富马酸喹硫平缓释片每日一次治疗急性精神分裂症的疗效和耐受性：一项随机、双盲、安慰剂对照研究。

Efficacy and tolerability of once-daily extended release quetiapine fumarate in acute schizophrenia: a randomized, double-blind, placebo-controlled study.

作者信息

Kahn René S, Schulz S Charles, Palazov Veselin D, Reyes Efren B, Brecher Martin, Svensson Ola, Andersson Henrik M, Meulien Didier

机构信息

Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center, Utrecht, The Netherlands.

出版信息

J Clin Psychiatry. 2007 Jun;68(6):832-42. doi: 10.4088/jcp.v68n0603.

DOI:10.4088/jcp.v68n0603

PMID:17592906

Abstract

OBJECTIVE

To evaluate the efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR) in a 6-week, double-blind, randomized study.

METHOD

Patients with a DSM-IV diagnosis of acute schizophrenia were randomly assigned to fixed-dose quetiapine XR 400, 600, or 800 mg/day (once daily in the evening), quetiapine immediate release (IR) 400 mg/day (200 mg twice daily), or placebo. Dual-matched placebo was used to maintain blinding. Quetiapine XR target doses were reached by day 2 (400 and 600 mg) and day 3 (800 mg). The primary endpoint was least squares mean change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score. PANSS response rate (percentage of patients with > or = 30% reduction in total score), Clinical Global Impressions-Improvement scale (CGI-I) response rate (percentage of patients with score < or = 3), change in CGI-Severity of Illness (CGI-S), and adverse events (AEs) were also assessed. The study was conducted from November 2004 to December 2005.

RESULTS

588 patients were enrolled and 446 (76%) completed the study. Improvement in PANSS total score at week 6 was significant versus placebo (-18.8) in all groups: -24.8 (p = .03), -30.9 (p < .001), and -31.3 (p < .001) for quetiapine XR 400, 600, and 800 mg, respectively, and -26.6 (p = .004) for quetiapine IR. There were also statistically significant differences in PANSS and CGI-I response rates for all active treatments versus placebo (all p < .05). The most common AEs in all quetiapine groups were somnolence and dizziness; there were no unexpected AEs with quetiapine XR. Incidence of AEs potentially related to extrapyramidal symptoms was similar to placebo.

CONCLUSION

Once-daily quetiapine XR (400-800 mg/day) was effective versus placebo in patients with acute schizophrenia. Treatment, including rapid dose escalation, was well tolerated, with a therapeutically effective dose reached by day 2.

CLINICAL TRIALS REGISTRATION

ClinicalTrials.gov identifier NCT00206115.

摘要

目的

在一项为期6周的双盲随机研究中评估富马酸喹硫平缓释片（quetiapine XR）的疗效和耐受性。

方法

符合《精神疾病诊断与统计手册》第四版（DSM-IV）急性精神分裂症诊断标准的患者被随机分配至固定剂量的quetiapine XR组，剂量分别为400、600或800毫克/天（每晚一次），quetiapine速释片（IR）组，剂量为400毫克/天（每日两次，每次200毫克），或安慰剂组。使用双重匹配安慰剂以维持盲法。quetiapine XR的目标剂量在第2天（400和600毫克）和第3天（800毫克）达到。主要终点是从基线到第6周阳性与阴性症状量表（PANSS）总分的最小二乘均值变化。还评估了PANSS缓解率（总分降低≥30%的患者百分比）、临床总体印象改善量表（CGI-I）缓解率（评分≤3的患者百分比）、CGI疾病严重程度（CGI-S）的变化以及不良事件（AE）。该研究于2004年11月至2005年12月进行。

结果

共纳入588例患者，446例（76%）完成研究。在第6周时，所有组的PANSS总分改善相对于安慰剂均有显著差异（-18.8）：quetiapine XR 400毫克组为-24.8（p = 0.03），600毫克组为-30.9（p < 0.001），800毫克组为-31.3（p < 0.001），quetiapine IR组为-26.6（p = 0.004）。所有活性治疗组与安慰剂组在PANSS和CGI-I缓解率方面也存在统计学显著差异（所有p < 0.05）。所有喹硫平组中最常见的不良事件是嗜睡和头晕；quetiapine XR未出现意外不良事件。与锥体外系症状潜在相关的不良事件发生率与安慰剂相似。