How should I manage acute attacks and preventive therapy for an adult with migraine, including medication options, dosing, contraindications, and non‑pharmacologic measures?

Management of Migraine in Adults

Acute Treatment Algorithm

First-Line Therapy for Mild-to-Moderate Attacks

Start with NSAIDs or acetaminophen as the initial treatment for mild-to-moderate migraine attacks. 1

• Ibuprofen 400–800 mg, naproxen sodium 500–825 mg, or aspirin 1000 mg are the recommended first-line agents with strong evidence for efficacy 1, 2
• Acetaminophen 1000 mg is an alternative when NSAIDs are contraindicated 1, 2
• Combination therapy (acetaminophen 250 mg + aspirin 250 mg + caffeine 65 mg) provides superior efficacy to single agents, achieving pain reduction in 59.3% of patients at 2 hours 1
• Administer medication as early as possible during the attack while pain is still mild, because early treatment dramatically improves outcomes: approximately 50% become pain-free at 2 hours versus only 28% when treatment is delayed until pain is moderate-to-severe 1

Escalation to Triptans for Moderate-to-Severe Attacks

Add a triptan to the NSAID regimen for moderate-to-severe attacks or when NSAIDs fail after 2–3 episodes. 1, 3

• Sumatriptan 50–100 mg PLUS naproxen sodium 500 mg is the strongest-rated combination, providing 130 additional patients per 1,000 who achieve sustained pain relief at 48 hours compared with either agent alone 1
• Alternative oral triptans include rizatriptan 10 mg (fastest oral triptan, reaching peak concentration in 60–90 minutes), eletriptan 40 mg, or zolmitriptan 2.5–5 mg 1, 3
• Subcutaneous sumatriptan 6 mg provides the highest efficacy (59% complete pain relief at 2 hours) with onset within 15 minutes, particularly effective for rapid progression to peak intensity or significant nausea/vomiting 1, 3
• Intranasal sumatriptan 5–20 mg or other nasal spray triptans are useful when significant nausea or vomiting is present 1

Adjunctive Antiemetic Therapy

Add metoclopramide or prochlorperazine 20–30 minutes before or with the acute medication to provide synergistic analgesia beyond antiemetic effects. 1, 3

• Metoclopramide 10 mg (oral or IV) provides direct analgesic effects through central dopamine receptor antagonism 1
• Prochlorperazine 10 mg IV or 25 mg oral/suppository offers comparable efficacy to metoclopramide 1
• Metoclopramide is contraindicated in pheochromocytoma, seizure disorder, GI bleeding, and GI obstruction 1
• Prochlorperazine carries additional risks of tardive dyskinesia, hypotension, and arrhythmias 1

Third-Line Options When Triptans Fail or Are Contraindicated

Try a different triptan first, because failure of one triptan does not predict failure of others; 25–81% of sumatriptan non-responders achieve pain relief with an alternative triptan. 3

If all triptans fail after adequate trials (2–3 headache episodes per agent), escalate to:

• Gepants (CGRP antagonists): ubrogepant 50–100 mg or rimegepant have no vasoconstriction, making them safe for patients with cardiovascular disease, uncontrolled hypertension, or cerebrovascular disease 1, 3
• Lasmiditan 50–200 mg is a 5-HT1F receptor agonist without vasoconstrictor activity, but patients cannot drive or operate machinery for 8 hours after use due to CNS effects (dizziness, somnolence) 1, 3
• Intranasal or IV dihydroergotamine (DHE) 0.5–1.0 mg has good evidence for efficacy as monotherapy 1

Parenteral Therapy for Severe Attacks or Emergency Department Presentation

The optimal IV "headache cocktail" combines metoclopramide 10 mg IV plus ketorolac 30 mg IV as first-line therapy. 1

• Ketorolac 30 mg IV (or 60 mg IM for patients <65 years) provides rapid onset with approximately 6 hours duration and minimal rebound headache risk 1
• Prochlorperazine 10 mg IV is an alternative to metoclopramide with comparable efficacy 1
• Dihydroergotamine (DHE) 0.5–1.0 mg IV can be repeated every hour up to 2 mg per day when NSAIDs are contraindicated 1
• DHE is contraindicated with concurrent triptan use within 24 hours, beta-blockers, uncontrolled hypertension, coronary artery disease, pregnancy, and sepsis 1

Critical Frequency Limitation to Prevent Medication-Overuse Headache

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, 3

• Medication-overuse headache occurs when NSAIDs/acetaminophen are used ≥15 days/month or triptans/combination analgesics are used ≥10 days/month 1
• If acute medication is needed more than twice weekly, initiate preventive therapy immediately 1, 3

Contraindicated Therapies

Avoid opioids (hydromorphone, codeine, oxycodone) and butalbital-containing compounds for migraine treatment because of questionable efficacy, high risk of medication-overuse headache, potential for dependence, and overall poorer long-term outcomes. 1, 3

• Opioids carry a two-fold higher risk of developing medication-overuse headache compared with NSAIDs and triptans 1
• If an opioid must be used (when all other evidence-based treatments are contraindicated, sedation is acceptable, and abuse risk has been addressed), butorphanol nasal spray has better evidence than other opioids 1

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Preventive Therapy

Indications for Initiating Preventive Therapy

Initiate preventive therapy when patients experience ≥2 migraine attacks per month with disability lasting ≥3 days, use acute medication more than twice weekly, have contraindications to or failure of acute treatments, or have uncommon migraine conditions (hemiplegic migraine, prolonged aura, migrainous infarction). 4

Additional factors prompting preventive treatment include significant adverse events from acute therapies, strong patient preference for prevention, and cost considerations 4

First-Line Preventive Medications

Beta-blockers without intrinsic sympathomimetic activity are the primary first-line oral preventives. 4

• Propranolol 80–240 mg/day (typically 160 mg once daily) is FDA-approved with strong randomized trial evidence 4
• Timolol 20–30 mg/day also has strong evidence for migraine prophylaxis 4
• Metoprolol, atenolol, and nadolol are supported by moderate-quality evidence 4

Topiramate 50–100 mg/day is the only oral preventive with strong RCT evidence specifically for chronic migraine and is preferred for patients with obesity because it promotes weight loss. 4

Candesartan is a first-line agent particularly useful for patients with comorbid hypertension 4

Second-Line Preventive Medications

Amitriptyline 30–150 mg/day is preferred when patients have comorbid depression, anxiety, or sleep disturbances, as it treats both migraine and mood disorders simultaneously. 4

• Amitriptyline lacks robust RCT evidence for chronic migraine prophylaxis; its efficacy is primarily demonstrated in episodic migraine and mixed migraine/tension-type headache 4

Sodium valproate 800–1500 mg/day or divalproex sodium 500–1500 mg/day are second-line options but are strictly contraindicated in women of childbearing potential due to teratogenic effects. 4

• Common adverse effects include weight gain, hair loss, tremor, and teratogenic potential 4

Third-Line Preventive Medications

CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) should be considered when 2–3 oral preventive medications have failed or are contraindicated. 4

• Administered monthly via subcutaneous injection (or quarterly for fremanezumab) 4
• Efficacy should be assessed after 3–6 months of treatment 4
• Annualized cost is $5,000–$6,000, significantly more expensive than oral agents 4

OnabotulinumtoxinA (Botox) 155–195 U injected across 31–39 sites every 12 weeks is the only FDA-approved preventive therapy specifically for chronic migraine (≥15 headache days per month). 1, 4

• Phase III PREEMPT trials demonstrated reduction in headache days, episodes, cumulative hours, and improved quality of life 1
• Efficacy should be evaluated after 6–9 months of treatment 1
• OnabotulinumtoxinA is specifically not recommended for episodic migraine prevention 4

Implementation Strategy

Start with a low dose and titrate slowly until clinical benefits are achieved or side effects limit further increases, with an adequate trial period of 2–3 months for oral agents. 4

• For CGRP monoclonal antibodies, efficacy requires 3–6 months 4
• For onabotulinumtoxinA, efficacy requires 6–9 months 1
• Use headache diaries to track attack frequency, severity, duration, disability, treatment response, and adverse effects 4

Consider tapering or discontinuing preventive treatment after 6–12 months of successful therapy to determine if it can be discontinued. 4

• A useful measure to quantify success is calculating the percentage reduction in monthly migraine days 4

Common Pitfalls in Preventive Therapy

• Do not maintain sub-therapeutic doses (e.g., propranolol <160 mg or amitriptyline <30 mg) indefinitely; doses should be optimized before declaring treatment failure 4
• Do not discontinue preventive therapy prematurely; an adequate trial requires 2–3 months at the target dose before assessing response 4
• Do not fail to recognize medication-overuse headache from frequent use of acute medications, which can interfere with preventive treatment 4

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Non-Pharmacologic Measures

Neuromodulatory devices, biobehavioral therapy (cognitive behavioral therapy, biofeedback, relaxation training), and acupuncture should be considered as adjuncts to medication or as stand-alone treatments when medications are contraindicated. 4

• Remote electrical neuromodulation has the strongest evidence for acute treatment 5
• Cognitive behavioral therapy, biofeedback, and relaxation training are effective adjuncts for migraine prevention 4

Identify and modify triggers through systematic tracking with a headache diary. 1, 4

• Modifiable triggers include sleep deprivation, stress, tobacco use, alcohol consumption, excessive caffeine intake, obesity, and obstructive sleep apnea 1, 4
• Weight loss can reduce migraine frequency in patients with obesity 4
• Stress management through behavioral interventions can modify responses to stressful events 4

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Special Populations

Pregnancy and Lactation

Acetaminophen 1000 mg is the safest first-line analgesic for intermittent headache during pregnancy. 1, 6

• NSAIDs may be used prior to the third trimester 6
• Opioids are reserved for refractory cases 6
• Valproate is strictly contraindicated due to teratogenic risk 4

Uncontrolled Hypertension

Acetaminophen 1000 mg is the safest and most appropriate first-line analgesic when hypertension is uncontrolled, because it does not raise blood pressure or cardiovascular risk. 1

• NSAIDs are contraindicated because they can further elevate blood pressure and increase cardiovascular risk 1
• Triptans are contraindicated in uncontrolled hypertension 1, 6

Cardiovascular Disease

Gepants (ubrogepant, rimegepant) or lasmiditan are the preferred acute treatments for patients with cardiovascular disease, uncontrolled hypertension, or cerebrovascular disease, because they have no vasoconstriction. 1, 3

• Triptans are contraindicated in ischemic heart disease, previous myocardial infarction, coronary artery vasospasm, uncontrolled hypertension, cerebrovascular disease, history of stroke or TIA, or basilar/hemiplegic migraine 1
• DHE is contraindicated in coronary artery disease 1

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Management of Medication-Overuse Headache in Chronic Migraine

Abrupt cessation of both the overused triptan and NSAID is recommended; evidence does not support a gradual taper. 1

• Patients should be warned that headache intensity may temporarily worsen for 2–10 days during withdrawal 1
• Substituting another acute medication during this period is discouraged because it merely transfers the overuse to a different agent 1

Initiate preventive therapy immediately with onabotulinumtoxinA (Botox) 155–195 U every 12 weeks, which is the only FDA-approved preventive therapy specifically for chronic migraine. 1

• Efficacy should be evaluated after 6–9 months of treatment 1
• Topiramate (higher dose/longer duration) is the only oral preventive with proven efficacy in randomized controlled trials for chronic migraine and should be considered if Botox cannot be accessed promptly 1

Once medication-overuse headache resolves (typically 2–4 weeks after discontinuation), acute treatment should be reserved for the most severe, disabling attacks and limited to ≤2 days per week. 1