The efficacy, safety, and adverse events of azapirones in anxiety disorders: A systematic review and meta-analysis of randomized controlled trials.

Abstract

Azapirones have been proposed as anxiety and mood modulators. We assessed azapirones' viability in anxiety disorders via systematic review and random-effects meta-analysis, inquiring PubMed/MEDLINE/CENTRAL/WHO-ICTRP/WebOfScience/VIP up-to 05/01/2023. We conducted sensitivity, and subgroup analyses assessing heterogeneity, publication bias, risk of bias, and confidence in the evidence within the GRADE framework. Symptom reduction (mean difference/MD), study-defined response (risk ratios/RRs), and acceptability were co-primary outcomes. Adverse events and withdrawal were secondary. Seventy studies were included. In generalized anxiety disorder (GAD), azapirones largely outperformed placebo (MD=-4.91, 95%C.I.[-5.91, -3.90], Hedges'g -1.37 [-1.02, -0.73]), k = 22, n = 2,567; RR=1.64, 95%C.I.[1.45, 1.86], k = 9, n = 1,346). While azapirones overlapped benzodiazepines in symptom reduction (MD=-0.12, 95%C.I.[-0.70, 0.45], k = 34, n = 3,160), they were slightly outperformed in response rate (RR=0.94, 95%C.I.[0.90, 0.99], k = 18, n = 2,423). Azapirones overlapped SRIs (MD=0.09, 95%C.I.[-0.49, 0.67], k = 8, n = 747; RR=0.97, 95%C.I.[0.89, 1.07], k = 7, n = 737). Confidence in estimates was high/moderate vs. placebo, moderate/low vs. benzodiazepine, very-low vs. SRIs. Azapirones failed to outperform the placebo in panic and social anxiety disorders. Azapirones overlapped placebo and SRIs in drop-out rates, while they showed higher treatment discontinuation rates than benzodiazepines (RR=1.33, 95%C.I.[1.16, 1.53], k = 23, n = 2,768). Azapirones caused less sedation/fatigue/drowsiness/weakness/cognitive issues than benzodiazepines, resembling placebo. They caused more nausea and dizziness than placebo, more headache and nausea than benzodiazepines, and less nausea and xerostomia than SRIs. Azapirones proved effective and relatively well-tolerated for GAD. They should be preferred over benzodiazepines, especially in the long-term, considering their lower sedation and addiction potential, representing a potential SRI alternative. Further research is warranted to prove efficacy in panic and social anxiety.

• Authors: Flavia Rossano, Claudio Caiazza, Nicolas Zotti, Luca Viacava, Antonella Irano, Niccolò Solini, Luca Pistone, Rosanna Pezone, Flavia Cilmi, Claudio Ricci, Michele De Prisco, Felice Iasevoli, Taro Kishi, Marco Solmi, Andrea de Bartolomeis, Michele Fornaro
• Journal: European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology (Eur Neuropsychopharmacol) Vol. 76 Pg. 23-51 (11 2023) ISSN: 1873-7862 [Electronic] Netherlands
• PMID: 37544075 (Publication Type: Meta-Analysis, Systematic Review, Journal Article)
• Copyright: Copyright © 2023 Elsevier B.V. and ECNP. All rights reserved.

Chemical References

• Benzodiazepines

Topics

• Humans
• Randomized Controlled Trials as Topic
• Anxiety Disorders (drug therapy)
• Anxiety (drug therapy)
• Benzodiazepines (therapeutic use)
• Nausea (drug therapy)