Doi: 10.32481/djph.2023.08.

011

Evaluation & Treatment of Psychological Effects of Stroke

Nancy Devereux PhD1 and Ashley M. Berns PsyD2
1. Clinical Neuropsychologist, ChristianaCare; Delaware Stroke System of Care Subcommittee
2. ChristianaCare Behavioral Health Department

Abstract
Strokes are a common medical condition in the United States, including in Delaware. An under-
recognized effect of stroke is the impact on mood that often occurs. Many individuals develop
depression, anxiety, PTSD, and other psychological sequelae. These disorders can significantly
affect their lives and their relationships. The emotional effects of stroke pose a public health
problem for our residents, leading to devastating decreases in the quality of life for the patient
and the family. These challenges negatively impact the community due to the associated
healthcare and economic burdens. The population of the State of Delaware is growing, and the
proportion of senior residents, who are also at greater risk for strokes, is also increasing. Strokes
will remain an ongoing important clinical concern for our healthcare providers. Emotional
changes after a stroke will occur in many Delaware residents who suffer a stroke. The emotional
sequelae of stroke are under-treated. It is critical for healthcare professionals to be trained to
recognize, assess, and treat the psychological disorders that can result from having a stroke. This
article provides an overview of the major psychological effects of stroke, recommended
assessment tools, promising treatment trends, and directions for further research. Improving our
ability to detect and treat these difficult emotional challenges can facilitate effective treatment
and prevention strategies and increase quality of life for stroke survivors, their loved ones, and
their communities.

Introduction
Strokes are unfortunately common across the world. Approximately 12.2 million new strokes
occur globally per year.1 In the United States, an estimated 795,000 people suffer a stroke
annually.2 In the state of Delaware, 3,139 strokes were recorded in 2022.3 Delaware’s population
was estimated at 1,018,392 in mid-20224; this suggests that the state’s per capita rate of strokes
was about 0.31%.
Survivors of stroke face enormous health, emotional, social, and economic impacts. These
effects are experienced at the personal, family, and community levels. Significant complications
of stroke include the psychological ramifications that often develop. Post-stroke mood disorders
are prevalent yet tend to be under-recognized and under-treated. This clinical challenge was
brought to the public’s eye when earlier this year a U.S. senator from our neighboring state of
Pennsylvania, John Fetterman, sought hospitalization for his post-stroke depression. He also had
a prior history of depression.
Mood disorders apart from stroke are also common around the globe. Approximately 280 million
people worldwide live with depression.5 In the United States, it is estimated that 21 million
adults aged 18 or older have experienced depression, which is about 8.4% of the adult
population.6 One study indicated that, according to standard diagnostic criteria, the twelve-month
and lifetime prevalence of major depressive disorder are 10.4% and 20.6% respectively.7
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Not surprisingly, stroke is one of the most disabling medical conditions in the US.8 Marked
changes in functional and psychosocial functioning are not only experienced by patients with
stroke. Psychiatric disorders can lead to disabling conditions as well. Depression is the leading
cause of disability in the United States.9 When stroke and mood disorders are co-occurring, they
often generate significant personal and public health consequences. Numerous studies over the
past few decades have indicated that post-stroke psychological sequelae can be varied as well as
pervasive.10,11 Psychological effects of stroke include depression, anxiety, post-traumatic stress
disorder (PTSD), mania, psychosis, irritability, and apathy, among other emotional and
behavioral conditions.12 This review will focus on the first three more commonly observed post-
stroke psychological sequelae.

Post Stroke Depression

The most thoroughly researched emotional issue following stroke is depression (PSD). A large
body of studies over several decades indicates that roughly 1/3 of individuals sustaining a stroke
develop PSD within a year to five years post-onset.13 These individuals have higher rates of
healthcare utilization, poorer functional outcomes, reduced quality of life (QOL), and higher
mortality.14,15 The depression these patients suffer is not simply due to having a serious medical
condition; for example, when compared with patients suffering myocardial infarctions, those
with PSD experience higher rates of mood disorders, particularly depression.16,17 While the one-
third prevalence rate for PSD is well-supported across studies, some studies have reported lower
rates ranging from 15.8% to 21%, depending on setting and time since stroke.18,19 Higher rates
have also been reported, and the cumulative incidence of PSD may be as high as 55%.20 The
varying rates of depression after stroke are due to combined factors, mostly related to
methodology. For example, there is a lack of standardization of assessment instruments, leading
to inconsistent criteria and cut-off scores. Subject inclusion and exclusion criteria are also
variable such that “minor depression” and depressive adjustment disorders may or may not be
included in investigations of stroke patients with depression, and aphasics and patients with
hemorrhagic strokes are often excluded. Time points of assessments relative to stroke onset vary
as well. Additionally, geographic region influences the selection and assessment processes.
These are only a sampling of the factors that contribute to the variability in the incidence and
prevalence of PSD reported across studies. Despite these limitations, it is evident that depression
is more common after stroke than its incidence in the general population.10 Understanding the
risk factors may assist in optimizing clinical assessment, honing treatments, and developing
prevention strategies.

Risk Factors
Post-stroke depression is a multifactorial condition.21 There are combined psychological, social,
and biological factors that play a role in its manifestation.22 Identification of risk factors is an
important area of study for clinical work. The research heterogeneity noted earlier for diagnostic
considerations applies to our understanding of risk factors for PSD as well. The variations in
research design lead to issues concerning methodology, selection criteria, population setting,
geographic location, assessment tools, cut-off scores, time since stroke, etcetera. These
irregularities cause difficulty in identifying a clear and consistent set of predictors of PSD across
studies. Despite this ambiguity, there are some PSD predictors that warrant comment and further
study. These risk factors include (though are not limited to) the following:
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Genetic
Studies suggest that there are many genes associated with post-stroke depression.21,23,24 These
genes include the serotonin transporter gene (SERT) polymorphisms, 5-HTTLPR and STin2
VNTR.21 Apolipoprotein E (ApoE) and methylenetetrahydrofolate reductase (MTHFR) appear to
be associated with a higher risk of major depressive disorder following a stroke, and research
continues into the identification of genetic contributions to risk for post-stroke depression.

Age
A systematic review, which included 23 studies and 18,374 participants, found that most studies
concluded that older age was not associated with an increased risk of depression following a
stroke.21 One review indicated that age of stroke at less than 70 years was predictive of PSD, but
limited sample size was a drawback.25 Given the mixed research findings, age remains an
ambiguous risk factor.

Sex
Research across the decades has yielded mixed results in relation to gender and susceptibility for
post-stroke depression.21 A large body of evidence had suggested that females were more likely
to develop depression post-stroke than males.16,25 There are also some research findings casting
doubt that a specific gender increases the risk of depression following a stroke.22,26

Stroke Severity
A number of studies have demonstrated that the severity of stroke is positively correlated with
depression.21,27 However, a recent review indicated that stroke severity was not predictive of
PSD, while level of physical disability was predictive during the first-year post-stroke.28 These
two constructs may be conflated in some cases, depending upon definition and assessment tools
employed in the study samples. Stroke severity therefore may be a consideration for PSD,
depending upon its definition and how it is measured.

Lesion Location
Research has demonstrated that the distance between the brain lesion and the frontal lobe plays
an essential role in determining the severity of post-stroke depression.21 More specifically,
comparisons between left prefrontal-subcortical lesions (i.e., lesion volume & location) versus
right hemisphere have demonstrated that individuals with left hemisphere lesions have a higher
incidence and severity of post-stroke depression. Numerous studies have questioned this trend.
For example, Robinson and Jorge12 reviewed meta-analyses which did not confirm a strong
association between lesion location and subsequent depression. They concluded that there may
be an association of PSD with left frontal or basal ganglia lesions within two months of an initial
clinical stroke. Findings from a separate review showed some support for this observation, while
also indicating that both frontal and subcortical lesions regardless of laterality may be somewhat
predictive of PSD.29 At this time, the relationship between lesion location and PSD is not fully
understood and may be mediated by other factors.
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Aphasia
Depression after stroke may be more likely when a patient has aphasia as compared to patients
without language impairments.19 A study of adults with aphasia in an acute care setting indicated
that the aphasic patients were seven times more likely to suffer PSD than non-aphasic patients.30

Other Factors
Research suggests that marital status, years of education, history of prior stroke and/or history of
myocardial infarction, recent life stressors, poverty, and lack of social supports are associated
with a higher incidence of depression following a stroke.18,21,31

Assessment
The assessment of PSD across sites and studies is highly variable in terms of methods,
instruments, cut-off scores, definitions of depression and types of depression, settings, and time
points of assessment. For example, brief screenings may be employed, usually administered by a
clinician; a lengthier structured interview adhering to DSM-5 Diagnostic and Statistical Manual
of Mental Disorders32 criteria can be conducted by a clinician; or a range of approaches in
between these methods might be used for depression assessment. The methods include self-
report inventories or checklists, mood scales, structured interviews, and clinician or collateral
observer ratings.
The studies reviewed in the literature tend to use the following validated instruments: Hospital
Anxiety and Depression Scale (HADS);33 Center for Epidemiologic Studies of Depression Scale
(CESD);34 Hamilton Depression Rating Scale (HAMD or HDRS);35 Patient Health
Questionnaire-9 (PHQ-9);36 Beck Depression Inventory (BDI);37 and Geriatric Depression Scale
(GDS).38 The instruments vary in administration time requirements and staff involvement;
therefore, practicality and efficiency needs may dictate instrument selection on a busy acute
inpatient or rehabilitation unit.
A few reviews of assessment instruments (Table 1) employed with stroke survivors indicate that
several types of methods may be useful. Clinician-administered structured clinical interviews and
screening scales for depression showed acceptable or better results for all validation measures
when used to screen for psychiatric disorders in patients with stroke in a review from 2016.39
Another review suggested that the CES-D, the HDRS and the PHQ-9 may be the best options for
adequate sensitivity and specificity.40 Other studies have indicated that despite limitations, the
Patient Health Questionnaire-2 (PHQ-2) may be practical for screening due to minimal time and
staff demands and acceptable sensitivity.41–43 The authors agree that ideally the instruments
should not be used in isolation. A follow-up evaluation utilizing more detailed assessment is
recommended, such as following a positive PHQ-2 with PHQ-9, other more focused clinical
instruments, and/or direct interview.
There is a potential confound with most of these instruments, in that some of the physiological
symptoms of depression overlap with those of stroke. For example, sleep quality, energy level,
and appetite are often diminished in hospital patients independent of presence of mood disorder.
Yet these symptoms are often altered in depression and are typically included in surveying
depression. To minimize the confound, and for practical clinical goals as indicated earlier, the
PHQ-2 may be preferable for depression screening purposes in hospital settings.
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Many of the studies addressing screening and diagnosis of post-stroke depression excluded
patients with aphasia. Assessment of depression in these patients can be particularly challenging.
Communicative disorders can impact comprehension, not just expression. Reading, writing,
spelling, and gesture can be compromised. Validity and reliability of the instruments may be
tenuous when used with aphasic patients. The Visual Analogue Mood Scale (VAMS)44 has been
utilized to help skirt the communication issue. Its utility may be questionable in some cases.
There are concerns that it has not been found to be consistently reliable,45 while other researchers
find it to be of value in assessing individuals with aphasia.46

Other Psychological Sequelae of Stroke

In addition to depression, there are other noteworthy psychological sequelae of stroke. Though
less common and less studied, these emotional effects pose potential burdens to patients,
families, and the community. Anxiety and PTSD are two of the emotional consequences that are
most often observed after depression in patients with strokes.
Anxiety is relatively common following a stroke. In the general population, 19.1% are estimated
to have anxiety.47 After stroke, it is estimated that 20-25% of patients develop anxiety.48–50
Anxiety disorders include specific phobias, generalized anxiety disorder (GAD), panic disorder,
agoraphobia, and social anxiety disorder. An adjustment disorder with anxiety may also account
for the observed symptoms. Anxiety due to another medical condition (other than stroke) and
substance use-induced anxiety are typically ruled out and not included in populations under
study in these investigations. Post-stroke anxiety (PSA) may tend to present as specific phobia
with or without associated GAD.51 PSA is closely associated with PSD and tends to endure for
longer periods when the two conditions co-occur.52,53 Pre-stroke depression, stroke severity,
early anxiety, and dementia or cognitive impairment after stroke appear to be predictive of post-
stroke anxiety.54 PSA is typically assessed by the GAD-7;55 the Beck Anxiety Inventory (BAI);56
HADS;33 and the Hamilton Anxiety Rating Scale (HAM-A).57 These instruments have not been
validated for stroke populations despite their use clinically and in research with this patient
group.
Post-traumatic stress disorder (PTSD) has been observed in some patients following stroke.
Suffering a stroke can be perceived as a disruptive and marked traumatic life event.58 Prevalence
estimates vary, generally from 10% to 31%, depending upon assessment method employed and
other factors.59 One study reported that 1 in 4 stroke survivors endorsed elevated symptoms of
PTSD within the first year.60 Of note, PTSD was removed from the Anxiety Disorders category
in 2013 in the 5th edition of the American Psychiatric Association’s Diagnostic and Statistical
Manual of Mental Disorders and placed in the “Trauma and Stressor-related Disorders”
section.61 Post-stroke PTSD (PS-PTSD) has been associated with nonadherence to medications62;
a heightened degree of disability;63,64 and a higher frequency of right cerebral and brainstem
lesions.65 Risk factors were not clearly specified, though there may be a greater tendency for PS-
PTSD to occur in women and at younger ages.58,63 Social support may confer protective
resilience against development of PTSD.63 Instruments used to assess PS-PTSD include the
Impact of Events Scale (IES-R);66 Primary Care-PTSD Screen (PC-PTSD);67 PCL/PCL-5;68,69
and clinical interview utilizing DSM-5 criteria.
Table 1. Post-Stroke Psychological Assessment Tools
Depression DSM-5, HADS, CESD, HAMD/HDRS, PHQ-9, BDI
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Anxiety DSM-5, HADS, BAI, HAM-A

PTSD DSM-5, IES-R, PCL/PCL-5

Pathophysiology
The pathophysiology of post-stroke mood disorders is posited to be multi-factorial. Proposed
mechanisms have been discussed in the literature for post-stroke depression more so than for
other psychological sequelae. The underlying mechanisms appear to involve decreased levels of
monoamines, abnormal neurotrophic response, inflammatory processes, and dysfunctional
regulation of hypothalamic-pituitary-adrenal axis and glutamate-mediated excitotoxicity.70
Genetic factors may also interact with the pathophysiological processes.

Prevention of Post Stroke Mood Disorders

There are suggestions that multimodal therapies combined with antidepressants may mitigate
against development of PSD.21,71 Studies have been mixed in terms of identifying any specific
best practice primarily due to heterogeneity of the designs, instruments, time courses and
populations. There is a lack of robust evidence to support the use of specific strategies to prevent
PSA and PSD.72 There may be a role for developing more personalized strategies incorporating
integrative interventions as improved studies are conducted.71 As mentioned earlier, social
support may be a protective factor in guarding against PTSD onset.63

Treatment
Many individuals surviving stroke are insufficiently or ineffectively treated for psychological
effects.73 Studies indicate that post-stroke depression may respond to a variety of treatments.74,75
Treatments of PSA and PS-PTSD are less well studied thus far.

Pharmacologic interventions
The bulk of research dedicated to treating mood disturbance after stroke focuses on
pharmacotherapies. Frank et al.70 reviewed numerous studies addressing the effects of various
antidepressants on PSD. They found that selective serotonin re-uptake inhibitors (SSRIs),
selective norepinephrine re-uptake inhibitors (SNRIs), bupropion, and tricyclic antidepressants
(TCAs) were effective in reducing depression scores compared with placebo or “treatment as
usual.” Time course in some of the studies was associated with differential effectiveness of
medication. The use of SSRI’s for treatment of PSD may improve recovery through
neuroprotective mechanisms and taming of inflammation, among other actions.70
It is well-known that not all depressed patients respond to pharmacological treatments.76 Also,
despite possible therapeutic response, in some cases the side effects are not well-tolerated. For
example, in the studies reviewed by Frank et al.,70 both SSRIs and SNRIs were often found to
produce uncomfortable physiological symptoms such as insomnia and sexual dysfunction. The
risk of intracerebral bleeding as well as gastrointestinal bleeding appears to be increased as
well.77,78
TCAs and Monoamine oxidase-inhibitors (MAOIs) are considered less preferred for
pharmacologic treatment due to side effects such as cardiac symptoms and preferential
responsivity.70
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In general, studies have suggested that antidepressants may improve mood, but the evidence is
mixed regarding whether antidepressants significantly facilitate participation in rehabilitation
and improvement in activities of daily living (ADLs).79 Not all post-stroke patients respond well
to medications.21 There is also no consensus as to the optimal pharmacologic agent, dosage, or
timing of administration. For patients with PSA, a Cochrane review indicated a dearth of high-
quality evidence to guide medication regimens.80
The limitations posed by pharmaceuticals suggest an important role for non-pharmacologic
treatments. A variety of interventions have been investigated.

Non-pharmacologic treatments

Cognitive-behavioral therapy (CBT)

Psychotherapeutic interventions, particularly CBT, have been studied in the PSD population.
CBT is a psychotherapeutic approach to help individuals learn how to identify and change
maladaptive thought patterns that negatively influence their behavior and emotions. This
therapeutic technique, whether delivered alone or in conjunction with antidepressant medication,
or in group formats, appears to decrease depression as well as anxiety symptoms that can
develop after stroke.81,82 However, the evidence for CBT as a treatment for PSD may be
inconclusive due to an array of qualitative and quantitative limitations inherent in the studies.
Wang and colleagues82 suggest the usefulness of high quality RCTs to address this potentially
beneficial treatment.
Related to CBT are treatments that appear potentially beneficial though not yet well studied.
These include problem-solving oriented therapies and motivational interviewing.83,84 Observed
results have been promising, but limited sample sizes and small effect sizes are problematic for
broader application until better designed studies are undertaken.

Neuromodulation
Non-invasive brain stimulation is a relatively recent treatment modality that may improve mood.
Neuromodulation techniques such as repetitive transcranial magnetic stimulation (rTMS) and
transcranial direct current stimulation (tDCS) have recently been used to treat depression in
patients without neurological disorders with beneficial outcomes.85 Recent studies with stroke
patients have reportedly demonstrated positive effects.70,86 Further research in this area seems
warranted.

Non-traditional therapies
Mind-body therapies, such as meditation, yoga, and tai chi, may be promising for offering relief
from emotional suffering after stroke. A review of mind-body interventions suggested a trend
toward beneficial psychological outcome but was not conclusive, possibly in part due to design
limitations and decreased power of the studies.73 Zou and colleagues87 concluded from their
analysis that yoga and tai chi are effective as “add-on” treatments to improve depression, ADLs,
and mobility. Most of the studies they reviewed were conducted in China. Chan and colleagues88
found that both yoga and exercise were significantly associated with a reduction in depression
symptoms over time; however, no remarkable group differences emerged. Both exercise and
yoga have been associated with positive mood and possible treatment of depression in
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individuals without stroke.89,90 Further study of these interventions for patients with PSD and
PSA may be worthwhile.
Other non-pharmacological therapies recently under study suggest positive trends, though more
rigorous design and replications are needed.83,86 These interventions include life review and
problem-solving therapy, music therapy, and robot-assisted neurorehabilitation.

Summary
The psychological effects of stroke such as depression, anxiety and post-traumatic stress disorder
are associated with decreased quality of life in many domains, which often impact interpersonal
relationships and participation in the community. PSD is one of the more common and better
studied complications that can have devastating consequences for the survivor, family, and other
interpersonal relationships. PSD is also associated with increased risk of stroke recurrence and
mortality. This unfortunate complication of stroke has implications for Delaware residents. The
population of Delaware is growing.91,92 Delaware’s proportion of senior residents is also
increasing.93 The incidence of strokes in our state is likely to increase, with concomitant effects
on emotional adjustment. Psychological sequelae of stroke such as PSD are treatable and perhaps
in the not-too-distant future, also preventable. Despite the promising trends in assessment and
therapies, the efforts to identify and treat emotionally afflicted patients following stroke are
suboptimal across the nation.
Ideally, all patients with stroke should be screened for potential post-stroke depression as
feasible. Screening at multiple time points over the course of a patient’s recovery appears to be
practical.94 Following initial screening, re-assessment at multiple specified time points across the
continuum of care (e.g., acute hospital care, rehabilitation transfer, discharge to subacute facility
or home) and at follow-up physician and outpatient rehabilitation therapy visits is helpful in
identifying and treating patients with psychological sequelae. The use of the PHQ-2 and PHQ-9
for this population appears to be supported in the literature. Clinician follow-up with a more
detailed clinical interview for those with positive mood screens can be arranged by a stroke care
team. In the State of Delaware, many of the hospitals and clinics have behavioral health
professionals available who can assist with emotional adjustment or can link patients to
providers in the community. Several of the hospitals also offer virtual or in-person support
groups for stroke survivors and their caregivers. Ongoing research addressing post-stroke
emotional sequelae is critical to optimizing the care that we clinicians provide to our patients
who may be suffering from the psychological effects of strokes. It is anticipated that the findings
from well-designed studies will help with prevention of these emotional disorders in addition to
refining effective treatments. These developments are anticipated to benefit Delaware residents
seeking care for the challenging effects of cerebrovascular disorders.
Dr. Devereux may be contacted at nancy.devereux@christianacare.org.

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