Previous studies have investigated the role of botulinum neurotoxin (BoNT) in lateral epicondylalgia, with controversial results. We hypothesized that BoNT would be effective and safe for the treatment of lateral epicondylalgia.

To investigate the effectiveness and safety of different doses of BoNT in participants with lateral epicondylalgia.

PubMed, Embase, and Cochrane Library were searched up to August 27, 2022, for randomized controlled trials (RCTs) of BoNT treatment for epicondylalgia. The Cochrane risk of bias tool was used for quality assessment. A network meta-analysis and a trial sequential analysis (TSA) were conducted on pain, grip strength and adverse events. Meta-regression was applied for high heterogeneity comparisons.

We included 8 RCTs consisting of 448 participants. Four studies scored low risk of bias in all categories, whereas the other 4 studies had unclear risk only in the selection bias category. The network meta-analysis and TSA revealed that corticosteroid (standardized mean difference [SMD]: −1.32, 95% CI: −2.13; −0.50), high-dose BoNT (SMD −1.32, −2.04; −0.61), and low-dose BoNT (SMD –0.52, −0.93; −0.10), relieved pain significantly better than placebo for up to 7 to 10 weeks. High-dose BoNT demonstrated a significantly greater reduction in pain than low-dose BoNT for up to 7 to 10 weeks (SMD −0.81, –1.39; −0.22). Finally, after low-dose BoNT, younger participants (p = 0.023) and women (p = 0.012) showed more pain decrease than older individuals and men at 2 to 6 weeks. As for grip strength and adverse events, only grip strength after low-dose BoNT versus placebo (SMD −0.49, −0.88; −0.10) and corticosteroid (SMD −1.36, −2.15; −0.57) at 2 to 6 weeks reached significance after threshold adjustment in TSA.

Our meta-analysis confirmed the effectiveness of low-dose BoNT in the reduction of pain for lateral epicondylalgia. Further conclusions cannot be drawn due to insufficient available data.