Stein Dan J
Department of Psychiatry, Groote Schuur Hospital J2, University of Cape Town, Anzio Rd, Observatory, Cape Town, 7925, South Africa,
Adv Ther. 2015 Jan;32(1):57-68. doi: 10.1007/s12325-015-0176-6. Epub 2015 Jan 27.
Adjustment disorder with anxiety (ADWA) is a highly prevalent condition, particularly in primary care practice. There are relatively few systematic treatment trials in the area of ADWA, and there are few data on predictors of treatment response. Etifoxine is a promising agent insofar as it is not associated with dependence, but in primary care settings benzodiazepines continue to be frequently prescribed for psychiatric symptoms. A randomized controlled trial of etifoxine versus alprazolam for ADWA was undertaken, focusing on efficacy and safety measures, and including an investigation of predictors of clinical response.
This was a comparative, multicenter, double-blind, randomized trial in two parallel groups of outpatients with ADWA. One group was treated with 150 mg/day for etifoxine, and the other with 1.5 mg/day for alprazolam for 28 days. Patients were followed for 4 weeks of treatment, and for an additional week after treatment discontinuation. The primary outcome measure was the Hamilton Anxiety Rating Scale (HAM-A), while secondary outcome measures included the Sheehan Disability Scale (SDS), the Clinical Global Impressions-Change Scale (CGI-C), and the Self-Report for the Assessment of Adjustment Disorders. Non-inferiority analysis was used to assess the primary outcome measure, and a multivariate logistic regression was employed to investigate predictors of response.
Two hundred and two adult outpatients with ADWA were enrolled at 17 primary care sites. One hundred and seventy seven patients completed the study (n = 87 in the etifoxine group; n = 90 in the alprazolam group). Etifoxine and alprazolam were accompanied by decreases in the HAM-A at day 28, with a difference between treatment groups in HAM-A score of 1.78 [90% CI; 0.23, 3.33] in favor of alprazolam. However, after medication discontinuation, HAM-A scores continued to improve in the etifoxine group, but increased in the alprazolam group; the difference between groups in mean change between day 28 and day 35 was significant (p = 0.019). Secondary outcome measures showed similar results for etifoxine and alprazolam at day 35. More treatment-related adverse events were reported in patients treated with alprazolam, particularly central nervous system-related AEs, and especially after medication discontinuation. No significant predictors of treatment response were found.
This randomized controlled trial provides support for the efficacy and safety of etifoxine in the management of adjustment disorder with anxiety, particularly when treatment discontinuation data are also assessed. Etifoxine has the important clinical advantage of having anxiolytic effects, which are not being associated with dependence. Pharmacotherapy was equally efficacious in patients with more severe anxiety symptoms at baseline. Additional work using longer-term follow-up and collecting data on cost-efficiency of management options would further advance the field of ADWA.
Sponsorship and article processing charges for this study were provided by Biocodex, Gentilly, France.
伴有焦虑的适应障碍（ADWA）是一种非常普遍的病症，在初级保健实践中尤为常见。ADWA领域的系统性治疗试验相对较少，关于治疗反应预测因素的数据也很少。依替福辛是一种有前景的药物，因为它不产生依赖性，但在初级保健环境中，苯二氮䓬类药物仍经常被用于治疗精神症状。针对ADWA开展了一项依替福辛与阿普唑仑的随机对照试验，重点关注疗效和安全性指标，并对临床反应的预测因素进行了调查。
这是一项针对两组平行的ADWA门诊患者的比较性、多中心、双盲、随机试验。一组患者接受依替福辛每日150毫克治疗，另一组接受阿普唑仑每日1.5毫克治疗，为期28天。对患者进行4周的治疗随访，并在停药后再随访1周。主要结局指标是汉密尔顿焦虑量表（HAM - A），次要结局指标包括希恩残疾量表（SDS）、临床总体印象变化量表（CGI - C）以及适应障碍评估的自我报告。采用非劣效性分析来评估主要结局指标，并使用多变量逻辑回归来研究反应的预测因素。
在17个初级保健机构招募了202名患有ADWA的成年门诊患者。177名患者完成了研究（依替福辛组87例；阿普唑仑组90例）。在第28天时，依替福辛和阿普唑仑均使HAM - A评分降低，治疗组间HAM - A评分差异为1.78[90%CI；0.23，3.33]，阿普唑仑组更优。然而，停药后，依替福辛组的HAM - A评分持续改善，而阿普唑仑组则升高；第28天至第35天两组间平均变化差异显著（p = 0.019）。次要结局指标在第35天时依替福辛和阿普唑仑显示出相似结果。接受阿普唑仑治疗的患者报告了更多与治疗相关的不良事件，尤其是中枢神经系统相关不良事件，特别是在停药后。未发现显著的治疗反应预测因素。
这项随机对照试验为依替福辛治疗伴有焦虑的适应障碍的疗效和安全性提供了支持，尤其是在评估停药数据时。依替福辛具有抗焦虑作用且不产生依赖性这一重要临床优势。对于基线焦虑症状较严重的患者，药物治疗同样有效。使用更长时间的随访并收集管理方案成本效益数据的进一步研究将推动ADWA领域的发展。
本研究的赞助和文章处理费用由法国金蒂利的Biocodex公司提供。
