Depressive and anxiety symptoms during CGRP-targeted migraine prevention: A systematic review and meta-analysis

BackgroundMigraine is frequently comorbid with depression and anxiety, conditions that amplify disease burden and may impair preventive treatment response. Calcitonin gene-related peptide (CGRP)-targeted therapies have demonstrated robust efficacy in reducing migraine frequency, with emerging evidence suggesting concurrent improvements in psychiatric symptom burden. However, findings derive from heterogeneous study designs and outcome instruments, limiting conclusions regarding consistency and magnitude of these effects.MethodsWe conducted a systematic review and meta-analysis of studies reporting changes in depressive and anxiety symptoms in adults with migraine receiving CGRP-targeted preventive therapies. PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and PsycINFO were searched from inception through July 2026. Eligible studies included randomised controlled trials, post hoc analyses, and real-world observational studies reporting validated self-report or clinician-rated symptom measures at baseline and follow-up. Risk of bias was assessed using the Jadad Scale for randomised trials and the Newcastle-Ottawa Scale for observational studies. Standardised mean differences with 95% confidence intervals were calculated using random-effects models.ResultsTwelve studies (n = 3603; 63% female) published between 2020 and 2026 met eligibility criteria, of which nine contributed to quantitative synthesis. Pooled analyses demonstrated consistent reductions in depressive symptoms across instruments at 3 months: Hospital Anxiety and Depression Scale - Depression subscale -1.35 points (95% CI, -1.63 to -1.07), Hamilton Depression Rating Scale -3.73 points (95% CI, -5.76 to -1.71), and Beck Depression Inventory -3.70 points (95% CI, -4.92 to -2.48). Anxiety outcomes improved similarly: Hospital Anxiety and Depression Scale - Anxiety subscale -1.50 points (95% CI, -2.45 to -0.55), Hamilton Anxiety Rating Scale -1.64 points (95% CI, -3.21 to -0.07), and Beck Anxiety Inventory -4.36 points (95% CI, -5.24 to -3.48). In the single placebo-controlled subgroup analysis, fremanezumab was numerically superior to placebo for depressive outcomes, though this difference did not reach statistical significance.ConclusionsCGRP-targeted therapies were consistently associated with reductions in depressive and anxiety symptom scores across multiple validated instruments, with improvements appearing to correlate with effective migraine control, although current study designs cannot differentiate between direct and indirect effects on psychiatric symptoms. Placebo-controlled evidence remains insufficient to draw firm conclusions, and adequately powered randomized controlled trials with psychiatric outcomes as prespecified endpoints are warranted before the nature and magnitude of these effects can be definitively characterized.