The impact of topiramate, botulinum toxin type A, and CGRP-antibodies on medication overuse headache in patients with chronic migraine: A protocol for systematic review and meta-analysis

Medication overuse headache (MOH) is defined as headache occurring ≥15 days/month developing as a consequence of regular overuse of acute or symptomatic headache medication for more than 3 months. MOH is present in more than 50% of patients with chronic migraine (CM). Although, studies have shown a positive impact for MOH patients of early introduction of preventive treatment and withdrawal of overused medication, uncertainties remain. The main purpose of this systematic review and meta-analysis is to assess the relative impact of topiramate, botulinum toxin type A, and human monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) or its receptor (CGRPr) among MOH patients with CM. The PRISMA guideline for conducting systematic review will be followed. CENTRAL, MEDLINE, Embase and Web of Science databases will be searched. RCTs reporting outcomes such as change in migraine/headache frequency, change from MOH to no MOH, and ≥50% response rate will be included. The effect will be measured as mean difference (MD) for continuous data and odds ratio (OR) for dichotomous data. Heterogeneity across studies will be assessed using the Cochrane I2 statistics. The Cochrane RoB2 tool will be used to assess risk of bias, and the quality of evidence for outcomes will be rated according to five factors defined in Cochrane GRADE approach. The revision of the included articles, data extraction, risk of bias assessment, and quality rating of evidence will be independently done by two reviewers. Any discrepancies will be resolved through consensus with the third reviewer.