What is the recommended acute prescription for an adult with episodic migraine and the first‑line preventive options if they have four or more migraine days per month?

Prescription for Episodic Migraine: Acute and Preventive Treatment

Acute Treatment for Episodic Migraine

For mild-to-moderate migraine attacks, start with an NSAID (naproxen 500–825 mg, ibuprofen 400–800 mg, or aspirin 1000 mg) or acetaminophen 1000 mg; for moderate-to-severe attacks or when NSAIDs fail after 2–3 episodes, use combination therapy with a triptan (sumatriptan 50–100 mg or rizatriptan 10 mg) PLUS an NSAID (naproxen 500 mg), which is superior to either agent alone. 1, 2

Acute Treatment Algorithm

First-line for mild-to-moderate attacks:

• NSAIDs: naproxen sodium 500–825 mg, ibuprofen 400–800 mg, or aspirin 1000 mg at migraine onset 1, 2
• Acetaminophen 1000 mg is an alternative when NSAIDs are contraindicated 1, 2
• Take medication early in the attack while pain is still mild for maximum effectiveness 2

First-line for moderate-to-severe attacks:

• Combination therapy: triptan PLUS NSAID provides 130 more patients per 1000 achieving sustained pain relief at 48 hours compared to either agent alone 2
• Sumatriptan 50–100 mg PLUS naproxen sodium 500 mg is the most evidence-based combination 2
• Alternative oral triptans: rizatriptan 10 mg (fastest oral triptan, peak in 60–90 minutes), eletriptan 40 mg, or zolmitriptan 2.5–5 mg 2, 3

For severe attacks with nausea/vomiting (non-oral routes):

• Subcutaneous sumatriptan 6 mg provides the highest efficacy (59% complete pain relief at 2 hours, onset within 15 minutes) 2, 3, 4
• Intranasal sumatriptan 5–20 mg or intranasal zolmitriptan are alternatives 2, 3

Second-line options when triptans are contraindicated:

• CGRP antagonists (gepants): ubrogepant 50–100 mg or rimegepant 75 mg have no vasoconstriction and are safe in cardiovascular disease 1, 2, 5, 3
• Lasmiditan 50–200 mg (5-HT1F agonist) is safe in cardiovascular disease but requires an 8-hour driving restriction due to CNS effects 2, 3
• Dihydroergotamine (DHE) intranasal or IV has good evidence for efficacy as monotherapy 1, 2

Critical Frequency Limitation to Prevent Medication-Overuse Headache

• Strictly limit all acute migraine medications to no more than 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
• If acute treatment is needed more than twice weekly, initiate preventive therapy immediately 1, 2, 6

Medications to Avoid

• Never use opioids (hydromorphone, oxycodone, codeine) or butalbital-containing compounds for migraine treatment due to questionable efficacy, high risk of dependency, medication-overuse headache, and loss of efficacy over time 1, 2, 3
• Reserve opioids only for cases where all other evidence-based treatments are contraindicated, sedation is acceptable, and abuse risk has been formally assessed 1, 2

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Preventive Therapy for ≥4 Migraine Days Per Month

Initiate preventive therapy immediately for patients with ≥4 migraine days per month, as this meets the threshold of ≥2 attacks per month producing disability, and begin with a beta-blocker (propranolol 80–240 mg/day or timolol 20–30 mg/day) as first-line due to the strongest evidence for efficacy. 2, 6, 7, 8

Indications for Preventive Therapy

• ≥2 migraine attacks per month producing disability lasting ≥3 days 2, 6
• Use of acute medication more than twice per week 2, 6
• Contraindication to or failure of acute treatments 2, 6
• Patient preference to reduce attack frequency 2

First-Line Preventive Medications

Beta-blockers (strongest evidence):

• Propranolol 80–240 mg/day (FDA-approved, most consistent evidence) 2, 6, 7, 8
• Timolol 20–30 mg/day (FDA-approved) 2, 8
• Metoprolol, atenolol, and nadolol have moderate-quality evidence 2, 8
• Contraindications: asthma, congestive heart failure, abnormal cardiac rhythms 8
• Common adverse effects: dizziness, fatigue 8

Anti-epileptic drugs:

• Topiramate 50–200 mg/day (FDA-approved, effective but higher adverse event rate) 2, 7, 8
• Divalproex sodium/sodium valproate 500–1500 mg/day (FDA-approved) 2, 8
• Strictly avoid valproate in women of childbearing potential due to teratogenic risk 2, 6
• Common adverse effects: weight gain, hair loss, tremor, cognitive slowing 2, 8

Tricyclic antidepressants:

• Amitriptyline 30–150 mg/day is preferred when patients have comorbid depression, anxiety, sleep disturbances, or mixed migraine plus tension-type headache 2, 6, 8
• Venlafaxine is an alternative antidepressant with evidence for migraine prevention 8

Second-Line Preventive Options

CGRP monoclonal antibodies:

• Consider when oral preventives have failed or are contraindicated 2, 6, 7
• Efficacy should be assessed after 3–6 months of treatment 2, 6
• Anti-CGRP monoclonal antibodies demonstrate the most consistent reduction in monthly migraine days (-3.2 to -4.4 days) with favorable tolerability 7

Gepants for prevention:

• Rimegepant 75 mg every other day reduced monthly migraine days by -0.8 days compared to placebo (Weeks 9–12), with 49.1% achieving ≥50% reduction in moderate-to-severe monthly migraine days 5

Timeline for Efficacy Assessment

• Oral preventive medications: 2–3 months 2
• CGRP monoclonal antibodies: 3–6 months 2, 6
• OnabotulinumtoxinA (for chronic migraine): 6–9 months 2

Common Pitfall to Avoid

• Do not allow patients to increase frequency of acute medication use while waiting for preventive therapy to take effect—this creates a vicious cycle of medication-overuse headache 2
• Failure of one preventive class does not predict failure of others; systematically trial different classes if the first choice is ineffective 2, 6