Effectiveness and tolerability of pharmacological prophylaxis for migraine headaches: a systematic review and network meta-analysis of randomised controlled trials

Abstract

OBJECTIVES: Migraine headaches are common and potentially disabling disorders, with several interventions available for prevention and symptom reduction. We explored the comparative effectiveness and tolerability of pharmacological prophylaxis for migraine through a network meta-analysis of randomised trials (RCTs). DESIGN: Our study design was a systematic review and network meta-analysis (PROSPERO registration CRD42023456915). ELIGIBILITY CRITERIA: We included randomised controlled trials of prophylactic pharmacological interventions that enrolled adults diagnosed with chronic and/or episodic migraine headaches. DATA SOURCES: Medline, Embase, Cochrane Central, PsycINFO, Web of Science and Scopus from inception to 15 January 2026. RISK OF BIAS AND CERTAINTY EVIDENCE: Risk of bias was assessed using the modified Cochrane risk-of-bias tool 2.0 and the certainty evidence was evaluated by using the Grading of Recommendations Assessment, Development and Evaluation approach. SYNTHESIS OF RESULTS: We performed a frequentist network meta-analysis using a random-effects model to compare the efficacy of interventions. RESULTS: We included 199 RCTs (47 420 participants). Overall, 29 trials (14.6) were at low risk of bias; an adequate random allocation sequence generation was reported in 92 trials (46.2), and missing outcome data was the most common limitation (110 trials, 55.3). Compared with placebo, calcium channel blockers (mean difference (MD) -1.78 (95 CI -2.96 to -0.60), moderate certainty), calcitonin gene-related peptide (CGRP)-targeted therapies (MD -1.69 (95 CI -2.16 to -1.23), high certainty) and beta-blockers (MD -1.50 (95 CI -2.54 to -0.47), moderate certainty) were the most effective in reducing monthly migraine days. Moderate certainty evidence suggests beta-blockers (MD -1.31 (95 CI -1.76 to -0.85)), calcium channel blockers (MD -1.11 (95 CI -1.65 to -0.57)), anticonvulsants (MD -1.12 (95 CI -1.66 to -0.58)) and CGRP-targeted therapies (MD -0.76 (95 CI -1.49 to -0.02)) probably reduce monthly migraine attacks. However, moderate to high certainty evidence found that patients were more likely to discontinue calcium channel blockers (relative risk (RR) 1.40, 95 CI 1.04 to 1.88) and anticonvulsants (RR 1.14, 95 CI 1.01 to 1.29), compared with placebo. CONCLUSIONS: When restricted to moderate or high certainty evidence, beta-blockers and CGRP-targeted therapies probably reduce migraine frequency and may be well-tolerated prophylactic options for migraine. Calcium channel blockers and anticonvulsants may also be effective for reducing migraine frequency but are less well tolerated by some patients. PROSPERO REGISTRATION NUMBER: CRD42023456915.