Psychiatric Neuroscience Group, Department of Neurological and Psychiatric Sciences, University of Bari, Bari, Italy.
Clin Ther. 2009 Dec;31(12):2851-9. doi: 10.1016/j.clinthera.2009.12.010.
Etizolam is an anxiolytic drug with a pharmacologic profile similar to that of the classic benzodiazepines. Neurochemical research suggests that etizolam may have selectivity for the subpopulation of Y-aminobutyric acid type A receptors associated with anxiety (ie, alpha1, beta2, gamma2). This property, plus its characterization as a ligand with fewer of the adverse events typical of full agonists (impaired cognitive function, tolerance, and dependence), led to its selection for this study.
The primary aim of this study was to test for the noninferiority of etizolam 0.5 mg BID versus placebo in affecting cognitive function in patients with mild to moderate anxiety disorder of recent onset (<1 month). Anxiety measures and tolerability were also assessed.
Patients between the ages of 18 and 65 years were eligible for enrollment. This double-blind, placebo-controlled study was performed in 5 centers in Italy using a 2-treatment, 3-period crossover design. Patients were randomized to 3-week sequences of either etizolam-placebo-placebo or placebo-etizolam-etizolam. They were evaluated at 4 scheduled visits (screening and days 7, 14, and 21). Cognitive function was assessed using scores from the Wechsler Adult Intelligence Scale (WAIS) Digit Span test (total forward and backward scores and the time required to perform the test). Anxiety was measured using the Hamilton Anxiety Rating Scale (HAM-A) and the State-Trait Anxiety Inventory (STAI) for screening and to monitor adequacy of therapy. Blood pressure, heart rate, weight, and adverse events were also recorded.
A total of 77 white patients were enrolled (mean age, 33.3 years [range, 22-60 years]; 62.3% female; mean weight, 65.2 kg). With a power of 0.80, the difference between the effects of etizolam and placebo on WAIS Digit Span performance was not significant for total score (0.102 [90% CI, -0.130 to 0.335]) or time required for completion (0.029 second [90% CI, -0.574 to 0.632]). Anxiety, as measured using the HAM-A and STAI instruments, did not differ significantly between groups. No significant differences were found between etizolam 0.5 mg BID and placebo for cardiovascular events, weight changes, or adverse events. Mild or moderate somnolence was reported by 7 of 77 patients (9.1% [3 patients while receiving etizolam and 4 patients while receiving etizolam and placebo]).
No significant differences between etizolam 0.5 mg BID and placebo were found for cognitive function or anxiety measures in these patients with anxiety. Etizolam was well tolerated.
依替唑仑是一种苯二氮䓬类抗焦虑药物，其药理学特征与经典苯二氮䓬类药物相似。神经化学研究表明，依替唑仑可能对与焦虑相关的γ-氨基丁酸 A 型受体亚群具有选择性（即α 1、β 2、γ 2）。这种特性，加上其作为一种配体的特征，与全激动剂（认知功能损害、耐受性和依赖性）的典型不良事件相比，不良事件更少，这导致了它在本研究中的选择。
本研究的主要目的是测试依替唑仑 0.5mg，每日 2 次（BID）与安慰剂相比，在影响新近发作（<1 个月）的轻度至中度焦虑障碍患者的认知功能方面是否具有非劣效性。还评估了焦虑测量和耐受性。
年龄在 18 至 65 岁之间的患者有资格入组。这是一项在意大利 5 个中心进行的双盲、安慰剂对照研究，采用 2 种治疗、3 期交叉设计。患者随机分为依替唑仑-安慰剂-安慰剂或安慰剂-依替唑仑-依替唑仑 3 周序列。他们在 4 次预定就诊时（筛选和第 7、14 和 21 天）进行评估。认知功能使用威斯康星州成人智力测验（WAIS）数字跨度测验（总分向前和向后得分以及完成测验所需的时间）的分数进行评估。焦虑使用汉密尔顿焦虑量表（HAM-A）和状态-特质焦虑量表（STAI）进行评估，用于筛查和监测治疗的充分性。还记录了血压、心率、体重和不良事件。
共有 77 名白人患者入组（平均年龄 33.3 岁[范围，22-60 岁]；62.3%为女性；平均体重 65.2kg）。在 0.80 的功效下，依替唑仑和安慰剂对 WAIS 数字跨度表现的影响在总分（0.102[90%CI，-0.130 至 0.335]）或完成时间（0.029 秒[90%CI，-0.574 至 0.632]）方面无显著差异。使用 HAM-A 和 STAI 工具测量的焦虑在组间无显著差异。依替唑仑 0.5mg BID 和安慰剂之间在心血管事件、体重变化或不良事件方面无显著差异。77 名患者中有 7 名（9.1%[3 名接受依替唑仑治疗，4 名接受依替唑仑和安慰剂治疗]）报告出现轻度或中度嗜睡。
在这些焦虑患者中，依替唑仑 0.5mg BID 与安慰剂在认知功能或焦虑测量方面未发现有统计学意义的差异。依替唑仑耐受性良好。
