Mood and Anxiety Disorders Section, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
J Clin Psychopharmacol. 2010 Apr;30(2):185-9. doi: 10.1097/JCP.0b013e3181d21951.
This 8-week, randomized, double-blind, placebo-controlled, flexible-dose trial assessed the efficacy, safety, and tolerability of ziprasidone in adults with treatment-resistant generalized anxiety disorder (GAD). Seventy-three subjects with treatment-resistant GAD were recruited, and 62 were randomized to either ziprasidone or placebo treatment at a ratio of 2:1 using a flexible dosing strategy (20-80 mg daily). Randomization was stratified into 2 subtypes of patients, those in whom the study drug was used as augmentation and those who have stopped their ineffective medications before entering the present trial (nonaugmented group). The subjects' clinical status was monitored weekly throughout the course of the study and included the Hamilton Anxiety Scale (primary outcome measure), the Clinical Global Impression Improvement and Severity of Illness scales, the Hamilton Depression Scale, the Sheehan Disability Scale, the Hospital Anxiety and Depression Scale, and the Abnormal Involuntary Movements Scale. Sixty-two patients were randomized to ziprasidone (n = 41) or placebo (n = 21). The dropout rate was 24%, consisting of 2 placebo patients and 13 ziprasidone patients. There was no statistically significant difference in the Hamilton Anxiety Scale score reduction between the drug and placebo groups. However, statistical trends were observed for an augmentation-study medication interaction effect, with ziprasidone patients producing more improvement in the nonaugmented than in the augmented group. This study provides pilot data for an augmentation-study medication interaction effect with ziprasidone patients producing more improvement in the nonaugmented than in the augmented group. Based on the data obtained in this trial and the subsequent power analyses, a future double-blind placebo-controlled trial should include at least 150 treatment-resistant GAD nonaugmented patients randomized to ziprasidone and placebo in a 1:1 ratio.
这项为期 8 周、随机、双盲、安慰剂对照、灵活剂量的试验评估了齐拉西酮治疗抵抗性广泛性焦虑症（GAD）成人患者的疗效、安全性和耐受性。共招募了 73 名患有抵抗性 GAD 的受试者，他们按照 2:1 的比例（每日 20-80mg），采用灵活剂量策略，随机分为齐拉西酮或安慰剂治疗组。随机分为两种患者亚组，一种是研究药物作为增效剂使用的患者，另一种是在进入本试验前停止使用无效药物的患者（非增效组）。在整个研究过程中，每周监测受试者的临床状态，包括汉密尔顿焦虑量表（主要结局指标）、临床总体印象改善和疾病严重程度量表、汉密尔顿抑郁量表、Sheehan 残疾量表、医院焦虑和抑郁量表以及异常不自主运动量表。62 名患者被随机分配至齐拉西酮（n = 41）或安慰剂（n = 21）组。脱落率为 24%，包括 2 名安慰剂患者和 13 名齐拉西酮患者。药物组和安慰剂组的汉密尔顿焦虑量表评分降低无统计学差异。然而，观察到增效-研究药物相互作用的统计趋势，非增效组的齐拉西酮患者的改善程度大于增效组。本研究提供了齐拉西酮增效-研究药物相互作用的初步数据，表明非增效组的齐拉西酮患者的改善程度大于增效组。基于该试验获得的数据和随后的功效分析，未来的双盲安慰剂对照试验应包括至少 150 名非增效性抵抗性 GAD 患者，以 1:1 的比例随机分配至齐拉西酮和安慰剂组。
