What is the recommended acute and preventive management for an adult with typical migraine attacks, including medication choices, contraindications, and lifestyle measures?

Migraine Management in Adults

Acute Treatment

First-Line Therapy for Mild to Moderate Attacks

For mild to moderate migraine attacks, start with NSAIDs (ibuprofen 400-800 mg, naproxen sodium 500-825 mg, or aspirin 1000 mg) or acetaminophen 1000 mg, taken at the first sign of headache while pain is still mild. 1

• Specific NSAIDs with strong evidence include ibuprofen, naproxen sodium, aspirin, and diclofenac potassium 1
• The combination of 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
• Take medication early in the attack for maximum effectiveness 2

Escalation to Triptan Therapy for Moderate to Severe Attacks

For moderate to severe attacks or when NSAIDs fail after 2-3 episodes, escalate to combination therapy with a triptan PLUS an NSAID taken simultaneously at migraine onset. 2

• The combination of sumatriptan 50-100 mg PLUS naproxen sodium 500 mg provides superior efficacy compared to either agent alone, with 130 more patients per 1000 achieving sustained pain relief at 48 hours 1, 2
• Alternative effective 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
• Subcutaneous sumatriptan 6 mg provides the highest efficacy (59% complete pain relief by 2 hours) with onset within 15 minutes, particularly useful for patients with rapid progression to peak intensity or significant nausea/vomiting 1
• Intranasal sumatriptan 5-20 mg is appropriate when significant nausea or vomiting is present 1

Adjunctive Antiemetic Therapy

Add metoclopramide 10 mg or prochlorperazine 25 mg orally 20-30 minutes before the triptan/NSAID to provide synergistic analgesia and improve outcomes. 1

• Metoclopramide provides direct analgesic effects through central dopamine receptor antagonism, not just antiemetic effects 1
• These antiemetics enhance absorption of co-administered medications by overcoming gastric stasis during migraine attacks 1

Intravenous Treatment for Severe Attacks

For severe migraine requiring IV treatment, use metoclopramide 10 mg IV PLUS ketorolac 30 mg IV as first-line combination therapy. 1

• Ketorolac has 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) IV or intranasal has good evidence for efficacy as monotherapy 1

Third-Line Options When Triptans Fail or Are Contraindicated

If triptans are contraindicated (ischemic heart disease, uncontrolled hypertension, cerebrovascular disease) or fail after adequate trials of multiple triptans, escalate to CGRP antagonists (gepants). 1

• Ubrogepant 50-100 mg or rimegepant 75 mg are recommended as third-line options with no vasoconstriction, making them safe for patients with cardiovascular disease 1, 3
• Lasmiditan 50-200 mg is a 5-HT1F receptor agonist without vasoconstrictor activity, but patients must not drive or operate machinery for at least 8 hours after taking it due to CNS effects 1
• Limit gepants to no more than 8 migraine attacks per 30-day period to prevent medication overuse headache 1

Critical Frequency Limitation to Prevent Medication-Overuse Headache

Strictly limit ALL acute migraine medications to no more than 2 days per week (approximately 8-10 days per month) to prevent medication-overuse headache (MOH). 1, 2, 4

• The threshold for MOH is ≥10 days per month for triptans and ≥15 days per month for NSAIDs 4
• MOH develops when acute medications are overused, leading to increasing headache frequency and potentially daily headaches 1, 4
• If acute treatment is needed more than twice weekly, immediately initiate preventive therapy 2

Medications to Absolutely Avoid

Never use opioids (hydromorphone, meperidine, codeine) or butalbital-containing compounds for routine migraine treatment. 1, 2

• These medications have questionable efficacy, lead to dependency, cause rebound headaches, and result in loss of efficacy over time 1, 2
• Reserve opioids only for cases where all other evidence-based treatments are contraindicated, sedation is acceptable, and abuse risk has been addressed 1

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Preventive Treatment

Indications for Preventive Therapy

Initiate preventive therapy immediately if the patient has ≥2 attacks per month producing disability for ≥3 days, uses acute medications more than 2 days per week, has contraindications to acute treatments, or continues to have impaired quality of life despite optimized acute therapy. 1, 2

• Preventive therapy reduces attack frequency by ≥50% and restores responsiveness to acute treatments 1
• Efficacy requires 2-3 months for oral agents, 3-6 months for CGRP monoclonal antibodies, and 6-9 months for onabotulinumtoxinA 1

First-Line Preventive Medications

Start with beta-blockers (propranolol 80-240 mg/day or timolol 20-30 mg/day), topiramate, divalproex sodium, or amitriptyline 30-150 mg/day as first-line preventive options. 1, 5

• Propranolol and timolol have consistent evidence of efficacy with mild to moderate adverse events 1, 5
• Amitriptyline is particularly appropriate for patients with mixed migraine and tension-type headache 1
• Topiramate and divalproex sodium are effective but may cause weight gain, hair loss, tremor, and are teratogenic (strictly contraindicated in pregnancy) 1, 5

Second-Line Preventive Options: CGRP Monoclonal Antibodies

For patients who fail at least two oral preventive medications, escalate to CGRP monoclonal antibodies (fremanezumab, erenumab, galcanezumab). 1, 6

• Fremanezumab (AJOVY) is administered as 225 mg subcutaneously monthly OR 675 mg (three consecutive 225 mg injections) every 3 months 6
• Allow fremanezumab to sit at room temperature for 30 minutes before injection; do not use if it has been at room temperature for 7 days or longer 6
• Assess efficacy after 3-6 months of treatment 1
• Contraindicated in patients with serious hypersensitivity to fremanezumab or excipients (anaphylaxis and angioedema have been reported) 6

Preventive Option for Chronic Migraine

For chronic migraine (≥15 headache days per month) after failing oral preventives, consider onabotulinumtoxinA with efficacy assessed after 6-9 months. 1

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Management of Medication-Overuse Headache (MOH)

Diagnosis and Withdrawal Strategy

If MOH develops (headache ≥15 days per month for at least 3 months due to regular overuse of acute medications), abruptly withdraw the overused medication—this is the necessary and only remedy for MOH. 4

• Complete cessation of analgesics is more feasible and effective than restricted intake, with a 44% reduction in medication dependence 4
• Non-opioid analgesics can be stopped abruptly without tapering; at least 1 month medication-free is required to determine effectiveness 4
• Warn patients explicitly that headaches will worsen before improving during withdrawal—this is temporary and expected, not treatment failure 4

Concurrent Preventive Therapy During Withdrawal

Start preventive medication on day 1 of withdrawal or even before stopping the overused medication. 4

• First-line preventive options during MOH withdrawal include topiramate, amitriptyline, or onabotulinumtoxinA 4
• For patients with hypertension, candesartan provides dual benefit for both migraine prophylaxis and blood pressure control 4
• Use prokinetic antiemetics (domperidone or metoclopramide) for nausea/vomiting during withdrawal rather than additional analgesics 4

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Lifestyle Measures and Non-Pharmacological Interventions

Educate patients on lifestyle modifications including adequate hydration, regular meals, sufficient sleep (consistent sleep schedule), regular physical activity, stress management techniques, and identifying/avoiding individual triggers. 4

• Behavioral treatments including biofeedback and relaxation training are recommended as first-line preventive options 1
• Acupuncture is a potential first-line intervention based on positive findings from randomized trials 1
• Riboflavin has shown efficacy in randomized trials and is considered a potentially useful first-line preventive intervention 1

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Special Populations

Pregnancy and Lactation

Acetaminophen is the safest acute migraine drug during pregnancy; sumatriptan may be an option for selected patients and is compatible with breast-feeding. 7

• Discuss adverse effects of pharmacologic treatments before initiating therapy during pregnancy and lactation 1
• Valproate is strictly contraindicated due to teratogenic risk 1

Contraindications to Triptans

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

• For these patients, use NSAIDs, combination analgesics (acetaminophen/aspirin/caffeine), dopamine antagonists (metoclopramide, prochlorperazine), or gepants (ubrogepant, rimegepant) 1