BACKGROUND Different effectiveness profiles among antipsychotics may be a key point to optimize treatment in patients suffering a first episode of psychosis to impact on long-term outcome. The aim of this study is to compare the clinical effectiveness of olanzapine, risperidone, haloperidol, aripiprazole, ziprasidone, and quetiapine in the treatment of first episode of psychosis at 3-year follow-up. METHOD From February 2001 to January 2011, 2 phases of a prospective, randomized, open-label study were undertaken. A total of 376 first-episode drug-naïve patients were randomly assigned to olanzapine (n = 55), risperidone (n = 63), haloperidol (n = 56), aripiprazole (n = 78), ziprasidone (n = 62), or quetiapine (n = 62) and followed up for 3 years. The primary effectiveness measure was all cause of treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted in the analysis for clinical efficacy. RESULTS The overall dropout rate at 3 years reached 20.75%. Treatment discontinuation rates were significantly different among treatment groups (olanzapine = 69.09, risperidone = 71.43, aripiprazole = 73.08%, ziprasidone = 79.03%, haloperidol = 89.28%, and quetiapine = 95.53%) (χ2 = 79.86; P = .000). Statistically significant differences in terms of lack of efficacy, adherence, and tolerability were observed among treatment groups along the 3-year follow-up, determining significant differences in time to all-cause discontinuation (log-rank = 92.240; P = .000). Significant differences between treatments were found in the categories of sleepiness/sedation, increased sleep duration, akinesia, weight gain, ejaculatory dysfunction, extrapyramidal-symptoms, and amenorrhea. CONCLUSIONS Olanzapine, risperidone, and aripiprazole presented advantages for the first-line treatment of first episode of psychosis in terms of effectiveness. Identifying different discontinuation patterns may contribute to optimize treatment selection after first episode of psychosis.ClinicalTrials.gov Identifier: NCT02526030 https://clinicaltrials.gov/show/NCT02526030.

中文翻译：

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首次精神病发作时抗精神病药物的治疗效果：比较氟哌啶醇、奥氮平、利培酮、阿立哌唑、喹硫平和齐拉西酮的 PAFIP 3 年随访随机临床试验。

背景抗精神病药物的不同疗效特征可能是优化首次精神病发作患者治疗以影响长期结果的关键点。本研究的目的是比较奥氮平、利培酮、氟哌啶醇、阿立哌唑、齐拉西酮和喹硫平治疗首次精神病发作 3 年随访的临床疗效。方法 从 2001 年 2 月到 2011 年 1 月，进行了 2 个阶段的前瞻性、随机、开放标签研究。总共 376 名首次用药患者被随机分配至奥氮平 (n = 55)、利培酮 (n = 63)、氟哌啶醇 (n = 56)、阿立哌唑 (n = 78)、齐拉西酮 (n = 62)、或喹硫平 (n = 62) 并随访 3 年。主要有效性衡量标准是治疗中断的所有原因。此外，在临床疗效分析中还进行了基于意向治疗原则的分析。结果3年总辍学率达20.75%。治疗组之间的治疗终止率存在显着差异（奥氮平 = 69.09、利培酮 = 71.43、阿立哌唑 = 73.08%、齐拉西酮 = 79.03%、氟哌啶醇 = 89.28% 和喹硫平 = 95.53%）（χ2 = 79.86；P = .000）。在 3 年随访期间，观察到治疗组之间在缺乏疗效、依从性和耐受性方面存在统计学上的显着差异，从而确定了全因停药时间的显着差异 (log-rank = 92.240；P = .000) 。在嗜睡/镇静、睡眠时间延长、运动不能、体重增加、射精功能障碍、锥体外系症状和闭经方面发现治疗之间的显着差异。结论 奥氮平、利培酮和阿立哌唑作为首发精神病的一线治疗在有效性方面具有优势。识别不同的停药模式可能有助于在首次精神病发作后优化治疗选择。ClinicalTrials.gov 标识符：NCT02526030 https://clinicaltrials.gov/show/NCT02526030。