依替福辛用于治疗焦虑障碍时在减轻焦虑症状方面与氯硝西泮相当：一项随机、双盲、非劣效性试验。

Etifoxine is non-inferior than clonazepam for reduction of anxiety symptoms in the treatment of anxiety disorders: a randomized, double blind, non-inferiority trial.

机构信息

Department of Psychiatry and Mental Health, Universidad de Concepción, Av. Juan Bosco s/n, Casilla 160-C, Concepción, Chile.

Ñuble Health Service, Bulnes 502, Chillán, Chile.

出版信息

Psychopharmacology (Berl). 2020 Nov;237(11):3357-3367. doi: 10.1007/s00213-020-05617-6. Epub 2020 Oct 2.

DOI:10.1007/s00213-020-05617-6

PMID:33009629

Abstract

OBJECTIVE

To determine whether etifoxine, a non-benzodiazepine drug of the benzoxazine family, is non-inferior compared with clonazepam in the treatment of anxiety disorders.

METHOD

A randomized controlled double blind trial with parallel groups was conducted. A total of 179 volunteer patients with a diagnosis of anxiety disorder (DSM-IV), between 18 and 64 years of age, participated in this study. The experimental group received 150 mg/day of etifoxine and the control 1 mg/day of clonazepam, both in three daily doses for 12 weeks. This treatment was completed by 87 participants, and 70 were available for follow-up at 24 weeks from start of treatment. The primary objective was a non-inferiority comparison between etifoxine and clonazepam in the decrease of anxiety symptoms (HAM-A) at 12 weeks of treatment. Secondary outcomes included the evaluation of medication side effects (UKU), anxiety symptoms at 24 weeks of treatment, and clinical improvement (CGI). Data analysis included multiple imputation of missing data. The effect of etifoxine on the HAM-A, UKU, and CGI was evaluated with the intention of treatment, and a sensitivity analysis of the results was conducted. Non-inferiority would be declared by a standardized mean difference (SMD) between clonazepam and etifoxine not superior to 0.31 in favour of clonazepam.

RESULTS

Using imputed data, etifoxine shows non-inferiority to clonazepam on the reduction of anxiety symptoms at the 12-week (SMD = 0.407; 95% CI, 0.069, 0.746) and 24-week follow-ups (SMD = 0.484; 95% CI, 0.163, 0.806) and presented fewer side effects (SMD = 0.58; 95% CI, 0.287, 0.889). LOCF analysis shows that etifoxine is non-inferior to clonazepam on reduction of anxiety symptoms and adverse symptoms even when no change was assigned as result to participant whom withdrew. Non-inferiority could be declared for clinical improvement (SMD = 0.326; 95% CI, - 0.20, 0.858).

CONCLUSION

Etifoxine was non-inferior to clonazepam on reduction of anxiety symptoms, adverse effects, and clinical improvement.

摘要

目的

确定苯并恶嗪家族的非苯二氮䓬类药物依替福辛是否在治疗焦虑症方面与氯硝西泮相当。

方法

这是一项采用平行分组、随机对照、双盲试验。共纳入 179 名年龄在 18 至 64 岁之间、符合 DSM-IV 焦虑症诊断标准的志愿者患者参与本研究。实验组给予依替福辛 150mg/天，对照组给予氯硝西泮 1mg/天，均每日 3 次，疗程 12 周。共有 87 名参与者完成了该治疗，70 名参与者在治疗开始后的 24 周时可进行随访。主要终点是在治疗 12 周时，比较依替福辛和氯硝西泮对焦虑症状（HAM-A）的非劣效性。次要结局包括药物不良反应（UKU）的评估、治疗 24 周时的焦虑症状以及临床改善（CGI）。数据分析包括对缺失数据进行多重插补。采用意向治疗分析依替福辛对 HAM-A、UKU 和 CGI 的影响，并进行结果敏感性分析。如果氯硝西泮与依替福辛之间的标准化均数差值（SMD）不超过 0.31 且有利于氯硝西泮，则宣布依替福辛具有非劣效性。

结果

采用插补数据，依替福辛在治疗 12 周（SMD=0.407；95%CI，0.069，0.746）和 24 周（SMD=0.484；95%CI，0.163，0.806）时的焦虑症状缓解方面与氯硝西泮相当，且不良反应更少（SMD=0.58；95%CI，0.287，0.889）。意向治疗分析表明，即使将退出的参与者的结果设定为无变化，依替福辛在焦虑症状和不良反应的缓解以及临床改善方面也不劣于氯硝西泮。非劣效性可宣告为临床改善（SMD=0.326；95%CI，-0.20，0.858）。