What are the recommended acute and preventive treatment options for migraine, including medication choices, dosages, and lifestyle modifications?

Migraine Treatment: Acute and Preventive Management

Acute Treatment Algorithm

For mild-to-moderate migraine attacks, start with NSAIDs (ibuprofen 400-800 mg, naproxen 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 NSAID, which provides superior efficacy with a number-needed-to-treat of 3.5. 1, 2

First-Line Acute Treatment

• NSAIDs are the initial choice for most patients, with the strongest evidence supporting aspirin, ibuprofen, naproxen sodium, and the combination of acetaminophen plus aspirin plus caffeine. 1
• Acetaminophen alone lacks evidence for migraine efficacy and should not be used as monotherapy. 1
• Treat early when pain is still mild—this achieves pain freedom in approximately 50% of patients at 2 hours versus only 28% when treatment is delayed until pain is moderate or severe. 2

Second-Line: Triptan Therapy

• When NSAIDs fail after 2-3 headache episodes, add a triptan to the NSAID regimen rather than using either agent alone. 1, 2
• Oral triptans with proven efficacy include sumatriptan 50-100 mg, rizatriptan 10 mg, naratriptan, zolmitriptan 2.5-5 mg, and eletriptan 40 mg. 1, 2
• Subcutaneous sumatriptan 6 mg provides the highest efficacy (59% pain-free at 2 hours) with onset within 15 minutes, making it ideal for severe attacks or when rapid progression occurs. 1, 2
• If one triptan fails, try a different triptan—failure of one does not predict failure of others. 1, 2

Route Selection Based on Symptoms

• Select non-oral routes (intranasal or subcutaneous triptans) when significant nausea or vomiting is present early in the attack. 1
• Intranasal sumatriptan 5-20 mg or DHE nasal spray are effective alternatives when oral administration is not feasible. 1, 2

Antiemetic Adjuncts

• Metoclopramide 10 mg IV or oral provides direct analgesic effects beyond its antiemetic properties through central dopamine receptor antagonism. 1, 2
• Prochlorperazine 10 mg IV is equally effective to metoclopramide and should not be restricted only to patients who are vomiting—nausea itself warrants treatment. 1, 2
• Administer antiemetics 20-30 minutes before NSAIDs or triptans to enhance absorption and provide synergistic analgesia. 2

Critical Frequency Limitation

• 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
• If acute treatment is needed more than twice weekly, immediately initiate preventive therapy. 1, 2

Medications to Absolutely Avoid

• Never use opioids (hydromorphone, morphine, codeine, tramadol) or butalbital-containing compounds for migraine—they provide questionable efficacy, cause dependency, precipitate rebound headaches, and worsen long-term outcomes. 1, 2
• Reserve opioids only for cases where all other evidence-based treatments are contraindicated, sedation is acceptable, and abuse risk has been formally assessed. 1

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Preventive Treatment Algorithm

Initiate preventive therapy when patients experience ≥2 migraine attacks per month producing disability lasting ≥3 days, use acute medications more than twice weekly, or have contraindications to acute treatments. 1

First-Line Preventive Agents

• Propranolol 80-240 mg/day is the first-line preventive agent with the strongest evidence base, FDA approval, and favorable cost-benefit profile. 1, 3, 4
• Timolol 20-30 mg/day has equally strong evidence for migraine prevention. 1
• Amitriptyline 30-150 mg/day is preferred when patients have comorbid depression, anxiety, sleep disturbances, or mixed migraine plus tension-type headache. 1, 3
• Divalproex sodium 500-1500 mg/day or sodium valproate 800-1500 mg/day are effective but must be strictly avoided in women of childbearing potential due to teratogenic risk. 1
• Topiramate has proven efficacy for episodic and chronic migraine but requires counseling about teratogenic effects and effective contraception in women of childbearing age. 1, 3

Choosing Among First-Line Agents

• Start with propranolol unless contraindications exist (asthma, heart failure, significant bradycardia, second or third-degree heart block). 3, 4
• Choose amitriptyline for patients with comorbid depression, anxiety, insomnia, or mixed headache types. 1, 3
• Avoid valproate entirely in women who could become pregnant. 1, 3
• Beta-blockers with intrinsic sympathomimetic activity (e.g., pindolol) are ineffective and should be avoided. 3, 4

Second-Line Preventive Options

• Flunarizine 5-10 mg/day is designated as second-line therapy after beta-blockers, topiramate, and valproate fail or are not tolerated. 3
• Flunarizine is absolutely contraindicated in patients with Parkinsonism or depression and can cause extrapyramidal symptoms, particularly in elderly patients. 3

Third-Line: Advanced Therapies

• CGRP monoclonal antibodies (fremanezumab 225 mg monthly or 675 mg quarterly, erenumab, galcanezumab) are reserved for patients who have failed three oral preventives. 5, 6
• OnabotulinumtoxinA 155-195 units every 12 weeks is the only FDA-approved preventive therapy specifically for chronic migraine (≥15 headache days per month). 2
• Efficacy of CGRP antibodies should be assessed after 3-6 months; onabotulinumtoxinA requires 6-9 months for full evaluation. 3, 2

Treatment Duration and Monitoring

• Allow 2-3 months at therapeutic dose before declaring treatment failure—clinical benefits may not manifest immediately. 1, 3, 4
• Use a headache diary to track attack frequency, severity, duration, disability, medication use, and adverse effects. 1
• After a period of stability (typically 6-12 months), consider tapering or discontinuing preventive therapy. 1, 4
• Reassess treatment every 6-12 months to adjust management as needed. 2, 4

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Lifestyle Modifications and Non-Pharmacologic Interventions

• Identify and avoid modifiable triggers including sleep deprivation, stress, excessive caffeine intake, alcohol, and specific dietary triggers. 2
• Address comorbidities that perpetuate migraine: obesity, obstructive sleep apnea, depression, anxiety, and uncontrolled hypertension. 2
• Behavioral interventions including biofeedback, relaxation training, and cognitive behavioral therapy are recommended as adjuncts to pharmacologic treatment, particularly in children and adolescents. 1, 2
• Maintain regular sleep schedules and avoid both sleep deprivation and excessive sleep. 2

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Special Populations

Children and Adolescents

• Ibuprofen is first-line for acute treatment in children and adolescents. 1
• In adolescents, consider sumatriptan/naproxen combination oral, zolmitriptan nasal, sumatriptan nasal, rizatriptan ODT, or almotriptan oral. 1
• For prevention, discuss with families that placebo was as effective as studied medications in many pediatric trials. 1
• Propranolol is specifically recommended for pediatric migraine prevention. 1, 3
• Amitriptyline combined with cognitive behavioral therapy has evidence for pediatric prevention. 1
• Topiramate and valproate require counseling about teratogenic effects in adolescent females and mandatory effective contraception plus folate supplementation. 1

Chronic Migraine with Medication-Overuse Headache

• Abruptly discontinue all overused acute medications—evidence does not support gradual tapering. 2
• Warn patients that headache intensity may temporarily worsen for 2-10 days during withdrawal. 2
• Do not substitute another acute medication during withdrawal, as this merely transfers the overuse pattern. 2
• Initiate onabotulinumtoxinA as first-line preventive therapy for chronic migraine, especially when three oral preventives have failed. 2
• Post-withdrawal, reserve acute treatment for the most severe attacks and maintain the ≤2 days per week limit. 2

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Common Clinical Pitfalls

• Do not allow patients to increase acute medication frequency in response to treatment failure—this creates a vicious cycle of medication-overuse headache. 2
• Do not declare triptan failure after a single unsuccessful attempt—try different triptans or different routes of administration. 1, 2
• Do not prescribe opioids or butalbital simply because a patient requests them or reports "nothing else works" without ensuring adequate trials of evidence-based therapies. 1, 2
• Do not delay preventive therapy while trialing multiple acute strategies—this undermines timely control of frequent migraine. 2
• Do not use beta-blockers with intrinsic sympathomimetic activity—they are ineffective for migraine prevention. 3, 4
• Do not prescribe valproate to women of childbearing potential without explicit contraception counseling and documentation of teratogenic risk. 1, 3