نبذة مختصرة : Background Botulinum neurotoxin A (BoNT-A) was the primary choice for preventive treatment of chronic migraine. Topiramate and acupuncture showed promising effect for chronic migraine, but their effectiveness relative to BoNT-A was rarely studied. We aimed to perform a network meta-analysis to compare the effectiveness and acceptability between topiramate, acupuncture, and BoNT-A. Methods We searched OVID Medline, Embase, the Cochrane register of controlled trials (CENTRAL), the Chinese Clinical Trial Register, and clinicaltrials.gov for randomized controlled trials (RCTs) that compared topiramate, acupuncture, and BoNT-A with any of them or placebo in the preventive treatment of chronic migraine. A network meta-analysis was performed by using a frequentist approach and a random-effects model. The primary outcomes were reduction in monthly headache days and monthly migraine days at week 12. Acceptability was defined as the number of dropouts owing to adverse events. Results We included 15 RCTs (n = 2545). Eleven RCTs were at low risk of bias. The network meta-analyses (n = 2061) showed that acupuncture (2061 participants; standardized mean difference [SMD] -1.61, 95% CI: -2.35 to -0.87) and topiramate (582 participants; SMD -0.4, 95% CI: -0.75 to -0.04) ranked the most effective in the reduction of monthly headache days and migraine days, respectively; but they were not significantly superior over BoNT-A. Topiramate caused the most treatment-related adverse events and the highest rate of dropouts owing to adverse events. Conclusions Topiramate and acupuncture were not superior over BoNT-A; BoNT-A was still the primary preventive treatment of chronic migraine. Large-scale RCTs with direct comparison of these three treatments are warranted to verified the findings.
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