Medications for Chronic Migraine Prevention

First-Line Preventive Medications

The American College of Physicians recommends CGRP monoclonal antibodies (erenumab, fremanezumab, or galcanezumab) as first-line treatment for chronic migraine prevention, given their strong evidence base and favorable tolerability profile 1
Erenumab, fremanezumab, and galcanezumab have "strong for" recommendations for chronic migraine prevention based on network meta-analysis of 6,979 patients demonstrating significant reductions in monthly migraine days and acute medication use 1
These agents reduce migraine headache days by approximately 2-4.8 days per month compared to baseline 1
Administered as monthly subcutaneous injections with minimal systemic side effects 1
The American College of Physicians notes that erenumab carries postmarketing warnings for development or worsening of hypertension—monitor blood pressure 1

The American Academy of Neurology recommends topiramate with a "weak for" recommendation for both episodic and chronic migraine 1
Topiramate is the only traditional preventive medication with randomized placebo-controlled trial evidence specifically in chronic migraine patients 2
Start topiramate at 25 mg daily, titrate slowly to 100-200 mg daily in divided doses 2
Common side effects of topiramate include cognitive slowing, paresthesias, weight loss, and kidney stones 2
Atogepant has a "weak for" recommendation for episodic migraine prevention, with meta-analysis of 2,466 patients showing statistically significant reductions in monthly migraine and headache days 1

Beta-blockers, such as propranolol, timolol, and metoprolol, have evidence primarily in episodic migraine but are commonly used off-label for chronic migraine 1, 3
Tricyclic antidepressants, such as amitriptyline, have evidence primarily in episodic migraine but are commonly used off-label for chronic migraine 2, 3
Other antiepileptics, such as divalproex sodium, have evidence primarily in episodic migraine but are commonly used off-label for chronic migraine 2, 3

The American College of Physicians recommends starting preventive medications at low doses and titrating slowly over 2-3 months to assess clinical benefit while minimizing adverse effects 3
The American Academy of Neurology notes that full benefit of preventive therapy may take 2-3 months to manifest, and therapy should not be abandoned prematurely 3
The American Headache Society recommends continuing appropriate acute therapy alongside preventive treatment 2

The American College of Physicians recommends considering preventive medications when episodic migraine occurs frequently or when acute treatment does not provide adequate response, with no absolute minimum number of headache days per month universally mandated for initiating prevention 4, 5
The International Headache Society criteria define chronic migraine as ≥15 headache days per month for >3 months, with migraine features on ≥8 days/month, and recommend referral for specialist management and preventive therapy for these patients 6, 7

The American College of Physicians guideline suggests being vigilant about medication overuse headache thresholds, including triptans, ergots, and combination analgesics at ≥10 days per month for ≥3 months, and simple analgesics at ≥15 days per month for ≥3 months 4, 5

The American College of Physicians guideline advises against waiting for an arbitrary number of headache days before considering prevention, and instead focusing on functional impairment and treatment response 4, 5
The guideline also recommends not withholding preventive therapy from patients with 8-14 headache days per month if they have significant disability or inadequate response to acute treatment 4, 5

The American Academy of Neurology recommends onabotulinumtoxinA as an FDA-approved option for chronic migraine prevention, defined as ≥15 headache days/month 8