We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of anti-CGRP monoclonal antibodies for chronic migraine (CM) patients with medication overuse (MO) and medication overuse headache (MOH). 

CM is frequently associated with excessive use of acute headache medications, leading to MOH, a secondary headache disorder that exacerbates disability, pain severity, comorbidities, and healthcare costs. Conventional MOH treatment prioritizes medication withdrawal, but high relapse rates and patient resistance highlight the need for alternative strategies. Anti-CGRP monoclonal antibodies offer a promising preventive approach for CM+MOH patients without requiring strict medication discontinuation; however, their effectiveness in this population remains uncertain. 

We searched PubMed, Embase, and Cochrane from inception to September 2024. Inclusion was limited to randomized trials involving CM patients with MO or MOH comparing anti-CGRP mAbs versus placebo. Outcomes included changes from baseline in Monthly Migraine Days (MMDs) and Headache Impact Test (HIT-6) score at 12 weeks, and the incidence of serious adverse events. A random-effects model was used to calculate the risk ratio (RR) and standardized mean difference (SMD) with 95% confidence intervals (CI). Statistical analysis was performed with Review Manager 5.4. 

We screened 77 articles and fully reviewed 15. A total of six studies (2,915 patients) were included. Anti-CGRP mAbs significantly reduced MMDs (SMD -0.30; CI -0.43 to -0.18; I² = 50%; p<0.0001) and HIT-6 scores (SMD -0.33; CI -0.45 to -0.21; I² = 0%; p<0.0001). No significant difference was found in serious adverse event rates (RR 3.06; CI 0.66 to 14.11; I² = 0%; p=0.15).

Anti-CGRP mAbs were associated with significant reductions in migraine burden and improved functionality in CM+MOH patients. No safety differences were observed compared to placebo. These findings reinforce the role of anti-CGRP therapy in CM+MOH management. However, further long-term RCTs are needed to assess relapse rates and optimize clinical application.