Comparative efficacy and acceptability of anxiolytic drugs for the treatment of anxiety disorders: a systematic review and network meta-analysis

Abstract Background Anti-anxiety medications’ side effects and dependency risks necessitate thorough consideration of their efficacy and acceptability when making treatment decisions. Methods A systematic review and Network Meta-Analysis (NMA) was conducted using three databases from 1980 to 2020, focusing on adults diagnosed with generalized anxiety disorder (GAD) or any relevant diagnostic classification of anxiety disorder or those for whom Hamilton Anxiety (HAM-A) data is available, and including any comparator (placebo and/or active comparator treatments). The primary outcomes were efficacy (mean difference in change from baseline in HAM-A total score) and acceptability (study discontinuations for any cause). This study is registered with Open Science Framework (OSF) database. Findings Analysis of 100 trials involving 28,637 participants showed that most active drugs were more effective than placebo in reducing anxiety. Notably, silexan was the only phytopharmaceutical included in the NMA. Clomipramine had the highest efficacy and vortioxetine the least. However, in terms of acceptability, clomipramine led to the most study discontinuations, while clobazam had the lowest discontinuation rate, indicating that efficacy and acceptability do not always align. Notably, silexan was both highly effective and as acceptable as a placebo. Only four treatments showed fewer adverse events than placebo (diazepam, agomelatine, clobazam, and silexan). Conclusion This network meta-analysis provides a unique comparison of the efficacy and acceptability of anxiolytics. It represents one of the most comprehensive evidence bases available to guide the first choice of treatment for anxiety disorders in adults.