What are the recommended acute and preventive medications for an adult with typical episodic migraine?

Recommended Medications for Adult Episodic Migraine

Acute Treatment

For mild-to-moderate migraine attacks, start with NSAIDs (ibuprofen 400–800 mg, naproxen sodium 500–825 mg, or aspirin 1000 mg) as first-line therapy; for moderate-to-severe attacks or when NSAIDs fail after 2–3 episodes, escalate to combination therapy with a triptan plus an NSAID, which provides superior efficacy compared to either agent alone. 1, 2

First-Line Acute Medications

NSAIDs (Mild-to-Moderate Attacks):

• Ibuprofen 400–800 mg at migraine onset 1, 3
• Naproxen sodium 500–825 mg at onset 1, 3
• Aspirin 1000 mg at onset 1, 3
• Combination: Acetaminophen 1000 mg + Aspirin 500–1000 mg + Caffeine 130 mg achieves pain reduction to mild or none in 59.3% of patients at 2 hours 1

Triptans (Moderate-to-Severe Attacks):

• Sumatriptan 50–100 mg (oral) 1, 4, 3
• Rizatriptan 10 mg (fastest oral triptan, peak concentration in 60–90 minutes) 1, 5
• Eletriptan 40 mg (more effective with fewer adverse reactions than sumatriptan) 5, 4
• Zolmitriptan 2.5–5 mg (oral or nasal spray) 1, 4
• Naratriptan (longest half-life, may decrease recurrence headaches) 5, 4

Optimal Combination Therapy

The American College of Physicians strongly recommends sumatriptan 50–100 mg PLUS naproxen sodium 500 mg for moderate-to-severe migraine, yielding 130 additional patients per 1,000 who achieve sustained pain relief at 48 hours compared to sumatriptan alone. 1, 2

• This combination has a number-needed-to-treat of 3.5 for headache relief at 2 hours 1
• Treating early (when pain is mild) results in ≈50% pain-free at 2 hours versus ≈28% when delayed 1
• Alternative NSAID options include aspirin, celecoxib, diclofenac, or ibuprofen if naproxen is unavailable 2

Non-Oral Routes (When Nausea/Vomiting Present)

• Subcutaneous sumatriptan 6 mg provides highest efficacy (59% complete pain relief by 2 hours, onset within 15 minutes) 1, 4
• Intranasal sumatriptan 5–20 mg 1, 4
• Intranasal or IV dihydroergotamine (DHE) 0.5–1.0 mg (good evidence for efficacy as monotherapy) 1, 5, 4

Second-Line Options (When First-Line Fails)

If triptans fail after 2–3 episodes, try a different triptan first—failure of one does not predict failure of others. 1, 5

CGRP Antagonists (Gepants):

• Ubrogepant 50–100 mg 1, 5
• Rimegepant 1, 5
• Zavegepant 2, 5
• These are third-line options for patients who do not tolerate or have inadequate response to triptan-NSAID combinations 1, 2

Lasmiditan (Ditan):

• Lasmiditan 50–200 mg (5-HT1F agonist without vasoconstriction, safe in cardiovascular disease) 1, 5
• Warning: Patients must not drive or operate machinery for at least 8 hours due to CNS effects 1

Adjunctive Antiemetics

• Metoclopramide 10 mg IV/oral (provides direct analgesic effects beyond antiemetic properties) 1, 2
• Prochlorperazine 10 mg IV/oral (comparable efficacy to metoclopramide) 1, 2
• Give 20–30 minutes before NSAID for synergistic analgesia 1

Critical Frequency Limitation

Limit all acute migraine medications to ≤2 days per week (≤10 days per month) to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches. 1, 2, 6, 3

• NSAIDs/acetaminophen: ≤15 days/month 2
• Triptans/combination analgesics: ≤10 days/month 1, 2
• If acute treatment needed more than twice weekly, initiate preventive therapy immediately 1, 2

Medications to Absolutely Avoid

Never use opioids (hydrocodone, oxycodone, morphine, codeine, tramadol) or butalbital-containing compounds for migraine—they provide questionable efficacy, carry high risk of dependence, cause rebound headaches, and worsen long-term outcomes. 1, 2, 5, 6, 4, 3

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Preventive Treatment

Initiate preventive therapy when a patient experiences ≥2 migraine attacks per month producing disability lasting ≥3 days, uses acute medication >2 days per week, has contraindications to or failure of acute treatments, or expresses strong preference for prevention. 1, 7, 8

First-Line Preventive Medications

Beta-Blockers (Without Intrinsic Sympathomimetic Activity):

• Propranolol 80–240 mg/day (FDA-approved, strong RCT evidence) 1, 7
• Timolol 20–30 mg/day (strong evidence) 1, 7
• Metoprolol, atenolol, nadolol (moderate evidence) 1

Antiepileptics:

• Topiramate (documented high efficacy, mild-to-moderate adverse events) 1, 7
• Divalproex sodium/sodium valproate 500–1500 mg/day (high efficacy but strictly contraindicated in women of childbearing potential due to teratogenic risk) 1, 7

Tricyclic Antidepressants:

• Amitriptyline 30–150 mg/day (preferred when comorbid depression, anxiety, sleep disturbances, or mixed migraine/tension-type headache) 1, 7

Second-Line Preventive Options

CGRP Monoclonal Antibodies:

• Erenumab (Aimovig) 70–140 mg subcutaneous once monthly 9
  • In clinical trials, 140 mg dose achieved 50% reduction in monthly migraine days in 50% of patients versus 26.6% with placebo 9
  • Efficacy assessed after 3–6 months of treatment 1
• Fremanezumab, galcanezumab (when oral preventives fail or are contraindicated) 1, 8

OnabotulinumtoxinA (Botox):

• 155–195 units injected across 31–39 sites every 12 weeks 1
• Only FDA-approved preventive specifically for chronic migraine (≥15 headache days/month) 1, 8
• Efficacy assessed after 6–9 months 1

Additional Preventive Options (Lower Evidence)

• Calcium channel antagonists (mild-to-moderate adverse events, lower documented efficacy) 7
• Gabapentin (mild-to-moderate adverse events, lower documented efficacy) 7
• Riboflavin (potentially useful first-line preventive, more than one positive RCT) 1, 7

Preventive Therapy Principles

• Start at low dose and titrate gradually 7
• Give each treatment an adequate trial: 2–3 months for oral agents 1, 7
• Avoid interfering, overused, and contraindicated drugs 7
• Re-evaluate therapy regularly (every 6–12 months) 1
• Ensure women of childbearing potential are aware of teratogenic risks (especially valproate) 1, 7
• Consider comorbidities when selecting preventive medication 7

When to Refer to Headache Specialist

• Diagnosis uncertain 1
• All treatments have failed 1
• Need for onabotulinumtoxinA administration 1
• Refractory chronic migraine requiring comprehensive management 1

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Common Pitfalls to Avoid

1. Delaying triptan use until pain is severe—early treatment (when pain is mild) doubles pain-free response rates 1
2. Abandoning triptan therapy after single failure—try different triptans, as failure of one does not predict failure of others 1, 5
3. Allowing patients to increase acute medication frequency—this creates medication-overuse headache; transition to preventive therapy instead 1, 2
4. Prescribing opioids or butalbital "because nothing else works"—ensure adequate trials of NSAIDs, triptans, and combination therapy first 1, 2, 3
5. Not initiating preventive therapy when acute medication use exceeds 2 days/week—this threshold mandates prevention 1, 2