喹硫平和氟哌啶醇治疗精神分裂症急性期兴奋激越的多中心随机对照研究

A randomized controlled study of effect and safety of quetiapine and haloperidol in treatment of schizophrenic patients with excitement and agitation

目的:评价喹硫平治疗中国精神分裂症患者急性期兴奋激越的疗效和安全性。方法:本研究为多中心随机对照研究。选取80例符合国际疾病与相关健康问题分类第十版(ICD-10)精神分裂症诊断标准并处于急性兴奋激越状态的患者,按1∶1随机分为喹硫平组(n=40)和氟哌啶醇组(n=40),接受28天的喹硫平或氟哌啶醇治疗。入组时和治疗第1、3、7、10、14、28天进行临床评估,采用阳性与阴性症状量表(PANSS)和总体印象量表中的疾病严重程度(CGI-SI)评估临床症状,并采用PANSS兴奋因子(PANSS-EC)的减分值以及起效时间(PANSS-EC减分率达20%的时间)为主要疗效指标,Simpson-Angus类帕金森综合征量表(SAS)评定锥体外系不良反应。每次临床评估时记录生命体征和服药情况,基线和治疗第28天进行体格检查及血、尿、血生化常规,血清催乳素,心电图等实验室检查。结果:治疗第28天,喹硫平组剂量为(672.9±88.3)mg,氟哌啶醇组剂量为(11.5±3.2)mg。喹硫平组和氟哌啶醇组PANSS-EC评分随着治疗时间的延长逐渐降低,治疗第1天两组均12.5%起效,治疗第7天起效率分别达到82.5%和75.0%。治疗第28天,两组PANSS、CGI-SI量表得分差异无统计学意义,喹硫平组的不良事件发生率(40.0%vs.87.5%)、SAS评分[(0.2±0.8)vs.(1.5±2.2)]和泌乳素水平[(375.0±388.2)μIU/mL vs.(1526.5±1300.6)μIU/mL]均低于氟哌啶醇组(均P<0.05)。喹硫平组的心电图QT间期治疗前后无明显变化,氟哌啶醇组则从(351.8±46.1)ms增加至(374.3±27.5)ms(P<0.05)。结论:喹硫平单药治疗精神分裂症急性期兴奋激越症状起效快速、疗效充分,安全性高、耐受性好。

Objective： To evaluate the efficacy and safety of quetiapine and haloperidol in the treatment of acute excitement and agitation symptoms in patients with schizophrenia. Methods： Totally 80 schizophrenic patients diagnosed according to the International Classification of Diseases and Related Health Problems, Tenth Revision （ICD-10） criteria were enrolled in a 28-day multi-center clinical trial, with 40 patients in quetiapine group and 40 patients in haloperidol group. The Positive and Negative Syndrome Scale （PANSS） and Clinical Global Impression- Severity of Illness （CGI-SI） were used to evaluate the severity of the clinical symptoms. The Positive and Negative Syndrome Scale Excited Component （PANSS-EC） and time to clinical response （ I〉20% improvement in score on PANSS-EC） were used as primary efficacy indices. The Simpson-Angus Rating Scale （SAS） was used to assess the safety, and the vital signs, routine blood test, routine urine test, blood biochemistrys, prolactine and electrocardiogram （ECG） examinations were measured. Results： On the 28th day, the dose of quetiapine was （672. 9± 88. 3） mg, and the dose of haloperidol was （ 11.5 ± 3.2） mg. The PANSS-EC scores was decreased both in quetiapine and haloperidol group, and the response rates were both 12. 5% on the first day in the two groups. On the 7th day, the rates of clinical response increased to 82. 5% and 75.0% in quetiapine and haloperidol group respectively. There were no significant differences between the two groups in scores of PANSS, CGI-SI on the 28th day. On the 28th day, the incidence of adverse reactions （40. 0% vs. 87.5%）, the SAS scores [（0. 2 ±0. 8） vs. （1.5±2. 2）] and the prolactin level [（375.0 ±388.2） uIU/mL vs. （1526. 5 ± 1300. 6） uIU/mL] were all lower in the quetiapine group than in the haloperidol group （Ps 〈0. 05）. On the 28the day, the QT interval of ECG was increased from （351.8 ± 46. 1） ms to （374. 3 ± 27.5） ms in haloperidol group, while not in the quetiapine group）. Conclusion： It suggests that quetiapine is as effective as haloperidol in the acute management of psychotic agitation in schizophrenic pa- tients, and with fewer adverse events.