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

被引:4
作者
Rossano, Flavia [1 ]
Caiazza, Claudio [1 ]
Zotti, Nicolas [1 ]
Viacava, Luca [1 ]
Irano, Antonella [1 ]
Solini, Niccolo [1 ]
Pistone, Luca [1 ]
Pezone, Rosanna [1 ]
Cilmi, Flavia [1 ]
Ricci, Claudio [1 ]
De Prisco, Michele [2 ,3 ,4 ]
Iasevoli, Felice [5 ,6 ]
Kishi, Taro [7 ]
Solmi, Marco [8 ,9 ,10 ]
de Bartolomeis, Andrea [5 ,6 ]
Fornaro, Michele [1 ,11 ]
机构
[1] Univ Sch Med Feder II, Dept Neurosci Reprod Sci & Odontostomatol, Clin Sect Psychiat & Psychol, Reprod Sci, Naples, Italy
[2] Hosp Clin Barcelona, Bipolar & Depress Disorders Unit, C Villarroel 170, Barcelona 08036, Spain
[3] Inst Invest Biomed August Pi & Sunyer IDIBAPS, C Villarroel 170, Barcelona 08036, Spain
[4] Inst Salud Carlos III, Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid, Spain
[5] Univ Sch Med Naples Feder II, Dept Neurosci Reprod Sci & Odontostomatol, Unit Treatment Resistant Psychosis, Sect Psychiat, Naples, Italy
[6] Univ Sch Med Naples Federico II, Lab Mol Translat & Psychiat, Naples, Italy
[7] Fujita Hlth Univ, Sch Med, Dept Psychiat, Toyoake, Aichi 4701192, Japan
[8] Univ Ottawa, Dept Psychiat, Ottawa, ON, Canada
[9] Ottawa Hosp, Dept Mental Hlth, On Track Champlain Episode Psychosis Program 1, Ottawa, ON, Canada
[10] Charite, Dept Child & Adolescent Psychiat, Berlin, Germany
[11] Univ Napoli Federico II, Psichiatria, Via Sergio Pansini n5,Edificio 18, I-80131 Naples, Italy
关键词
Azapirones; Anxiety; Systematic review; Meta-analysis; GENERALIZED ANXIETY; DOUBLE-BLIND; PANIC DISORDER; CLINICAL-EVALUATION; BENZODIAZEPINE USE; LOCUS-COERULEUS; BUSPIRONE; DIAZEPAM; PLACEBO; MULTICENTER;
D O I
10.1016/j.euroneuro.2023.07.008
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Azapirones have been proposed as anxiety and mood modulators. We assessed azapirones' vi-ability 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 differ-ence/MD), study-defined response (risk ratios/RRs), and acceptability were co-primary out-comes. Adverse events and withdrawal were secondary. Seventy studies were included. In gen-eralized 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. Aza-pirones 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 benzodi-azepines, resembling placebo. They caused more nausea and dizziness than placebo, more headache and nausea than benzodiazepines, and less nausea and xerostomia than SRIs. Aza-pirones 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 ef-ficacy in panic and social anxiety.& COPY; 2023 Elsevier B.V. and ECNP. All rights reserved.
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页码:23 / 51
页数:29
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