Serotonin Reuptake Inhibition for the Prevention of Vasovagal Syncope: A Systematic Review and Meta-Analysis

Abstract Purpose: Vasovagal syncope is a common clinical condition that lacks effective medical therapies despite being associated with significant morbidity. Current guidelines suggest that serotonin-specific reuptake inhibitors, might suppress vasovagal syncope but supporting studies have been small and heterogenous. The purpose was to evaluate the efficacy of serotonin-specific reuptake inhibitors to prevent syncope in patients with recurrent vasovagal syncope by conducting a systematic review and meta-analysis of published studies. Methods: Relevant randomized controlled trials were identified from the MEDLINE and Embase databases without language restriction from inception to August 2022, and clinicaltrials.gov. All studies were conducted in clinical syncope populations and compared the benefit of serotonin versus placebo. Weighted relative risks were estimated using random effects meta-analysis techniques. Results: Three studies (n=204) met inclusion criteria. Patients were 42±13 years of age and 51% female. Serotonin-specific reuptake inhibitors were found to substantially reduce the likelihood of a patient having at least one recurrence of vasovagal syncope (relative risk [RR]=0.34 (0.20-0.60), p<0.01) with minimal between-study heterogeneity (I2=0%, p = 0.67). Serotonin-specific reuptake inhibitors in two reports provided significant protection against clinical presyncope (RR = 0.43 (0.24-0.77, p <0.01), with minimal between-study heterogeneity (I2 = 0%, p = 0.80). Conclusions: Serotonin-specific reuptake inhibitors may be effective in preventing syncope induced by head-up-tilt testing and in syncope in the community in randomized, double-blinded clinical trials.