Comparative Effectiveness of Pharmacologic Treatments for the Prevention of Episodic Migraine Headache: A Systematic Review and Network Meta-analysis for the American College of Physicians

Background: Various treatments for preventing episodic migraine are available. Purpose: To evaluate the comparative effectiveness and harms of pharmacologic prevention of episodic migraine, focusing on treatments already determined to be superior to placebo. Data Sources: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from inception until April 2024. Study Selection: Randomized trials evaluating selected efficacious pharmacologic treatments in adults with episodic migraine. Selection was done independently by 2 reviewers. Data Extraction: Data were extracted by 1 reviewer and checked by a second. Risk of bias and certainty of the evidence were assessed using the Cochrane Risk of Bias tool and the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, respectively. Data Synthesis: Sixty-one studies (20 680 patients) evaluating 16 treatments were included. Nineteen studies had low risk of bias. All selected treatments were deemed efficacious against placebo on the basis of previous systematic reviews. In network meta-analyses, calcitonin gene–related peptide antagonist monoclonal antibodies (CGRP-mAbs) probably resulted in fewer discontinuations due to adverse events than topiramate (risk difference, −16.2% [95% CI, −18.4% to −12.8%]; moderate-certainty evidence), and CGRP-mAbs may result in less migraine-related disability and improved quality of life compared with gepants (mean differences, −4.12 [CI, −9.30 to 1.05] and 2.25 [CI, −0.85 to 5.34], respectively; low-certainty evidence). For other outcomes and comparisons, there was moderate- or low-certainty evidence of no clinically important differences, uncertain evidence, or no evidence. Limitations: Limited literature was available to determine the minimal important differences. The number of head-to-head comparisons of treatments was limited. Conclusion: No high-certainty evidence favored one pharmacologic treatment for prevention of episodic migraine over another. Evidence was mostly insufficient or of low certainty.