,303). Such risk scores should not take the place of clinical judgment.
Rather, clinicians should use specific PDMP information about medications prescribed to their patient in the context of other
clinical information, including their patient’s history, physical findings, and other relevant testing, to help them communicate with
and protect their patient.

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 47 of 89
:
 Experts raised varying points regarding frequency of PDMP use, with many agreeing that PDMPs should be consulted before
every opioid prescription, several agreeing that universal application would mitigate bias in application to different patients, and
others believing it might not be warranted or feasible to check the PDMP in all cases, particularly before prescribing opioids for
acute pain for a small number of days. Ideally, PDMP data should be reviewed before every opioid prescription for acute, subacute,
or chronic pain. This practice is recommended in all jurisdictions where PDMP availability and access policies make it practicable
(e.g., clinician and delegate access permitted). At a minimum, PDMP data should be reviewed before initial opioid prescriptions for
subacute or chronic pain and then every 3 months or more frequently during long-term opioid therapy. Recommendation category
B acknowledges variation in PDMP availability and circumstances (e.g., a clinician might reasonably determine that a patient with
severe acute pain in the emergency department during a PDMP system access failure would be adversely affected by waiting
hours for a prescription). However, because PDMP information can be most helpful when results are unexpected and, to minimize
bias in application, clinicians should apply this recommendation when feasible to all patients rather than differentially on the basis
of assumptions about what they will learn about specific patients.

Clinicians should review PDMP data for prescription opioids and other controlled medications patients might have received from
additional prescribers to determine the total amount of MME prescribed and to assess if the total dosage or combinations (e.g.,
opioids combined with benzodiazepines) put the patient at high risk for overdose. If patients are found to have total opioid
dosages or combinations of medications that might put them at risk for overdose, or multiple controlled substance prescriptions
written by different clinicians, clinicians should take actions to improve patient safety (see Recommendation 9, Implementation
Considerations).

Recommendation 10
When prescribing opioids for subacute or chronic pain, clinicians should consider the benefits and risks of toxicology testing
to assess for prescribed medications as well as other prescribed and nonprescribed controlled substances (recommendation
category: B; evidence type: 4).

Implementation Considerations
Toxicology testing should not be used in a punitive manner but should be used in the context of other clinical information to
inform and improve patient care. Clinicians should not dismiss patients from care on the basis of a toxicology test result.
Dismissal could have adverse consequences for patient safety, potentially including the patient obtaining opioids or other
drugs from alternative sources and the clinician missing opportunities to facilitate treatment for substance use disorder.
Before starting opioids and periodically (at least annually) during opioid therapy, clinicians should consider the benefits and
risks of toxicology testing to assess for prescribed opioids and other prescription and nonprescription controlled substances
that increase risk for overdose when combined with opioids, including nonprescribed and illicit opioids and benzodiazepines.
Clinicians, practices, and health systems should aim to minimize bias in testing and should not apply this recommendation
differentially on the basis of assumptions about patients.
Predicting risk is challenging, and available tools do not allow clinicians to reliably identify patients who are at low risk for
substance use or substance use disorders. Clinicians should consider toxicology screening results as potentially useful data,
in the context of other clinical information, for all patients and consider toxicology screening whenever its potential
limitations can be addressed.
Clinicians should explain to patients that toxicology testing will not be used to dismiss patients from care and is intended to
improve their safety.
Clinicians should explain expected results (e.g., presence of prescribed medication and absence of drugs, including
nonprescribed controlled substances not reported by the patient) and ask patients in a nonjudgmental manner about use of
prescribed and other drugs and whether there might be unexpected results.
Limited toxicology screening can be performed with a relatively inexpensive presumptive immunoassay panel that tests for
opiates as a class, benzodiazepines as a class, and several nonprescribed substances. Toxicology screening for a class of
drugs might not detect all drugs in that class. For example, fentanyl testing is not included in widely used toxicology assays
that screen for opiates as a class.
Clinicians should be familiar with the drugs included in toxicology screening panels used in their practice and should
understand how to interpret results for these drugs. For example, a positive opiates immunoassay detects morphine, which

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 48 of 89
:
 might reflect patient use of morphine, codeine, or heroin, but does not detect synthetic opioids and might not detect
semisynthetic opioids. In some cases, positive results for specific opioids might reflect metabolites from opioids the patient is
taking and might not mean the patient is taking the specific opioid that resulted in the positive test.
Confirmatory testing should be used when
toxicology results will inform decisions with major clinical or nonclinical implications for the patient;
a need exists to detect specific opioids or other drugs within a class, such as those that are being prescribed, or those
that cannot be identified on standard immunoassays; or
a need exists to confirm unexpected screening toxicology test results.
Restricting confirmatory testing to situations and substances for which results can reasonably be expected to affect patient
management can reduce costs of toxicology testing.
Clinicians might want to discuss unexpected results with the local laboratory or toxicologist and should discuss unexpected
results with the patient.
Clinicians should discuss unexpected results with patients in a nonjudgmental manner, avoiding use of potentially
stigmatizing language (e.g., avoid describing a specimen as testing “clean” or “dirty”).
Discussion with patients before specific confirmatory testing can sometimes yield a candid explanation of why a particular
substance is present or absent and remove the need for confirmatory testing during that visit. For example, a patient might
explain that the test is negative for prescribed opioids because they felt opioids were no longer helping and discontinued
them. If unexpected results from toxicology screening are not explained, a confirmatory test on the same sample using a
method selective enough to differentiate specific opioids and metabolites (e.g., gas or liquid chromatography–mass
spectrometry) might be warranted.
Clinicians should use unexpected results to improve patient safety (e.g., optimize pain management strategy [see
Recommendation 2], carefully weigh benefits and risks of reducing or continuing opioid dosage [see Recommendation 5],
reevaluate more frequently [see Recommendation 7], offer naloxone [see Recommendation 8], and offer treatment or refer
the patient for treatment with medications for opioid use disorder [see Recommendation 12], all as appropriate).

Supporting Rationale
The clinical evidence reviews did not find studies evaluating the effectiveness of toxicology screening for risk mitigation during
opioid prescribing for pain. However, concurrent use of opioid pain medications with other opioid pain medications,
benzodiazepines, or heroin or other nonpharmaceutical opioids can increase patients’ risk for overdose. Toxicology tests can
provide information about drug use that is not reported by the patient. In addition, toxicology tests can assist clinicians in
identifying when patients are not taking opioids prescribed for them, which might in certain cases indicate diversion or other
clinically important issues such as difficulties with adverse effects. The most commonly drug-tested bodily specimen is urine. Oral
fluid (saliva) testing also is available (304), although testing protocols using oral fluid are not as well established. On October 25,
2019, SAMHSA published guidelines for the inclusion of oral fluid specimens in toxicology testing programs of federal executive
branch agencies (305), effective January 1, 2020. Toxicology testing results can be associated with outcomes and practices that
harm patients (e.g., stigmatization and inappropriate termination from care). False positive and false negative presumptive results
are not uncommon, a problem that can be compounded because clinicians commonly misinterpret results (306,307), leading to
inappropriate consequences for patients. Urine toxicology tests do not provide accurate information about how much or what
doses of opioids or other drugs a patient took. Testing for fentanyl is not available in widely used toxicology assays, potentially
leading to false assurance. Ideally, clinicians would only test for substances for which results could affect patient management.
However, it can be challenging for clinicians in many settings to tailor widely used toxicology panels to include the specific
substances most relevant to clinical decisions for their patient. Toxicology testing costs are not always covered fully by insurance
and can be a burden for patients, and clinician time is needed to interpret, confirm, and communicate results.

Experts from OWG had concerns that biases and disparities affecting which patients undergo toxicology testing could have
disproportionately negative consequences among Black and Hispanic patients. In addition, testing costs would have the greatest
consequences for patients with the least ability to pay. Because of these concerns, some experts said that grading the
recommendation as category A could potentially reduce bias and disparities. However, others indicated that although universal
application could mitigate bias in who is tested, it would not mitigate stigma associated with testing. In addition, experts had
concerns about accuracy, clinician interpretation, testing costs, and potential for a delay in care while waiting for test results.

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 49 of 89
:
 Because of these concerns, the recommendation is rated category B. However, clinicians, practices, and health systems should aim
to minimize bias in its application and should not apply this recommendation differentially on the basis of assumptions about what
they will learn about specific patients. Predicting risk is challenging, and available tools do not allow clinicians to reliably identify
patients who are at low risk for substance use disorder (7). Rather, clinicians should consider toxicology test results as potentially
useful data, in the context of other clinical information, for all patients and consider toxicology testing whenever its potential
problems can be mitigated. For example, clinicians can become familiar with the drugs included in toxicology testing panels used
in their practice and understand how to interpret results; practices and health systems can ensure a laboratorian or toxicologist is
available to discuss unexpected results, that costs to patients are not burdensome, and that practice policies regarding testing and
frequency can minimize bias. For example, routine use of testing with standardized policies at the practice or clinic level might help
destigmatize their use. Because truly random testing might not be feasible in clinical practice, some clinics obtain a specimen at
every visit but only send it for testing on a random schedule.

Before starting opioids and periodically (at least annually) during opioid therapy, clinicians should consider benefits and risks of
toxicology testing to assess for prescribed opioids and other prescription and nonprescribed substances that increase risk for
overdose when combined with opioids, including nonprescribed and illicit opioids and benzodiazepines. Before ordering toxicology
testing, clinicians should have a plan for responding to unexpected results. Clinicians should explain to patients that toxicology
testing will not be used punitively (e.g., will not be used to dismiss patients from care) and is intended to improve their safety.
Clinicians should also explain expected results (e.g., presence of prescribed medication and absence of substances, including
nonprescribed substances, not reported by the patient). Clinicians should ask patients about use of prescribed medications and
other substances and ask whether there might be unexpected results. This will provide an opportunity for patients to provide
information about changes in their use of prescribed opioids or other drugs.

In most situations, initial toxicology testing can be performed with a relatively inexpensive immunoassay panel that tests for
opiates and benzodiazepines as classes and for multiple nonprescribed substances. Patients prescribed oxycodone or
nonmorphine-based opioids (e.g., buprenorphine or methadone) require specific testing for those agents. The use of confirmatory
testing can add costs and should be used when toxicology results will inform decisions with major clinical or nonclinical
implications for the patient, a need exists to detect a specific opioid that is prescribed or that cannot be identified on standard
immunoassays, or to confirm unexpected toxicology screening results for which there is no other explanation. Clinicians and health
systems can work to minimize inequitable cost burdens for patients and limit specific testing to situations when it is necessary.
Clinicians should be familiar with the compounds included in toxicology testing panels used in their practice and should
understand how to interpret results. For example, a positive opiate immunoassay test result detects morphine, which might reflect
patient use of morphine, codeine, or heroin, but this immunoassay does not detect synthetic opioids (e.g., fentanyl or methadone)
and might not detect semisynthetic opioids (e.g., oxycodone or buprenorphine). Many laboratories use an oxycodone immunoassay
that detects oxycodone and oxymorphone; however, these agents might need to be ordered or identified separately in a toxicology
testing panel. In some cases, positive results for specific opioids might reflect metabolites from opioids the patient is taking and
might not mean the patient is taking the specific opioid for which the test was positive. For example, hydromorphone is a
metabolite of hydrocodone, and oxymorphone is a metabolite of oxycodone. Detailed considerations for interpretation of urine
toxicology test results, including which tests to order and expected results, drug detection time in urine, and drug metabolism,
have been published previously (308). A review including interpretation of oral fluid sample toxicology test results is also
available (304). Restricting confirmatory testing to situations and substances for which results can reasonably be expected to
affect patient management can reduce costs of toxicology testing.

Clinicians might want to discuss unexpected results with the local laboratory or toxicologist and should discuss unexpected
results with the patient. Discussion with patients before specific confirmatory testing can sometimes yield a candid explanation of
why a particular substance is present or absent and obviate the need for confirmatory testing on that visit. For example, a patient
might explain that the test is negative for prescribed opioids because they felt opioids were no longer helping and discontinued
them. If unexpected results are not explained, a confirmatory test using a method selective enough to differentiate specific opioids
and metabolites (e.g., gas or liquid chromatography–mass spectrometry) might be warranted to clarify the situation.

Clinicians should use unexpected results to improve patient safety (e.g., change pain management strategy [see Recommendation
2], carefully weigh benefits and risks of reducing or continuing opioid dosage [see Recommendation 5], reevaluate more frequently
[see Recommendation 7], offer naloxone [see Recommendation 8], and offer or refer patients for substance use disorder treatment

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 50 of 89
:
 [see Recommendation 12], all as appropriate). If tests for prescribed opioids are repeatedly negative, including confirmatory tests,
and the clinician has verified that the patient is not taking the prescribed opioid, clinicians can discontinue the prescription without
a taper and discuss options for safe disposal of unused opioids (154).

Clinicians should not dismiss patients from care on the basis of a toxicology test result. Dismissal could have adverse
consequences for patient safety, potentially including the patient obtaining opioids from alternative sources and the clinician
missing opportunities to facilitate treatment for a substance use disorder.

Recommendation 11
Clinicians should use particular caution when prescribing opioid pain medication and benzodiazepines concurrently and
consider whether benefits outweigh risks of concurrent prescribing of opioids and other central nervous system depressants
(recommendation category: B; evidence type: 3).

Implementation Considerations
Although in some circumstances it might be appropriate to prescribe opioids to a patient who is also prescribed
benzodiazepines (e.g., severe acute pain in a patient taking long-term, stable low-dose benzodiazepine therapy), clinicians
should use particular caution when prescribing opioid pain medication and benzodiazepines concurrently. In addition,
clinicians should consider whether benefits outweigh risks for concurrent use of opioids with other central nervous system
depressants (e.g., muscle relaxants, nonbenzodiazepine sedative hypnotics, and potentially sedating anticonvulsant
medications such as gabapentin and pregabalin).
Buprenorphine or methadone for opioid use disorder should not be withheld from patients taking benzodiazepines or other
medications that depress the central nervous system.
Clinicians should check the PDMP for concurrent controlled medications prescribed by other clinicians (see Recommendation
9) and should consider involving pharmacists as part of the management team when opioids are coprescribed with other
central nervous system depressants.
In patients receiving opioids and benzodiazepines long term, clinicians should carefully weigh the benefits and risks of
continuing therapy with opioids and benzodiazepines and discuss with patients and other members of the patient’s care
team.
Risks of concurrent opioid and benzodiazepine use are likely to be greater with unpredictable use of either medication, with
use of higher-dosage opioids and higher-dosage benzodiazepines in combination, or with use with other substances
including alcohol (compared with long-term, stable use of lower-dosage opioids and lower-dosage benzodiazepines without
other substances).
In specific situations, benzodiazepines can be beneficial, and stopping benzodiazepines can be destabilizing.
Clinicians should taper benzodiazepines gradually before discontinuation because abrupt withdrawal can be associated with
rebound anxiety, hallucinations, seizures, delirium tremens, and, rarely, death. The rate of tapering should be individualized.
If benzodiazepines prescribed for anxiety are tapered or discontinued, or if patients receiving opioids require treatment for
anxiety, evidence-based psychotherapies (e.g., cognitive behavioral therapy), specific antidepressants or other
nonbenzodiazepine medications approved for anxiety, or both, should be offered.
Clinicians should communicate with other clinicians managing the patient to discuss the patient’s needs, prioritize patient
goals, weigh risks of concurrent benzodiazepine and opioid exposure, and coordinate care.

Supporting Rationale
Benzodiazepines and opioids both cause central nervous system depression, and benzodiazepines can potentiate opioid-induced
decreases in respiratory drive. Epidemiologic studies find concurrent benzodiazepine use in large proportions of opioid-related
overdose deaths (203,309,310). The clinical evidence reviews identified three cohort studies that found an association between
concurrent use of benzodiazepines and opioids versus opioids alone and increased risk for overdose (7). A case-cohort study found
concurrent benzodiazepine prescription with opioid prescription to be associated with a near-quadrupling of risk for overdose
death compared with opioid prescription alone (311). The clinical evidence reviews did not find studies evaluating the

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 51 of 89
:
 effectiveness of avoiding coprescribing of benzodiazepines and opioids on risk for overdose (7). The clinical evidence reviews
identified three observational studies that found an association between concurrent use of gabapentinoids and opioids versus
opioids alone and increased risk for overdose, with higher risks at increased gabapentinoid doses (7).

Experts from OWG noted that rather than necessarily being a direct cause of overdose, benzodiazepines might serve as a marker
of risk for overdose because of underlying conditions, in specific situations benzodiazepines can be beneficial, and that stopping
benzodiazepines can be destabilizing. In addition, experts noted that long-term, stable use might be safer than erratic,
unpredictable use. Because of these considerations, multiple experts indicated that recommending extreme caution with
concurrent prescription of opioid pain medications and benzodiazepines was more appropriate than a recommendation to avoid
prescribing opioid pain medication and benzodiazepines concurrently and that category B would be more appropriate than
category A for this recommendation.

Although in certain circumstances it might be appropriate to prescribe opioids to a patient receiving benzodiazepines (e.g., severe
acute pain in a patient taking long-term, stable low-dosage benzodiazepine therapy), clinicians should use particular caution when
prescribing opioid pain medication and benzodiazepines concurrently. In addition, because other central nervous system
depressants (e.g., muscle relaxants, nonbenzodiazepine sedative hypnotics, and potentially sedating anticonvulsant medications
such as gabapentin and pregabalin) (312) can potentiate respiratory depression associated with opioids, clinicians should consider
whether benefits outweigh risks of concurrent use of these medications. Clinicians should check PDMPs for concurrent controlled
medications prescribed by other clinicians (see Recommendation 9) and should consider involving pharmacists as part of the
management team when opioids are coprescribed with other central nervous system depressants.

In patients receiving opioids and benzodiazepines long-term, clinicians should carefully weigh the benefits and risks of continuing
therapy with opioids and benzodiazepines and discuss with patients and other members of the patient’s care team, as appropriate.
In specific situations, benzodiazepines can be beneficial, and stopping benzodiazepines can be destabilizing. As emphasized in an
FDA advisory (313), buprenorphine or methadone for opioid use disorder should not be withheld from patients taking
benzodiazepines or other medications that depress the central nervous system. Whereas the combined use of these medications
increases risks, the harm caused by untreated opioid use disorder can outweigh these risks.

If risks are determined to outweigh benefits of continuing opioids for pain and benzodiazepine therapy at current dosages,
decisions about tapering medications (e.g., whether to taper opioids first, taper benzodiazepines first, or consider carefully
transitioning from full agonist opioids to buprenorphine before tapering benzodiazepines) should be individualized and
reevaluated over time. Considerations include patient priorities, the patient’s clinical considerations, the patient’s response to
therapeutic changes, consultation with other clinicians managing the patient’s care, and, consultation with other specialists (e.g.,
an addiction specialist) if needed. Clinicians should taper benzodiazepines gradually before discontinuation because abrupt
withdrawal can be associated with rebound anxiety, hallucinations, seizures, delirium tremens, and, rarely, death (222,223).
Tapering rates should be individualized. Examples of benzodiazepine tapers and tips for managing benzodiazepine withdrawal are
available (314). Cognitive behavioral therapy increases tapering success rates and might be particularly helpful for patients
struggling with a benzodiazepine taper (315). If benzodiazepines prescribed for anxiety are tapered or discontinued, or if patients
receiving opioids require treatment for anxiety, evidence-based psychotherapies (e.g., cognitive behavioral therapy), specific
antidepressants or other nonbenzodiazepine medications approved for anxiety, or both, should be offered. Clinicians should
communicate with mental health professionals managing the patient to discuss the patient’s needs, prioritize patient goals, weigh
risks of concurrent benzodiazepine and opioid exposure, and coordinate care.

Recommendation 12
Clinicians should offer or arrange treatment with evidence-based medications to treat patients with opioid use disorder.
Detoxification on its own, without medications for opioid use disorder, is not recommended for opioid use disorder because of
increased risks for resuming drug use, overdose, and overdose death (recommendation category: A; evidence type: 1).

Implementation Considerations
Although stigma can reduce the willingness of persons with opioid use disorder to seek treatment, opioid use disorder is a
chronic, treatable disease from which persons can recover and continue to lead healthy lives.
If clinicians suspect opioid use disorder, they should discuss their concern with their patient in a nonjudgmental manner and

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 52 of 89
:
 provide an opportunity for the patient to disclose related concerns or problems.
Clinicians should assess for the presence of opioid use disorder using DSM-5 criteria.
For patients meeting criteria for opioid use disorder, particularly if moderate or severe, clinicians should offer or arrange for
patients to receive evidence-based treatment with medications for opioid use disorder.
Clinicians should not dismiss patients from their practice because of opioid use disorder because this can adversely affect
patient safety.
Medication treatment of opioid use disorder has been associated with reduced risk for overdose and overall deaths.
Identification of opioid use disorder represents an opportunity for a clinician to initiate potentially life-saving interventions,
and the clinician should collaborate with the patient regarding their safety to increase the likelihood of successful treatment.
For pregnant persons with opioid use disorder, medication for opioid use disorder (buprenorphine or methadone) is the
recommended therapy and should be offered as early as possible in pregnancy to prevent harms to both the patient and the
fetus.
Clinicians unable to provide treatment themselves should arrange for patients with opioid use disorder to receive care from a
substance use disorder treatment specialist (e.g., an office-based buprenorphine or naltrexone treatment provider), or from an
opioid treatment program certified by SAMHSA to provide methadone or buprenorphine for patients with opioid use disorder.
All clinicians, and particularly clinicians prescribing opioids in communities without sufficient treatment capacity for opioid
use disorder, should obtain a waiver to prescribe buprenorphine for opioid use disorder.
Clinicians prescribing opioids should identify treatment resources for opioid use disorder in the community, establish a
network of referral options that span the levels of care that patients might need to enable rapid collaboration and referral,
when needed, and work together to ensure sufficient treatment capacity for opioid use disorder at the practice level.
Although identification of an opioid use disorder can alter the expected benefits and risks of opioid therapy for pain, patients
with co-occurring pain and opioid use disorder require ongoing pain management that maximizes benefits relative to risks.

Supporting Rationale
Opioid use disorder (previously known as opioid abuse or opioid dependence in the Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition [DSM-IV]) (316) is defined in DSM-5 as a problematic pattern of opioid use leading to clinically
significant impairment or distress (317). Treatment with opioids for pain is associated with increased risk for opioid use disorder,
particularly if opioids are prescribed for >90 days (54). A systematic review found the rate of opioid addiction among patients with
chronic pain averaged 8%–12% in studies published during 2000–2013 (318). More recent studies have found prevalence
estimates of 23.9%–26.5% for any prescription opioid use disorder and 5.2%–9.0% for moderate to severe opioid use disorder
(using DSM-5 diagnostic criteria) among adults receiving long-term opioid therapy for pain, with slightly lower prevalence (21.5%
for any and 4.2% for moderate to severe opioid use disorder) in clinics with more consistent use of risk reduction practices
(319,320).

Opioid use disorder is manifested by at least two of 11 defined criteria occurring within a year (317):

1. Opioids are often taken in larger amounts or over a longer period than was intended.
2. There is a persistent desire or unsuccessful attempts to cut down or control opioid use.
3. A great deal of time is spent in activities necessary to obtain the opioid, use the opioid, or recover from its effects.
4. Craving, or a strong desire or urge to use opioids.
5. Recurrent opioid use resulting in a failure to fulfill major role obligations at work, school, or home.
6. Continued opioid use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the
effects of opioids.
7. Important social, occupational, or recreational activities are given up or reduced because of opioid use.
8. Recurrent opioid use in situations in which it is physically hazardous.
9. Continued opioid use despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to
have been caused or exacerbated by the substance.
10. Tolerance, as defined by either of the following:

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 53 of 89
:
 a. a need for markedly increased amounts of opioids to achieve intoxication or desired effect, or
b. a markedly diminished effect with continued use of the same amount of an opioid.
11. Withdrawal, as manifested by either of the following:
a. the characteristic opioid withdrawal syndrome, or
b. opioids (or a closely related substance) are taken to relieve or avoid withdrawal symptoms.

Criteria 10 and 11 are not considered to be met for those persons taking opioids solely under appropriate medical supervision
(317). Severity is specified as mild (2–3 criteria), moderate (4–5 criteria), or severe (≥6 criteria) (317).

FDA-approved medications indicated for the treatment of opioid use disorder include buprenorphine (a partial agonist opioid),
methadone (a full agonist opioid), and naltrexone (an opioid antagonist). Experts from OWG stated that partial agonist opioid, full
agonist opioid, and opioid antagonist treatment should not be framed as equal options for opioid use disorder, noting that partial
and full agonist opioid treatments have stronger evidence for better outcomes, do not require abstinence, have less challenges
with initiation, and are much more widely used than opioid antagonist treatment. Clinical evidence reviews found evidence on the
effectiveness of interventions (e.g., medications and behavioral treatments) for opioid use disorder related to prescription opioids
to be limited (7). However, moderate-quality evidence indicated buprenorphine (a partial agonist opioid) and methadone (a full
agonist opioid) to be effective in preventing return to drug use among patients with opioid use disorder involving heroin (321–
323), although the presence of pain among patients in these studies is generally not described. In addition, a small number of
studies have evaluated buprenorphine for patients with prescription opioid dependence (using DSM-IV criteria) (316) and found it
to be effective in preventing return to drug use (324,325). One study found that among persons with opioid use disorder, previous
prescription opioid use predicts stabilization on buprenorphine (326). Another trial that performed buprenorphine initiation and
then randomized patients to buprenorphine taper versus maintenance was terminated early without reporting of planned
outcomes because all patients randomized to the taper arm switched to maintenance or experienced a return to drug use; five of
six patients in the maintenance arm completed the trial (327). In another trial identified by the clinical evidence reviews, no
difference was found between buprenorphine/naloxone and methadone in likelihood of retention in the study and in pain, function,
or self-reported side effects (328). Buprenorphine and methadone treatment of opioid use disorder has been associated with
reduced overdose deaths (329) and reduced all-cause deaths (330). Naltrexone (an opioid antagonist) also can be used for opioid
use disorder, particularly for highly motivated persons (331,332). Naltrexone blocks the effects of opioids if they are used.
Naltrexone has not been evaluated in persons with concomitant pain and opioid use disorder, and opioid medications for pain
generally cannot be used in patients receiving naltrexone. Naltrexone requires adherence to monthly, long-acting injections. The
effectiveness of oral naltrexone can be limited by poor medication adherence (332), and oral naltrexone should not be used except
under very limited circumstances (96) (e.g., for patients who would be able to comply with observed daily dosing to enhance
adherence) (96,317). Naltrexone also must be started after full withdrawal from opioids, which is a challenge for some patients;
however, for patients who have completed or are able to complete withdrawal, naltrexone has comparable effectiveness as
buprenorphine in prevention of return to drug use (333).

Certain studies suggest that using behavioral therapies in combination with medications for opioid use disorder can reduce opioid
misuse and increase retention during treatment (334,335). At the same time, a study of treatment for prescription opioid
dependence (using DSM-IV criteria) (316) found buprenorphine treatment combined with standard medical management
(including basic counseling recommending abstinence and self-help group participation) as effective as buprenorphine combined
with more intensive opioid dependence counseling (i.e., addiction, recovery, and prevention of return to drug use education with
self-help and lifestyle change recommendations, interactive exercises, and take-home assignments delivered by trained substance
use treatment or mental health professionals in 45–60 minute sessions using drug counseling manuals with demonstrated
efficacy); neither standard medical management nor opioid dependence counseling alone, without buprenorphine, was effective in
preventing return to drug use (325). Recommendations for treatment of opioid use disorder include assessing the patient’s
psychosocial needs and offering or referring the patient to psychosocial treatment in collaboration with qualified behavioral health
care providers based on those needs; however, a patient’s decision to decline psychosocial treatment or the absence of available
psychosocial treatment should not preclude or delay medications for opioid use disorder (96). Additional recommendations have
been published on goals, components of, and types of effective psychosocial treatment to use in conjunction with pharmacologic
treatment of opioid use disorder (96).

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 54 of 89
:
 If clinicians suspect opioid use disorder on the basis of patient concerns or behaviors or on findings in PDMP data (see
Recommendation 9) or from toxicology testing (see Recommendation 10), they should discuss their concern with their patient and
provide an opportunity for the patient to disclose related concerns or problems. Clinicians should assess for the presence of opioid
use disorder using DSM-5 criteria (317). Opioid use disorder can coexist with other substance use disorders, and patients who are
actively using substances during opioid use disorder treatment might require greater support, potentially including involvement of
an addiction specialist (96). Clinicians should ask about use of alcohol and other substances (see Recommendation 8).
Alternatively, clinicians can arrange for a substance use disorder treatment specialist to assess for the presence of opioid and
other substance use disorders.

For patients meeting criteria for opioid use disorder, particularly if moderate or severe, clinicians should offer or arrange for
patients to receive evidence-based treatment with medications for opioid use disorder. Patients with opioid use disorder might
benefit from counseling and referrals to mutual help groups such as Narcotics Anonymous (336), although this should not take
the place of treatment with medication. Clinicians also should offer naloxone and training on proper use for overdose reversal to
patients with opioid use disorder and to their household members and significant others (96) (see Recommendation 8). Clinicians
should not dismiss patients from their practice because of opioid use disorder because this can adversely affect patient safety.
Identification of opioid use disorder represents an opportunity for a clinician to initiate potentially life-saving interventions, and it is
important for the clinician to collaborate with the patient regarding their safety to increase the likelihood of successful treatment.
Detoxification on its own, without medications for opioid use disorder, is not recommended for opioid use disorder because of
increased risks for return to drug use, overdose, and overdose death (96).

For pregnant persons with opioid use disorder, medications for opioid use disorder (buprenorphine or methadone) have been
associated with improved maternal outcomes and should be offered as early as possible in pregnancy to prevent harms to both
the patient and the fetus (see Recommendation 8) (133,220). Previous recommendations have suggested that transmucosal
buprenorphine (without naloxone) is preferred during pregnancy to avoid potential prenatal exposure to naloxone, especially if
injected, and evidence on the safety of naloxone in pregnant persons remains limited (96,274). However, combination
buprenorphine/naloxone products are frequently used, a systematic review did not find reports of serious maternal or neonatal
outcomes associated with maternal buprenorphine/naloxone use (337), and experts have noted that combination products are
likely to be safe and effective for pregnant persons when taken as prescribed (96,274). ACOG also recommends that if a person is
stable on naltrexone before pregnancy, the decision regarding whether to continue naltrexone treatment during pregnancy should
involve a careful discussion between the clinician and the patient, weighing the limited safety data on naltrexone with the
potential risk for return to drug use with discontinuation of treatment (274). For persons receiving buprenorphine or methadone for
opioid use disorder and considering breastfeeding, AAP recommends breastfeeding be supported if there has been no return to
drug use for ≥90 days and there are no other contraindications, considered if there has been no return to drug use within 30–90
days, and discouraged if there is active substance use or has been a return to drug use within the last 30 days (280).

In April 2021, to expand access to buprenorphine, the Practice Guidelines for the Administration of Buprenorphine for Treating
Opioid Use Disorder (338) exempted eligible physicians, physician assistants, nurse practitioners, clinical nurse specialists,
certified registered nurse anesthetists, and certified nurse midwives from previous Controlled Substances Act certification
requirements related to training, counseling and other ancillary services (i.e., psychosocial services). To prescribe buprenorphine
for opioid use disorder for up to 30 patients in an office-based setting, clinicians can forgo or choose to undertake training but
must still receive a waiver from SAMHSA. Information about qualifications and the process to obtain a waiver are available from
SAMHSA (339).

Additional recommendations have been published on initiation, use, and monitoring of buprenorphine treatment for opioid use
disorder (96,336). Buprenorphine for treatment of opioid use disorder is usually combined with naloxone in a sublingual or buccal
film or tablet (e.g., Suboxone), to reduce the potential for misuse of buprenorphine when injected. Naloxone is poorly absorbed
orally; however, if buprenorphine/naloxone is manipulated and injected, naloxone can trigger opioid withdrawal (340). In 2018,
long-acting injectable formulations of buprenorphine became available (341). As a partial agonist, buprenorphine should
generally not be initiated until there are objective signs of withdrawal, to avoid precipitating withdrawal. As an alternative for
patients not yet in opioid withdrawal, certain studies have described a low-dose initiation approach (sometimes referred to as
microdosing) (342,343) to avoid precipitating withdrawal when initiating buprenorphine, although evidence regarding this
approach is limited. Low-dose buprenorphine initiation is a potential option for patients with opioid use disorder who are taking
opioid medications for pain. With this dosing strategy, full agonist opioids can be continued while buprenorphine is initiated, and

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 55 of 89
:
 the patient does not need to experience opioid withdrawal symptoms. For standard (not low-dose) buprenorphine initiation, after
objective signs of withdrawal are observed, buprenorphine should be initiated (96) and titrated upward under supervision at
approximately 2-hour intervals as needed to control withdrawal symptoms. Protocols for initiating buprenorphine by patients at
home after an initial encounter with a clinician to establish the diagnosis of opioid use disorder and discuss medication options are
in use by more experienced clinicians (344).

Importantly, opioid dosage thresholds for caution in the treatment of pain are not applicable to opioid agonist treatment of opioid
use disorder (345) because recommended dosages of methadone and buprenorphine for opioid use disorder (96) differ from those
for pain management. No recommended duration limit exists for treatment of opioid use disorder with buprenorphine or
methadone, and discontinuation is associated with risks for return to drug use and opioid overdose (96). If discontinued,
buprenorphine should be tapered very gradually (over several months) (96).

Compared with buprenorphine, which can be prescribed by clinicians with a waiver in any setting or dispensed from a SAMHSA-
certified opioid treatment program, ongoing methadone treatment for opioid use disorder can only be provided through an opioid
treatment program. As short-term exceptions, any clinician may administer (but not prescribe) methadone or buprenorphine to
treat acute opioid withdrawal for up to 3 days, while working to refer the patient to opioid use disorder treatment (346).
Previously, up to a 1-day supply could be administered per day for up to 3 days; in December 2020, Congress directed the Drug
Enforcement Administration (DEA) to revise regulations to allow for a 3-day supply of medication to be dispensed at one time
(347); DEA subsequently advised practitioners how to request exceptions to the 1-day supply limitation pending amendment of
21 CFR 1306.07(b) (348). Patients already receiving treatment for opioid use disorder and admitted for other medical reasons may
continue to directly receive methadone or buprenorphine treatment in an emergency department or in a hospital throughout
inpatient hospitalization (336,346,349).

Naltrexone does not require a waiver and can be prescribed in any setting. Additional recommendations have been published
previously on naltrexone treatment for opioid use disorder (96). A minimum of 7–10 days free of opioids is recommended before
the first naltrexone dose to avoid precipitation of severe opioid withdrawal (350). Extended-release injectable naltrexone is
typically administered every 4 weeks by deep intramuscular injection in the gluteal muscle at 380 mg per injection (96),
alternating buttocks for each subsequent injection (350). Certain patients, including those who metabolize naltrexone more
rapidly, might benefit from dosing as frequently as every 3 weeks (96). Oral naltrexone is no longer recommended and should not
be used except under very limited circumstances (96). No recommended duration limit exists for treatment of opioid use disorder
with naltrexone. If discontinued, naltrexone can be stopped abruptly without precipitating withdrawal symptoms (96). Clinicians
should warn patients who discontinue naltrexone of the risk for potentially fatal opioid overdose if opioid use is resumed (96),
because of the loss of tolerance to the previous opioid dosage.

Clinicians are strongly encouraged to provide medication treatment for their patients with opioid use disorder. Those unable to
provide treatment themselves should arrange for patients with opioid use disorder to receive care from a colleague who is able to
provide treatment, from a substance use disorder treatment specialist (e.g., an office-based buprenorphine or naltrexone treatment
clinician), or from an opioid treatment program certified by SAMHSA to provide methadone or buprenorphine for patients with
opioid use disorder. Resources to help clinicians arrange for treatment include SAMHSA’s buprenorphine physician locator
(https://www.samhsa.gov/medication-assisted-treatment/find-treatment/treatment-practitioner-locator  ) and SAMHSA’s Opioid
Treatment Program Directory (https://dpt2.samhsa.gov/treatment/directory.aspx  ). Clinicians should assist patients in finding
qualified treatment specialists, should arrange for patients to follow up with these specialists, and should coordinate continuing
care with these specialists. Rapidly identifying appropriate care can be challenging. Treatment need in a community is often not
met by capacity to provide buprenorphine or methadone therapy (351). Clinicians prescribing opioids in communities without
sufficient treatment capacity for opioid use disorder should obtain a waiver to prescribe buprenorphine. SAMHSA’s Providers
Clinical Support System (https://pcssnow.org/  ) offers training, technical assistance, and mentors to assist clinicians in
assessment for and treatment of substance use disorders, specifically opioid use disorder, and on the interface of pain and opioid
misuse. Clinicians prescribing opioids should identify treatment resources for substance use disorders including opioid use
disorders in the community, establish a network of referral options that span the levels of care that patients might need to enable
rapid collaboration and referral, when needed, and work together to ensure sufficient treatment capacity at the practice level.

Management of Opioid Misuse That Does Not Meet Criteria for Opioid Use Disorder

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 56 of 89
:
 Clinicians can have challenges distinguishing between opioid misuse behaviors without opioid use disorder and mild or moderate
opioid use disorder (352). For patients with opioid misuse that does not meet criteria for opioid use disorder (e.g., taking opioids in
larger amounts than intended without meeting other criteria for opioid use disorder), clinicians should reassess the patient’s pain,
ensure that therapies for pain management have been optimized (see Recommendation 2), discuss with patients, and carefully
weigh benefits and risks of continuing opioids at the current dosage (see Recommendation 5). For patients who choose to but are
unable to taper, clinicians can reassess for opioid use disorder and offer buprenorphine treatment or refer for buprenorphine or
methadone treatment if criteria for opioid use disorder are met. Even without a diagnosis of opioid use disorder, transitioning to
buprenorphine for pain also can be considered because of reduced risk for overdose with buprenorphine compared with risk
associated with full agonist opioids (see Recommendation 5).

Pain Management for Patients with Opioid Use Disorder

Although identification of an opioid use disorder can alter the expected benefits and risks of opioid therapy for pain, patients with
co-occurring pain and substance use disorder require ongoing pain management that maximizes benefits relative to risks.
Clinicians should use nonpharmacologic and nonopioid pharmacologic pain treatments as appropriate (96) (see Recommendations
1 and 2) to provide optimal pain management. For patients with pain who have an active opioid use disorder but are not in
treatment, clinicians should consider buprenorphine or methadone treatment for opioid use disorder, which also can help with
concurrent management of pain (96). For patients who are treated with buprenorphine for opioid use disorder and experience
acute pain, clinicians can consider temporarily increasing the buprenorphine dosing frequency (e.g., to twice per day) (96) to help
manage pain because the duration of effects of buprenorphine is shorter for pain than for suppression of withdrawal (242). For
severe acute pain (e.g., from trauma or unplanned major surgery) in patients receiving buprenorphine for opioid use disorder,
clinicians can consider additional as-needed doses of buprenorphine. In supervised settings, adding a short-acting full agonist
opioid to the patient’s regular dosage of buprenorphine can be considered without discontinuing the patient’s regular
buprenorphine dosage; however, if a decision is made to discontinue buprenorphine to allow for more µ-opioid receptor
availability, patients should be monitored closely because high doses of a full agonist opioid might be required, potentially leading
to oversedation and respiratory depression as buprenorphine’s partial agonist effect lessens (96). For patients receiving naltrexone
for opioid use disorder, short-term use of higher-potency nonopioid analgesics (e.g., NSAIDs) can be considered to manage severe
acute pain (96). Patients receiving methadone for opioid use disorder who require additional opioids as treatment for severe acute
pain management should be monitored carefully, and when feasible, should optimally be treated by a clinician experienced in the
treatment of pain in consultation with their opioid treatment program (96). The ASAM National Practice Guideline for the
Treatment of Opioid Use Disorder (2020 Focused Update) provides additional recommendations (see Part 9) (96) for the
management of patients receiving medications for opioid use disorder who have planned surgeries for which nonopioid therapies
are not anticipated to provide sufficient pain relief.
Top

Conclusion and Future Directions

CDC indicated the intent to evaluate and reassess the 2016 CDC Opioid Prescribing Guideline as new evidence became available
and determine when sufficient new evidence would prompt an update (56). CDC funded AHRQ to conduct systematic reviews of
the scientific evidence. The following five areas were assessed: 1) noninvasive nonpharmacologic treatments for chronic pain, 2)
nonopioid pharmacologic treatments for chronic pain, 3) opioid treatments for chronic pain, 4) treatments for acute pain, and 5)
acute treatments for episodic migraine (7–11). An update to the 2016 CDC Opioid Prescribing Guideline was warranted on the
basis of these reviews.

The new evidence reviews conducted by AHRQ’s Evidence-based Practice Centers affirmed the appropriateness of the
recommendations in the 2016 CDC Opioid Prescribing Guideline for using opioids to treat chronic pain. The reviews also prompted
CDC to modify the recommendations to include acute and subacute pain more explicitly. This updated clinical practice guideline
also includes a new topline recommendation for patients who are already receiving ongoing opioid therapy for pain. Specifically,
the clinical practice guideline outlines how clinicians and patients should work together in assessing the benefits and risks of
continued opioid use and if or when to taper opioids to a lower dosage or discontinue opioids altogether in accordance with the
HHS Tapering Guide (219,353).

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 57 of 89
:
 Four key areas are covered in this clinical practice guideline for prescribing of opioid pain medication for patients aged ≥18 years
for pain, excluding pain management related to sickle cell disease, cancer-related pain treatment, palliative care, and end-of-life
care. These areas are 1) determining whether or not to initiate opioids for pain; 2) selecting opioids and determining opioid
dosages; 3) deciding duration of initial opioid prescription and conducting follow-up; and 4) assessing risk and addressing
potential harms of opioid use. In addition, five guiding principles were identified to inform implementation across
recommendations. These guiding principles focus on 1) the appropriate treatment of pain; 2) flexibility to meet the care needs and
clinical circumstances of each patient; 3) a multimodal and multidisciplinary approach to pain management; 4) avoiding
misapplication of the clinical practice guideline beyond its intended use; and 5) vigilance in attending to health inequities and
ensuring access to appropriate, affordable, diversified, coordinated, and effective nonpharmacologic and pharmacologic pain
treatment for all persons.

A central tenet of this clinical practice guideline is that acute, subacute, and chronic pain needs to be appropriately and effectively
treated regardless of whether opioids are part of a treatment regimen. Clinicians should select nonpharmacologic or
pharmacologic treatment modalities, or both, that maximize patient safety and optimize outcomes in pain, function, and quality of
life. A multimodal and multidisciplinary approach to pain management that considers the biologic, psychological, and social
characteristics of each person is critical (6). The care provided needs to be individualized and person centered (6). Clinicians and
patients should work together to identify treatment goals, including functional goals, and tailor an approach that considers both
the benefits and risks of available options (6). Progress should be monitored over time and treatment protocols adjusted
accordingly. Health systems and payers can work to ensure multimodal treatment options are available, accessible, and
reimbursed for patients. Public and private payers can support a broader array of nonpharmacologic interventions such as
exercise, multidisciplinary rehabilitation, mind-body interventions, cognitive behavioral therapy, and certain complementary and
integrative medicine therapies (e.g., acupuncture and spinal manipulation) that increasingly are known to be effective (9).
Reimbursement often is cited as a principle barrier to why these nonpharmacologic treatments are not more widely used (9).

An integral part of providing access to and delivery of high-quality health care, including pain treatment, is understanding how the
social determinants of health influence the health care provided and the differential outcomes observed (354). Social, economic,
educational, and neighborhood-level factors might create and exacerbate health inequities that certain persons experience
throughout their lives (354). These social determinants of health are borne out of historical and contemporary injustices that
advantage some and disadvantage others in society, leading to the systemic marginalization or oppression of some groups (355).
These inequities affect persons from some racial and ethnic groups, women, persons living in rural areas, persons experiencing
homelessness, persons with disabilities, persons with substance use disorders, justice-involved populations, persons with diverse
sexual orientation, identity, or gender, and non-U.S. born persons, among others (356).

Outcomes such as function and quality of life also are influenced by the health care context (354). Differential access to and
coverage for high-quality, culturally and linguistically appropriate, health-literate care might influence attitudes toward health care
and use of available services (354). Prejudice, bias, discrimination, and stereotyping by clinicians, practices, health systems, and
payers serve to reinforce these health disparities (355). Clinicians, practices, health systems, and payers should attend to health
inequities to protect patient safety; guard against unnecessary risks; and ensure access to appropriate, diversified, effective
nonpharmacologic and pharmacologic pain management options that are person centered, affordable, accessible, and well
coordinated. This begins with raising awareness and acknowledging the presence of these inequities, strengthening patient-
clinician communication, leveraging community health workers, implementing multidisciplinary care teams, tracking and
monitoring performance measures, and integrating quality improvement initiatives that support and invest in guideline-concordant
care for all persons (355).

To avoid unintended consequences for patients, this clinical practice guideline should not be misapplied, or policies derived from it,
beyond its intended use (67). Examples of misapplication or inappropriate policies include being inflexible on opioid dosage and
duration, discontinuing or dismissing patients from a practice, rapidly and noncollaboratively tapering patients who might be
stable on a higher dosage, and applying recommendations to populations that are not a focus of the clinical practice guideline
(e.g., patients with cancer-related pain, patients with sickle cell disease, or patients during end-of-life care) (67).

This clinical practice guideline provides overarching voluntary recommendations on the use of opioids to manage pain. To assist in
the uptake and understanding of this new clinical practice guideline, CDC will provide tools and resources for clinicians, health
systems, patients, and others on the use of opioid and nonopioid pain treatments. The uptake and widespread use of the 2016

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 58 of 89
:
 CDC Opioid Prescribing Guideline hinged on its successful dissemination, and CDC supported its translation and integration in
clinical practice. CDC produced a checklist and mobile app so clinicians could more readily apply guideline recommendations;
developed fact sheets, posters, and public service announcements to make the guideline more accessible and understandable to
clinicians and patients; and developed a 14-module interactive, web-based training with self-paced learning, case-based content,
knowledge checks, and integrated resources for clinicians (57). Updated and new resources and tools will align with this new
clinical practice guideline and will support health equity.

CDC will work with public and private payers by sharing evidence that can be used to inform decisions about coverage for
nonpharmacologic treatments, access to nonopioid pain medication, support for patient counseling and coordination of care,
access to evidence-based treatments of opioid use disorder, and availability of multidisciplinary and multimodal care. Robust
coverage and access (e.g., limited utilization management and cost sharing for evidence-based treatments) and decision support
(e.g., adjustment of EHR prescribing defaults) can be used to facilitate and encourage evidence-based treatments as default
treatments for pain (357,358).

This clinical practice guideline updates and expands the recommendations in the 2016 CDC Opioid Prescribing Guideline using
the best available evidence as interpreted and informed by expert opinion and attending to the values and preferences expressed
by patients, caregivers, and clinicians. Although the strength of the evidence is sometimes low quality and research gaps remain
(Box 5), clinical scientific evidence continues to advance and supports the recommendations in this clinical practice guideline (6–
11,359).

The principal aim of this clinical practice guideline is to ensure persons have equitable access to safe and effective pain
management that improves their function and quality of life while illuminating and reducing risks associated with prescription
opioids. CDC will evaluate this clinical practice guideline to identify the effects of the recommendations on clinician and patient
outcomes and on health disparities, including intended and unintended consequences. Communication between clinicians and
patients about the benefits and risks of opioids should be central to treatment decisions for patients in pain. This clinical practice
guideline can help inform those decisions and assist clinicians in meeting the unique needs of each person. CDC will revisit this
clinical practice guideline when remaining evidence gaps have sufficiently been addressed and another update is warranted.
Top
Acknowledgments
The Board of Scientific Counselors of the National Center for Injury Prevention and Control; the Board of Scientific Counselors of
the National Center for Injury Prevention and Control Opioid Workgroup; peer reviewers; members of the public who provided
comments during meetings; members of the public who provided comments through Federal Register opportunities; patients,
caregivers, and clinicians who participated in telephone or video conversations; and participants of the codesign workshops.
Guidehouse: Marissa R. Kessler; Cara M. Klansek, MPH; Laura Riley, MPH; Bintu Fofana, MPH; Truc Pham, MPH; Chamnan Po, MS;
Shelby Scott, PhD; Gillian Shulman, MPH; and Rachel Travis, MBA. The Lab at the U.S. Office of Personnel Management:
Benjamin P. Winter, Sarah E. Hughes, Jennifer Gardner, and Katherine Fisher; federal partners; CDC Office of the Director:
Rochelle P. Walensky, MD; Anne Schuchat, MD (Retired); Debra Houry, MD; and Celeste Philip, MD. CDC National Center for
Injury Prevention and Control: Amy B. Peeples, MPA; Arlene I. Greenspan, DrPH; Gwendolyn H. Cattledge, PhD (Retired);
Elizabeth J. Solhtalab, MPA; Kelly Holton; S. Kinzie Lee, MPH; Erica Reott, MPH; C. Leah Chan, MPH; Valerie Godoshian, MPH;
Tonia Lindley; Victor Cabada, MPH; Board of Scientific Counselors of the National Center for Injury Prevention and Control support
staff; Jan L. Losby, PhD, Division of Overdose Prevention; Melanie R. Ross, MPH, Division of Overdose Prevention; Christine R.
Curtis, MD, Division of Overdose Prevention; Christina A. Mikosz, MD, Division of Overdose Prevention; Amy Holmes-Chavez,
MPH, Division of Overdose Prevention; Michelle Putnam, MPH, Division of Overdose Prevention; Parul Parikh, JD, Division of
Overdose Prevention; JinYoung Kim, MPH, Division of Overdose Prevention, LeShaundra Cordier, MPH, Division of Overdose
Prevention; Helen Kingery, MPH, Division of Overdose Prevention; Loretta Jackson Brown, PhD, Division of Overdose Prevention;
Robin A. Rinker, MPH, Division of Overdose Prevention; Takeydra Jones, MPH, Division of Overdose Prevention; Kristin M. Holland,
PhD, Division of Overdose Prevention; Erin M. Parker, PhD, Division of Overdose Prevention; Lara DePadilla, PhD, Division of
Overdose Prevention; Elizabeth Hazelwood, MPH, Division of Overdose Prevention; and Terry W. Davis, EdD, Division of Overdose
Prevention.

Opioid Workgroup

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 59 of 89
:
 Chair: Chinazo O. Cunningham, MD.

Workgroup Members: Anne L. Burns; Beth Darnall, PhD; Frank Floyd, MD; Christine Goertz, DC, PhD; Elizabeth Habermann, PhD;
Joseph Hsu, MD; Marjorie Meyer, MD; Paul Moore, DMD, PhD; Aimee Moulin, MD; Kate Nicholson, JD; Tae Woo Park, MD;
Jeanmarie Perrone, MD; Travis Rieder, PhD; Roberto Salinas, MD; Doreleena Sammons-Hackett, SM; Wally R. Smith, MD; Jennifer
Waljee, MD; Mark Wallace, MD.

Ex Officio Members: Wilson Compton, MD; Neeraj Gandotra, MD; Mallika Mundkur, MD; Stephen Rudd, MD.

Designated Federal Officer: Melanie R. Ross, MPH.

Peer Reviewers
Anika Alvanzo, MD, Pyramid Healthcare, Inc.; Michael Englesbe, MD, University of Michigan; Joseph Frank, MD, University of
Colorado Hospital; Ajay D. Wasan, MD, University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine.

Board of Scientific Counselors of the National Center for Injury Prevention and
Control
Co-Chairs: Amy Bonomi, PhD (04/20/2021–08/31/2024); Chinazo O. Cunningham, MD (04/20/2021–12/01/2021); Victoria Frye,
DrPH (07/17/2019–02/28/2021); Daniel J. Whitaker, PhD (11/04/2019–02/28/2021).

Members: Donna H. Barnes, PhD (09/01/2018–02/28/2021); Amy Bonomi, PhD (04/20/2021–08/31/2024); Roger Chou, MD
(09/01/2019–08/31/2023); Phillip Coffin, MD (01/03/2017–02/28/2021); Kermit A. Crawford, PhD (01/31/2017–02/28/2021);
Chinazo O. Cunningham, MD (09/01/2018–12/01/2021); Wendy Ellis, DrPH (04/22/2021–08/31/2024); Frank Floyd, MD
(09/01/2019–08/31/2022); Frank A. Franklin II, PhD, JD (09/01/2018–08/31/2022); Victoria Frye, DrPH (01/27/2017–2/28/2021);
Kevin M. Guskiewicz, PhD (09/01/2018–01/14/2020); Elizabeth Habermann, PhD (09/01/2019–08/31/2023); James H. Hedlund,
PhD (01/30/2017–02/28/2021); Todd Herrenkohl, PhD (09/01/2018–02/28/2021); Mark S. Kaplan, DrPH (09/01/2018–
08/31/2022); Karen D. Liller, PhD (09/01/2018–08/31/2022); Angela Lumber-Brown, MD (04/22/2021–08/31/2022); Jeffrey P.
Michael, EdD (04/20/2021–08/31/2023); Elizabeth Miller, MD, PhD (04/20/2021–08/31/2024); Steven J. Ondersma, PhD
(04/21/2021–08/31/2024); Rosalie Liccardo Pacula, PhD (04/20/2021–08/31/2023); Christina A. Porucznik, PhD (09/01/2019–
08/31/2023); John Armand Rich, MD (04/22/2021–08/31/2024); David C. Schwebel, PhD (02/03/2017–02/28/2021); Lyle Ungar,
PhD (04/22/2021–08/31/2024); Daniel J. Whitaker, PhD (01/31/2017–02/28/2021).

Ex Officio Members: Melissa L. Brodowski, PhD; Dawn Castillo, MPH; Mindy J. D. Chai, PhD; Wilson Compton, MD; Jennifer Fan,
PhD; Meredith A. Fox, PhD; Holly Hedegaard, MD; John Howard, MD; Lyndon J. O. Joseph, PhD; Valerie Maholmes, PhD; Bethany
D. Miller, MEd; Constantinos Miskis, JD; Judy A. Staffa, PhD; Kelly M. Taylor, MS.
Top
Corresponding author: Division of Overdose Prevention, National Center for Injury Prevention and Control, CDC. Email:
cdcinfo@cdc.gov.
Top

1
Division of Overdose Prevention, National Center for Injury Prevention and Control, CDC; 2Office of the Director, National Center
for Injury Prevention and Control, CDC; 3Pacific Northwest Evidence-based Practice Center and Oregon Health & Science
University, Portland, Oregon
Top
Conflicts of Interest and Disclosures of Relationship
All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential
conflicts of interest; no significant conflicts of interest were disclosed.The National Center for Injury Prevention and Control
(NCIPC) Associate Director for Science reviewed peer reviewers’ conflict of interest disclosure forms and determined no conflicts
of interest were present.The Opioid Workgroup’s (OWG’s) Designated Federal Officer (DFO); the Board of Scientific Counselors of
NCIPC’s (BSC/NCIPC’s) DFO; and CDC’s Strategic Business Initiatives Unit (SBIU), which oversees the Federal Advisory

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 60 of 89
:
 Committee Act program, reviewed OWG members’ conflict of interest disclosure forms and determined all reported potential
financial or other conflicts of interest were not present or nonsignificant.OWG members disclosed the following activities related
to the content of this clinical practice guideline: Anne L. Burns disclosed that she is employed by the American Pharmacists
Association, a nonprofit 501c6 organization, where she is involved in advancing pharmacists’ patient care services, including pain
management services, and she serves on the board of directors for the Pharmacy Quality Alliance, a nonprofit organization that
develops quality measures, including opioid-related measures. Beth Darnall disclosed that she consulted with AppliedVR, a
virtual reality for chronic and acute pain company. Neeraj Gandotra disclosed that he provided expert testimony before the Senate
Judiciary Committee on December 17, 2019, on behalf of the Substance Abuse and Mental Health Services Administration
(SAMHSA) regarding the opioid epidemic. Christine Goertz disclosed that she served as a consultant to the American Chiropractic
Association until September 30, 2019, and that she has received National Institutes of Health (NIH) foundation funding to conduct
research on nonpharmacologic approaches to pain management. Jennifer Waljee disclosed that she received research support
funding from CDC, NIH, the Michigan Department of Health and Human Services, and SAMHSA for research examining the effect
of opioid use before and after surgery on postoperative outcomes.SBIU reviewed BSC/NCIPC members’ Office of Government
Ethics Form 450 and determined all reported potential financial or other conflicts of interest were not present or nonsignificant.
Three BSC/NCIPC members (Chinazo O. Cunningham, Frank Floyd, and Elizabeth Habermann) served on OWG. Roger Chou is a
BSC/NCIPC member and coauthor of the clinical practice guideline and AHRQ-sponsored systematic clinical evidence reviews. Dr.
Chou disclosed that he receives funding to conduct reviews on opioids and recused himself from the July 16, 2021, BSC/NCIPC
meeting and discussion of the OWG report on the draft clinical practice guideline. Wilson Compton disclosed that he has long-
term stock holdings in General Electric, Pfizer, and 3M Companies.
Top

* Financial conflict of interest means a significant financial interest that could directly and significantly affect the design, conduct,
or reporting of Public Health Service-funded research (42 CFR 50.603). Although certain members reported receiving research
support totaling or equivalent to more than $10,000, SBIU determined these activities did not constitute a substantial conflict of
interest pertaining to the content of this clinical practice guideline.
Top

References
1. Schappert SM, Burt CW. Ambulatory care visits to physician offices, hospital outpatient departments, and emergency
departments: United States, 2001–02. Vital Health Stat 13 2006;(159):1–66. PMID:16471269 
2. Institute of Medicine. Relieving pain in America: a blueprint for transforming prevention, care, education, and research.
Washington, DC: National Academies Press; 2011.
3. Tighe P, Buckenmaier CC 3rd, Boezaart AP, et al. Acute pain medicine in the United States: a status report. Pain Med
2015;16:1806–26. https://doi.org/10.1111/pme.12760  PMID:26535424 
4. Banerjee S, Argáez C. Multidisciplinary treatment programs for patients with acute or subacute pain: a review of clinical
effectiveness, cost-effectiveness, and guidelines [Internet]. Ottawa, ON: Canadian Agency for Drugs and Technologies in
Health; 2019 May 7. https://www.ncbi.nlm.nih.gov/books/NBK546002/ 
5. Zelaya CE, Dahlhamer JM, Lucas JW, Connor EM. Chronic pain and high-impact chronic pain among U.S. adults, 2019. NCHS
Data Brief 2020;390:1–8. PMID:33151145 
6. US Department of Health and Human Services. Pain management best practices inter-agency task force report: updates,
gaps, inconsistencies, and recommendations. Washington, DC: US Department of Health and Human Services; 2019.
7. Chou R, Hartung D, Turner J, et al. Opioid treatments for chronic pain. Comparative effectiveness review no. 229. Rockville,
MD: Agency for Healthcare Research and Quality; 2020.
8. McDonagh M, Selph S, Buckley D, et al. Nonopioid pharmacologic treatments for chronic pain. Comparative effectiveness
review no. 228. Rockville, MD: Agency for Healthcare Research and Quality; 2020.
9. Skelly A, Chou R, Dettori J, et al. Noninvasive nonpharmacological treatment for chronic pain: a systematic review update.
Comparative effectiveness review no. 227. Rockville, MD: Agency for Healthcare Research and Quality; 2020.
10. Chou R, Wagner J, Ahmed A, et al. Treatments for acute pain: a systematic review. Comparative effectiveness review no. 240.
Rockville, MD: Agency for Healthcare Research and Quality; 2020.
11. Halker Singh R, VanderPluym J, Morrow A, et al. Acute treatments for episodic migraine. Comparative effectiveness review

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 61 of 89
:
 no. 239. Rockville, MD: Agency for Healthcare Research and Quality; 2020.
12. Hooten WM. Chronic pain and mental health disorders: shared neural mechanisms, epidemiology, and treatment. Mayo Clin
Proc 2016;91:955–70. https://doi.org/10.1016/j.mayocp.2016.04.029  PMID:27344405 
13. Morasco BJ, Gritzner S, Lewis L, Oldham R, Turk DC, Dobscha SK. Systematic review of prevalence, correlates, and treatment
outcomes for chronic non-cancer pain in patients with comorbid substance use disorder. Pain 2011;152:488–97.
https://doi.org/10.1016/j.pain.2010.10.009  PMID:21185119 
14. Smith MT, Edwards RR, Robinson RC, Dworkin RH. Suicidal ideation, plans, and attempts in chronic pain patients: factors
associated with increased risk. Pain 2004;111:201–8. https://doi.org/10.1016/j.pain.2004.06.016  PMID:15327824 
15. Racine M. Chronic pain and suicide risk: a comprehensive review. Prog Neuropsychopharmacol Biol Psychiatry 2018;87(Pt
B):269–80. https://doi.org/10.1016/j.pnpbp.2017.08.020  PMID:28847525 
16. Petrosky E, Harpaz R, Fowler KA, et al. Chronic pain among suicide decedents, 2003 to 2014: findings from the National
Violent Death Reporting System. Ann Intern Med 2018;169:448–55. https://doi.org/10.7326/M18-0830  PMID:30208405


17. Becker WC, Dorflinger L, Edmond SN, Islam L, Heapy AA, Fraenkel L. Barriers and facilitators to use of non-pharmacological
treatments in chronic pain. BMC Fam Pract 2017;18:41. https://doi.org/10.1186/s12875-017-0608-2  PMID:28320337


18. Bazargan M, Yazdanshenas H, Gordon D, Orum G. Pain in community-dwelling elderly African Americans. J Aging Health
2016;28:403–25. https://doi.org/10.1177/0898264315592600  PMID:26115668 
19. Evans MC, Bazargan M, Cobb S, Assari S. Pain intensity among community-dwelling African American older adults in an
economically disadvantaged area of Los Angeles: social, behavioral, and health determinants. Int J Environ Res Public Health
2019;16:20. https://doi.org/10.3390/ijerph16203894  PMID:31615105 
20. Rupp T, Delaney KA. Inadequate analgesia in emergency medicine. Ann Emerg Med 2004;43:494–503.
https://doi.org/10.1016/j.annemergmed.2003.11.019  PMID:15039693 
21. Simon R, Snow R, Wakeman S. Understanding why patients with substance use disorders leave the hospital against medical
advice: a qualitative study. Subst Abus 2020;41:519–25. https://doi.org/10.1080/08897077.2019.1671942 
PMID:31638862 
22. Yazdanshenas H, Bazargan M, Smith J, Martins D, Motahari H, Orum G. Pain treatment of underserved older African
Americans. J Am Geriatr Soc 2016;64:2116–21. https://doi.org/10.1111/jgs.14302  PMID:27590566 
23. Phillips S, Chen Y, Masese R, et al. Perspectives of individuals with sickle cell disease on barriers to care. PLoS One
2022;17:e0265342. https://doi.org/10.1371/journal.pone.0265342  PMID:35320302 
24. Morden NE, Chyn D, Wood A, Meara E. Racial inequality in prescription opioid receipt—role of individual health systems. N
Engl J Med 2021;385:342–51. https://doi.org/10.1056/NEJMsa2034159  PMID:34289277 
25. Ly DP. Racial and ethnic disparities in the evaluation and management of pain in the outpatient setting, 2006–2015. Pain
Med 2019;20:223–32. https://doi.org/10.1093/pm/pny074  PMID:29688509 
26. Joynt M, Train MK, Robbins BW, Halterman JS, Caiola E, Fortuna RJ. The impact of neighborhood socioeconomic status and
race on the prescribing of opioids in emergency departments throughout the United States. J Gen Intern Med 2013;28:1604–
10. https://doi.org/10.1007/s11606-013-2516-z  PMID:23797920 
27. Johnson JD, Asiodu IV, McKenzie CP, et al. Racial and ethnic inequities in postpartum pain evaluation and management.
Obstet Gynecol 2019;134:1155–62. https://doi.org/10.1097/AOG.0000000000003505  PMID:31764724 
28. Goyal MK, Kuppermann N, Cleary SD, Teach SJ, Chamberlain JM. Racial disparities in pain management of children with
appendicitis in emergency departments. JAMA Pediatr 2015;169:996–1002.
https://doi.org/10.1001/jamapediatrics.2015.1915  PMID:26366984 
29. Lee P, Le Saux M, Siegel R, et al. Racial and ethnic disparities in the management of acute pain in US emergency
departments: meta-analysis and systematic review. Am J Emerg Med 2019;37:1770–7.
https://doi.org/10.1016/j.ajem.2019.06.014  PMID:31186154 
30. Hausmann LRM, Gao S, Lee ES, Kwoh KC. Racial disparities in the monitoring of patients on chronic opioid therapy. Pain
2013;154:46–52. https://doi.org/10.1016/j.pain.2012.07.034  PMID:23273103 

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 62 of 89
:
 31. Majedi H, Dehghani SS, Soleyman-Jahi S, et al. Assessment of factors predicting inadequate pain management in chronic pain
patients. Anesth Pain Med 2019;9:e97229. https://doi.org/10.5812/aapm.97229  PMID:32280619 
32. Schieber LZ, Guy GP Jr, Seth P, Losby JL. Variation in adult outpatient opioid prescription dispensing by age and sex—United
States, 2008–2018. MMWR Morb Mortal Wkly Rep 2020;69:298–302. https://doi.org/10.15585/mmwr.mm6911a5 
PMID:32191686 
33. Prunuske JP, St Hill CA, Hager KD, et al. Opioid prescribing patterns for non-malignant chronic pain for rural versus non-rural
US adults: a population-based study using 2010 NAMCS data. BMC Health Serv Res 2014;14:563.
https://doi.org/10.1186/s12913-014-0563-8  PMID:25407745 
34. Wilson N, Kariisa M, Seth P, Smith H 4th, Davis NL. Drug and opioid-involved overdose deaths—United States, 2017–2018.
MMWR Morb Mortal Wkly Rep 2020;69:290–7. https://doi.org/10.15585/mmwr.mm6911a4  PMID:32191688 
35. Becker WC, Starrels JL, Heo M, Li X, Weiner MG, Turner BJ. Racial differences in primary care opioid risk reduction strategies.
Ann Fam Med 2011;9:219–25. https://doi.org/10.1370/afm.1242  PMID:21555749 
36. Gaither JR, Gordon K, Crystal S, et al. Racial disparities in discontinuation of long-term opioid therapy following illicit drug
use among black and white patients. Drug Alcohol Depend 2018;192:371–6.
https://doi.org/10.1016/j.drugalcdep.2018.05.033  PMID:30122319 
37. Soares WE 3rd, Knowles KJ 2nd, Friedmann PD. A thousand cuts: racial and ethnic disparities in emergency medicine. Med
Care 2019;57:921–3. https://doi.org/10.1097/MLR.0000000000001250  PMID:31688566 
38. Pletcher MJ, Kertesz SG, Kohn MA, Gonzales R. Trends in opioid prescribing by race/ethnicity for patients seeking care in US
emergency departments. JAMA 2008;299:70–8. https://doi.org/10.1001/jama.2007.64  PMID:18167408 
39. Ghoshal M, Shapiro H, Todd K, Schatman ME. Chronic noncancer pain management and systemic racism: time to move
toward equal care standards. J Pain Res 2020;13:2825–36. https://doi.org/10.2147/JPR.S287314  PMID:33192090 
40. Nelson SC, Hackman HW. Race matters: perceptions of race and racism in a sickle cell center. Pediatr Blood Cancer
2013;60:451–4. https://doi.org/10.1002/pbc.24361  PMID:23023789 
41. Jamison RN, Sheehan KA, Scanlan E, Matthews M, Ross EL. Beliefs and attitudes about opioid prescribing and chronic pain
management: survey of primary care providers. J Opioid Manag 2014;10:375–82. https://doi.org/10.5055/jom.2014.0234 
PMID:25531955 
42. Lin DH, Jones CM, Compton WM, et al. Prescription drug coverage for treatment of low back pain among US Medicaid,
Medicare Advantage, and commercial insurers. JAMA Netw Open 2018;1:e180235.
https://doi.org/10.1001/jamanetworkopen.2018.0235  PMID:30646077 
43. Heyward J, Jones CM, Compton WM, et al. Coverage of nonpharmacologic treatments for low back pain among US public and
private insurers. JAMA Netw Open 2018;1:e183044. https://doi.org/10.1001/jamanetworkopen.2018.3044 
PMID:30646222 
44. Benzing AC, Bell C, Derazin M, Mack R, MacIntosh T. Disparities in opioid pain management for long bone fractures. J Racial
Ethn Health Disparities 2020;7:740–5. https://doi.org/10.1007/s40615-020-00701-1  PMID:32378160 
45. Saluja B, Bryant Z. How implicit bias contributes to racial disparities in maternal morbidity and mortality in the United States.
J Womens Health (Larchmt) 2021;30:270–3. https://doi.org/10.1089/jwh.2020.8874  PMID:33237843 
46. Sabin JA, Greenwald AG. The influence of implicit bias on treatment recommendations for 4 common pediatric conditions:
pain, urinary tract infection, attention deficit hyperactivity disorder, and asthma. Am J Public Health 2012;102:988–95.
https://doi.org/10.2105/AJPH.2011.300621  PMID:22420817 
47. Chou R, Deyo R, Devine B, et al. The effectiveness and risks of long-term opioid treatment of chronic pain. Evidence
report/technology assessment no. 218. AHRQ publication no. 14–E005-EF. Rockville, MD: Agency for Healthcare Research
and Quality; 2014.
48. Dahlhamer JM, Connor EM, Bose J, Lucas JL, Zelaya CE. Prescription opioid use among adults with chronic pain: United States,
2019. Natl Health Stat Rep 2021;162:1–9. https://doi.org/10.15620/cdc:107641  PMID:34524076 
49. Food and Drug Administration. Letter to application holders: ER/LA opioid analgesic class labeling changes and postmarket
requirements. Silver Spring, MD: US Department of Health and Human Services, Food and Drug Administration.
https://www.fda.gov/media/86875/download 

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 63 of 89
:
 50. Food and Drug Administration. FDA announces enhanced warnings for immediate-release opioid pain medications related to
risks of misuse, abuse, addiction, overdose and death. Silver Spring, MD: US Department of Health and Human Services,
Food and Drug Administration; 2016. https://www.fda.gov/news-events/press-announcements/fda-announces-enhanced-
warnings-immediate-release-opioid-pain-medications-related-risks-misuse-abuse 
51. Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality. Key
substance use and mental health indicators in the United States: results from the 2020 National Survey on Drug Use and
Health. Rockville, MD: US Department of Health and Human Services, Substance Abuse and Mental Health Services
Administration, Center for Behavioral Health Statistics and Quality; 2021. https://www.samhsa.gov/data/ 
52. Paulozzi L, Jones C, Mack K, Rudd R; CDC. Vital signs: overdoses of prescription opioid pain relievers—United States, 1999–
2008. MMWR Morb Mortal Wkly Rep 2011;60:1487–92. PMID:22048730 
53. Han B, Compton WM, Jones CM, Cai R. Nonmedical prescription opioid use and use disorders among adults aged 18 through
64 years in the United States, 2003–2013. JAMA 2015;314:1468–78. https://doi.org/10.1001/jama.2015.11859 
PMID:26461997 
54. Edlund MJ, Martin BC, Russo JE, DeVries A, Braden JB, Sullivan MD. The role of opioid prescription in incident opioid abuse
and dependence among individuals with chronic noncancer pain: the role of opioid prescription. Clin J Pain 2014;30:557–64.
https://doi.org/10.1097/AJP.0000000000000021  PMID:24281273 
55. Bohnert ASB, Valenstein M, Bair MJ, et al. Association between opioid prescribing patterns and opioid overdose-related
deaths. JAMA 2011;305:1315–21. https://doi.org/10.1001/jama.2011.370  PMID:21467284 
56. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain—United States, 2016. MMWR
Recomm Rep 2016;65(No. RR-1):1–49. https://doi.org/10.15585/mmwr.rr6501e1  PMID:26987082 
57. CDC. CDC’s clinical practice guideline for prescribing opioids for pain. Atlanta, GA: US Department of Health and Human
Services, CDC; 2022. https://www.cdc.gov/opioids/healthcare-professionals/prescribing/guideline/index.html
58. Bohnert ASB, Guy GP Jr, Losby JL. Opioid prescribing in the United States before and after the Centers for Disease Control
and Prevention’s 2016 opioid guideline. Ann Intern Med 2018;169:367–75. https://doi.org/10.7326/M18-1243 
PMID:30167651 
59. Salvatore PP, Guy GP Jr, Mikosz CA. Changes in opioid dispensing by medical specialties after the release of the 2016 CDC
guideline for prescribing opioids for chronic pain. Pain Med 2022;pnac068. https://doi.org/10.1093/pm/pnac068 
PMID:35482492 
60. Goldstick JE, Guy GP, Losby JL, Baldwin GT, Myers MG, Bohnert ASB. Patterns in nonopioid pain medication prescribing after
the release of the 2016 guideline for prescribing opioids for chronic pain. JAMA Netw Open 2022;5:e2216475.
https://doi.org/10.1001/jamanetworkopen.2022.16475  PMID:35687334 
61. Substance Use-Disorder Prevention That Promotes Opioid Recovery and Treatment for Patients and Communities Act of
2018. 115th Congress. Pub. L. No. 115–271, Sect. 1010. US Government Publishing Office; 2018.
https://www.govinfo.gov/content/pkg/PLAW-115publ271/html/PLAW-115publ271.htm 
62. Centers for Medicare & Medicaid Services. Medicaid strategies for non-opioid pharmacologic and non-pharmacologic chronic
pain management. CMCS Informational Bulletin. Baltimore, MD: US Department of Health and Human Services, Centers for
Medicare & Medicaid Services; 2019. https://www.medicaid.gov/federal-policy-guidance/downloads/cib022219.pdf  
63. National Conference of State Legislatures. Prescribing policies: states confront opioid overdose epidemic. Washington, DC:
National Conference of State Legislatures; 2019. https://www.ncsl.org/research/health/prescribing-policies-states-confront-
opioid-overdose-epidemic.aspx 
64. US Department of Health and Human Services. Substance use disorder prevention that promotes opioid recovery and
treatment for patients and communities (SUPPORT) Act section 7024: report to congress on opioid prescribing limits.
Washington, DC: US Department of Health and Human Services; 2020.
65. Haffajee RL, Cherney S, Smart R. Legal requirements and recommendations to prescribe naloxone. Drug Alcohol Depend
2020;209:107896. https://doi.org/10.1016/j.drugalcdep.2020.107896  PMID:32058248 
66. Kroenke K, Alford DP, Argoff C, et al. Challenges with implementing the Centers for Disease Control and Prevention opioid
guideline: a consensus panel report. Pain Med 2019;20:724–35. https://doi.org/10.1093/pm/pny307  PMID:30690556 
67. Dowell D, Haegerich T, Chou R. No shortcuts to safer opioid prescribing. N Engl J Med 2019;380:2285–7.

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 64 of 89
:
 https://doi.org/10.1056/NEJMp1904190  PMID:31018066 
68. Food and Drug Administration. FDA identifies harm reported from sudden discontinuation of opioid pain medicines and
requires label changes to guide prescribers on gradual, individualized tapering. Silver Spring, MD: US Department of Health
and Human Services, Food and Drug Administration; 2019. https://www.fda.gov/drugs/drug-safety-and-availability/fda-
identifies-harm-reported-sudden-discontinuation-opioid-pain-medicines-and-requires-label-changes 
69. Demidenko MI, Dobscha SK, Morasco BJ, Meath THA, Ilgen MA, Lovejoy TI. Suicidal ideation and suicidal self-directed
violence following clinician-initiated prescription opioid discontinuation among long-term opioid users. Gen Hosp Psychiatry
2017;47:29–35. https://doi.org/10.1016/j.genhosppsych.2017.04.011  PMID:28807135 
70. Coffin PO, Rowe C, Oman N, et al. Illicit opioid use following changes in opioids prescribed for chronic non-cancer pain. PLoS
One 2020;15:e0232538. https://doi.org/10.1371/journal.pone.0232538  PMID:32365132 
71. Mark TL, Parish W. Opioid medication discontinuation and risk of adverse opioid-related health care events. J Subst Abuse
Treat 2019;103:58–63. https://doi.org/10.1016/j.jsat.2019.05.001  PMID:31079950 
72. Gordon KS, Manhapra A, Crystal S, et al. All-cause mortality among males living with and without HIV initiating long-term
opioid therapy, and its association with opioid dose, opioid interruption and other factors. Drug Alcohol Depend
2020;216:108291. https://doi.org/10.1016/j.drugalcdep.2020.108291  PMID:33011662 
73. James JR, Scott JM, Klein JW, et al. Mortality after discontinuation of primary care-based chronic opioid therapy for pain: a
retrospective cohort study. J Gen Intern Med 2019;34:2749–55. https://doi.org/10.1007/s11606-019-05301-2 
PMID:31468341 
74. Krebs EE, Gravely A, Nugent S, et al. Effect of opioid vs nonopioid medications on pain-related function in patients with
chronic back pain or hip or knee osteoarthritis pain: The SPACE randomized clinical trial. JAMA 2018;319:872–82.
https://doi.org/10.1001/jama.2018.0899  PMID:29509867 
75. Shah A, Hayes CJ, Martin BC. Characteristics of initial prescription episodes and likelihood of long-term opioid use—United
States, 2006–2015. MMWR Morb Mortal Wkly Rep 2017;66:265–9. https://doi.org/10.15585/mmwr.mm6610a1 
PMID:28301454 
76. Deyo RA, Hallvik SE, Hildebran C, et al. Association between initial opioid prescribing patterns and subsequent long-term
use among opioid-naïve patients: a statewide retrospective cohort study. J Gen Intern Med 2017;32:21–7.
https://doi.org/10.1007/s11606-016-3810-3  PMID:27484682 
77. Hill MV, McMahon ML, Stucke RS, Barth RJ Jr. Wide variation and excessive dosage of opioid prescriptions for common
general surgical procedures. Ann Surg 2017;265:709–14. https://doi.org/10.1097/SLA.0000000000001993 
PMID:27631771 
78. Hill MV, Stucke RS, McMahon ML, Beeman JL, Barth RJ Jr. An educational intervention decreases opioid prescribing after
general surgical operations. Ann Surg 2018;267:468–72. https://doi.org/10.1097/SLA.0000000000002198 
PMID:28267689 
79. Howard R, Waljee J, Brummett C, Englesbe M, Lee J. Reduction in opioid prescribing through evidence-based prescribing
guidelines. JAMA Surg 2018;153:285–7. https://doi.org/10.1001/jamasurg.2017.4436  PMID:29214318 
80. Hales CM, Martin CB, Gu Q. Prevalence of prescription pain medication use among adults: United States, 2015–2018. NCHS
Data Brief 2020;369:1–8. PMID:32600518 
81. CDC. U.S. state opioid dispensing rates, 2020. Atlanta, GA: US Department for Health and Human Services, CDC; 2021.
https://www.cdc.gov/drugoverdose/rxrate-maps/state2020.html
82. Schieber LZ, Guy GP Jr, Seth P, et al. Trends and patterns of geographic variation in opioid prescribing practices by state,
United States, 2006–2017. JAMA Netw Open 2019;2:e190665. https://doi.org/10.1001/jamanetworkopen.2019.0665 
PMID:30874783 
83. Guy GP Jr, Zhang K. Opioid prescribing by specialty and volume in the U.S. Am J Prev Med 2018;55:e153–5.
https://doi.org/10.1016/j.amepre.2018.06.008  PMID:30219212 
84. Mikosz CA, Zhang K, Haegerich T, et al. Indication-specific opioid prescribing for US patients with Medicaid or private
insurance, 2017. JAMA Netw Open 2020;3:e204514. https://doi.org/10.1001/jamanetworkopen.2020.4514 
PMID:32391892 
85. Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality. Key

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 65 of 89
:
 substance use and mental health indicators in the United States: results from the 2019 National Survey on Drug Use and
Health. Rockville, MD: US Department of Health and Human Services, Substance Abuse and Mental Health Services
Administration, Center for Behavioral Health Statistics and Quality; 2020. https://www.samhsa.gov/data/ 
86. National Academies of Sciences, Engineering, and Medicine. Framing opioid prescribing guidelines for acute pain: developing
the evidence. Washington, DC: National Academies Press; 2019.
87. Brandow AM, Carroll CP, Creary S, et al. American Society of Hematology 2020 guidelines for sickle cell disease:
management of acute and chronic pain. Blood Adv 2020;4:2656–701. https://doi.org/10.1182/bloodadvances.2020001851
 PMID:32559294 

88. Michigan Opioid Prescribing Engagement Network. Opioid prescribing recommendations: pediatric prescribing
recommendations. Ann Arbor, MI: Michigan Opioid Prescribing Engagement Network. https://michigan-open.org/prescribing-
recommendations 
89. National Comprehensive Cancer Network. Clinical practice guidelines in oncology: adolescent and young adult (AYA)
oncology, version 1.2023. Plymouth Meeting, PA: National Comprehensive Cancer Network; 2023. https://www.nccn.org 
90. Swarm RA, Paice JA, Anghelescu DL, et al.; BCPS. Adult cancer pain, version 3.2019, NCCN clinical practice guidelines in
oncology. J Natl Compr Canc Netw 2019;17:977–1007. https://doi.org/10.6004/jnccn.2019.0038  PMID:31390582 
91. Tevaarwerk A, Denlinger CS, Sanft T, et al. Survivorship, version 1.2021. J Natl Compr Canc Netw 2021;19:676–85.
https://doi.org/10.6004/jnccn.2021.0028  PMID:34214969 
92. Paice JA, Portenoy R, Lacchetti C, et al. Management of chronic pain in survivors of adult cancers: American Society of Clinical
Oncology clinical practice guideline. J Clin Oncol 2016;34:3325–45. https://doi.org/10.1200/JCO.2016.68.5206 
PMID:27458286 
93. National Consensus Project for Quality Palliative Care. Clinical practice guidelines for quality palliative care, 4th ed.
Richmond, VA: National Coalition for Hospice and Palliative Care; 2018. https://www.nationalcoalitionhpc.org/ncp/ 
94. Committee on Approaching Death: Addressing Key End of Life Issues: Institute of Medicine. Dying in America: improving
quality and honoring individual preferences near the end of life. Washington, DC: National Academies Press; 2015.
95. Schatz AA, Oliver TK, Swarm RA, et al. Bridging the gap among clinical practice guidelines for pain management in cancer
and sickle cell disease. J Natl Compr Canc Netw 2020;18:392–9. https://doi.org/10.6004/jnccn.2019.7379 
PMID:32259777 
96. American Society of Addiction Medicine. The ASAM national practice guideline for the treatment of opioid use disorder: 2020
focused update. J Addict Med 2020;14(Suppl 1):1–91. https://doi.org/10.1097/ADM.0000000000000633 
PMID:32511106 
97. Chou R, Turner JA, Devine EB, et al. The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic
review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med 2015;162:276–86.
https://doi.org/10.7326/M14-2559  PMID:25581257 
98. Contextual evidence review for the CDC Guideline for Prescribing Opioids for Chronic Pain—United States, 2016. Atlanta,
GA: US Department of Health and Human Services, CDC; 2016. https://stacks.cdc.gov/view/cdc/38027
https://doi.org/10.23970/AHRQEPCSURVEILLANCEOPIOIDCHRONIC 
99. Berkman ND, Lohr KN, Ansari MT, et al. Grading the strength of a body of evidence when assessing health care interventions:
an EPC update. J Clin Epidemiol 2015;68:1312–24. https://doi.org/10.1016/j.jclinepi.2014.11.023  PMID:25721570 
100. Ahmed F, Temte JL, Campos-Outcalt D, Schünemann HJ; ACIP Evidence Based Recommendations Work Group (EBRWG).
Methods for developing evidence-based recommendations by the Advisory Committee on Immunization Practices (ACIP) of
the U.S. Centers for Disease Control and Prevention (CDC). Vaccine 2011;29:9171–6.
https://doi.org/10.1016/j.vaccine.2011.08.005  PMID:21839794 
101. Lee G, Carr W, Reingold A, et al.; ACIP Evidence-Based Recommendations Work Group; ACIP Evidence Based
Recommendations Work Group. Updated framework for development of evidence-based recommendations by the Advisory
Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep 2018;67:1271–2.
https://doi.org/10.15585/mmwr.mm6745a4  PMID:30439877 
102. Guyatt GH, Oxman AD, Vist GE, et al.; GRADE Working Group. GRADE: an emerging consensus on rating quality of evidence
and strength of recommendations. BMJ 2008;336:924–6. https://doi.org/10.1136/bmj.39489.470347.AD 

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 66 of 89
:
 PMID:18436948 
103. Balshem H, Helfand M, Schünemann HJ, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol
2011;64:401–6. https://doi.org/10.1016/j.jclinepi.2010.07.015  PMID:21208779 
104. Andrews JC, Schünemann HJ, Oxman AD, et al. GRADE guidelines: 15. Going from evidence to recommendation-
determinants of a recommendation’s direction and strength. J Clin Epidemiol 2013;66:726–35.
https://doi.org/10.1016/j.jclinepi.2013.02.003  PMID:23570745 
105. Welch VA, Akl EA, Guyatt G, et al. GRADE equity guidelines 1: considering health equity in GRADE guideline development:
introduction and rationale. J Clin Epidemiol 2017;90:59–67. https://doi.org/10.1016/j.jclinepi.2017.01.014 
PMID:28412464 
106. Ahmed F. Advisory Committee on Immunization Practices handbook for developing evidence-based recommendations.
Version 1.2. Atlanta, GA: US Department of Health and Human Services, CDC; 2013.
https://www.cdc.gov/vaccines/acip/recs/grade/downloads/handbook.pdf 
107. CDC. Board of Scientific Counselors: 2019 Opioid Workgroup. Atlanta, GA: US Department of Health and Human Services,
CDC; 2021. https://www.cdc.gov/injury/bsc/opioid-workgroup-2019.html
108. CDC. Opioid Workgroup of the National Center for Injury Prevention and Control Board of Scientific Counselors roster.
Atlanta, GA: US Department of Health and Human Services, CDC; 2020. https://www.cdc.gov/injury/pdfs/bsc/OWG-Roster-
External-10-13-2020-FINAL-a.pdf 
109. CDC. Opioid Workgroup of the Board of Scientific Counselors of the National Center for Injury Prevention and Control, CDC
terms of reference. Atlanta, GA: US Department of Health and Human Services, CDC; 2020.
https://www.cdc.gov/injury/pdfs/bsc/OWG_Terms-of-Ref_FINAL-7-6-2020-r.pdf 
110. CDC. Federal advisory committee management handbook. Atlanta, GA: US Department of Health and Human Services, CDC,
Management Analysis and Services Office; 2008. https://www.cdc.gov/maso/facm/pdfs/Committeehandbook.pdf 
111. BSC/NCIPC Opioid Workgroup Members. Observations of the Opioid Workgroup of the Board of Scientific Counselors of the
National Center for Injury Prevention and Control on the updated CDC guideline for prescribing opioids; 2021.
https://www.cdc.gov/injury/pdfs/bsc/OWG-Report-of-Recs-1-12-06.30.21-FINAL-508.pdf 
112. CDC. Draft CDC clinical practice guideline for prescribing opioids—United States, 2022: Board of Scientific Counselors of the
National Center for Injury Prevention and Control’s Opioid Workgroup report and CDC response. Atlanta, GA: US Department
of Health and Human Services, CDC; 2022. https://www.regulations.gov/document/CDC-2022-0024-0004 
113. CDC. Draft CDC clinical practice guideline for prescribing opioids—United States, 2022: overview of community engagement
and public comment opportunities. Atlanta, GA: US Department of Health and Human Services, CDC; 2022.
https://www.regulations.gov/document/CDC-2022-0024-0005 
114. CDC. NCIPC peer review agenda. Atlanta, GA: US Department of Health and Human Services, CDC; 2022.
https://www.cdc.gov/injury/fundedprograms/peerReview.html
115. CDC. CDC/ATSDR peer review agenda. Atlanta, GA: US Department of Health and Human Services, CDC; 2022.
https://www.cdc.gov/os/quality/support/peer-review.htm
116. CDC. Advisory Committee on Immunization Practices (ACIP): evidence-based recommendations—GRADE. Atlanta, GA: US
Department of Health and Human Services, CDC; 2018. https://www.cdc.gov/vaccines/acip/recs/GRADE/about-
grade.html#resources
117. US Department of Health and Human Services, Office of Minority Health. Behavioral health implementation guide for the
national standards for culturally and linguistically appropriate services in health and health care. Rockville, MD: US
Department of Health and Human Services, Office of Minority Health; 2021.
https://www.minorityhealth.hhs.gov/Assets/PDF/clas%20standards%20doc_v06.28.21.pdf  
118. Doherty C, Bleakley C, Delahunt E, Holden S. Treatment and prevention of acute and recurrent ankle sprain: an overview of
systematic reviews with meta-analysis. Br J Sports Med 2017;51:113–25. https://doi.org/10.1136/bjsports-2016-096178 
PMID:28053200 
119. Qaseem A, Wilt TJ, McLean RM, Forciea MA; Clinical Guidelines Committee of the American College of Physicians.
Noninvasive treatments for acute, subacute, and chronic low back pain: a clinical practice guideline from the American
College of Physicians. Ann Intern Med 2017;166:514–30. https://doi.org/10.7326/M16-2367  PMID:28192789 

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 67 of 89
:
 120. Qaseem A, McLean RM, O’Gurek D, Batur P, Lin K, Kansagara DL; Clinical Guidelines Committee of the American College of
Physicians; Commission on Health of the Public and Science of the American Academy of Family Physicians.
Nonpharmacologic and pharmacologic management of acute pain from non-low back, musculoskeletal injuries in adults: a
clinical guideline from the American College of Physicians and American Academy of Family Physicians. Ann Intern Med
2020;173:739–48. https://doi.org/10.7326/M19-3602  PMID:32805126 
121. Karmali RN, Skinner AC, Trogdon JG, Weinberger M, George SZ, Hassmiller Lich K. The association between the supply of
select nonpharmacologic providers for pain and use of nonpharmacologic pain management services and initial opioid
prescribing patterns for Medicare beneficiaries with persistent musculoskeletal pain. Health Serv Res 2021;56:275–88.
https://doi.org/10.1111/1475-6773.13561  PMID:33006158 
122. Busse JW, Sadeghirad B, Oparin Y, et al. Management of acute pain from non-low back, musculoskeletal injuries: a systematic
review and network meta-analysis of randomized trials. Ann Intern Med 2020;173:730–8. https://doi.org/10.7326/M19-3601
 PMID:32805127 

123. American Dental Association. Statement on the use of opioids in the treatment of dental pain. Chicago, IL: American Dental
Association; 2016. https://www.ada.org/about/governance/current-policies 
124. Teichman JM. Clinical practice. Acute renal colic from ureteral calculus. N Engl J Med 2004;350:684–93.
https://doi.org/10.1056/NEJMcp030813  PMID:14960744 
125. Cordell WH, Larson TA, Lingeman JE, et al. Indomethacin suppositories versus intravenously titrated morphine for the
treatment of ureteral colic. Ann Emerg Med 1994;23:262–9. https://doi.org/10.1016/S0196-0644(94)70038-9 
PMID:8304606 
126. Cordell WH, Wright SW, Wolfson AB, et al. Comparison of intravenous ketorolac, meperidine, and both (balanced analgesia)
for renal colic. Ann Emerg Med 1996;28:151–8. https://doi.org/10.1016/S0196-0644(96)70055-0  PMID:8759578 
127. Udén P, Rentzhog L, Berger T. A comparative study on the analgesic effects of indomethacin and hydromorphinechloride-
atropine in acute, ureteral-stone pain. Acta Chir Scand 1983;149:497–9. PMID:6637313 
128. Cole RS, Fry CH, Shuttleworth KE. The action of the prostaglandins on isolated human ureteric smooth muscle. Br J Urol
1988;61:19–26. https://doi.org/10.1111/j.1464-410X.1988.tb09155.x  PMID:3422576 
129. Food and Drug Administration. FDA approves new treatment for patients with migraine. Silver Spring, MD: US Department of
Health and Human Services, Food and Drug Administration; 2019. https://www.fda.gov/news-events/press-
announcements/fda-approves-new-treatment-patients-migraine 
130. Shapiro RE, Hochstetler HM, Dennehy EB, et al. Lasmiditan for acute treatment of migraine in patients with cardiovascular
risk factors: post-hoc analysis of pooled results from 2 randomized, double-blind, placebo-controlled, phase 3 trials. J
Headache Pain 2019;20:90. https://doi.org/10.1186/s10194-019-1044-6  PMID:31464581 
131. Buse DC, Reed ML, Fanning KM, Kurth T, Lipton RB. Cardiovascular events, conditions, and procedures among people with
episodic migraine in the US population: results from the American Migraine Prevalence and Prevention (AMPP) study.
Headache 2017;57:31–44. https://doi.org/10.1111/head.12962  PMID:27861837 
132. Lipton RB, Reed ML, Kurth T, Fanning KM, Buse DC. Framingham-based cardiovascular risk estimates among people with
episodic migraine in the US population: results from the American Migraine Prevalence and Prevention (AMPP) study.
Headache 2017;57:1507–21. https://doi.org/10.1111/head.13179  PMID:28990165 
133. American College of Obstetricians and Gynecologists’ Committee on Clinical Consensus—Obstetrics. Pharmacologic
stepwise multimodal approach for postpartum pain management: ACOG clinical consensus no. 1. Obstet Gynecol
2021;138:507–17. https://doi.org/10.1097/AOG.0000000000004517  PMID:34412076 
134. Chang AK, Bijur PE, Esses D, Barnaby DP, Baer J. Effect of a single dose of oral opioid and nonopioid analgesics on acute
extremity pain in the emergency department: a randomized clinical trial. JAMA 2017;318:1661–7.
https://doi.org/10.1001/jama.2017.16190  PMID:29114833 
135. Friedman BW, Dym AA, Davitt M, et al. Naproxen with cyclobenzaprine, oxycodone/acetaminophen, or placebo for treating
acute low back pain: a randomized clinical trial. JAMA 2015;314:1572–80. https://doi.org/10.1001/jama.2015.13043 
PMID:26501533 
136. Lewis RA, Williams NH, Sutton AJ, et al. Comparative clinical effectiveness of management strategies for sciatica: systematic
review and network meta-analyses. Spine J 2015;15:1461–77. https://doi.org/10.1016/j.spinee.2013.08.049 

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 68 of 89
:
 PMID:24412033 
137. Moore PA, Hersh EV. Combining ibuprofen and acetaminophen for acute pain management after third-molar extractions:
translating clinical research to dental practice. J Am Dent Assoc 2013;144:898–908.
https://doi.org/10.14219/jada.archive.2013.0207  PMID:23904576 
138. Pathan SA, Mitra B, Cameron PA. A systematic review and meta-analysis comparing the efficacy of nonsteroidal anti-
inflammatory drugs, opioids, and paracetamol in the treatment of acute renal colic. Eur Urol 2018;73:583–95.
https://doi.org/10.1016/j.eururo.2017.11.001  PMID:29174580 
139. Franklin GM, Stover BD, Turner JA, Fulton-Kehoe D, Wickizer TM; Disability Risk Identification Study Cohort. Early opioid
prescription and subsequent disability among workers with back injuries: the Disability Risk Identification Study Cohort. Spine
2008;33:199–204. https://doi.org/10.1097/BRS.0b013e318160455c  PMID:18197107 
140. Webster BS, Verma SK, Gatchel RJ. Relationship between early opioid prescribing for acute occupational low back pain and
disability duration, medical costs, subsequent surgery and late opioid use. Spine 2007;32:2127–32.
https://doi.org/10.1097/BRS.0b013e318145a731  PMID:17762815 
141. Brummett CM, Waljee JF, Goesling J, et al. New persistent opioid use after minor and major surgical procedures in US adults.
JAMA Surg 2017;152:e170504. https://doi.org/10.1001/jamasurg.2017.0504  PMID:28403427 
142. Goesling J, Moser SE, Zaidi B, et al. Trends and predictors of opioid use after total knee and total hip arthroplasty. Pain
2016;157:1259–65. https://doi.org/10.1097/j.pain.0000000000000516  PMID:26871536 
143. Johnson SP, Chung KC, Zhong L, et al. Risk of prolonged opioid use among opioid-naïve patients following common hand
surgery procedures. J Hand Surg Am 2016;41:947–957.e3. https://doi.org/10.1016/j.jhsa.2016.07.113  PMID:27692801


144. Lee JS, Hu HM, Edelman AL, et al. New persistent opioid use among patients with cancer after curative-intent surgery. J Clin
Oncol 2017;35:4042–9. https://doi.org/10.1200/JCO.2017.74.1363  PMID:29048972 
145. Deyo RA, Hallvik SE, Hildebran C, et al. Use of prescription opioids before and after an operation for chronic pain (lumbar
fusion surgery). Pain 2018;159:1147–54. https://doi.org/10.1097/j.pain.0000000000001202  PMID:29521813 
146. Sun EC, Darnall BD, Baker LC, Mackey S. Incidence of and risk factors for chronic opioid use among opioid-naive patients in
the postoperative period. JAMA Intern Med 2016;176:1286–93. https://doi.org/10.1001/jamainternmed.2016.3298 
PMID:27400458 
147. Katsarava Z, Schneeweiss S, Kurth T, et al. Incidence and predictors for chronicity of headache in patients with episodic
migraine. Neurology 2004;62:788–90. https://doi.org/10.1212/01.WNL.0000113747.18760.D2  PMID:15007133 
148. Chou R, Gordon DB, de Leon-Casasola OA, et al. Management of postoperative pain: a clinical practice guideline from the
American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of
Anesthesiologists’ Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain
2016;17:131–57. Erratum in: J Pain 2016;17:508–10. https://doi.org/10.1016/j.jpain.2015.12.008  PMID:26827847 
149. Overton HN, Hanna MN, Bruhn WE, Hutfless S, Bicket MC, Makary MA; Opioids After Surgery Workgroup. Opioid-prescribing
guidelines for common surgical procedures: an expert panel consensus. J Am Coll Surg 2018;227:411–8.
https://doi.org/10.1016/j.jamcollsurg.2018.07.659  PMID:30118896 
150. Hill MV, Stucke RS, Billmeier SE, Kelly JL, Barth RJ Jr. Guideline for discharge opioid prescriptions after inpatient general
surgical procedures. J Am Coll Surg 2018;226:996–1003. https://doi.org/10.1016/j.jamcollsurg.2017.10.012 
PMID:29198638 
151. Michigan Opioid Prescribing Engagement Network. Prescribing recommendations. Ann Arbor, MI: Michigan Opioid
Prescribing Engagement Network. https://michigan-open.org/prescribing-recommendations 
152. Loder E, Weizenbaum E, Frishberg B, Silberstein S; American Headache Society Choosing Wisely Task Force. Choosing
wisely in headache medicine: the American Headache Society’s list of five things physicians and patients should question.
Headache 2013;53:1651–9. https://doi.org/10.1111/head.12233  PMID:24266337 
153. Langer-Gould AM, Anderson WE, Armstrong MJ, et al. The American Academy of Neurology’s top five choosing wisely
recommendations. Neurology 2013;81:1004–11. https://doi.org/10.1212/WNL.0b013e31828aab14  PMID:23430685 
154. Food and Drug Administration. Disposal of unused medicines: what you should know. Silver Spring, MD: US Department of
Health and Human Services, Food and Drug Administration; 2020. https://www.fda.gov/drugs/safe-disposal-

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 69 of 89
:
 medicines/disposal-unused-medicines-what-you-should-know 
155. US Department of Veterans Affairs, US Department of Defense. VA/DoD clinical practice guideline for the use of opioids in
the management of chronic pain. Washington, DC: US Department of Veterans Affairs; 2022.
https://www.healthquality.va.gov/guidelines/Pain/cot/VADoDOpioidsCPG.pdf  
156. American College of Occupational and Environmental Medicine. Chronic pain guideline. Westminster, CO: ReedGroup; 2017.
http://www.das.ca.gov/dwc/MTUS/ACOEM-Guidelines/Chronic-Pain-Guideline.pdf  
157. Federation of State Medical Boards. Guidelines for the chronic use of opioid analgesics. Euless, TX: Federation of State
Medical Boards; 2017. https://www.fsmb.org/siteassets/advocacy/policies/opioid_guidelines_as_adopted_april-2017_final.pdf
 

158. Chou R, Qaseem A, Snow V, et al.; Clinical Efficacy Assessment Subcommittee of the American College of Physicians;
American College of Physicians; American Pain Society Low Back Pain Guidelines Panel. Diagnosis and treatment of low back
pain: a joint clinical practice guideline from the American College of Physicians and the American Pain Society. Ann Intern
Med 2007;147:478–91. https://doi.org/10.7326/0003-4819-147-7-200710020-00006  PMID:17909209 
159. Hooten WM, Timming R, Belgrade M, et al.; Institute for Clinical Systems Improvement. Assessment and management of
chronic pain. https://www.mnmed.org/getattachment/about-us/committees-task-forces/Prescription-OpioidTask-
Force/Resources-for-physicians/ChronicPain.pdf.aspx?lang=en-US 
160. Fitzcharles M-A, Cohen SP, Clauw DJ, Littlejohn G, Usui C, Häuser W. Nociplastic pain: towards an understanding of
prevalent pain conditions. Lancet 2021;397:2098–110. https://doi.org/10.1016/S0140-6736(21)00392-5 
PMID:34062144 
161. Bannuru RR, Osani MC, Vaysbrot EE, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular
osteoarthritis. Osteoarthritis Cartilage 2019;27:1578–89. https://doi.org/10.1016/j.joca.2019.06.011  PMID:31278997


162. Chaparro LE, Furlan AD, Deshpande A, Mailis-Gagnon A, Atlas S, Turk DC. Opioids compared with placebo or other
treatments for chronic low back pain: an update of the Cochrane Review. Spine 2014;39:556–63.
https://doi.org/10.1097/BRS.0000000000000249  PMID:24480962 
163. Gaskell H, Moore RA, Derry S, Stannard C. Oxycodone for neuropathic pain and fibromyalgia in adults. Cochrane Database
Syst Rev 2014;6:CD010692. PMID:24956205 
164. Goldenberg DL, Clauw DJ, Palmer RE, Clair AG. Opioid use in fibromyalgia: a cautionary tale. Mayo Clin Proc 2016;91:640–8.
https://doi.org/10.1016/j.mayocp.2016.02.002  PMID:26975749 
165. By the 2019 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2019 updated
AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2019;67:674–94.
https://doi.org/10.1111/jgs.15767  PMID:30693946 
166. Hochberg MC, Altman RD, April KT, et al.; American College of Rheumatology. American College of Rheumatology 2012
recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee.
Arthritis Care Res (Hoboken) 2012;64:465–74. https://doi.org/10.1002/acr.21596  PMID:22563589 
167. Hayden JA, van Tulder MW, Malmivaara A, Koes BW. Exercise therapy for treatment of non-specific low back pain. Cochrane
Database Syst Rev 2005;(3):CD000335. https://doi.org/10.1002/14651858.CD000335.pub2  PMID:16034851 
168. Fransen M, McConnell S, Harmer AR, Van der Esch M, Simic M, Bennell KL. Exercise for osteoarthritis of the knee. Cochrane
Database Syst Rev 2015;(1):CD004376. PMID:25569281 
169. Fransen M, McConnell S, Hernandez-Molina G, Reichenbach S. Exercise for osteoarthritis of the hip. Cochrane Database Syst
Rev 2014;(4):CD007912. PMID:24756895 
170. Busch AJ, Barber KAR, Overend TJ, Peloso PMJ, Schachter CL. Exercise for treating fibromyalgia syndrome. Cochrane
Database Syst Rev 2007;(4):CD003786. PMID:17943797 
171. Macfarlane GJ, Kronisch C, Dean LE, et al. EULAR revised recommendations for the management of fibromyalgia. Ann Rheum
Dis 2017;76:318–28. https://doi.org/10.1136/annrheumdis-2016-209724  PMID:27377815 
172. Michelotti A, Iodice G, Vollaro S, Steenks MH, Farella M. Evaluation of the short-term effectiveness of education versus an
occlusal splint for the treatment of myofascial pain of the jaw muscles. J Am Dent Assoc 2012;143:47–53.
https://doi.org/10.14219/jada.archive.2012.0018  PMID:22207667 

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 70 of 89
:
 173. List T, Axelsson S. Management of TMD: evidence from systematic reviews and meta-analyses. J Oral Rehabil 2010;37:430–
51. https://doi.org/10.1111/j.1365-2842.2010.02089.x  PMID:20438615 
174. 2018 Physical Activity Guidelines Advisory Committee. 2018 Physical Activity Guidelines Advisory Committee scientific
report. Washington, DC: US Department of Health and Human Services, Office of Disease Prevention and Health Promotion;
2018. https://health.gov/our-work/nutrition-physical-activity/physical-activity-guidelines/current-guidelines/scientific-report


175. Mannion AF, Müntener M, Taimela S, Dvorak J. A randomized clinical trial of three active therapies for chronic low back pain.
Spine 1999;24:2435–48. https://doi.org/10.1097/00007632-199912010-00004  PMID:10626305 
176. Allen KD, Woolson S, Hoenig HM, et al. Stepped exercise program for patients with knee osteoarthritis: a randomized
controlled trial. Ann Intern Med 2021;174:298–307. https://doi.org/10.7326/M20-4447  PMID:33370174 
177. Williams AC, Eccleston C, Morley S. Psychological therapies for the management of chronic pain (excluding headache) in
adults. Cochrane Database Syst Rev 2012;(11):CD007407. https://doi.org/10.1002/14651858.CD007407.pub3 
PMID:23152245 
178. Food and Drug Administration. FDA drug safety communication: FDA strengthens warning that non-aspirin nonsteroidal anti-
inflammatory drugs (NSAIDs) can cause heart attacks or strokes. Silver Spring, MD: US Department of Health and Human
Services, Food and Drug Administration; 2015. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-
communication-fda-strengthens-warning-non-aspirin-nonsteroidal-anti-inflammatory 
179. Mujakperuo HR, Watson M, Morrison R, Macfarlane TV. Pharmacological interventions for pain in patients with
temporomandibular disorders. Cochrane Database Syst Rev 2010;(10):CD004715.
https://doi.org/10.1002/14651858.CD004715.pub2  PMID:20927737 
180. Kulkarni S, Thambar S, Arora H. Evaluating the effectiveness of nonsteroidal anti-inflammatory drug(s) for relief of pain
associated with temporomandibular joint disorders: a systematic review. Clin Exp Dent Res 2020;6:134–46.
https://doi.org/10.1002/cre2.241  PMID:32067407 
181. Howe CQ, Sullivan MD. The missing ‘P’ in pain management: how the current opioid epidemic highlights the need for
psychiatric services in chronic pain care. Gen Hosp Psychiatry 2014;36:99–104.
https://doi.org/10.1016/j.genhosppsych.2013.10.003  PMID:24211157 
182. Sullivan MD, Edlund MJ, Zhang L, Unützer J, Wells KB. Association between mental health disorders, problem drug use, and
regular prescription opioid use. Arch Intern Med 2006;166:2087–93. https://doi.org/10.1001/archinte.166.19.2087 
PMID:17060538 
183. Banerjee S, McCormack S. Medical cannabis for the treatment of chronic pain: a review of clinical effectiveness and guidelines.
Ottawa, ON: Canadian Agency for Drugs and Technologies in Health; 2019.
184. Krebs EE, Lorenz KA, Bair MJ, et al. Development and initial validation of the PEG, a three-item scale assessing pain intensity
and interference. J Gen Intern Med 2009;24:733–8. https://doi.org/10.1007/s11606-009-0981-1  PMID:19418100 
185. Ostelo RWJG, Deyo RA, Stratford P, et al. Interpreting change scores for pain and functional status in low back pain: towards
international consensus regarding minimal important change. Spine 2008;33:90–4.
https://doi.org/10.1097/BRS.0b013e31815e3a10  PMID:18165753 
186. Wallen M, Gillies D. Intra-articular steroids and splints/rest for children with juvenile idiopathic arthritis and adults with
rheumatoid arthritis. Cochrane Database Syst Rev 2006;(1):CD002824. https://doi.org/10.1002/14651858.CD002824.pub2
 PMID:16437446 

187. Bellamy N, Campbell J, Robinson V, Gee T, Bourne R, Wells G. Intraarticular corticosteroid for treatment of osteoarthritis of
the knee. Cochrane Database Syst Rev 2006;(2):CD005328. PMID:16625636 
188. Buchbinder R, Green S, Youd JM. Corticosteroid injections for shoulder pain. Cochrane Database Syst Rev 2003;
(1):CD004016. PMID:12535501 
189. Chou R, Fu R, Dana T, Pappas M, Hart E, Mauer K. Interventional treatments for acute and chronic pain: systematic review
[Internet]. Comparative effectiveness review no. 247. AHRQ publication no. 21–EHC030. Rockville, MD: Agency for
Healthcare Research and Quality; 2021.
190. Food and Drug Administration. FDA drug safety communication: FDA requires label changes to warn of rare but serious
neurologic problems after epidural corticosteroid injections for pain. Silver Spring, MD: US Department of Health and Human

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 71 of 89
:
 Services, Food and Drug Administration; 2014. https://www.fda.gov/media/88483/download 
191. Interagency Pain Research Coordinating Committee. National pain strategy: a comprehensive population health-level
strategy for pain. Bethesda, MD: US Department of Health and Human Services, National Institutes of Health; 2015.
https://www.iprcc.nih.gov/sites/default/files/documents/NationalPainStrategy_508C.pdf  
192. Miller M, Barber CW, Leatherman S, et al. Prescription opioid duration of action and the risk of unintentional overdose among
patients receiving opioid therapy. JAMA Intern Med 2015;175:608–15. https://doi.org/10.1001/jamainternmed.2014.8071 
PMID:25686208 
193. Food and Drug Administration. FDA blueprint for prescriber education for extended-release and long-acting opioid
analgesics. Silver Spring, MD: US Department of Health and Human Services, Food and Drug Administration; 2017.
https://www.fmda.org/2017/Blueprint%20Opioid%20LA.ER%20REMS%20as%20of%201.20.2017.pdf  
194. Von Korff M, Merrill JO, Rutter CM, Sullivan M, Campbell CI, Weisner C. Time-scheduled vs. pain-contingent opioid dosing in
chronic opioid therapy. Pain 2011;152:1256–62. https://doi.org/10.1016/j.pain.2011.01.005  PMID:21296498 
195. Food and Drug Administration. Abuse-deterrent opioids—evaluation and labeling: guidance for industry. Silver Spring, MD:
US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research;
2015. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/abuse-deterrent-opioids-evaluation-and-
labeling 
196. Paulozzi L, Mack K, Jones C; CDC. Vital signs: risk for overdose from methadone used for pain relief—United States, 1999–
2010. MMWR Morb Mortal Wkly Rep 2012;61:493–7. PMID:22763888 
197. Lugo RA, Satterfield KL, Kern SE. Pharmacokinetics of methadone. J Pain Palliat Care Pharmacother 2005;19:13–24.
https://doi.org/10.1080/J354v19n04_05  PMID:16431829 
198. Grissinger M. Keeping patients safe from methadone overdoses. P T 2011;36:462–6. PMID:21935293 
199. Stringer J, Welsh C, Tommasello A. Methadone-associated Q-T interval prolongation and torsades de pointes. Am J Health
Syst Pharm 2009;66:825–33. https://doi.org/10.2146/ajhp070392  PMID:19386945 
200. Chou R, Cruciani RA, Fiellin DA, et al.; American Pain Society; Heart Rhythm Society. Methadone safety: a clinical practice
guideline from the American Pain Society and College on Problems of Drug Dependence, in collaboration with the Heart
Rhythm Society. J Pain 2014;15:321–37. https://doi.org/10.1016/j.jpain.2014.01.494  PMID:24685458 
201. Coyle DT, Pratt C-Y, Ocran-Appiah J, Secora A, Kornegay C, Staffa J. Opioid analgesic dose and the risk of misuse, overdose,
and death: a narrative review. Pharmacoepidemiol Drug Saf 2018;27:464–72. https://doi.org/10.1002/pds.4366 
PMID:29243305 
202. Dunn KM, Saunders KW, Rutter CM, et al. Opioid prescriptions for chronic pain and overdose: a cohort study. Ann Intern Med
2010;152:85–92. https://doi.org/10.7326/0003-4819-152-2-201001190-00006  PMID:20083827 
203. Gomes T, Mamdani MM, Dhalla IA, Paterson JM, Juurlink DN. Opioid dose and drug-related mortality in patients with
nonmalignant pain. Arch Intern Med 2011;171:686–91. https://doi.org/10.1001/archinternmed.2011.117 
PMID:21482846 
204. Bohnert ASB, Logan JE, Ganoczy D, Dowell D. A detailed exploration into the association of prescribed opioid dosage and
overdose deaths among patients with chronic pain. Med Care 2016;54:435–41.
https://doi.org/10.1097/MLR.0000000000000505  PMID:26807540 
205. Dahan A, Yassen A, Romberg R, et al. Buprenorphine induces ceiling in respiratory depression but not in analgesia. Br J
Anaesth 2006;96:627–32. https://doi.org/10.1093/bja/ael051  PMID:16547090 
206. Dasgupta N, Wang Y, Bae J, et al. Inches, centimeters, and yards: overlooked definition choices inhibit interpretation of
morphine equivalence. Clin J Pain 2021;37:565–74. PMID:34116543 
207. SpecGx LLC. Hydrocodone bitartrate and acetaminophen–hydrocodone bitartrate and acetaminophen tablet.
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=d621b526-4d9a-48a9-9a3e-
d29d6aea2f31&type=display#LINK_f1b36741-318c-44d7-a2bc-b7435530b1e4 
208. State of Washington Department of Health. Provider letter: clarification of opioid prescribing rules. Olympia, WA: State of
Washington Department of Health; 2019. https://wmc.wa.gov/sites/default/files/public/documents/Clarification-opioid-
rules_9-20-2019.pdf  

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 72 of 89
:
 209. Kaplovitch E, Gomes T, Camacho X, Dhalla IA, Mamdani MM, Juurlink DN. Sex differences in dose escalation and overdose
death during chronic opioid therapy: a population-based cohort study. PLoS One 2015;10:e0134550.
https://doi.org/10.1371/journal.pone.0134550  PMID:26291716 
210. Agnoli A, Xing G, Tancredi DJ, Magnan E, Jerant A, Fenton JJ. Association of dose tapering with overdose or mental health
crisis among patients prescribed long-term opioids. JAMA 2021;326:411–9. https://doi.org/10.1001/jama.2021.11013 
PMID:34342618 
211. Hallvik SE, El Ibrahimi S, Johnston K, et al. Patient outcomes after opioid dose reduction among patients with chronic opioid
therapy. Pain 2022;163:83–90. https://doi.org/10.1097/j.pain.0000000000002298  PMID:33863865 
212. Perez HR, Buonora M, Cunningham CO, Heo M, Starrels JL. Opioid taper is associated with subsequent termination of care: a
retrospective cohort study. J Gen Intern Med 2020;35:36–42. https://doi.org/10.1007/s11606-019-05227-9 
PMID:31428983 
213. Glanz JM, Binswanger IA, Shetterly SM, Narwaney KJ, Xu S. Association between opioid dose variability and opioid overdose
among adults prescribed long-term opioid therapy. JAMA Netw Open 2019;2:e192613.
https://doi.org/10.1001/jamanetworkopen.2019.2613  PMID:31002325 
214. Oliva EM, Bowe T, Manhapra A, et al. Associations between stopping prescriptions for opioids, length of opioid treatment,
and overdose or suicide deaths in US veterans: observational evaluation. BMJ 2020;368:m283.
https://doi.org/10.1136/bmj.m283  PMID:32131996 
215. Fenton JJ, Magnan E, Tseregounis IE, Xing G, Agnoli AL, Tancredi DJ. Long-term risk of overdose or mental health crisis after
opioid dose tapering. JAMA Netw Open 2022;5:e2216726. https://doi.org/10.1001/jamanetworkopen.2022.16726 
PMID:35696163 
216. Binswanger IA, Glanz JM, Faul M, et al. The association between opioid discontinuation and heroin use: a nested case-control
study. Drug Alcohol Depend 2020;217:108248. https://doi.org/10.1016/j.drugalcdep.2020.108248  PMID:32927194 
217. Lagisetty P, Zhang K, Haffajee RL, et al. Opioid prescribing history prior to heroin overdose among commercially insured
adults. Drug Alcohol Depend 2020;212:108061. https://doi.org/10.1016/j.drugalcdep.2020.108061  PMID:32428788 
218. Frank JW, Lovejoy TI, Becker WC, et al. Patient outcomes in dose reduction or discontinuation of long-term opioid therapy: a
systematic review. Ann Intern Med 2017;167:181–91. https://doi.org/10.7326/M17-0598  PMID:28715848 
219. US Department of Health and Human Services Working Group on Patient-Centered Reduction or Discontinuation of Long-
term Opioid Analgesics. HHS guide for clinicians on the appropriate dosage reduction or discontinuation of long-term opioid
analgesics. Rockville, MD: US Department of Health and Human Services; 2019.
https://www.hhs.gov/opioids/sites/default/files/2019-10/Dosage_Reduction_Discontinuation.pdf  
220. Substance Abuse and Mental Health Services Administration. Clinical guidance for treating pregnant and parenting women
with opioid use disorder and their infants. HHS publication no. (SMA) 18–5054. Rockville, MD: US Department of Health and
Human Services, Substance Abuse and Mental Health Services Administration; 2018.
https://store.samhsa.gov/product/Clinical-Guidance-for-Treating-Pregnant-and-Parenting-Women-With-Opioid-Use-
Disorder-and-Their-Infants/SMA18-5054 
221. Ecker J, Abuhamad A, Hill W, et al. Substance use disorders in pregnancy: clinical, ethical, and research imperatives
of the opioid epidemic: a report of a joint workshop of the Society for Maternal-Fetal Medicine, American College of
Obstetricians and Gynecologists, and American Society of Addiction Medicine. Am J Obstet Gynecol 2019;221:B5–28.
https://doi.org/10.1016/j.ajog.2019.03.022  PMID:30928567 
222. Haque W, Watson DJ, Bryant SG. Death following suspected alprazolam withdrawal seizures: a case report. Tex Med
1990;86:44–7. PMID:2300914 
223. Lann MA, Molina DK. A fatal case of benzodiazepine withdrawal. Am J Forensic Med Pathol 2009;30:177–9.
https://doi.org/10.1097/PAF.0b013e3181875aa0  PMID:19465812 
224. Dowell D, Haegerich TM. Changing the conversation about opioid tapering. Ann Intern Med 2017;167:208–9.
https://doi.org/10.7326/M17-1402  PMID:28715842 
225. Berna C, Kulich RJ, Rathmell JP. Tapering long-term opioid therapy in chronic noncancer pain: evidence and recommendations
for everyday practice. Mayo Clin Proc 2015;90:828–42. https://doi.org/10.1016/j.mayocp.2015.04.003  PMID:26046416


https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 73 of 89
:
 226. Darnall BD, Ziadni MS, Stieg RL, Mackey IG, Kao M-C, Flood P. Patient-centered prescription opioid tapering in community
outpatients with chronic pain. JAMA Intern Med 2018;178:707–8. https://doi.org/10.1001/jamainternmed.2017.8709 
PMID:29459978 
227. Goesling J, DeJonckheere M, Pierce J, et al. Opioid cessation and chronic pain: perspectives of former opioid users. Pain
2019;160:1131–45. https://doi.org/10.1097/j.pain.0000000000001493  PMID:30889052 
228. Sullivan MD, Turner JA, DiLodovico C, D’Appollonio A, Stephens K, Chan Y-F. Prescription opioid taper support for outpatients
with chronic pain: a randomized controlled trial. J Pain 2017;18:308–18. https://doi.org/10.1016/j.jpain.2016.11.003 
PMID:27908840 
229. Manhapra A, Arias AJ, Ballantyne JC. The conundrum of opioid tapering in long-term opioid therapy for chronic pain: a
commentary. Subst Abus 2018;39:152–61. https://doi.org/10.1080/08897077.2017.1381663  PMID:28929914 
230. Sturgeon JA, Sullivan MD, Parker-Shames S, Tauben D, Coelho P. Outcomes in long-term opioid tapering and buprenorphine
transition: a retrospective clinical data analysis. Pain Med 2020;21:3635–44. https://doi.org/10.1093/pm/pnaa029 
PMID:32163149 
231. Sullivan MD. Depression effects on long-term prescription opioid use, abuse, and addiction. Clin J Pain 2018;34:878–84.
https://doi.org/10.1097/AJP.0000000000000603  PMID:29505419 
232. US Department of Veterans Affairs, Pharmacy Benefits Management, National Academic Detailing Services. Pain
management opioid taper decision tool: a VA clinician’s guide. Washington, DC: US Department of Veterans Affairs; 2016.
https://www.pbm.va.gov/PBM/AcademicDetailingService/Documents/Pain_Opioid_Taper_Tool_IB_10_939_P96820.pdf 


233. Henry SG, Paterniti DA, Feng B, et al. Patients’ experience with opioid tapering: a conceptual model with recommendations
for clinicians. J Pain 2019;20:181–91. https://doi.org/10.1016/j.jpain.2018.09.001  PMID:30243859 
234. Rich RC, Chou R, Mariano ER, Dopp AL, Sullenger R, Burstin H; Pain Management Guidelines and Evidence Standards
Working Group. Best practices, research gaps, and future priorities to support tapering patients on long-term opioid therapy
for chronic non-cancer pain in outpatient settings. NAM Perspect 2020;2020:10.31478/202008c.
https://doi.org/10.31478/202008c  PMID:35291734 
235. Berlin D, Farmer B, Rao R, et al.; CDC. Deaths and severe adverse events associated with anesthesia-assisted rapid opioid
detoxification—New York City, 2012. MMWR Morb Mortal Wkly Rep 2013;62:777–80. PMID:24067581 
236. Gowing L, Farrell M, Ali R, White JM. Alpha2-adrenergic agonists for the management of opioid withdrawal. Cochrane
Database Syst Rev 2016;(5):CD002024. https://doi.org/10.1002/14651858.CD002024.pub5  PMID:27140827 
237. Chou R, Ballantyne J, Lembke A. Rethinking opioid dose tapering, prescription opioid dependence, and indications for
buprenorphine. Ann Intern Med 2019;171:427–9. https://doi.org/10.7326/M19-1488  PMID:31450240 
238. Fishman MA, Kim PS. Buprenorphine for chronic pain: a systemic review. Curr Pain Headache Rep 2018;22:83.
https://doi.org/10.1007/s11916-018-0732-2  PMID:30291571 
239. Pade PA, Cardon KE, Hoffman RM, Geppert CMA. Prescription opioid abuse, chronic pain, and primary care: a co-occurring
disorders clinic in the chronic disease model. J Subst Abuse Treat 2012;43:446–50. https://doi.org/10.1016/j.jsat.2012.08.010
 PMID:22980449 

240. Paone D, Tuazon E, Stajic M, et al. Buprenorphine infrequently found in fatal overdose in New York City. Drug Alcohol Depend
2015;155:298–301. https://doi.org/10.1016/j.drugalcdep.2015.08.007  PMID:26305073 
241. Cohen SM, Weimer MB, Levander XA, Peckham AM, Tetrault JM, Morford KL. Low dose initiation of buprenorphine: a
narrative review and practical approach. J Addict Med 2022;16:399–406. https://doi.org/10.1097/ADM.0000000000000945
 PMID:34954746 

242. Alford DP, Compton P, Samet JH. Acute pain management for patients receiving maintenance methadone or buprenorphine
therapy. Ann Intern Med 2006;144:127–34. https://doi.org/10.7326/0003-4819-144-2-200601170-00010 
PMID:16418412 
243. Lagisetty PA, Healy N, Garpestad C, Jannausch M, Tipirneni R, Bohnert ASB. Access to primary care clinics for patients with
chronic pain receiving opioids. JAMA Netw Open 2019;2:e196928. https://doi.org/10.1001/jamanetworkopen.2019.6928 
PMID:31298712 
244. Mundkur ML, Franklin JM, Abdia Y, et al. Days’ supply of initial opioid analgesic prescriptions and additional fills for acute pain

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 74 of 89
:
 conditions treated in the primary care setting—United States, 2014. MMWR Morb Mortal Wkly Rep 2019;68:140–3.
https://doi.org/10.15585/mmwr.mm6806a3  PMID:30763301 
245. Coste J, Delecoeuillerie G, Cohen de Lara A, Le Parc JM, Paolaggi JB. Clinical course and prognostic factors in acute low back
pain: an inception cohort study in primary care practice. BMJ 1994;308:577–80. https://doi.org/10.1136/bmj.308.6928.577
 PMID:8148683 

246. McCarthy DM, Kim HS, Hur SI, et al. Patient-reported opioid pill consumption after an ED visit: how many pills are people
using? Pain Med 2021;22:292–302. https://doi.org/10.1093/pm/pnaa048  PMID:32219431 
247. Daoust R, Paquet J, Cournoyer A, et al. Quantity of opioids consumed following an emergency department visit for acute pain:
a Canadian prospective cohort study. BMJ Open 2018;8:e022649. https://doi.org/10.1136/bmjopen-2018-022649 
PMID:30224393 
248. Robinson KA, Thiels CA, Stokes S, et al. Comparing clinician consensus recommendations to patient-reported opioid use
across multiple hospital systems. Ann Surg 2022;275:e361–5. https://doi.org/10.1097/SLA.0000000000003986 
PMID:32590547 
249. Mallama CA, Greene C, Alexandridis AA, McAninch JK, Dal Pan G, Meyer T. Patient-reported opioid analgesic use after
discharge from surgical procedures: a systematic review. Pain Med 2022;23:29–44. https://doi.org/10.1093/pm/pnab244 
PMID:34347101 
250. Thiels CA, Ubl DS, Yost KJ, et al. Results of a prospective, multicenter initiative aimed at developing opioid-prescribing
guidelines after surgery. Ann Surg 2018;268:457–68. https://doi.org/10.1097/SLA.0000000000002919  PMID:30004924


251. Reznikoff C. How acute pain leads to chronic opioid use. Cleve Clin J Med 2018;85:837–41.
https://doi.org/10.3949/ccjm.85a.18038  PMID:30395519 
252. Brat GA, Agniel D, Beam A, et al. Postsurgical prescriptions for opioid naive patients and association with overdose and
misuse: retrospective cohort study. BMJ 2018;360:j5790. https://doi.org/10.1136/bmj.j5790  PMID:29343479 
253. Bartels K, Mayes LM, Dingmann C, Bullard KJ, Hopfer CJ, Binswanger IA. Opioid use and storage patterns by patients after
hospital discharge following surgery. PLoS One 2016;11:e0147972. https://doi.org/10.1371/journal.pone.0147972 
PMID:26824844 
254. Bicket MC, Long JJ, Pronovost PJ, Alexander GC, Wu CL. Prescription opioid analgesics commonly unused after surgery: a
systematic review. JAMA Surg 2017;152:1066–71. https://doi.org/10.1001/jamasurg.2017.0831  PMID:28768328 
255. Neuman MD, Bateman BT, Wunsch H. Inappropriate opioid prescription after surgery. Lancet 2019;393:1547–57.
https://doi.org/10.1016/S0140-6736(19)30428-3  PMID:30983590 
256. Joo SS, Hunter OO, Tamboli M, et al. Implementation of a patient-specific tapering protocol at discharge decreases total
opioid dose prescribed for 6 weeks after elective primary spine surgery. Reg Anesth Pain Med 2020;45:474–8.
https://doi.org/10.1136/rapm-2020-101324  PMID:32238478 
257. Tamboli M, Mariano ER, Gustafson KE, et al. A multidisciplinary patient-specific opioid prescribing and tapering protocol is
associated with a decrease in total opioid dose prescribed for six weeks after total hip arthroplasty. Pain Med 2020;21:1474–
81. https://doi.org/10.1093/pm/pnz260  PMID:31710680 
258. Kalso E, Simpson KH, Slappendel R, Dejonckheere J, Richarz U. Predicting long-term response to strong opioids in patients
with low back pain: findings from a randomized, controlled trial of transdermal fentanyl and morphine. BMC Med 2007;5:39.
https://doi.org/10.1186/1741-7015-5-39  PMID:18154644 
259. DeRigne L, Stoddard-Dare P, Collins C, Quinn L. Paid sick leave and preventive health care service use among U.S. working
adults. Prev Med 2017;99:58–62. https://doi.org/10.1016/j.ypmed.2017.01.020  PMID:28189802 
260. Yudko E, Lozhkina O, Fouts A. A comprehensive review of the psychometric properties of the Drug Abuse Screening Test. J
Subst Abuse Treat 2007;32:189–98. https://doi.org/10.1016/j.jsat.2006.08.002  PMID:17306727 
261. McNeely J, Wu L-T, Subramaniam G, et al. Performance of the Tobacco, Alcohol, Prescription medication, and other Substance
use (TAPS) tool for substance use screening in primary care patients. Ann Intern Med 2016;165:690–9.
https://doi.org/10.7326/M16-0317  PMID:27595276 
262. Reinert DF, Allen JP. The alcohol use disorders identification test: an update of research findings. Alcohol Clin Exp Res
2007;31:185–99. https://doi.org/10.1111/j.1530-0277.2006.00295.x  PMID:17250609 

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 75 of 89
:
 263. Bush K, Kivlahan DR, McDonell MB, Fihn SD, Bradley KA. The AUDIT alcohol consumption questions (AUDIT-C): an effective
brief screening test for problem drinking. Ambulatory Care Quality Improvement Project (ACQUIP). Alcohol Use Disorders
Identification Test. Arch Intern Med 1998;158:1789–95. https://doi.org/10.1001/archinte.158.16.1789  PMID:9738608 
264. Zedler B, Xie L, Wang L, et al. Risk factors for serious prescription opioid-related toxicity or overdose among Veterans Health
Administration patients. Pain Med 2014;15:1911–29. https://doi.org/10.1111/pme.12480  PMID:24931395 
265. Broussard CS, Rasmussen SA, Reefhuis J, et al.; National Birth Defects Prevention Study. Maternal treatment with opioid
analgesics and risk for birth defects. Am J Obstet Gynecol 2011;204:314.e1–11. https://doi.org/10.1016/j.ajog.2010.12.039
 PMID:21345403 

266. Lind JN, Interrante JD, Ailes EC, et al. Maternal use of opioids during pregnancy and congenital malformations: a systematic
review. Pediatrics 2017;139:e20164131. https://doi.org/10.1542/peds.2016-4131  PMID:28562278 
267. Yazdy MM, Desai RJ, Brogly SB. Prescription opioids in pregnancy and birth outcomes: a review of the literature. J Pediatr
Genet 2015;4:56–70. https://doi.org/10.1055/s-0035-1556740  PMID:26998394 
268. Yazdy MM, Mitchell AA, Tinker SC, Parker SE, Werler MM. Periconceptional use of opioids and the risk of neural tube defects.
Obstet Gynecol 2013;122:838–44. https://doi.org/10.1097/AOG.0b013e3182a6643c  PMID:24084542 
269. Hadi I, da Silva O, Natale R, Boyd D, Morley-Forster PK. Opioids in the parturient with chronic nonmalignant pain: a
retrospective review. J Opioid Manag 2006;2:31–4. https://doi.org/10.5055/jom.2006.0005  PMID:17319115 
270. Sinclair DC 2nd, Hegmann KT, Holland JP. Acceptable risk of sudden incapacitation among safety critical transportation
workers: a comprehensive synthesis. J Occup Environ Med 2021;63:329–42.
https://doi.org/10.1097/JOM.0000000000002140  PMID:33769399 
271. Edlund MJ, Steffick D, Hudson T, Harris KM, Sullivan M. Risk factors for clinically recognized opioid abuse and dependence
among veterans using opioids for chronic non-cancer pain. Pain 2007;129:355–62. https://doi.org/10.1016/j.pain.2007.02.014
 PMID:17449178 

272. Turner BJ, Liang Y. Drug overdose in a retrospective cohort with non-cancer pain treated with opioids, antidepressants, and/or
sedative-hypnotics: interactions with mental health disorders. J Gen Intern Med 2015;30:1081–96.
https://doi.org/10.1007/s11606-015-3199-4  PMID:25650263 
273. Larochelle MR, Liebschutz JM, Zhang F, Ross-Degnan D, Wharam JF. Opioid prescribing after nonfatal overdose and
association with repeated overdose: a cohort study. Ann Intern Med 2016;164:1–9. https://doi.org/10.7326/M15-0038 
PMID:26720742 
274. American College of Obstetricians and Gynecologists Committee on Obstetric Practice, American Society of Addiction
Medicine. ACOG committee opinion no. 711: opioid use and opioid use disorder in pregnancy. Obstet Gynecol 2017;130:e81–
94. https://doi.org/10.1097/AOG.0000000000002235  PMID:28742676 
275. Whiteman VE, Salemi JL, Mogos MF, Cain MA, Aliyu MH, Salihu HM. Maternal opioid drug use during pregnancy and its
impact on perinatal morbidity, mortality, and the costs of medical care in the United States. J Pregnancy 2014;2014:906723.
https://doi.org/10.1155/2014/906723  PMID:25254116 
276. American College of Obstetricians and Gynecologists and Society for Maternal-Fetal Medicine. Obstetric care consensus no.
8: interpregnancy care. Obstet Gynecol 2019;133:e51–72. https://doi.org/10.1097/AOG.0000000000003025 
PMID:30575677 
277. American College of Obstetricians and Gynecologists. ACOG committee opinion no. 762: prepregnancy counseling. Obstet
Gynecol 2019;133:e78–89. https://doi.org/10.1097/AOG.0000000000003013  PMID:30575679 
278. American College of Obstetricians and Gynecologists’ Committee on Health Care for Underserved Women, Contraceptive
Equity Expert Work Group, and Committee on Ethics. Patient-centered contraceptive counseling: ACOG committee statement
number 1. Obstet Gynecol 2022;139:350–3. https://doi.org/10.1097/AOG.0000000000004659  PMID:35061341 
279. American Medical Association Opioid Task Force. 2019 recommendations of the AMA Opioid Task Force. Chicago, IL:
American Medical Association; 2019. https://end-overdose-epidemic.org/wp-content/uploads/2020/06/2019-AMA-Opioid-
Task-Force-Recommendations-FINAL.pdf  
280. Patrick SW, Barfield WD, Poindexter BB, et al.; Committee on Fetus and Newborn, Committee on Substance Use and
Prevention. Neonatal opioid withdrawal syndrome. Pediatrics 2020;146:e2020029074. https://doi.org/10.1542/peds.2020-
029074  PMID:33106341 

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 76 of 89
:
 281. Goodman LS, Limberd LE. Goodman and Gilman’s the pharmacologic basis of therapeutics. 9th ed. New York, NY: McGraw-
Hill; 1996.
282. Bernabei R, Gambassi G, Lapane K, et al. Management of pain in elderly patients with cancer. SAGE Study Group. Systematic
Assessment of Geriatric Drug Use via Epidemiology. JAMA 1998;279:1877–82. https://doi.org/10.1001/jama.279.23.1877
 PMID:9634258 

283. Hegmann KT, Weiss MS, Bowden K, et al. ACOEM practice guidelines: opioids and safety-sensitive work. J Occup Environ
Med 2014;56:e46–53. https://doi.org/10.1097/JOM.0000000000000237  PMID:24988108 
284. Kroenke K, Spitzer RL, Williams JBW, Löwe B. The Patient Health Questionnaire somatic, anxiety, and depressive symptom
scales: a systematic review. Gen Hosp Psychiatry 2010;32:345–59. https://doi.org/10.1016/j.genhosppsych.2010.03.006 
PMID:20633738 
285. Reid MC, Engles-Horton LL, Weber MB, Kerns RD, Rogers EL, O’Connor PG. Use of opioid medications for chronic noncancer
pain syndromes in primary care. J Gen Intern Med 2002;17:173–9. https://doi.org/10.1046/j.1525-1497.2002.10435.x 
PMID:11929502 
286. Edlund MJ, Martin BC, Devries A, Fan M-Y, Braden JB, Sullivan MD. Trends in use of opioids for chronic noncancer pain among
individuals with mental health and substance use disorders: the TROUP study. Clin J Pain 2010;26:1–8.
https://doi.org/10.1097/AJP.0b013e3181b99f35  PMID:20026946 
287. Gladden RM, O’Donnell J, Mattson CL, Seth P. Changes in opioid-involved overdose deaths by opioid type and presence of
benzodiazepines, cocaine, and methamphetamine—25 states, July–December 2017 to January–June 2018. MMWR Morb
Mortal Wkly Rep 2019;68:737–44. https://doi.org/10.15585/mmwr.mm6834a2  PMID:31465320 
288. Jones CM, Paulozzi LJ, Mack KA; CDC. Alcohol involvement in opioid pain reliever and benzodiazepine drug abuse-related
emergency department visits and drug-related deaths—United States, 2010. MMWR Morb Mortal Wkly Rep 2014;63:881–
5. PMID:25299603 
289. Krist AH, Davidson KW, Mangione CM, et al.; US Preventive Services Task Force. Krist AH, Davidson KW, Mangione CM.
Screening for unhealthy drug use: US Preventive Services Task Force recommendation statement. JAMA 2020;323:2301–9.
https://doi.org/10.1001/jama.2020.8020  PMID:32515821 
290. Saitz R, Cheng DM, Allensworth-Davies D, Winter MR, Smith PC. The ability of single screening questions for unhealthy
alcohol and other drug use to identify substance dependence in primary care. J Stud Alcohol Drugs 2014;75:153–7.
https://doi.org/10.15288/jsad.2014.75.153  PMID:24411807 
291. Smith PC, Schmidt SM, Allensworth-Davies D, Saitz R. A single-question screening test for drug use in primary care. Arch
Intern Med 2010;170:1155–60. https://doi.org/10.1001/archinternmed.2010.140  PMID:20625025 
292. Larochelle MR, Bernson D, Land T, et al. Medication for opioid use disorder after nonfatal opioid overdose and association
with mortality: a cohort study. Ann Intern Med 2018;169:137–45. https://doi.org/10.7326/M17-3107  PMID:29913516


293. Walley AY, Xuan Z, Hackman HH, et al. Opioid overdose rates and implementation of overdose education and nasal naloxone
distribution in Massachusetts: interrupted time series analysis. BMJ 2013;346(jan30 5):f174. https://doi.org/10.1136/bmj.f174
 PMID:23372174 

294. Enteen L, Bauer J, McLean R, et al. Overdose prevention and naloxone prescription for opioid users in San Francisco. J Urban
Health 2010;87:931–41. https://doi.org/10.1007/s11524-010-9495-8  PMID:20967505 
295. Coffin PO, Behar E, Rowe C, et al. Nonrandomized intervention study of naloxone coprescription for primary care patients
receiving long-term opioid therapy for pain. Ann Intern Med 2016;165:245–52. https://doi.org/10.7326/M15-2771 
PMID:27366987 
296. Chua K-P, Brummett CM, Ng S, Bohnert ASB. Association between receipt of overlapping opioid and benzodiazepine
prescriptions from multiple prescribers and overdose risk. JAMA Netw Open 2021;4:e2120353.
https://doi.org/10.1001/jamanetworkopen.2021.20353  PMID:34374769 
297. Lin DH, Lucas E, Murimi IB, et al. Physician attitudes and experiences with Maryland’s prescription drug monitoring program
(PDMP). Addiction 2017;112:311–9. https://doi.org/10.1111/add.13620  PMID:27658522 
298. US Government Accountability Office. Report to congressional committees. Prescription drug monitoring programs: views on
usefulness and challenges of programs. GAO-21–22. Washington, DC: US Government Accountability Office; 2020.

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 77 of 89
:
 https://www.gao.gov/products/gao-21-22 
299. CDC. Integrating & expanding prescription drug monitoring program data: lessons from nine states. Atlanta, GA: US
Department of Health and Human Services, CDC; 2017. https://stacks.cdc.gov/view/cdc/45241
300. Irvine JM, Hallvik SE, Hildebran C, Marino M, Beran T, Deyo RA. Who uses a prescription drug monitoring program and how?
Insights from a statewide survey of Oregon clinicians. J Pain 2014;15:747–55. https://doi.org/10.1016/j.jpain.2014.04.003 
PMID:24787089 
301. Lee B, Zhao W, Yang K-C, Ahn Y-Y, Perry BL. Systematic evaluation of state policy interventions targeting the US opioid
epidemic, 2007–2018. JAMA Netw Open 2021;4:e2036687. https://doi.org/10.1001/jamanetworkopen.2020.36687 
PMID:33576816 
302. Oliva JD. Dosing discrimination: regulating PDMP risk scores. Calif Law Rev 2022;110:1–47.
https://lawcat.berkeley.edu/record/1228027  .
303. Cochran G, Brown J, Yu Z, et al. Validation and threshold identification of a prescription drug monitoring program clinical
opioid risk metric with the WHO alcohol, smoking, and substance involvement screening test. Drug Alcohol Depend
2021;228:109067. https://doi.org/10.1016/j.drugalcdep.2021.109067  PMID:34610516 
304. Cone EJ, Huestis MA. Interpretation of oral fluid tests for drugs of abuse. Ann N Y Acad Sci 2007;1098:51–103.
https://doi.org/10.1196/annals.1384.037  PMID:17332074 
305. Substance Abuse and Mental Health Services Administration, US Department of Health and Human Services. Mandatory
guidelines for federal workplace drug testing programs—oral/fluid. 84 Fed. Reg. 57554–600 (October 25, 2019).
https://www.federalregister.gov/documents/2019/10/25/2019-22684/mandatory-guidelines-for-federal-workplace-drug-
testing-programs-oralfluid#citation-1-p57578 
306. Starrels JL, Fox AD, Kunins HV, Cunningham CO. They don’t know what they don’t know: internal medicine residents’
knowledge and confidence in urine drug test interpretation for patients with chronic pain. J Gen Intern Med 2012;27:1521–7.
https://doi.org/10.1007/s11606-012-2165-7  PMID:22815062 
307. Chua I, Petrides AK, Schiff GD, et al. Provider misinterpretation, documentation, and follow-up of definitive urine drug testing
results. J Gen Intern Med 2020;35:283–90. https://doi.org/10.1007/s11606-019-05514-5  PMID:31713040 
308. Washington State Agency Medical Directors’ Group. AMDG 2015 interagency guideline on prescribing opioids for pain.
Olympia, WA: Washington State Agency Medical Directors’ Group; 2015. https://amdg.wa.gov/guidelines 
309. Jones CM, McAninch JK. Emergency department visits and overdose deaths from combined use of opioids and
benzodiazepines. Am J Prev Med 2015;49:493–501. https://doi.org/10.1016/j.amepre.2015.03.040  PMID:26143953 
310. Dasgupta N, Funk MJ, Proescholdbell S, Hirsch A, Ribisl KM, Marshall S. Cohort study of the impact of high-dose opioid
analgesics on overdose mortality. Pain Med 2016;17:85–98. PMID:26333030 
311. Park TW, Saitz R, Ganoczy D, Ilgen MA, Bohnert ASB. Benzodiazepine prescribing patterns and deaths from drug overdose
among US veterans receiving opioid analgesics: case-cohort study. BMJ 2015;350(jun10 9):h2698.
https://doi.org/10.1136/bmj.h2698  PMID:26063215 
312. Food and Drug Administration. FDA drug safety communication: FDA warns about serious breathing problems with seizure
and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR) when used with CNS
depressants or in patients with lung problems. Silver Spring, MD: US Department of Health and Human Services, Food and
Drug Administration; 2019. https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-serious-breathing-
problems-seizure-and-nerve-pain-medicines-gabapentin-neurontin 
313. Food and Drug Administration. FDA drug safety communication: FDA urges caution about withholding opioid addiction
medications from patients taking benzodiazepines or CNS depressants: careful medication management can reduce risks.
Silver Spring, MD: US Department of Health and Human Services, Food and Drug Administration; 2017.
https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-urges-caution-about-
withholding-opioid-addiction-medications 
314. US Department of Veterans Affairs, Pharmacy Benefits Management, National Academic Detailing Services. Re-evaluating
the use of benzodiazepines: a quick reference guide. Washington, DC: US Department of Veterans Affairs; 2016.
https://www.pbm.va.gov/PBM/AcademicDetailingService/Documents/Academic_Detailing_Educational_Material_Catalog/23_Benzodiaze
 

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 78 of 89
:
 315. Paquin AM, Zimmerman K, Rudolph JL. Risk versus risk: a review of benzodiazepine reduction in older adults. Expert Opin
Drug Saf 2014;13:919–34. https://doi.org/10.1517/14740338.2014.925444  PMID:24905348 
316. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed., text rev. Washington, DC:
American Psychiatric Association; 2000.
317. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, VA: American
Psychiatric Publishing; 2013.
318. Vowles KE, McEntee ML, Julnes PS, Frohe T, Ney JP, van der Goes DN. Rates of opioid misuse, abuse, and addiction in chronic
pain: a systematic review and data synthesis. Pain 2015;156:569–76.
https://doi.org/10.1097/01.j.pain.0000460357.01998.f1  PMID:25785523 
319. Boscarino JA, Withey CA, Dugan RJ, Hu Y, Auciello J, Alfieri T. Opioid medication use among chronic non-cancer pain patients
assessed with a modified drug effects questionnaire and the association with opioid use disorder. J Pain Res 2020;13:2697–
705. https://doi.org/10.2147/JPR.S275397  PMID:33122939 
320. Von Korff M, Walker RL, Saunders K, et al. Prevalence of prescription opioid use disorder among chronic opioid therapy
patients after health plan opioid dose and risk reduction initiatives. Int J Drug Policy 2017;46:90–8.
https://doi.org/10.1016/j.drugpo.2017.05.053  PMID:28666143 
321. Mattick RP, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid
dependence. Cochrane Database Syst Rev 2014;(6):CD002207. https://doi.org/10.1002/14651858.CD002207.pub4 
PMID:24500948 
322. Mattick RP, Breen C, Kimber J, Davoli M. Methadone maintenance therapy versus no opioid replacement therapy for opioid
dependence. Cochrane Database Syst Rev 2009;(3):CD002209. https://doi.org/10.1002/14651858.CD002209.pub2 
PMID:19588333 
323. Fullerton CA, Kim M, Thomas CP, et al. Medication-assisted treatment with methadone: assessing the evidence. Psychiatr
Serv 2014;65:146–57. https://doi.org/10.1176/appi.ps.201300235  PMID:24248468 
324. Fiellin DA, Schottenfeld RS, Cutter CJ, Moore BA, Barry DT, O’Connor PG. Primary care-based buprenorphine taper vs
maintenance therapy for prescription opioid dependence: a randomized clinical trial. JAMA Intern Med 2014;174:1947–54.
https://doi.org/10.1001/jamainternmed.2014.5302  PMID:25330017 
325. Weiss RD, Potter JS, Fiellin DA, et al. Adjunctive counseling during brief and extended buprenorphine-naloxone treatment for
prescription opioid dependence: a 2-phase randomized controlled trial. Arch Gen Psychiatry 2011;68:1238–46.
https://doi.org/10.1001/archgenpsychiatry.2011.121  PMID:22065255 
326. Varisco T, Shen C, Thornton D. Chronic prescription opioid use predicts stabilization on buprenorphine for the treatment of
opioid use disorder. J Subst Abuse Treat 2020;117:108073. https://doi.org/10.1016/j.jsat.2020.108073  PMID:32811630


327. Blondell RD, Ashrafioun L, Dambra CM, Foschio EM, Zielinski AL, Salcedo DM. A clinical trial comparing tapering doses of
buprenorphine with steady doses for chronic pain and co-existent opioid addiction. J Addict Med 2010;4:140–6.
https://doi.org/10.1097/ADM.0b013e3181ba895d  PMID:20959867 
328. Neumann AM, Blondell RD, Jaanimägi U, et al. A preliminary study comparing methadone and buprenorphine in patients with
chronic pain and coexistent opioid addiction. J Addict Dis 2013;32:68–78. https://doi.org/10.1080/10550887.2012.759872
 PMID:23480249 

329. Krawczyk N, Mojtabai R, Stuart EA, et al. Opioid agonist treatment and fatal overdose risk in a state-wide US population
receiving opioid use disorder services. Addiction 2020;115:1683–94. https://doi.org/10.1111/add.14991  PMID:32096302


330. Pearce LA, Min JE, Piske M, et al. Opioid agonist treatment and risk of mortality during opioid overdose public health
emergency: population based retrospective cohort study. BMJ 2020;368:m772. https://doi.org/10.1136/bmj.m772 
PMID:32234712 
331. Krupitsky E, Nunes EV, Ling W, Illeperuma A, Gastfriend DR, Silverman BL. Injectable extended-release naltrexone for opioid
dependence: a double-blind, placebo-controlled, multicentre randomised trial. Lancet 2011;377:1506–13.
https://doi.org/10.1016/S0140-6736(11)60358-9  PMID:21529928 
332. Minozzi S, Amato L, Vecchi S, Davoli M, Kirchmayer U, Verster A. Oral naltrexone maintenance treatment for opioid

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 79 of 89
:
 dependence. Cochrane Database Syst Rev 2011;(2):CD001333.
333. Lee JD, Nunes EV Jr, Novo P, et al. Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone
for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial. Lancet 2018;391:309–18.
https://doi.org/10.1016/S0140-6736(17)32812-X  PMID:29150198 
334. Amato L, Minozzi S, Davoli M, Vecchi S. Psychosocial and pharmacological treatments versus pharmacological treatments for
opioid detoxification. Cochrane Database Syst Rev 2011;(9):CD005031. https://doi.org/10.1002/14651858.CD005031.pub4
 PMID:21901695 

335. Connock M, Juarez-Garcia A, Jowett S, et al. Methadone and buprenorphine for the management of opioid dependence: a
systematic review and economic evaluation. Health Technol Assess 2007;11:1–171, iii–iv. https://doi.org/10.3310/hta11090
 PMID:17313907 

336. Substance Abuse and Mental Health Services Administration. Medications for opioid use disorder. Treatment Improvement
Protocol (TIP) series 63 publication no. PEP21–02–01–002. Rockville, MD: US Department of Health and Human Services,
Substance Abuse and Mental Health Services Administration; 2021. https://store.samhsa.gov/product/TIP-63-Medications-
for-Opioid-Use-Disorder-Full-Document/PEP21-02-01-002 
337. Link HM, Jones H, Miller L, Kaltenbach K, Seligman N. Buprenorphine-naloxone use in pregnancy: a systematic review and
metaanalysis. Am J Obstet Gynecol MFM 2020;2:100179. https://doi.org/10.1016/j.ajogmf.2020.100179 
PMID:33345863 
338. Office of the Secretary, US Department of Health and Human Services. Practice guidelines for the administration of
buprenorphine for treating opioid use disorder. 86 Fed. Reg. 22439–40.
https://www.federalregister.gov/documents/2021/04/28/2021-08961/practice-guidelines-for-the-administration-of-
buprenorphine-for-treating-opioid-use-disorder 
339. Substance Abuse and Mental Health Services Administration. Medication-assisted treatment: become a buprenorphine
waivered practitioner. Rockville, MD: US Department of Health and Human Services, Substance Abuse and Mental Health
Services Administration; 2021. https://www.samhsa.gov/medication-assisted-treatment/become-buprenorphine-waivered-
practitioner 
340. Indivior Inc. Suboxone medication guide. Reference ID: 4055394; revised Feb. 2017. North Chesterfield, VA: Indivior; 2017.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022410s023lbl.pdf  
341. Indivior Inc. Sublocade medication guide. Reference ID: 4555989. North Chesterfield, VA: Indivior; 2020.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209819s012lbl.pdf  
342. Randhawa PA, Brar R, Nolan S. Buprenorphine-naloxone “microdosing”: an alternative induction approach for the treatment
of opioid use disorder in the wake of North America’s increasingly potent illicit drug market. CMAJ 2020;192:E73.
https://doi.org/10.1503/cmaj.74018  PMID:31959660 
343. Robbins JL, Englander H, Gregg J. Buprenorphine microdose induction for the management of prescription opioid
dependence. J Am Board Fam Med 2021;34(Suppl):S141–6. https://doi.org/10.3122/jabfm.2021.S1.200236 
PMID:33622829 
344. Lee JD, Vocci F, Fiellin DA. Unobserved “home” induction onto buprenorphine. J Addict Med 2014;8:299–308.
https://doi.org/10.1097/ADM.0000000000000059  PMID:25254667 
345. Houry D. Letter to American Society of Addiction Medicine (ASAM) on buprenorphine and CDC’s guideline. Atlanta, GA: US
Department of Health and Human Services, CDC; 2018. https://www.asam.org/docs/default-source/advocacy/letters-and-
comments/2018-1-4-letter-on-buprenorphine-and-cdcs-guideline-(002).pdf?sfvrsn=7fa840c2_2  
346. Code of Federal Regulations. Title 21. Chapter 2. Part 1306. General Information. §1306.07.
https://www.ecfr.gov/current/title-21/chapter-II/part-1306/subject-group-ECFR1eb5bb3a23fddd0/section-1306.07 
347. H.R. 8900—116th Congress (2019–2020): Further Continuing Appropriations Act, 2021, and Other Extensions Act. 2020
Dec 11. https://www.congress.gov/bill/116th-congress/house-bill/8900/text 
348. US Department of Justice Drug Enforcement Administration, Diversion Control Division. Registration: instructions to request
exception to 21 CFR 1306.07(b) 3-day rule (EO-DEA248). Springfield, VA: US Department of Justice Drug Enforcement
Administration, Diversion Control Division; 2022. https://www.deadiversion.usdoj.gov/drugreg/ 
349. Hawk K, Hoppe J, Ketcham E, et al. Consensus recommendations on the treatment of opioid use disorder in the emergency

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 80 of 89
:
 department. Ann Emerg Med 2021;78:434–42. https://doi.org/10.1016/j.annemergmed.2021.04.023  PMID:34172303


350. Alkermes. Vivitrol. Full prescribing information. Dublin, Ireland: Alkermes; 2021.
https://www.vivitrol.com/content/pdfs/prescribing-information.pdf  
351. Jones CM, Campopiano M, Baldwin G, McCance-Katz E. National and state treatment need and capacity for opioid agonist
medication-assisted treatment. Am J Public Health 2015;105:e55–63. https://doi.org/10.2105/AJPH.2015.302664 
PMID:26066931 
352. Hruschak V, Cochran G, Wasan AD. Psychosocial interventions for chronic pain and comorbid prescription opioid use
disorders: a narrative review of the literature. J Opioid Manag 2018;14:345–58. https://doi.org/10.5055/jom.2018.0467 
PMID:30387858 
353. Dowell D, Compton WM, Giroir BP. Patient-centered reduction or discontinuation of long-term opioid analgesics: the HHS
guide for clinicians. JAMA 2019;322:1855–6. https://doi.org/10.1001/jama.2019.16409  PMID:31600366 
354. Agency for Healthcare Research and Quality. About SDOH in healthcare. Rockville, MD: US Department of Health and
Human Services, Agency for Healthcare Research and Quality; 2020. https://www.ahrq.gov/sdoh/about.html 
355. Institute of Medicine (US) Committee on Understanding and Eliminating Racial and Ethnic Disparities in Health Care. Unequal
treatment: confronting racial and ethnic disparities in health care. Smedley BD, Stith AY, Nelson AR, eds. Washington, DC:
National Academies Press; 2003.
356. CDC. CDC COVID-19 response health equity strategy: accelerating progress towards reducing COVID-19 disparities and
achieving health equity. Atlanta, GA: US Department of Health and Human Services, CDC; 2020.
https://www.cdc.gov/coronavirus/2019-ncov/community/health-equity/cdc-strategy.html
357. Ancker JS, Gossey JT, Nosal S, et al. Effect of an electronic health record “nudge” on opioid prescribing and electronic health
record keystrokes in ambulatory care. J Gen Intern Med 2021;36:430–7. https://doi.org/10.1007/s11606-020-06276-1 
PMID:33105005 
358. Montoy JCC, Coralic Z, Herring AA, Clattenburg EJ, Raven MC. Association of default electronic medical record settings with
health care professional patterns of opioid prescribing in emergency departments: a randomized quality improvement study.
JAMA Intern Med 2020;180:487–93. https://doi.org/10.1001/jamainternmed.2019.6544  PMID:31961377 
359. National Academies of Sciences, Engineering, and Medicine. Pain management and the opioid epidemic: balancing societal
and individual benefits and risks of prescription opioid use. Washington, DC: National Academies Press; 2017.
Top

BOX
BOX 11. Executive
Executive summary
summary of
of the
the CDC
CDC Clinical
Clinical Practice
Practice Guideline
Guideline for
for Prescribing
Prescribing Opioids
Opioids for
for Pain
Pain
—
— United
United States,
States, 2022
2022

This clinical practice guideline updates and expands the CDC Guideline for Prescribing Opioids for Chronic Pain — United
States, 2016 (MMWR Recomm Rep 2016;65[No. RR-1]:1–49]) and provides evidence-based recommendations for primary
care and other clinicians (including physicians, nurse practitioners and other advanced practice registered nurses, physician
assistants, and oral health practitioners) providing pain care, including those prescribing opioids, for outpatients aged ≥18
years with acute (duration of <1 month) pain, subacute (duration of 1–3 months) pain, or chronic (duration of >3 months) pain.
Recommendations on use of opioids for acute pain and on tapering opioids for patients already receiving opioid therapy have
been substantially expanded in this update. These recommendations do not apply to patients experiencing pain associated
with the following conditions or settings: pain management related to sickle cell disease, cancer-related pain treatment,
palliative care, and end-of-life care. Applicable outpatient settings include clinician offices, clinics, and urgent care centers.
The recommendations do not apply to providing care to patients who are hospitalized or in an emergency department or other
observational setting from which they might be admitted to inpatient care. These recommendations do apply to prescribing
for pain management when patients are discharged from hospitals, emergency departments, or other facilities.

This clinical practice guideline addresses the following areas:

1. Determining whether or not to initiate opioids for pain

2. Selecting opioids and determining opioid dosages

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 81 of 89
:
 3. Deciding duration of initial opioid prescription and conducting follow-up
4. Assessing risk and addressing potential harms of opioid use

CDC developed this clinical practice guideline using the Grading of Recommendations Assessment, Development, and
Evaluation (GRADE) framework, and recommendations are made based on a systematic review of the available scientific
evidence while considering benefits and harms; values and preferences of patients, caregivers, and clinicians; and resource
allocation (e.g., costs to patients or health systems, including clinician time). CDC obtained input on this clinical practice
guideline through individual conversations with patients, caregivers, and clinicians and public comment opportunities
available via Federal Register notices. CDC also sought input from the Board of Scientific Counselors of the National Center
for Injury Prevention and Control (BSC/NCIPC) (a federally chartered advisory committee), federal partners, and peer
reviewers with scientific and clinical expertise.

The clinical evidence reviews found that a number of nonpharmacologic treatments and a number of nonopioid medications
are associated with improvements in pain, function, or both, that appear comparable to improvements associated with opioid
use. Multiple noninvasive nonpharmacologic interventions (e.g., exercise and psychological therapies) are associated with
improvements in pain, function, or both, that are sustained after treatment and are not associated with serious harms.
Nonopioid drugs, including serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressants, pregabalin and
gabapentin, and nonsteroidal anti-inflammatory drugs (NSAIDs), are associated with small to moderate improvements in
chronic pain and function for certain chronic pain conditions. Nonopioid drug class–specific adverse events include serious
cardiovascular, gastrointestinal, or renal effects with NSAIDs and sedation with anticonvulsants. Opioid therapy is associated
with similar or decreased effectiveness for pain and function versus NSAIDs across several acute pain conditions and with
small improvements in short-term (1 to <6 months) pain and function compared with placebo; evidence was found of
attenuated pain reduction over time with opioids (between 3 and 6 months versus between 1 and 3 months). Opioid therapy
is associated with increased risk for serious harms (including opioid use disorder and overdose) that appears to increase with
increase in opioid dosage, without a clear threshold below which there is no risk. No validated, reliable way exists to predict
which patients will suffer serious harm from opioid therapy. Evidence was sparse for long-term improvement of pain or
function for any treatment for chronic pain. Some evidence indicated that beneficial effects of some nonpharmacologic
therapies persist for up to 12 months after the end of a course of a treatment. Among 154 trials of nonopioid medications
rated as good or fair quality, eight were long term (≥1 year). A single trial evaluated outcomes at 1 year for opioid medications
(compared with nonopioid medications).

CDC invited input on the draft clinical practice guideline and received approximately 5,500 public comments. Many of these
comments were related to experiences with pain or with the aftermath of a family member’s, friend’s, or significant person’s
overdose; barriers to and access to pain care and evidence-based treatment; concerns about the level of specificity of
recommendations; and overall communication and implementation of the clinical practice guideline. Some respondents
expressed concerns that insufficient specificity of recommendations might leave clinicians without sufficient practical advice or
context, whereas others were concerned that inclusion of more-specific recommendations or information in the guideline
could facilitate misapplication through adaption of the clinical practice guideline or components of the guideline into rigid
policies and laws. CDC incorporated insights from public comments into the clinical practice guideline, including special
considerations for each recommendation. To help prevent misapplication of recommendations as inflexible rules and enable
clinicians to account for individualized, person-centered clinical considerations, specific prescription dosages and durations are
generally not included in the summary recommendation statements, which highlight general principles. Greater specificity is
provided in implementation considerations and supporting rationales, which can offer more flexibility to help clinicians weigh
benefits and risks of different therapeutic courses for specific patients.

Recommendation statements emphasize that opioids should be used only when benefits for pain and function are expected to
outweigh risks. Before initiating opioid therapy for patients with pain, clinicians should discuss with patients the realistic
benefits and known risks of opioid therapy. Before starting ongoing opioid therapy for patients with subacute or chronic pain,
clinicians should work with patients to establish treatment goals for pain and function and consider how opioid therapy will
be discontinued if benefits do not outweigh risks. When opioids are initiated, clinicians should prescribe the lowest effective
dosage of immediate-release opioids for no longer than needed for the expected duration of pain severe enough to require
opioids. During ongoing opioid therapy, clinicians should collaborate with patients to evaluate and carefully weigh benefits

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 82 of 89
:
 and risks of continuing opioid therapy and exercise care when increasing, continuing, or reducing opioid dosage. Before
starting and periodically during continuation of opioid therapy, clinicians should evaluate risk for opioid-related harms and
should work with patients to incorporate relevant strategies to mitigate risk, including offering naloxone and reviewing
potential interactions with any other prescribed medications or substances used. Clinicians should offer or arrange treatment
with evidence-based medications to treat patients with opioid use disorder.

CDC recommends that persons with pain receive appropriate pain treatment with careful consideration of the benefits and
risks of all treatment options in the context of the patient’s circumstances. Clinicians should collaborate with patients when
making treatment decisions and designing a treatment plan, including when initiating or changing pain management
strategies and particularly when considering initiating, increasing, tapering, or discontinuing opioids. Clinicians should avoid
abrupt discontinuation of opioids, especially for patients receiving high dosages of opioids, should avoid dismissing patients
from care, and should ensure (provide or arrange) appropriate care for patients with pain and patients with complications from
opioid use (e.g., opioid use disorder). Quality and equitable care across sociodemographic groups requires attention to
mitigation of potential barriers to care, such as through linguistically tailored care and cost-assistance programs to ensure
access to appropriate pharmacotherapy, psychological support, and physical therapy as needed.

This voluntary clinical practice guideline provides recommendations only and is intended to support, not supplant, clinical
judgment and individualized, person-centered decision-making. This clinical practice guideline should not be applied as
inflexible standards of care across patient populations by health care professionals; health systems; pharmacies; third-party
payers; or state, local, or federal organizations or entities. This clinical practice guideline is intended to improve
communication between clinicians and patients about the benefits and risks of pain treatment, including opioid therapy for
pain; improve the safety and effectiveness of pain treatment; mitigate pain; improve function and quality of life for patients
with pain; and reduce risks associated with opioid pain therapy, including opioid use disorder, overdose, and death.

Top

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 83 of 89
:
 BOX
BOX 22. Intended
Intended use
use of
of CDC’s
CDC’s Clinical
Clinical Practice
Practice Guideline
Guideline for
for Prescribing
Prescribing Opioids
Opioids for
for Pain
Pain —
—
United
United States,
States, 2022
2022

This clinical practice guideline is

a clinical tool to improve communication between clinicians and patients and empower them to make informed, person-
centered decisions related to pain care together;
intended for primary care clinicians and other clinicians providing pain care for outpatients aged ≥18 years with
acute pain (duration of <1 month),
subacute pain (duration of 1–3 months), or
chronic pain (duration of >3 months); and
intended to be flexible to enable person-centered decision-making, taking into account a patient’s expected health
outcomes and well-being.

This clinical practice guideline is not

a replacement for clinical judgment or individualized, person-centered care;

intended to be applied as inflexible standards of care across patients or patient populations by health care professionals,
health systems, pharmacies, third-party payers, or governmental jurisdictions or to lead to the rapid tapering or abrupt
discontinuation of opioids for patients;
a law, regulation, or policy that dictates clinical practice or as a substitute for Food and Drug Administration–approved
labeling;
applicable to
management of pain related to sickle cell disease,
management of cancer-related pain, or
palliative care or end-of-life care; or
focused on opioids prescribed for opioid use disorder.

Top

BOX
BOX 33. Recommendations
Recommendations for for prescribing
prescribing opioids
opioids for
for outpatients
outpatients with
with pain,
pain, excluding
excluding pain
pain
management
management related
related to
to sickle
sickle cell
cell disease,
disease, cancer-related
cancer-related pain
pain treatment,
treatment, palliative
palliative care,
care, and
and
end-of-life
end-of-life care;
care; recommendation
recommendation categories;
categories; and
and evidence
evidence types
types —— CDC
CDC Clinical
Clinical Practice
Practice Guideline
Guideline for
for
Prescribing
Prescribing Opioids
Opioids for
for Pain
Pain —— United
United States,
States, 2022
2022

Determining Whether or Not to Initiate Opioids for Pain (Recommendations 1 and 2)

1. Nonopioid therapies are at least as effective as opioids for many common types of acute pain. Clinicians should maximize
use of nonpharmacologic and nonopioid pharmacologic therapies as appropriate for the specific condition and patient and
only consider opioid therapy for acute pain if benefits are anticipated to outweigh risks to the patient. Before prescribing
opioid therapy for acute pain, clinicians should discuss with patients the realistic benefits and known risks of opioid
therapy (recommendation category: B; evidence type: 3).
2. Nonopioid therapies are preferred for subacute and chronic pain. Clinicians should maximize use of nonpharmacologic and
nonopioid pharmacologic therapies as appropriate for the specific condition and patient and only consider initiating opioid
therapy if expected benefits for pain and function are anticipated to outweigh risks to the patient. Before starting opioid
therapy for subacute or chronic pain, clinicians should discuss with patients the realistic benefits and known risks of opioid
therapy, should work with patients to establish treatment goals for pain and function, and should consider how opioid
therapy will be discontinued if benefits do not outweigh risks (recommendation category: A; evidence type: 2).

Selecting Opioids and Determining Opioid Dosages (Recommendations 3, 4, and 5)

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 84 of 89
:
 3. When starting opioid therapy for acute, subacute, or chronic pain, clinicians should prescribe immediate-release opioids
instead of extended-release and long-acting (ER/LA) opioids (recommendation category: A; evidence type: 4).
4. When opioids are initiated for opioid-naïve patients with acute, subacute, or chronic pain, clinicians should prescribe the
lowest effective dosage. If opioids are continued for subacute or chronic pain, clinicians should use caution when
prescribing opioids at any dosage, should carefully evaluate individual benefits and risks when considering increasing
dosage, and should avoid increasing dosage above levels likely to yield diminishing returns in benefits relative to risks to
patients (recommendation category: A; evidence type: 3).
5. For patients already receiving opioid therapy, clinicians should carefully weigh benefits and risks and exercise care when
changing opioid dosage. If benefits outweigh risks of continued opioid therapy, clinicians should work closely with patients
to optimize nonopioid therapies while continuing opioid therapy. If benefits do not outweigh risks of continued opioid
therapy, clinicians should optimize other therapies and work closely with patients to gradually taper to lower dosages or, if
warranted based on the individual circumstances of the patient, appropriately taper and discontinue opioids. Unless there
are indications of a life-threatening issue such as warning signs of impending overdose (e.g., confusion, sedation, or slurred
speech), opioid therapy should not be discontinued abruptly, and clinicians should not rapidly reduce opioid dosages from
higher dosages (recommendation category: B; evidence type: 4).

Deciding Duration of Initial Opioid Prescription and Conducting Follow-Up (Recommendations 6 and 7)

6. When opioids are needed for acute pain, clinicians should prescribe no greater quantity than needed for the expected
duration of pain severe enough to require opioids (recommendation category: A; evidence type: 4).
7. Clinicians should evaluate benefits and risks with patients within 1–4 weeks of starting opioid therapy for subacute or
chronic pain or of dosage escalation. Clinicians should regularly reevaluate benefits and risks of continued opioid therapy
with patients (recommendation category: A; evidence type: 4).

Assessing Risk and Addressing Potential Harms of Opioid Use (Recommendations 8, 9, 10, 11, and 12)

8. Before starting and periodically during continuation of opioid therapy, clinicians should evaluate risk for opioid-related
harms and discuss risk with patients. Clinicians should work with patients to incorporate into the management plan
strategies to mitigate risk, including offering naloxone (recommendation category: A; evidence type: 4).
9. When prescribing initial opioid therapy for acute, subacute, or chronic pain, and periodically during opioid therapy for
chronic pain, clinicians should review the patient’s history of controlled substance prescriptions using state prescription
drug monitoring program (PDMP) data to determine whether the patient is receiving opioid dosages or combinations that
put the patient at high risk for overdose (recommendation category: B; evidence type: 4).
10. When prescribing opioids for subacute or chronic pain, clinicians should consider the benefits and risks of toxicology
testing to assess for prescribed medications as well as other prescribed and nonprescribed controlled substances
(recommendation category: B; evidence type: 4).
11. Clinicians should use particular caution when prescribing opioid pain medication and benzodiazepines concurrently and
consider whether benefits outweigh risks of concurrent prescribing of opioids and other central nervous system
depressants (recommendation category: B; evidence type: 3).
12. Clinicians should offer or arrange treatment with evidence-based medications to treat patients with opioid use disorder.
Detoxification on its own, without medications for opioid use disorder, is not recommended for opioid use disorder because
of increased risks for resuming drug use, overdose, and overdose death (recommendation category: A; evidence type: 1).

Recommendation categories (on basis of evidence type, balance between desirable and undesirable effects, values and
preferences, and resource allocation [cost]).

Category A recommendation: Applies to all persons; most patients should receive the recommended course of action.
Category B recommendation: Individual decision-making needed; different choices will be appropriate for different
patients. Clinicians help patients arrive at a decision consistent with patient values and preferences and specific clinical
situations.

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 85 of 89
:
 Evidence types (on basis of study design and as a function of limitations in study design or implementation, imprecision of
estimates, variability in findings, indirectness of evidence, publication bias, magnitude of treatment effects, dose-response
gradient, and constellation of plausible biases that could change effects).

Type 1 evidence: Randomized clinical trials or overwhelming evidence from observational studies.
Type 2 evidence: Randomized clinical trials with important limitations, or exceptionally strong evidence from observational
studies.
Type 3 evidence: Observational studies or randomized clinical trials with notable limitations.
Type 4 evidence: Clinical experience and observations, observational studies with important limitations, or randomized
clinical trials with several major limitations.

Top

BOX
BOX 44. Guiding
Guiding principles
principles for
for implementation
implementation ofof the
the CDC
CDC Clinical
Clinical Practice
Practice Guideline
Guideline for
for
Prescribing
Prescribing Opioids
Opioids for
for Pain
Pain —— United
United States,
States, 2022
2022 recommendations
recommendations

1. Acute, subacute, and chronic pain needs to be appropriately assessed and treated independent of whether opioids are part
of a treatment regimen.
2. Recommendations are voluntary and are intended to support, not supplant, individualized, person-centered care. Flexibility
to meet the care needs and the clinical circumstances of a specific patient is paramount.
3. A multimodal and multidisciplinary approach to pain management attending to the physical health, behavioral health,
long-term services and supports, and expected health outcomes and well-being of each person is critical.
4. Special attention should be given to avoid misapplying this clinical practice guideline beyond its intended use or
implementing policies purportedly derived from it that might lead to unintended and potentially harmful consequences for
patients.
5. Clinicians, practices, health systems, and payers should vigilantly attend to health inequities; provide culturally and
linguistically appropriate communication, including communication that is accessible to persons with disabilities; and
ensure access to an appropriate, affordable, diversified, coordinated, and effective nonpharmacologic and pharmacologic
pain management regimen for all persons.

Top

TABLE. Morphine milligram equivalent doses for

commonly prescribed opioids for pain
management

Opioid Conversion factor*

Codeine 0.15

Fentanyl transdermal (in mcg/hr) 2.4

Hydrocodone 1.0

Hydromorphone 5.0

Methadone 4.7

Morphine 1.0

Oxycodone 1.5

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 86 of 89
:
 Oxymorphone 3.0

Tapentadol† 0.4

Tramadol§ 0.2

Sources: Adapted from Von Korff M, Saunders K, Ray GT, et al. Clin J Pain 2008;24:521–7 and Nielsen S, Degenhardt L, Hoban B,
Gisev N. Pharmacoepidemiol Drug Saf 2016;25:733–7.
Abbreviations: mcg/hr = microgram per hour; mg = milligram; MME = morphine milligram equivalent.
* Multiply the dose for each opioid by the conversion factor to determine the dose in MMEs. For example, tablets containing
hydrocodone 5 mg and acetaminophen 325 mg taken four times a day would contain a total of 20 mg of hydrocodone daily,
equivalent to 20 MME daily; extended-release tablets containing oxycodone 10 mg and taken twice a day would contain a total of
20 mg of oxycodone daily, equivalent to 30 MME daily. The following cautions should be noted: 1) All doses are in mg/day except
for fentanyl, which is mcg/hr. 2) Equianalgesic dose conversions are only estimates and cannot account for individual variability in
genetics and pharmacokinetics. 3) Do not use the calculated dose in MMEs to determine the doses to use when converting one
opioid to another; when converting opioids, the new opioid is typically dosed at a substantially lower dose than the calculated
MME dose to avoid overdose because of incomplete cross-tolerance and individual variability in opioid pharmacokinetics. 4) Use
particular caution with methadone dose conversions because methadone has a long and variable half-life, and peak respiratory
depressant effect occurs later and lasts longer than peak analgesic effect. 5) Use particular caution with transdermal fentanyl
because it is dosed in mcg/hr instead of mg/day, and its absorption is affected by heat and other factors. 6) Buprenorphine
products approved for the treatment of pain are not included in the table because of their partial µ-receptor agonist activity and
resultant ceiling effects compared with full µ-receptor agonists. 7) These conversion factors should not be applied to dosage
decisions related to the management of opioid use disorder.
†
Tapentadol is a µ-receptor agonist and norepinephrine reuptake inhibitor. MMEs are based on degree of µ-receptor agonist
activity; however, it is unknown whether tapentadol is associated with overdose in the same dose-dependent manner as observed
with medications that are solely µ-receptor agonists.
§
Tramadol is a µ-receptor agonist and norepinephrine and serotonin reuptake inhibitor. MMEs are based on degree of µ-receptor
agonist activity; however, it is unknown whether tramadol is associated with overdose in the same dose-dependent manner as
observed with medications that are solely µ-receptor agonists.
Top

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 87 of 89
:
 BOX
BOX 55. Areas
Areas for
for additional
additional research
research to
to build
build the
the evidence
evidence base
base for
for optimal
optimal pain
pain management
management

Efficacy of screening tools to assess risk for opioid misuse and developing an opioid use disorder.
Effective management of patients on high-dosage opioids, the application of multidisciplinary and multimodal models of
pain treatment, and service delivery modalities including telehealth.
Long-term comparative effectiveness of pharmacologic and nonpharmacologic therapies for chronic pain, including effects
of treatment combinations, dosage variation, and comorbidities.
Comparative effectiveness and comparative risks of partial agonist opioids (e.g., buprenorphine) versus full agonist opioids
for pain.
Comparative effectiveness and risks of interventional procedures as part of a comprehensive pain management plan.
Effects of therapies on nonpain outcomes.
Treatment outcomes for specific pain conditions and how benefits and risks of therapies vary among subpopulations.
Adapting evidence-based opioid prescribing and pain management strategies to meet the needs of special populations,
including persons from some racial and ethnic groups, older adults, and persons living in rural communities.
Effectiveness of clinician and health system strategies to promote equitable access to high-quality pain management.
Improved diagnostics in measuring pain.
Enhanced clinician and patient education about pain and the use of opioids, and the assessment of practice-level strategies
in health systems to improve management and care coordination for patients on opioid therapy.
Transition from acute to chronic pain and how to apply effective diagnostic, preventive, and therapeutic approaches.
Effects of stigma as a barrier for treating pain and receiving treatment for an opioid use disorder, and effective ways to
counter the effects of stigma on access to treatment for pain and opioid use disorder.

Top

View Appendix
Top

Suggested citation for this article: Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. CDC Clinical Practice Guideline for
Prescribing Opioids for Pain — United States, 2022. MMWR Recomm Rep 2022;71(No. RR-3):1–95. DOI:
http://dx.doi.org/10.15585/mmwr.rr7103a1  .

MMWR and Morbidity and Mortality Weekly Report are service marks of the U.S. Department of Health and Human Services.
Use of trade names and commercial sources is for identification only and does not imply endorsement by the U.S. Department of Health and Human Services.
References to non-CDC sites on the Internet are provided as a service to MMWR readers and do not constitute or imply endorsement of these organizations or their
programs by CDC or the U.S. Department of Health and Human Services. CDC is not responsible for the content of pages found at these sites. URL addresses listed in
MMWR were current as of the date of publication.

All HTML versions of MMWR articles are generated from final proofs through an automated process. This conversion might result in character translation or format errors in
the HTML version. Users are referred to the electronic PDF version (https://www.cdc.gov/mmwr) and/or the original MMWR paper copy for printable versions of official text,
figures, and tables.

Questions or messages regarding errors in formatting should be addressed to mmwrq@cdc.gov.

Last Reviewed: November 3, 2022
Source: Centers for Disease Control and Prevention

Was this page helpful?

Yes Partly No

https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 88 of 89
:
https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm#suggestedcitation 11/30/24, 11 18 AM
Page 89 of 89
: