What are the diagnostic criteria and recommended acute and prophylactic treatment options for an adult migraine patient without major cardiovascular disease, uncontrolled hypertension, pregnancy, or severe psychiatric comorbidity?

Diagnosis and Treatment of Migraine

Diagnostic Criteria

Migraine diagnosis relies entirely on clinical history using ICHD-3 criteria—no imaging or laboratory testing is required unless red flags are present. 1

Migraine Without Aura

Requires at least five attacks fulfilling all of the following 1:

• Headache duration: 4–72 hours when untreated
• At least two pain characteristics:
  • Unilateral location
  • Pulsating quality
  • Moderate or severe intensity
  • Aggravation by routine physical activity 1
• At least one associated symptom:
  • Nausea and/or vomiting
  • Photophobia and phonophobia 1
• Not better explained by another diagnosis 1

Migraine With Aura

Requires at least two attacks with 1:

• Fully reversible aura symptoms: visual, sensory, speech/language, motor, brainstem, or retinal 1
• At least three characteristics:
  • At least one aura symptom spreads gradually over ≥5 minutes
  • Two or more aura symptoms occur in succession
  • Each aura symptom lasts 5–60 minutes
  • At least one aura symptom is unilateral
  • At least one aura symptom is positive (not just loss of function)
  • Aura accompanied by or followed by headache within 60 minutes 1

Chronic Migraine

Defined as ≥15 headache days per month for >3 months, with migraine features on ≥8 days per month. 1 Ask patients directly: "Do you feel like you have a headache of some type on 15 or more days per month?" because patients typically under-report milder headaches. 1

Medication-Overuse Headache (MOH)

Suspect when 1:

• Headache ≥15 days/month in someone with pre-existing headache disorder
• Regular overuse for >3 months: non-opioid analgesics on ≥15 days/month OR triptans/combination medications on ≥10 days/month 1

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Acute Treatment

First-Line: Mild to Moderate Attacks

For mild to moderate migraine, start with NSAIDs or acetaminophen; if inadequate after 2–3 episodes, escalate to triptans. 1

NSAIDs (choose one):

• Ibuprofen 400–800 mg 1, 2
• Naproxen sodium 500–825 mg 1, 2
• Aspirin 1000 mg 1, 2
• Diclofenac potassium 50–100 mg 3

Acetaminophen:

• 1000 mg (lower doses lack efficacy) 1, 2

Combination therapy for enhanced efficacy:

• Aspirin 500–1000 mg + acetaminophen 500 mg + caffeine 130 mg provides synergistic benefit 2, 3

First-Line: Moderate to Severe Attacks

Add a triptan to an NSAID for moderate to severe migraine—this combination is superior to either agent alone. 1

Oral triptans (choose one):

• Sumatriptan 50–100 mg (most evidence) 1, 2
• Rizatriptan 10 mg (fastest oral triptan, reaches peak in 60–90 minutes) 2
• Eletriptan 40 mg 2
• Zolmitriptan 2.5–5 mg 1
• Naratriptan 2.5 mg (longest half-life, may reduce recurrence) 2
• Almotriptan 12.5 mg 3
• Frovatriptan 2.5 mg 3

If one triptan fails after 2–3 episodes, try a different triptan—failure of one does not predict failure of others. 2

Non-oral routes for severe nausea/vomiting or rapid progression:

• Subcutaneous sumatriptan 6 mg (highest efficacy: 59% pain-free at 2 hours, onset within 15 minutes) 2
• Intranasal sumatriptan 5–20 mg 2
• Intranasal zolmitriptan 2

Adjunctive Antiemetics

Add metoclopramide or prochlorperazine 20–30 minutes before analgesics—they provide direct analgesic effects beyond treating nausea. 2

• Metoclopramide 10 mg (oral or IV) 1, 2
• Prochlorperazine 10 mg (oral or IV) or 25 mg (rectal) 1, 2

Second-Line: Refractory Attacks

For severe attacks unresponsive to NSAIDs and triptans:

• Dihydroergotamine (DHE) intranasal or IV 1, 2

IV "migraine cocktail" for emergency/urgent care:

• Metoclopramide 10 mg IV + ketorolac 30 mg IV (first-line combination) 2
• Alternative: Prochlorperazine 10 mg IV + ketorolac 30 mg IV 2

Third-Line: When Triptans Contraindicated or Failed

CGRP antagonists (gepants):

• Ubrogepant 50–100 mg 2
• Rimegepant 75 mg 2
• Zavegepant (intranasal) 2

5-HT1F agonist (ditan):

• Lasmiditan 50–200 mg (no vasoconstriction; do not drive for 8 hours after use) 2

Critical Frequency Limitation

Limit ALL acute medications to ≤2 days per week (≤10 days per month) to prevent medication-overuse headache. 1, 2 This applies to NSAIDs, triptans, acetaminophen, and all other acute agents. 1, 2 If acute treatment is needed more than twice weekly, initiate preventive therapy immediately. 2

Medications to Avoid

Never use opioids or butalbital-containing compounds for migraine—they have questionable efficacy, cause dependency, trigger rebound headaches, and lose effectiveness over time. 1, 2 Reserve opioids only when all other treatments are contraindicated, sedation is acceptable, and abuse risk has been formally assessed. 1, 2

Contraindications to Triptans and DHE

Triptans and DHE are contraindicated in 2:

• Ischemic heart disease or previous myocardial infarction
• Uncontrolled hypertension
• Cerebrovascular disease or history of stroke/TIA
• Basilar or hemiplegic migraine
• Peripheral vascular disease 2

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Preventive Therapy

Indications for Preventive Treatment

Initiate preventive therapy when 1:

• ≥2 migraine attacks per month producing disability lasting ≥3 days
• Acute medication use >2 days per week
• Contraindication to or failure of acute treatments
• Uncommon migraine conditions (hemiplegic, basilar)
• Patient preference or significant adverse effects from acute therapies 1

First-Line Preventive Medications

Beta-blockers without intrinsic sympathomimetic activity:

• Propranolol 80–240 mg/day (FDA-approved, strongest evidence) 1, 2
• Timolol 20–30 mg/day 1, 2
• Metoprolol, atenolol, nadolol (moderate evidence) 2

Antiepileptics:

• Topiramate 50–200 mg/day (preferred for patients with obesity due to weight loss effect; only oral preventive with RCT evidence for chronic migraine) 1
• Divalproex sodium/sodium valproate 500–1500 mg/day (strictly contraindicated in women of childbearing potential due to teratogenic risk) 1, 2

Tricyclic antidepressants:

• Amitriptyline 30–150 mg/day (preferred for comorbid depression, anxiety, sleep disturbances, or mixed migraine/tension-type headache) 1

Second-Line Preventive Medications

• Gabapentin 1200–2400 mg/day 1
• Tizanidine 2–8 mg/day 1
• Fluoxetine 20–40 mg/day 1

Third-Line: CGRP Monoclonal Antibodies

For chronic migraine when ≥2 oral preventives have failed:

• Erenumab 70–140 mg subcutaneous monthly 1
• Fremanezumab 225 mg subcutaneous monthly or 675 mg quarterly 1
• Galcanezumab 240 mg loading dose, then 120 mg monthly 1

Efficacy requires 3–6 months for assessment. 2

OnabotulinumtoxinA (Botox)

OnabotulinumtoxinA is the only FDA-approved therapy specifically for chronic migraine prophylaxis. 1 Administer 155–195 units across 31–39 injection sites every 12 weeks. 2 Efficacy requires 6–9 months for assessment. 1, 2 Reserve for patients who have failed ≥2 oral preventives. 1

Preventive Therapy Duration and Goals

• Goal: ≥50% reduction in attack frequency 2
• Continue effective preventive therapy for 6–12 months, then consider tapering 1
• Oral preventives require 2–3 months for efficacy assessment 2

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Management of Medication-Overuse Headache

When MOH is present, abruptly withdraw the overused medication—gradual taper is not supported by evidence (except for opioids). 1 Warn patients that headache may worsen for 2–10 days during withdrawal. 2 Simultaneously initiate preventive therapy; do not substitute another acute medication during withdrawal. 1, 2

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Special Populations: Pregnancy

Acute Treatment in Pregnancy

First-line: Acetaminophen 1000 mg 4, 3

Second-line (second trimester only): Ibuprofen or naproxen 4

For nausea: Metoclopramide 10 mg 4

Sumatriptan may be used sporadically under specialist supervision when other treatments fail (Swedish registry data show no increased malformation risk: OR 0.95% CI 0.80–1.12). 4

Strictly avoid:

• Ergotamine derivatives and DHE (oxytocic properties) 4
• Topiramate, candesartan, sodium valproate (teratogenic) 4
• Opioids and butalbital (dependency, rebound headaches, fetal harm) 4
• CGRP antagonists (insufficient safety data) 4

Preventive Therapy in Pregnancy

Best avoided; if absolutely necessary:

• Propranolol (best safety data) 4
• Amitriptyline (if propranolol contraindicated) 4

Postpartum and Breastfeeding

Acetaminophen, ibuprofen, and sumatriptan are considered safe during breastfeeding. 4 Propranolol is the preferred preventive agent. 4

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Comorbidities and Drug Selection

• Obesity: Topiramate (causes weight loss) 1
• Depression, anxiety, insomnia: Amitriptyline 1
• Hypertension: Beta-blockers, candesartan 1
• Cardiovascular disease: Avoid triptans and DHE; use NSAIDs, acetaminophen, gepants, or lasmiditan 2
• Uncontrolled hypertension: Acetaminophen 1000 mg (NSAIDs contraindicated) 2

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Common Pitfalls

• Do not abandon triptan therapy after a single failed attempt—try a different triptan or route of administration. 2
• Do not allow patients to increase acute medication frequency in response to treatment failure—this creates MOH. Instead, transition to preventive therapy. 2
• Do not prescribe opioids or butalbital simply because a patient requests them or reports "nothing else works" without ensuring adequate trials of NSAIDs, triptans, and combination therapy. 2
• Do not delay preventive therapy while trialing multiple acute strategies—this undermines timely control. 2
• Do not use valproate in women of childbearing potential—teratogenic risk is unacceptable. 1, 2