利培酮、奥氮平和喹硫平治疗未服药的精神分裂症患者的疗效和不良反应：1年自然观察研究

背景第二代抗精神病药被日益广泛地用于治疗精神分裂症首次发作,但其疗效是否一致尚有争议。假设利培酮、奥氮平、喹硫平治疗未服药的首次发病的精神分裂症或分裂样精神障碍患者,其1年的疗效是一致的。方法采用自然观察研究方法,对病程≤5年,符合ICD-10精神分裂症或分裂样精神障碍研究用诊断标准的未服药门诊患者随访1年。纳入398例患者,分别用利培酮（131例）、奥氮平（136例）、喹硫平（131例）单药治疗。在开始治疗后的第2周,2、3、6、8以及12个月时采用阳性与阴性综合征量表（Positive and Negative Syndrome Scale,PANSS）评估疗效,用副反应量表（Treatment Emergent Symptom Scale,TESS）评估治疗中出现的不良反应,非盲法评定。结果共269例（67%）患者完成1年随访。利培酮组、奥氮平组和喹硫平组的停药率分别为35.1%（46/131）、31.6%（43/136）和32.1%（42/131）,χ^2=0.43,P=0.809。对脱落患者的资料采用末次观察结转法,1年时利培酮组、奥氮平组和喹硫平组的PANSS总分平均值（标准差）分别减少46.8%（17.0%）,48.6%（19.6%）和47.3%（16.2%）,F=0.38,P=0.688。重复测量的方差分析显示,无论是PANSS总分还是分量表分,治疗各时点三组间差异均无统计学意义。治疗第2周时利培酮组发生震颤和静坐不能的比例高于其他两组。1年时,3组中常见的不良反应是体重增加和嗜睡,奥氮平组体重增加的比例（69.9%）高于其他两组。根据持续存在不良反应症状的时点数与总随访时点数的比值衡量不良反应的持续时间,锥体外系症状在利培酮组最明显,体重增加在奥氮平组最明显,心动过速在喹硫平组最明显。结论利培酮、奥氮平、喹硫平单药治疗未服药的精神分裂症或分裂样精神障碍患者1年疗效相似,但不良反应有所不同。

Efficacy and side effects of monotherapy risperidone,olanzapine and quetiapine in previously untreated patients with schizophrenia:a one-year prospectivecohort study

Background：Second-generation antipsychotics are widely used in the initial episode of schizophrenia,but it remains unclear whether or not they have differential efficacy in this situation.Hypothesis：There are no significant differences in the comparative therapeutic efficacy of risperidone,olanzapine,and quetiapine over the first year of treatment in drug-nave,first-episode patients with schizophrenia or schizophreniform disorder.Methods：398 previously untreated patients with a duration of illness of less than 5 years who met ICD-10 diagnostic criteria for schizophrenia or schizophreniform disorder and were treated with either monotherapy risperidone（n=131）,olanzapine（n=136）or quetiapine（n=131）were followed for one year.The Positive and Negative Syndrome Scale（PANSS）was used to evaluate therapeutic efficacy and the Treatment Emergent Symptom Scale（TESS）was used to evaluate adverse reactions at 2 weeks and at 2,3,6,8 and 12 months after initiating treatment.Results：In total,267 patients（67%）completed the entire study.The discontinuation rates in the risperdone,olanzapine and quetiapine groups were 35.1%（46/131）,31.6%（43/136）and 32.1%（42/131）,respectively（χ2=0.43,P=0.809）.Using the last observation carried forward method to assess final outcome in those who dropped out,the mean（SD）percent decrease in the total PANSS scores at the one-year endpoint in the risperidone,olanzapine,and quetiapine groups were 46.8%（17.0%）,48.6%（19.6%）and 47.3%（16.2%）,respectively,（F=0.38,P=0.688）.Repeated measures analysis of variance analysis found no differences between the groups over time in the total PANSS score or in PANSS subscale scores.The prevalence of tremor and akithesia in the risperidone group at week 2 of treatment was significantly higher than that in the other two groups.At the one-year assessment the most common side effects in all three groups were weight gain and drowsiness,but the prevalence of weight gain in the olanzapine group（69.9%）was much higher than in the other two groups.The persistence（i.e.,the proportion of the follow-up period during which the symptoms were present）of extrapyramidal symptoms were greatest for risperidone,the persistence of weight gain was greatest for olanzapine and the persistence of tachycardia was greatest for quetiapine.Conclusion：There are no significant therapeutic differences when treating drug-naive patients with schizophrenia or schizophreniform disorder with monotherapy risperidone,olanzapine or quetiapine for one year.However,the profile of adverse reactions is somewhat different for the three medications.