Adverse effects associated with facial application of botulinum toxin: a systematic review with meta-analysis

Purpose: To estimate the occurrence of adverse effects associated with the use of botulinum toxin by performing a systematic review and meta-analysis. Methods: A systematic literature search of MEDLINE and Cochrane Library was conducted until September 2007. The occurrence of the adverse effects was estimated of the relative frequency for case report and of the relative risk for randomized trials. Heterogeneity was evaluated with the Q test and I-2 index. Egger's significance test was used to identify the publication bias. Sensitivity analysis was performed to evaluate the effect of the publication biases. Results: Eight randomized trials and thirteen case reports filled the inclusion criteria. In the systematic review of case reports, 1,003 subjects were studied and 182 (18.14%) showed adverse effects. Eyelid ptosis was the most frequent adverse effect, presenting in 34 (3.39%) patients of the case reports. In the meta-analysis of randomized trials, the overall relative risk for adverse effects as headache, eyelid ptosis, local reaction and infection was respectively: 1.07, 3.25, 0.99 and 0.94. For all comparisons, P values were greater than 0.05. Conclusion: Ptosis was the most frequent adverse effect and showed the higher relative risk associated with botulinum toxin. It is necessary to perform a pattern of adverse effects related for better understanding the relationship between adverse effects and use of botulinum toxin.