¹University Hospital of Psychiatry and Psychotherapy, Clinical Neuroscience Bern, Bern, Switzerland, ²University Hospital of Psychiatry and Psychotherapy, Department of Clinical Research, Bern, Switzerland, ³Heidelberg University Hospital, Department of General Psychiatry, Heidelberg, Germany, ⁴University Hospital Zurich, Department of Consultation-Liaison-Psychiatry and Psychosomatic Medicine, Zurich, Switzerland, ⁵Centre for Anxiety and Depression Treatment, Division of Adult Psychiatry, Zurich, Switzerland, ⁶Psychiatric Services of the Canton Aargau, Clinic for Psychiatry and Psychotherapy, Windisch, Switzerland, ⁷Solothurner Spitäler AG, Psychiatric Services, Solothurn, Switzerland, ⁸University of Basel, Gesundheitszentrum St. Johann, Basel, Switzerland, ⁹University of Basel, Department Clinical Research, Basel, Switzerland, ¹⁰University Medical Center Göttingen, Department of Psychiatry and Psychotherapy, Göttingen, Germany, ¹¹Psychiatric Hospital, University of Zurich, Department of Adult Psychiatry and Psychotherapy, Zurich, Switzerland, ¹²Medical University of Vienna, Center for Brain Research, Department of Molecular Neuroscience, Vienna, Austria

Background: Anxiolytic medications’ side effects and dependency risks necessitate thorough consideration of their efficacy and acceptability when making treatment decisions.

Aims & Objectives: To build on the evidence from previously conducted NMAs by comparing the efficacy and acceptability evidence of various anxiolytic drugs, including silexan for the first time, as the only included phytomedicine, to determine the most advantageous agents for treating anxiety disorders, including GAD.

Method: 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.

Results: Analysis of 100 trials involving 28,637 participants showed that most active drugs were more effective than placebo in reducing anxiety. Notably, Silexan¹ 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.

Discussion & Conclusions: 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 choice of treatment for anxiety disorders in adults.

¹ Silexan^® is a proprietary essential oil from Lavandula angustifolia, Dr. Willmar Schwabe GmbH & Co. KG, Karlsruhe, Germany