Pharmacotherapy for chronic migraine prevention: a narrative review.

INTRODUCTION: Chronic migraine (CM) is a disabling neurological disorder with evolving diagnostic criteria that have influenced how we interpret the evidence base for preventive treatment. Affecting 1-2% of the population, CM imposes substantial individual and societal burden. AREAS COVERED: This narrative review summarizes the evidence for CM prevention. Literature was identified through PubMed and Google Scholar through April 2026. We review traditional oral preventives, onabotulinumtoxinA, calcitonin gene-related peptide (CGRP)-targeted monoclonal antibodies, gepants, and emerging therapeutic targets, emphasizing CM-specific efficacy, safety, and outcomes in patients with medication overuse and prior treatment failures. EXPERT OPINION: Although traditional oral preventives remain widely used in CM, most lack CM-specific trial data under current diagnostic criteria and their use largely reflects extrapolation from episodic migraine. Therapies targeting migraine pathophysiology, including CGRP-targeted agents and onabotulinumtoxinA, offer more robust CM-specific evidence, although effect sizes are modest and comparative efficacy data against established oral preventives remain limited. Despite guidelines endorsing CGRP-targeting therapies as first-line, access barriers limit real-world implementation. Incomplete response and the lack of predictive biomarkers, reflecting disease heterogeneity, pose major challenges in CM management. Future progress may lie in strengthening the evidence for combination therapy, expanding therapeutic targets, and developing clinically actionable biomarkers for individualized care.