Kahn René S, Schulz S Charles, Palazov Veselin D, Reyes Efren B, Brecher Martin, Svensson Ola, Andersson Henrik M, Meulien Didier
Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center, Utrecht, The Netherlands.
J Clin Psychiatry. 2007 Jun;68(6):832-42. doi: 10.4088/jcp.v68n0603.
To evaluate the efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR) in a 6-week, double-blind, randomized study.
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.
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.
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.
ClinicalTrials.gov identifier NCT00206115.
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。
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。
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。
对于急性精神分裂症患者，每日一次的quetiapine XR（400 - 800毫克/天）相对于安慰剂有效。包括快速剂量递增在内的治疗耐受性良好，在第2天即可达到治疗有效剂量。
ClinicalTrials.gov标识符NCT00206115。
