Efficacy and safety of botulinum toxin type a for upper-limb essential tremor: a systematic review and meta-analysis of randomized placebo-controlled trials

Background Botulinum toxin type A (BoNT-A) is used as a targeted treatment for upper-limb essential tremor, but uncertainty remains regarding the magnitude and certainty of its benefits and harms. We evaluated the efficacy and safety of BoNT-A compared with placebo in adults with upper-limb essential tremor. Methods We systematically searched bibliographic databases, trial registries, and eligible grey-literature sources from inception to July 20, 2026. We included randomized placebo-controlled trials of BoNT-A in adults with upper-limb essential tremor. Primary outcomes were short-term clinician-rated upper-limb tremor severity and muscular weakness through Week 24. Continuous outcomes were summarized using mean differences or Hedges’ g, and binary safety outcomes using risk differences. Random-effects meta-analyses were performed. Risk of bias was assessed at the result level using the Cochrane Risk of Bias 2 tool, and certainty of evidence was evaluated using GRADE. Results Three trials with outcome data from 231 participants contributed to the primary efficacy analysis. BoNT-A reduced short-term clinician-rated upper-limb tremor severity compared with placebo (Hedges’ g, −0.66; 95% CI, −0.94 to −0.38; I 2 = 0%; moderate-certainty evidence). Muscular weakness was more frequent with BoNT-A (2 trials; 107 participants; risk difference, 0.19; 95% CI, 0.06 to 0.32; I 2 = 29%; low-certainty evidence), approximately 190 more participants per 1,000 treated. BoNT-A may improve investigator-rated global treatment response (Hedges’ g, 0.70; 95% CI, 0.06 to 1.34) and patient-rated global treatment response (Hedges’ g, 0.40; 95% CI, 0.14 to 0.67), although certainty was low. Maximum grip strength was reduced (mean difference, −7.13 kg; 95% CI, −11.42 to −2.85; low-certainty evidence). Evidence regarding treatment-related adverse events was very uncertain, whereas estimates for serious adverse events and discontinuation due to adverse events were too imprecise to exclude clinically important benefit or harm. Conclusion BoNT-A probably reduces short-term clinician-rated upper-limb tremor severity but may increase muscular weakness and reduce grip strength. Evidence for global treatment response and less frequent adverse outcomes remains limited or very uncertain. Treatment decisions should balance the expected reduction in tremor against the individualized risk of weakness and functional impairment.