What are the recommended medications for migraine prevention?

Migraine Prevention Medications

Beta-blockers (propranolol 80-240 mg/day or timolol 20-30 mg/day), topiramate (100 mg/day in divided doses), and candesartan are the first-line medications for migraine prevention, with CGRP monoclonal antibodies reserved for patients who fail or cannot tolerate these initial options. 1, 2

When to Initiate Preventive Therapy

Start preventive treatment when patients experience any of the following:

• ≥2 migraine attacks per month with disability lasting ≥3 days per month 1
• Using abortive medications more than twice weekly (risk of medication overuse headache) 1
• Contraindications to or failure of acute treatments 1
• Uncommon migraine conditions including hemiplegic migraine, prolonged aura, or migrainous infarction 1

First-Line Preventive Medications

Beta-Blockers

• Propranolol 80-240 mg/day is FDA-approved with strong efficacy evidence 1, 3
• Timolol 20-30 mg/day is equally effective 1
• These agents are particularly useful for patients with comorbid hypertension or anxiety 1

Topiramate

• Target dose: 100 mg/day (typically 50 mg twice daily) 1, 4
• Start at 25 mg daily and titrate by 25 mg weekly to minimize side effects 5, 6
• No additional benefit at 200 mg/day compared to 100 mg/day, but significantly more side effects 4, 7
• Especially preferred for patients concerned about weight gain or who are overweight, as it causes weight loss rather than gain 4, 6
• Most common side effects: paresthesia (dose-related), fatigue, decreased appetite, cognitive dysfunction 4, 5
• Efficacy demonstrated as early as the first month of treatment 6

Angiotensin Receptor Blockers

• Candesartan or telmisartan are effective first-line agents 1, 2
• Particularly useful for patients with comorbid hypertension 1

CGRP Monoclonal Antibodies (First-Line per Recent Guidelines)

• Erenumab, fremanezumab, or galcanezumab receive strong recommendations for both episodic and chronic migraine 2
• Eptinezumab (IV) is a second-line CGRP option 2
• These should be considered when traditional preventives fail or are contraindicated 1
• Require 3-6 months to assess efficacy (longer than traditional agents) 1

Second-Line Preventive Medications

Tricyclic Antidepressants

• Amitriptyline 30-150 mg/day 1
• Particularly effective for patients with mixed migraine and tension-type headache 1

Anticonvulsants

• Sodium valproate 800-1500 mg/day or divalproex sodium 500-1500 mg/day 1, 8
• STRICTLY CONTRAINDICATED in women of childbearing potential due to teratogenic effects 1, 2, 9
• Common side effects include weight gain, hair loss, and gastrointestinal symptoms (approximately 24% each) 8

Other Second-Line Options

• Lisinopril for episodic migraine 2
• Oral magnesium 2
• Memantine for episodic migraine 2
• Atogepant for episodic migraine 2
• OnabotulinumtoxinA injection specifically for chronic migraine only (NOT for episodic migraine) 2

Implementation Strategy

Titration and Trial Period

• Start with low doses and titrate slowly until clinical benefits achieved or side effects limit increases 1
• Allow 2-3 months for adequate trial before determining efficacy 1, 6
• Exception: CGRP antibodies require 3-6 months for assessment 1

Monitoring

• Use headache diaries to track attack frequency, severity, duration, disability, treatment response, and adverse effects 1
• Monitor for medication overuse, which can interfere with preventive treatment 1
• Calculate percentage reduction in monthly migraine days as a measure of success 1

Duration of Therapy

• Consider tapering after 6-12 months of successful therapy to determine if discontinuation is possible 1

Medications to Avoid

• Gabapentin is NOT recommended for episodic migraine prevention 2
• Botulinum toxin injections (abobotulinum or onabotulinum) are NOT recommended for episodic migraine 2
• Galcanezumab is NOT recommended for chronic cluster headache 2

Critical Pitfalls to Avoid

• Failing to recognize medication overuse headache from frequent acute medication use 1
• Inadequate trial duration (less than 2-3 months) before declaring treatment failure 1
• Starting with excessively high doses, leading to poor tolerability and discontinuation 1
• Prescribing valproate to women of childbearing potential without considering teratogenic risk 1, 2
• Not addressing comorbidities that influence treatment selection (e.g., hypertension favors candesartan or beta-blockers; concern about weight gain favors topiramate) 1

Drug Interactions to Consider

For propranolol:

• Increases warfarin bioavailability and prothrombin time 3
• Concentrations increased by CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine) 3
• Increases zolmitriptan concentrations by 56% and rizatriptan by 67% 3

For valproate:

• Aspirin increases valproate free fraction 4-fold and inhibits metabolism 9
• Enzyme-inducing drugs (phenytoin, carbamazepine, phenobarbital) double valproate clearance 9