Which medications actually work for chronic migraine?

Several calcitonin gene-related peptide-targeted therapies show potential efficacy for the treatment of chronic migraine, suggest the results of a systematic review.

Forty-three randomized controlled trials (RCTs), including a total of 14,725 participants, met the eligibility criteria.

High- and moderate-certainty evidence showed reduced monthly migraine headache days with the use of eptinezumab (mean difference [MD], ‒2.34, 95 percent confidence interval [CI], ‒2.76 to ‒1.92), erenumab (MD, ‒2.08, 95 percent CI, ‒2.82 to ‒1.33), fremanezumab (MD, ‒1.77, 95 percent CI, ‒2.45 to ‒1.09), galcanezumab (MD, ‒2.00, 95 percent CI, ‒2.96 to ‒1.04), and atogepant (MD, ‒2.10, 95 percent CI, ‒3.06 to ‒1.14) compared with placebo.

Botulinum toxin appeared to slightly reduce monthly migraine days (MD, ‒1.34, 95 percent CI, ‒2.27 to ‒0.41; low certainty), but rimegepant did not seem to have any effect (MD, ‒1.20, 95 percent CI, ‒2.59 to 0.19; moderate certainty).

Furthermore, galcanezumab potentially reduced dropout due to any cause relative to placebo (relative risk [RR], 0.52, 95 percent CI, 0.33‒0.83; moderate certainty), while botulinum toxin seemed to increase discontinuation because of adverse events (RR, 3.36, 95 percent CI, 1.75‒6.45; moderate certainty).

“Evidence for botulinum toxin, propranolol, topiramate, and valproate mostly had high risk of bias,” the investigators said.

Independent paired reviewers identified RCTs of prophylactic pharmacologic interventions for adults with chronic migraine using the databases of Medline, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, Web of Science, and Scopus to October 2025.

These reviewers extracted data and assessed risk of bias using the Cochrane Risk of Bias 2 tool. They also performed random-effects meta-analysis and assessed certainty of evidence using the GRADE approach.