What are the recommended acute and preventive treatment options for an adult patient with typical episodic migraine?

Migraine Management in Adults

Acute Treatment for Episodic Migraine

For mild-to-moderate migraine attacks, start with NSAIDs (ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 1000 mg) or acetaminophen 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 (sumatriptan 50-100 mg) PLUS an NSAID (naproxen 500 mg), which is superior to either agent alone. 1, 2

First-Line Acute Treatment Algorithm

• Mild-to-moderate attacks: Begin with NSAIDs—ibuprofen 400-800 mg, naproxen sodium 500-825 mg, or aspirin 1000 mg—taken at the earliest sign of headache while pain is still mild. 1, 2
• Alternative for NSAID intolerance: Acetaminophen 1000 mg (lower doses of 500-650 mg lack statistical efficacy). 2
• Moderate-to-severe attacks or NSAID failure: Escalate to sumatriptan 50-100 mg PLUS naproxen sodium 500 mg—this combination provides 130 additional patients per 1,000 achieving sustained pain relief at 48 hours compared to sumatriptan alone, with a number-needed-to-treat of 3.5 for 2-hour headache relief. 1, 2
• Early treatment is critical: Treating when pain is mild yields ~50% pain-free response at 2 hours versus ~28% when delayed until pain is moderate-to-severe. 1, 2

Alternative Triptan Options

• If sumatriptan fails after 2-3 episodes, try a different triptan—failure of one does not predict failure of others. 2, 3
• Rizatriptan 10 mg reaches peak concentration in 60-90 minutes (fastest oral triptan). 2
• Eletriptan 40 mg or zolmitriptan 2.5-5 mg are reportedly more effective with fewer adverse reactions than sumatriptan. 2
• Naratriptan has the longest half-life, potentially decreasing recurrence headaches. 2

Non-Oral Routes for Severe Nausea/Vomiting

• Subcutaneous sumatriptan 6 mg provides the highest efficacy (59% complete pain relief at 2 hours) with onset within 15 minutes—use when oral route is compromised or attacks rapidly reach peak intensity. 2, 4
• Intranasal sumatriptan 5-20 mg is an alternative when IV access is unavailable. 2, 4

Third-Line Options When Triptans Are Contraindicated or Ineffective

• CGRP antagonists (gepants): Ubrogepant 50-100 mg or rimegepant—no vasoconstriction, safe in cardiovascular disease, uncontrolled hypertension, or cerebrovascular disease. 1, 2
• Lasmiditan 50-200 mg (5-HT1F agonist without vasoconstrictor activity)—requires 8-hour driving restriction due to CNS effects (dizziness, somnolence). 2

Parenteral Options for Emergency/Urgent Care Settings

• Metoclopramide 10 mg IV PLUS ketorolac 30 mg IV is the most evidence-based IV combination—metoclopramide provides direct analgesic effects through central dopamine antagonism (not just antiemetic), and ketorolac offers rapid onset with 6-hour duration and minimal rebound risk. 2, 4
• Prochlorperazine 10 mg IV has comparable efficacy to metoclopramide with a more favorable side-effect profile (21% vs. 50% adverse events). 2, 4
• Dihydroergotamine (DHE) 0.5-1.0 mg IV (can repeat hourly up to 2 mg/day) or intranasal has good evidence as monotherapy—contraindicated with concurrent triptans within 24 hours, beta-blockers, uncontrolled hypertension, coronary artery disease, pregnancy, or sepsis. 2, 4

Critical Frequency Limitation to Prevent Medication-Overuse Headache

• Limit ALL acute migraine medications to ≤2 days per week (≤10 days per month)—exceeding this threshold paradoxically increases headache frequency and can lead to daily headaches. 1, 2, 4
• If acute treatment is needed >2 days/week, initiate preventive therapy immediately. 1, 4

Medications to Absolutely Avoid

• Opioids (hydromorphone, oxycodone, codeine) and butalbital-containing compounds should not be used—they have questionable efficacy, lead to dependency, cause rebound headaches, and result in loss of efficacy over time. 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; if an opioid must be used, butorphanol nasal spray has better evidence than other opioids. 2

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Preventive Therapy for Episodic Migraine

Initiate preventive therapy when patients experience ≥2 migraine attacks per month producing disability lasting ≥3 days, use acute medication >2 days per week, have contraindications to or failure of acute treatments, or express strong preference for prevention. 1, 4, 5

Indications for Preventive Therapy

• ≥2 migraine attacks per month with disability lasting ≥3 days. 1, 4
• Acute medication use >2 days per week (to prevent medication-overuse headache). 1, 4
• Failure, contraindication, or intolerable side effects from acute medications. 1, 5
• Special circumstances: hemiplegic migraine or other uncommon migraine conditions. 1, 5
• Patient preference for a preventive approach. 1, 5

First-Line Preventive Medications (Based on 2025 ACP Guidelines)

The 2025 American College of Physicians guideline emphasizes cost as a key factor when choosing among treatments with similar net benefits, recommending less costly options first. 1

• Beta-blockers without intrinsic sympathomimetic activity:

  • Propranolol 80-240 mg/day (FDA-approved, strongest evidence). 1, 4, 6, 7
  • Timolol 20-30 mg/day (strong evidence). 1, 6
  • Metoprolol, atenolol, nadolol (moderate evidence). 1, 6

• Antiseizure medications:

  • Topiramate (proven efficacy, but adverse events include weight gain, cognitive effects). 1, 6, 7
  • Divalproex sodium/valproate 500-1500 mg/day (proven efficacy, but strictly contraindicated in women of childbearing potential due to teratogenic risk). 1, 6, 7

• Tricyclic antidepressant:

  • Amitriptyline 30-150 mg/day (particularly useful for comorbid depression, anxiety, sleep disturbances, or mixed migraine and tension-type headache). 1, 6, 7

Second-Line Preventive Options (When First-Line Fails or Is Not Tolerated)

• ACE inhibitor: Lisinopril (limited evidence from small studies, but some efficacy). 1
• Angiotensin II-receptor blockers (ARBs): Candesartan or telmisartan (limited evidence from small studies). 1
• SSRI: Fluoxetine (limited evidence from small studies). 1

Third-Line Preventive Options (For Refractory or Chronic Migraine)

• CGRP monoclonal antibodies: Eptinezumab, erenumab, fremanezumab, or galcanezumab—assess efficacy after 3-6 months; consider when oral preventives have failed or are contraindicated. 1, 4
• CGRP antagonist-gepants: Atogepant or rimegepant (for prevention). 1
• OnabotulinumtoxinA (Botox): The only FDA-approved preventive therapy specifically for chronic migraine (≥15 headache days/month)—administer 155-195 U across 31-39 sites every 12 weeks; assess efficacy after 6-9 months. 4

Preventive Therapy Principles

• Start at a low dose and gradually titrate until desired outcomes are achieved or intolerable side effects occur. 1
• Give each treatment an adequate trial: generally 2-3 months for oral agents, 3-6 months for CGRP monoclonal antibodies, 6-9 months for onabotulinumtoxinA. 1, 4
• Switch medications if inadequate response after a reasonable trial period or if adverse events occur. 1
• Emphasize adherence—improvement occurs gradually, often becoming apparent after the first few weeks. 1
• Use a headache diary (paper or smartphone) to determine treatment efficacy, identify analgesic overuse, and monitor migraine progression. 1, 4
• Discuss adverse effects during pregnancy and lactation in people of childbearing potential before initiating therapy. 1

Non-Pharmacologic Adjuncts

• Behavioral interventions (cognitive behavioral therapy, relaxation training, mindfulness-based treatment, biofeedback) may decrease migraine frequency and improve disability. 1
• Lifestyle modifications: Identify and mitigate modifiable triggers (sleep deprivation, stress, dehydration, irregular physical activity, tobacco, alcohol). 1, 4

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Common Pitfalls and Caveats

• Do not allow patients to increase acute medication frequency in response to treatment failure—this creates a vicious cycle of medication-overuse headache; instead, transition to preventive therapy while optimizing acute treatment strategy. 2, 4
• Failure of one triptan does not predict failure of others—try at least 2-3 different triptans (each for 2-3 episodes) before abandoning the class. 2, 3
• Never use triptans and ergotamines (Cafergot, DHE) within 24 hours of each other due to additive vasoconstrictive effects. 2
• Triptans are contraindicated in ischemic heart disease, previous myocardial infarction, coronary artery vasospasm, uncontrolled hypertension, cerebrovascular disease, history of stroke/TIA, basilar or hemiplegic migraine. 2
• Metoclopramide and prochlorperazine are contraindicated in pheochromocytoma, seizure disorder, GI bleeding, GI obstruction, or CNS depression. 2
• Avoid NSAIDs in uncontrolled hypertension, renal impairment (CrCl <30 mL/min), aspirin/NSAID-induced asthma, or active GI bleeding. 2
• Medication-overuse headache (MOH) is defined as: acute medication use ≥10 days/month for triptans/ergots/combination analgesics or ≥15 days/month for NSAIDs/acetaminophen for >3 months. 2, 4
• If MOH is present, abrupt cessation of the overused medication is recommended (not gradual taper)—warn patients of 2-10 days of transient worsening—and initiate preventive therapy simultaneously. 4

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Special Populations

• Women of childbearing potential: Discuss teratogenic risks—valproate is strictly contraindicated; topiramate carries risk; propranolol and amitriptyline are generally safer options. 1, 7
• Pregnant or breastfeeding patients: Discuss adverse effects of all pharmacologic treatments; acetaminophen is the safest acute option. 1, 2
• Patients with cardiovascular disease: Avoid triptans and ergotamines; use gepants (ubrogepant, rimegepant) or lasmiditan as alternatives. 2
• Patients with uncontrolled hypertension: Avoid NSAIDs and triptans; use acetaminophen 1000 mg for acute treatment. 2