• Johanna A A Damen, Bada Yang, Demy L Idema, Robin W M Vernooij, Linde Huis In 't Veld, Mike Kusters, Rene Spijker, Kim van der Braak, Pauline Heus, Kevin Jenniskens, and Lotty Hooft.
• Cochrane Netherlands, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands (J.A.A.D., B.Y., D.L.I., R.W.M.V., L.H.V., M.K., R.S., K.v.d.B., P.H., K.J., L.H.).
• Ann. Intern. Med. 2025 Feb 4.

BackgroundVarious treatments for preventing episodic migraine are available.PurposeTo evaluate the comparative effectiveness and harms of pharmacologic prevention of episodic migraine, focusing on treatments already determined to be superior to placebo.Data SourcesMEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from inception until April 2024.Study SelectionRandomized trials evaluating selected efficacious pharmacologic treatments in adults with episodic migraine. Selection was done independently by 2 reviewers.Data ExtractionData 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 SynthesisSixty-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.LimitationsLimited literature was available to determine the minimal important differences. The number of head-to-head comparisons of treatments was limited.ConclusionNo high-certainty evidence favored one pharmacologic treatment for prevention of episodic migraine over another. Evidence was mostly insufficient or of low certainty.Primary Funding SourceAmerican College of Physicians. (PROSPERO: CRD42023414305).

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