奥氮平换用齐拉西酮治疗精神分裂症的安全性和有效性研究

Switching from olanzapine to ziprasidone:a 12-Week,open-label,multicenter study evaluating the effectiveness and safety of ziprasidone in patients with schizophrenia

目的观察不能耐受奥氮平治疗或经奥氮平治疗无效的精神分裂症患者换用齐拉西酮治疗12周的安全性和有效性。方法 100例不能耐受奥氮平治疗或治疗无效、符合美国精神疾病诊断与统计手册第4版(DSM-IV)精神分裂症诊断标准、首次发作或非难治性复发精神分裂症患者,换用可变剂量的齐拉西酮治疗12周。分别于基线和治疗第2、4、8、12周末进行疗效评估,包括阳性和阴性综合征量表(PANSS)、卡尔加里抑郁量表(CDSS)、临床总体印象量表(CGI)、生活质量量表(SF-12)。分别于基线和治疗第4、8周末进行安全性评估,包括锥体外系不良反应量表(SAS)、实验室检查和心电图检查。采用重复测量方差分析进行统计学分析。结果86例患者完成实验。PANSS总分随观察时点变化有显著性降低(P<0.001),多项抑郁症状(CDSS评估)、临床总体印象(CGI评分)及社会功能(SF-12评估)随观察时点变化有显著改善(P<0.001)。有完整的不良反应记录共61例,常见的锥体外系不良反应22例(36.07%),相对少见的不良反应10例(16.39%),包括激越2例(3.28%)、恶心1例(1.64%)、便秘1例(1.64%)、失眠1例(1.64%)、头晕1例(1.64%)、头痛1例(1.64%)、焦虑1例(1.64%)、口干1例(1.64%)、心动过速1例(1.64%)。空腹血糖、糖化血红蛋白、甘油三酯、总胆固醇和催乳素以及心电图QTc间期和心率随观察时点的变化无统计学意义(P>0.05)。结论不能耐受奥氮平治疗或经奥氮平治疗无效的患者换用齐拉西酮治疗后,临床症状显著改善,不良反应较少,对代谢指标的影响小。

Objective To evaluate the effectiveness and safety of switching to ziprasidone from olanzapine because of inadequate response or intolerance. Methods A total of 100 patients with first-episode or non-refractory schizophrenia （diagnosed according with the criteria of DSM-IV ） who had no response to olanzapine or showed poor tolerance to alanzapine were enrolled in a 12-week, open-label, flexible-dose ziprasidone trial. All patients were assessed with Positive and Negative Syndrome Scale （PANSS）, Calgary Depression Scale （CDSS）, global impression scale （CGI） and Social Functions （SF-12） at baseline and the end of 2nd, 4th, 8th, 12th week to evaluate the efficacy. Extrapyramidal Side Effects Scale （SAS）, laboratory examination and electrocardiogram examination were performed to evaluate the safety at baseline and the end of the 4th, 8th week of the treatment. Results A total of 86 patients completed the trial. Scores of PANSS, CDSS, CGI and SF-12 all decreased significantly with the advance of the treatment （P 〈 0. 001 ）. 61 complete records of adverse reactions were collected. The most common adverse reaction was extrapyramidal effect （ 32 cases, 36.07% ）. The prevalence of relatively rare adverse reactions was 16. 39% （ 10 cases） , which consisted of agitation （2 cases） , nausea （ 1 case） , constipation （ 1 case） , insomnia （ 1 case） , dizziness （1 case）, headache （1 case）, anxiety （1 case）, dry mouth （1 case） and tachycardia （1 case）. There were no significant changes in fasting glucose, HbA1 c, triglyceride, total cholesterol, prolactin, QTc interval, heart rate at different observation time-points with the advance of the treatment. Conclusion Ziprasidone can improve the clinical symptoms effectively in patients who had no response to olanzapine or showed poor tolerance to alanzapine. Ziprasidone has less adverse reactions and has little effect on metabolism.