Effectiveness and Tolerability of Pharmacologic Prophylaxis for Chronic Migraine : A Systematic Review of Randomized Controlled Trials
Abstract
Background: Migraine headaches are considered chronic when they occur on 15 or more days per month. Newer medications are available for prevention.
Purpose: To explore the effectiveness and tolerability of pharmacologic prophylaxis for chronic migraine.
Data sources: Medline, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, Web of Science, and Scopus to October 2025.
Study selection: Independent paired reviewers identified randomized controlled trials (RCTs) of prophylactic pharmacologic interventions for adults with chronic migraine.
Data extraction: Paired reviewers independently extracted data and assessed risk of bias using the Cochrane Risk of Bias 2 tool. Random-effects meta-analysis and assessment of certainty of evidence were performed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.
Data synthesis: The review included 43 RCTs (14 725 participants). High- and moderate-certainty evidence suggests that eptinezumab (mean difference [MD], -2.34 [95% CI, -2.76 to -1.92]), erenumab (MD, -2.08 [CI, -2.82 to -1.33]), fremanezumab (MD, -1.77 [CI, -2.45 to -1.09]), galcanezumab (MD, -2.00 [CI, -2.96 to -1.04]), and atogepant (MD, -2.10 [CI, -3.06 to -1.14]) reduce monthly migraine headache days by 2 versus placebo. Botulinum toxin may slightly reduce monthly migraine days (MD, -1.34 [CI, -2.27 to -0.41]; low certainty), whereas rimegepant probably has no effect (MD, -1.20 [CI, -2.59 to 0.19]; moderate certainty).…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 14 participants or records.
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