Factor S A, Friedman J H, Lannon M C, Oakes D, Bourgeois K
Albany Medical College, New York, USA.
Mov Disord. 2001 Jan;16(1):135-9. doi: 10.1002/1531-8257(200101)16:1<135::aid-mds1006>3.0.co;2-q.
To report the results of the 12-week, prospective, open label extension of the 4-week, multicenter, placebo-controlled, double-blind PSYCLOPS (PSYchosis and CLOzapine in the treatment of Parkinsonism) trial. This extension examined the chronic safety and efficacy of clozapine in the treatment of drug-induced psychosis in Parkinson's disease (PD).
Psychosis is a serious late complication of PD and may be a harbinger to increased mortality. Clozapine, the first atypical antipsychotic, was shown in several small open label studies to improve psychosis without worsening of motor symptoms. This was recently confirmed in the double-blind PSYCLOPS trial.
The 53 patients who completed the double-blind portion of PSYCLOPS were evaluated on their original randomized treatment (clozapine or placebo), then had study medication stopped. All were started on clozapine. The patients from both treatment groups were evaluated every 4 weeks over a 12-week period using standardized measures for psychosis and PD.
The mean dose of clozapine was 28.78 mg/day. Those originally treated with placebo improved significantly in Brief Psychiatric Rating Scale and clinical global scores for psychosis to the same degree as the group originally randomized to clozapine in the double-blind study. Both groups maintained their response to week 16 (end of the combined double-blind and open label portions). There was no worsening of motor features as measured by the Unified Parkinson's disease rating scale. Eighteen patients were either hospitalized or died during the trial. The most common reasons were pulmonary.
Low-dose clozapine is effective in treating drug-induced psychosis without worsening motor features of PD, and the response is maintained for at least 4 months. Patients with psychosis and PD were previously described as a group with high risk for morbidity and mortality. The high risk continues despite antipsychotic therapy.
报告为期4周的多中心、安慰剂对照、双盲PSYCLOPS（帕金森病中的精神病与氯氮平治疗）试验的12周前瞻性开放标签扩展试验结果。该扩展试验考察了氯氮平治疗帕金森病（PD）药物性精神病的长期安全性和疗效。
精神病是PD的一种严重晚期并发症，可能是死亡率增加的先兆。氯氮平作为首个非典型抗精神病药物，在多项小型开放标签研究中显示可改善精神病症状且不加重运动症状。这一结果最近在双盲PSYCLOPS试验中得到证实。
对完成PSYCLOPS双盲部分的53例患者，先根据其最初随机接受的治疗（氯氮平或安慰剂）进行评估，然后停用研究药物。所有患者均开始服用氯氮平。在12周期间，每4周使用精神病和PD的标准化测量方法对两个治疗组的患者进行评估。
氯氮平的平均剂量为28.78毫克/天。最初接受安慰剂治疗的患者在简明精神病评定量表和精神病临床总体评分方面有显著改善，程度与双盲研究中最初随机分配接受氯氮平治疗的组相同。两组在第16周（双盲和开放标签部分联合结束时）均维持了疗效。根据统一帕金森病评定量表测量，运动特征未恶化。18例患者在试验期间住院或死亡。最常见的原因是肺部问题。
低剂量氯氮平可有效治疗药物性精神病，且不加重PD的运动特征，疗效至少维持4个月。患有精神病和PD的患者此前被描述为发病率和死亡率高的群体。尽管进行了抗精神病治疗，高风险仍然存在。
