Opipramol for the treatment of generalized anxiety disorder:: A placebo-controlled trial including an alprazolam-treated group
Opipramol for the treatment of generalized anxiety disorder:: A placebo-controlled trial including an alprazolam-treated group
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DOI：
10.1097/00004714-200102000-00011
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发表时间：
2001-02-01
影响因子：
2.9
通讯作者：
Stoll, KD
中科院分区：
文献类型：
--
作者：
Möller, HJ;Volz, HP;Stoll, KD
Opipramol是一种在德国广泛使用的药物，是一种三环化合物，没有再摄取抑制特性。然而，它具有显著的D-2-、5-HT 2-和H-1-阻断潜力和对σ受体（σ-1和σ-2）的高亲和力。在早期的对照试验中，抗焦虑作用仅仅被发现。然而，这些研究是在广泛性焦虑症（GAD）的概念建立之前进行的。由于有趣的受体结合特征和早期临床试验的有希望的结果，作者使用阿普唑仑作为活性对照进行了一项最先进的安慰剂对照试验。纳入307例GAD门诊患者。在7天的单盲安慰剂洗脱期后，患者被随机分配接受奥匹哌醇（最终剂量，200 mg/天）、阿普唑仑（2 mg/天）或安慰剂，治疗28天。两种活性化合物的疗效均高于安慰剂治疗的效果。在主要结果标准（汉密尔顿焦虑量表总分的意向治疗分析的基线校正最终平均值）和次要疗效参数方面仅有统计学显著性差异（p <0.05，根据协方差分析），安慰剂组总体改善47%，奥匹哌醇组（63%）和阿普唑仑组（64%）显著改善更多。关于安全性和耐受性，治疗组间观察到的不良事件数量无明显实质性差异。阿普唑仑治疗的镇静作用似乎比奥匹哌醇或安慰剂更明显。在该试验中，首次证明奥匹哌醇，一种强但非选择性的σ位点配体，在治疗GAD中具有优于安慰剂的抗焦虑功效上级。
Opipramol, a drug widely prescribed in Germany, is a tricyclic compound with no reuptake-inhibiting properties. However, it has pronounced D-2-, 5-HT2-, and H-1-blocking potential and high affinity to sigma receptors (sigma-1 and sigma-2). In early controlled trials, anxiolytic effects mere revealed. However, those studies were performed before the concept of generalized anxiety disorder (GAD) was established. Because of the interesting receptor-binding profile and promising results of the early clinical trials, the authors performed a state-of-the-art placebo-controlled trial using alprazolam its an active control. Three hundred seven outpatients with GAD were included. After a 7-day single-blind placebo washout, patients were randomly assigned to receive either opipramol (final dose, 200 mg/day), alprazolam (2 mg/day), or placebo and were treated for 28 days. The efficacy of both active compounds was higher than the effects with placebo treatment. There mere statistically significant differences (p < 0.05, according to the analysis of covariance) in the main outcome criterion (baseline-adjusted final means of an intent-to-treat analysis of the total scores on the Hamilton Rating Scale for Anxiety) and in secondary efficacy parameters, with global improvement of 47% for placebo and significantly more for opipramol (63%) and alprazolam (64%). Regarding safety and tolerability, no substantial differences in the number of adverse events observed between treatment groups mere obvious. Sedation seemed more pronounced with alprazolam treatment than with opipramol or placebo. In this trial, it was demonstrated for the first time that opipramol, a strong but nonselective sigma site ligand, possesses anxiolytic efficacy superior to placebo in the treatment of GAD.