Abstract Chronic migraine (CM) is often complicated by medication-overuse headache (MOH), worsening disability. Although withdrawal of overused medications is recommended, adherence is poor and relapse is frequent. Monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway may offer an effective preventive option without requiring discontinuation, but current evidence is limited by few and heterogeneous randomized controlled trials (RCTs). To systematically assess the efficacy and safety of anti-CGRP mAbs in treating CM with MOH (CM + MOH) under a conservative approach. The PubMed, Embase, and Cochrane Central databases were searched for RCTs comparing anti-CGRP mAbs with placebo in adults with CM + MOH. The primary outcome was the mean change in monthly migraine days (MMDs) at 3 months. The secondary outcomes included acute medication use, disability, drug overuse resolution, response rate, and adverse events (AEs). Random-effects models with Sidik-Jonkman estimator and Knapp-Hartung adjustments pooled effect sizes. We included seven RCTs, totalling 3,094 patients. Anti-CGRP mAbs significantly reduced MMDs (mean difference MD = -0.35; 95%CI: -0.43 to -0.26) and acute medication use (MD = -0.35; 95%CI: -0.51 to -0.19) compared with placebo. Higher rates, of ≥ 50%, of response (risk ratio RR = 1.94; 95%CI: 1.60–2.34) and drug overuse resolution (RR = 1.38; 95%CI: 1.04–1.83) were observed, with no significant increase in AEs (RR = 1.09; 95%CI: 0.85–1.40). Anti-CGRP mAbs were effective and well tolerated in CM + MOH, representing a viable alternative, especially for patients unable to discontinue acute medications. Further research should assess long-term outcomes and subgroup effects.
Makita et al. (2026) studied this question.