Migraines:

Diagnosis &
Management
J Dawe MD FRCPC
(Neurology)
April 29, 2022
Disclosures

• Clinical fellowship in Headache Medicine funded by the Canadian Headache

Society
• I will be mentioning off-label treatments
Disclaimer

• There is more to discuss about migraine and migraine management than can be
discussed in 20 minutes
• Email: jessica.dawe@dal.ca
 Red Flags for secondary causes of headache.

Recognition of migraine in primary care.

Principles of migraine management including non-

pharmacologic and pharmacologic strategies.

Objectives
About Migraine in Primary Care
• Although the most common primary headache worldwide is TTH, the most likely
headache disorder to be seen in any health care setting is migraine
o 94% of primary headache in clinical practice is migraine or probable migraine

• Lifetime prevalence for migraine is estimated at 14-16% (18% female, 9% male)

• Migraine attacks are often debilitating

o About 90% of patients with migraine report functional impairment
o 50% report severe headache and 75% report impaired function
o 1/3 report missing at least 1 day of work or school within 3-months
Approach to Patients Presenting With Headache
Investigate for
Secondary Causes /
Yes Treat Underlying
Condition

CC: Any Red

“Headache” Flags?
Yes

Determine Primary
Headache D/o Based on Any Unusual
No Pattern / Features Features?
+ Screen for Comorbidities
No

Develop Appropriate
Treatment Plan for
Primary Headache
Disorder
 “SNOOP” 4 Red Flags
• Systemic symptoms, signs, disease
• Neurologic symptoms/signs
• Onset
• Older
• Pattern change
• Papilledema
• Postural/positional/provoked
• Pregnancy and postpartum

Adapted from Dodick D.W., Adv Stud Med 2003; Semin Neurol 2010
 Migraine without Aura (ICHD-3)
A. At least five attacks fulfilling criteria B-D
B. Headache attacks lasting 4-72 hr (untreated or unsuccessfully
treated)
C. Headache has at least two of the following four characteristics:
1. Unilateral location
2. Pulsating quality
3. Moderate or severe pain intensity
4. aggravation by or causing avoidance of routine physical activity (eg,
walking or climbing stairs)
D. During headache at least one of the following:
1. Nausea and/or vomiting
2. photophobia and phonophobia
E. Not better accounted for by another ICHD-3 diagnosis.

https://ichd-3.org/1-migraine/
 Migraine with Aura (ICHD-3)
A. At least two attacks fulfilling C. At least three of the following six
criteria B and C characteristics:
B. One or more of the following 1. At least one aura symptom spreads
fully reversible aura gradually over ≥5 minutes
symptoms: 2. Two or more aura symptoms occur in
succession
1. Visual 3. Each individual aura symptom lasts 5-60
2. Sensory minutes
3. Speech and/or language 4. At least one aura symptom is unilateral
4. Motor 5. At least one aura symptom is positive
5. Brainstem 6. The aura is accompanied, or followed
6. Retinal within 60 minutes, by headache
D. Not better accounted for by
another diagnosis.

https://ichd-3.org/1-migraine/
 Screener for Migraine in Patients Complaining of Headache
(ID Migraine)

• Strongest predictors of migraine diagnosis

• Photophobia → Does light bother you when you have a headache?
• Impairment/Disability → Has a headache limited your activities for a day or
more in the last three months?
• Nausea → Are you nauseated or sick to your stomach when you have a
headache?

• 2/3 “yes” effectively identifies migraine sufferers:

• Sensitivity of 0.84, specificity of 0.76, Positive Predictive Value 93.3%

Lipton et al., 2003

 Reconsider “Sinus” Headache
• “Sinus headache” → term used to attribute facial pain to allergies
or a sinus infection; however, most sinus headaches are migraine
• Multiple studies suggest 50-80% of patients with self-identified sinus
headache likely have migraine

• Migraine
• Cranial autonomic symptoms (congestion, rhinorrhoea, and facial pain)
are very common in migraine, ranging from 26-71.3%
• Osmophobia with headache – 87.6% PPV for migraine

(Robblee & Secora, 2021)

 Lifestyle Factors &
Triggers

Comprehensive Acute
Migraine Headache
Management Management

Preventative
Headache
Management
Using a Migraine Diary
• Frequency, duration and severity of headaches
• How many headaches in total
• Associated features (aura, nausea, photophobia, etc.)
• Identify patterns/triggers
• Consider relationship to menstrual cycle
• Medication use and response
• Monitor for Medication Overuse
Lifestyle Counselling
• Adequate and good-quality sleep
• Sleep hygiene strategies; always screen for sleep apnea
• Maintaining good hydration
• 1.5-2L water daily
• Avoid irregular or skipped meals
• No specific diet has any evidence for efficacy, but individual patients may find
a specific diet helpful; protein with breakfast
• Caffeine limited to a modest level
• Regular physical activity
• Consistency is key; type irrelevant (yoga, cardio, strength/conditioning, etc.)
• Stress management
Acute Migraine
Medication
Principles of Acute Migraine Management
• Goal → Pain freedom 2hrs after treatment (or at least able to function at 2hrs)
• Evidence-based treatments should be used when possible
• Migraine attacks should be treated early

• Consider:
• Cost of medication – paying out of pocket vs. insurance; generic options
• Safety and tolerability – consider patient co-morbidities
• Patient preference
Strategies – Stepwise vs. Stratified

▪ Step care → treatment is escalated after first-line medications fail

▪ Either within an attack or across attacks over time
▪ i.e., start with behavioural strategies, then escalate to non-specific analgesics like
acetaminophen or Ibuprofen, then escalate to triptan

▪ Stratified care → initial treatment is based on patient judgement of severity or

other factors
▪ i.e., sudden-onset attack with associated nausea may be best managed with non-oral
triptan, gradual onset mild attack may respond to ibuprofen 400mg; patient dependant
 Acute Management of Migraine Guideline Summary

Medication AHS (2015) CHS (2013)

Acetaminophen 1000mg for milder attacks Level A Strong evidence

NSAIDs Level A Strong evidence

(Aspirin 500mg, Diclofenac 50-100mg,
Ibuprofen 400mg, Naproxen 500-550mg)
Triptans (entire class) Level A Strong evidence
Dihydroergotamine Level A/B Weak evidence;
May use first line in some cases
Codeine Level B/C Weak evidence; Should not use

Tramadol Level B Weak evidence; Should not use

(Adapted from: Ailani, 2021)

 Triptans
Medication Route of Administration + Dose
Tablet DT* Nasal Spray Injection

Sumitriptan 50mg, 100mg 10mg/20mg 6mg

Zolmitriptan 2.5mg 2.5mg 2.5mg/5mg
Rizatriptan 10mg 5mg/10mg
Eletriptan 20mg/40mg
Almotriptan 6.25mg/12.5mg
Naratriptan 1mg/2.5mg
Frovatriptan 2.5mg
*Disintegrating Tablet

(Adapted from: Worthington, 2013)

Prescribing Triptans
▪ Best if taken early in migraine attack → counsel patients to take at onset of pain
▪ If not pain-free at 2hrs, can repeat dose (Maximum of 2 doses in 24hrs)

▪ Common Side Effects: Nausea, vomiting, palpitations, chest tightness, chest pain, dizziness,
light-headedness, flushing, and worsening headache, tingling in fingertips, somnolence

▪ Contraindications: History of stroke, heart attack, coronary artery disease, hemiplegic

migraine, uncontrolled hypertension, migraine with brainstem aura, and peripheral vascular
disease
Combination Triptan + NSAID
▪ Evidence for use of combination sumatriptan + naproxen
▪ Effective for acute treatment of migraine compared to placebo
▪ Some studies also showing statistical superiority to sumatriptan or naproxen monotherapy

▪ Options:
• Two separate pills taken at the same time - Sumitriptan 50mg + Naproxen 500 mg
• RCT → 46% pain freedom at 2hrs
• One combination pill – Sumitriptan / Naproxen 85mg / 500mg
• 2xRCT → 57-65% pain freedom at 2 hrs
Medication Overuse Headache (MOH)
▪ Always educate patient on the risks of MOH
▪ Headache occurring on ≥15 d/mo. in a patient with a pre-existing headache
disorder and regular overuse for >3 months of one or more drugs that can be
taken for acute and/or symptomatic treatment of headache
▪ ≥ 10 d/mo. for ergot derivatives, triptans, opioids, combination analgesics, and a
combination of drugs from different classes that are not individually overused.
▪ ≥15 d/mo. for nonopioid analgesics, acetaminophen, and NSAIDs
Newer Options for Acute Management
• Lasmitidan – NOT AVAILABLE IN CANADA

• Gepants – Small molecule CGRP-receptor antagonists

• Ubrogepant, Rimegepant
• CGRP is a vasodilator; CGRP antagonists have not been shown to produce
vasoconstriction
• Not studied in patients with recent (within 6 months) vascular event (MI or stroke
• Could consider gepants in…
• Patient is ≥18y.o. with migraine with or without aura, and
• Either: (1) contraindication to or inability to tolerate triptans or (2) inadequate response to ≥2
oral triptans
Prophylactic
Migraine
Medication
When to Consider Reduction Strategies
1. ≥ 3 moderate or severe headache days a month when acute Rx are
not reliably effective
2. ≥ 8 headache days a month even if responsive to acute Rx (due to risk
of medication overuse headache)
3. Highly disabling migraine attacks (i.e., hemiplegic migraine or
migraine with brainstem aura)
4. Acute migraine treatment is ineffective or contraindicated
Goals of preventive/Reduction therapy:

1. Reduce the frequency, duration, and/or severity of attacks

2. Improve response to acute/abortive therapy

3. Decrease risk of episodic migraine progressing to chronic migraine

What Are the Options?
• Guidelines exist for selecting oral medications for reduction/prevention of
episodic migraine
• Many options including beta-blockers, anti-depressants, calcium-channel blockers,
antiseizure medications, supplements, etc.
• CGRP monoclonal antibodies approved after the most recently published guidelines

• Only 3 agents are approved for reduction/prevention of chronic migraine

• Topiramate, OnabotulinumtoxinA, and CGRP monoclonal antibodies
Strategies for Selecting Oral Medications
• First Time Strategy: Beta-blockers (propranolol, nadolol, metoprolol) or TCA
(amitriptyline, nortriptyline)
• Low Side Effect Strategy: Candesartan, Lisinopril, (or supplements)

• Comorbidities:
• Increased BMI Strategy: Topiramate
• Hypertension Strategy: Propranolol, nadolol, metoprolol, candesartan,
lisinopril
• Depression/Anxiety Strategy: Amitriptyline, venlafaxine, (nortriptyline)
• Other Monotherapy Options:
• Topiramate, Divalproex, Gabapentin, Flunarizine, Pizotifen, Verapamil
 Select Herbal/Nutritional Supplements

Name Common dosing Common SE AAN/AHS (2012) CHS Guidelines

(2012)
Magnesium 400-600mg daily or Diarrhea, cramping, Level B Strong
Citrate 200-300mg twice per bloating, nausea recommendation,
day low quality
Riboflavin (B2) 400mg once daily Bright yellow urine Level B evidence
discolouration
Coenzyme Q10 300mg once daily None reported Level C
Melatonin 3mg nightly Sedation, fatigue N/A N/A

(Adapted from: Burch, 2021)

 Select Oral Medications for Migraine Reduction
Medication Starting Dose Target Dose/Therapeutic Range AHS 2012 Guideline CHS 2012 Guideline
1st Propranolol 20mg twice daily 40-120mg twice daily Level A Strong recommendation,
Line High quality evidence
Metoprolol* 25mg twice daily 50-100mg twice daily Level A Strong recommendation,
High quality evidence
Nadolol* 40mg daily 80-160mg daily N/A Strong recommendation,
Moderate evidence
Amitriptyline* 10mg nightly 10-100mg nightly (usually 50mg) Level B Strong recommendation,
High quality evidence
2nd Topiramate 25mg daily 50mg twice daily Level A Strong recommendation,
Line High quality evidence
Candesartan* 4-8mg daily 16mg daily Level C Strong recommendation,
Moderate evidence
Gabapentin* 300mg daily 1200-1800mg/d in 3 divided doses Level U Strong recommendation,
Moderate evidence
Other Venlafaxine* 37.5mg daily 150mg daily Level B Weak recommendation,
Low quality evidence
Lisinopril* 5mg daily 10-40mg daily Level C Weak recommendation,
Low quality evidence
Pizotifen 0.5mg daily 1-2mg twice daily N/A Weak recommendation,
High quality evidence

* Off-label
(Becker et al., 2015; Holland et al., 2012; Pringsheim et al., 2012)
CGRP Monoclonal Antibodies
• Erenumab, Galcanezumab, Fremanezumab, Epitenezumab
• Newer therapy options, so not in 2012 guidelines

• Efficacy:
• Placebo-controlled RCTs have showed that CGRP monoclonal antibodies are effective for
both episodic and chronic migraine
• On average, 50% responder rates were around 50-60% in treatment groups (similar to
topiramate, propranolol, onabotunlinumtoxinA)
• Sustained benefit over 1-3 years reported (so far)
CGRP Monoclonal Antibodies
• Advantages:
• Does not interact with other medications
• Possibly less side effects or better tolerated
• Convenient – Monthly or Quarterly injections

• Disadvantages:
• Newer medication class; we may not know all adverse effects
• Expensive $$$
• Not tested in peds (trials ongoing) or >70 years of age

• Consider for patients who have an inability to tolerate or inadequate response

to 6-8 week trials of two conventional preventive therapies
OnabotulinumtoxinA
• Indication → Prophylaxis of chronic migraine (≥15 headache days/month) only
• Approval was based on strong evidence from PREEMPT I and II (2010)
• Most insurance companies require adequate trials of at least 2 oral prophylactic medications, or
contraindications to other prophylactic treatments

• Benefit → About 50-70% of patients have reduction of headache days ≥ 50% after 3 cycles
• Well tolerated; Main adverse effects include ptosis and neck pain

• Administration:
• 115-195 units over 35-39 injection sites based on PREEMPT protocol every 3 months
Final Thoughts
• Migraine is common, debilitating, often underdiagnosed and undertreated

• Comprehensive migraine management includes:

• Optimization of Lifestyle Factors
• Adequate Acute Treatment of migraine attacks
• Consider Preventative Treatment if indicated

• There are many options for migraine management, including new agents
References:
• Ailani, J. (2021). Acute Migraine Treatment. Continuum (Minneapolis, Minn.), 27(3), 597–612.
• Becker, W. J., Findlay, T., Moga, C., Scott, N. A., Harstall, C., & Taenzer, P. (2015). Guideline for primary care management of headache in adults. In
Canadian Family Physician (Vol. 61, Issue 8).
• Burch. (2021). Preventive Migraine Treatment. Continuum (Minneapolis, Minn.), 27(3), 613–632. https://doi.org/10.1212/CON.0000000000000957
• Diener, H., Holle-Lee, D., Nägel, S., Dresler, T., Gaul, C., Göbel, H., Heinze-Kuhn, K., Jürgens, T., Kropp, P., Meyer, B., May, A., Schulte, L., Solbach, K.,
Straube, A., Kamm, K., Förderreuther, S., Gantenbein, A., Petersen, J., Sandor, P., & Lampl, C. (2019). Treatment of migraine attacks and prevention of
migraine: Guidelines by the German Migraine and Headache Society and the German Society of Neurology. Clinical and Translational Neuroscience,
3(1), 2514183–. https://doi.org/10.1177/2514183X18823377
• Dodick. (2010). Pearls: Headache. Seminars in Neurology, 30(1), 074–081. https://doi.org/10.1055/s-0029-1245000
• Lipton, R. B., Dodick, D., Sadovsky, R., Kolodner, K., Endicott, J., Hettiarachchi, J., & Harrison, W. (2003). A self-administered screener for migraine in
primary care: The ID migraineTM validation study. Neurology, 61(3). https://doi.org/10.1212/01.WNL.0000078940.53438.83
• Lipton, R. B., Stewart, W. F., Stone, A. M., Láinez, M. J. A., & Sawyer, J. P. C. (2000). Stratified Care vs Step Care Strategies for Migraine: The Disability in
Strategies of Care (DISC) Study: A Randomized Trial. JAMA : the Journal of the American Medical Association, 284(20), 2599–2605.
https://doi.org/10.1001/jama.284.20.2599
• Pohl, H., Do, T. P., García‐Azorín, D., Hansen, J. M., Kristoffersen, E. S., Nelson, S. E., Obermann, M., Sandor, P. S., Schankin, C. J., Schytz, H. W., Sinclair, A.,
Schoonman, G. G., & Gantenbein, A. R. (2021). Green Flags and headache: A concept study using the Delphi method. Headache, 61(2), 300–309.
• Pringsheim T., Davenport WP, Mackie G, et al. Canadian Headache Society Guideline for Migraine Prophylaxis. Canadian Journal of Neurological
Sciences. 2012; 39 (2) Suppl 2:S1-62.
• Robblee, J., & Secora, K. A. (2021). Debunking Myths: Sinus Headache. Current Neurology and Neuroscience Reports, 21, 42–42.
https://doi.org/10.1007/s11910-021-01127-w/Published
• The American Headache Society Position Statement On Integrating New Migraine Treatments Into Clinical Practice. (2019). Headache, 59(1), 1–18.
https://doi.org/10.1111/head.13456
• Worthington, I., Pringsheim, T., Gawel, M. J., Gladstone, J., Cooper, P., Dilli, E., Aube, M., Leroux, E., & Becker, W. J. (2013). Canadian Headache Society
Guideline: Acute Drug Therapy for Migraine Headache. Canadian Journal of Neurological Sciences, 40(S3), S1–S3.
https://doi.org/10.1017/S0317167100118943
Bonus Slides
What to Ask About on History
• Headache onset and duration • Relationship of headache attacks to
• Thunderclap, head or neck trauma, precipitating factors
etc. • Stress, posture, cough, exertion, straining,
neck movement, jaw pain, etc
• Previous attacks
• Progression of symptoms • Headache severity/disability
• effect on work and family activities
• Days per month with headache
• Acute and preventive medications tried,
• Pain location response, and side effects
• Unilateral, bilateral, neck pain, etc. • Presence of coexistent conditions that
• Headache-associated symptoms might influence treatment choice
• Nausea, vomiting, photophobia, • Insomnia, depression, anxiety, hypertension,
conjunctival injection, rhinorrhea, etc. asthma, and history of heart disease or
stroke
Physical Exam in Headache
• Screening neurologic examination • Neck examination
• General assessment of mental status • Posture, range of motion, and palpation for
• Cranial nerve examination muscle tender points
• Assessment for unilateral limb weakness, • Blood pressure measurement
reflex asymmetry, and coordination in the
• If indicated by associated jaw complaints, an
arms
examination for temporomandibular disorders
• Assessment of gait and balance, including
• Assessment of jaw opening
tandem gait
• Palpation of muscles of mastication for
tender points
Ubrogepant
▪ Indication: acute treatment of migraine headache
▪ Dosing: 50mg/100mg tablet as needed, may take 2nd dose after 2 hours (Max 200mg/24hrs)

▪ Efficacy in 2 RCTs
▪ 2-hr pain freedom: 50mg = 19%, 100mg = 22% (placebo 12-14%)
▪ 2-hr freedom of MBS: 50mg = 38%, 100mg = 39% (placebo 28%)
▪ 2nd dose provided pain freedom at 2hr in 55% of pts

▪ Good safety and tolerability

▪ Most common AE → nausea, somnolence, and dry mouth
▪ No evidence of MOH, hepatotoxicity, or serious AEs
▪ 1 year follow-up study showed no new safety signals or side effects when used for ≤8 days per month
Rimegepant
▪ Indication: both acute and preventative treatment of episodic migraine
▪ Dosing: 75mg orally dissolving tablet as needed per 24hrs (Max 75mg/24hrs)

▪ Efficacy and tolerability in multiple RCTs

▪ 2-hr pain freedom: 20-21% (placebo 11-12%)
▪ 2-hr freedom of MBS: 35% (placebo 25%)
▪ Good safety and tolerability when used for up to 1 year
▪ Most common AE → nausea
▪ Does not constrict blood vessels
▪ Does not appear to be associated with MOH taken up to 15d/month
Atogepant
▪ Indication: prevention of episodic migraine in adults
▪ Trial for chronic migraine ongoing
▪ Dosing: 10mg, 30mg, 60mg daily

▪ Efficacy in RCT
▪ Reduction of mean number of migraine days per month of >50% → 55-60% (placebo 29%)
▪ Rapidly reaches peak plasma concentrations in 1-2 hrs
▪ Most common AE → constipation, nausea
▪ Largely eliminated within approximately 2 days