N Engl J Med. 1999 Mar 11;340(10):757-63. doi: 10.1056/NEJM199903113401003.
Drug-induced psychosis is a difficult problem to manage in patients with Parkinson's disease. Multiple open-label studies have reported that treatment with clozapine at low doses ameliorates psychosis without worsening parkinsonism.
We conducted a randomized, double-blind, placebo-controlled trial of low doses of clozapine (6.25 to 50 mg per day) in 60 patients at six sites over a period of 14 months. The patients (mean age, 72 years) had idiopathic Parkinson's disease and drug-induced psychosis of at least four weeks' duration. All the patients continued to receive fixed doses of antiparkinsonian drugs during the four weeks of the trial. Blood counts were monitored weekly in all the patients.
The mean dose of clozapine was 24.7 mg per day. The patients in the clozapine group had significantly more improvement than those in the placebo group in all three of the measures used to determine the severity of psychosis. The mean (+/-SE) scores on the Clinical Global Impression Scale improved by 1.6+/-0.3 points for the patients receiving clozapine, as compared with 0.5+/-0.2 point for those receiving placebo (P<0.001). The score on the Brief Psychiatric Rating Scale improved by 9.3+/-1.5 points for the patients receiving clozapine, as compared with 2.6+/-1.3 points for those receiving placebo (P=0.002). The score on the Scale for the Assessment of Positive Symptoms improved by 11.8+/-2.0 points for the patients receiving clozapine, as compared with 3.8+/-1.9 points for those receiving placebo (P=0.01). Seven patients treated with clozapine had an improvement of at least three on the seven-point Clinical Global Impression Scale, as compared with only one patient given placebo. Clozapine treatment improved tremor and had no deleterious effect on the severity of parkinsonism. In one patient, clozapine was discontinued because of leukopenia.
Clozapine, at daily doses of 50 mg or less, is safe and significantly improves drug-induced psychosis without worsening parkinsonism.
药物性精神病是帕金森病患者治疗中一个棘手的问题。多项开放标签研究报告称，低剂量氯氮平治疗可改善精神病症状，且不会加重帕金森综合征。
我们在六个地点对60例患者进行了一项为期14个月的随机、双盲、安慰剂对照试验，给予低剂量氯氮平（每天6.25至50毫克）。这些患者（平均年龄72岁）患有特发性帕金森病且药物性精神病持续至少四周。在试验的四周期间，所有患者继续接受固定剂量的抗帕金森病药物治疗。所有患者每周监测血常规。
氯氮平的平均剂量为每天24.7毫克。在用于确定精神病严重程度的所有三项指标上，氯氮平组患者的改善程度均显著高于安慰剂组。接受氯氮平治疗的患者临床总体印象量表的平均（±标准误）评分提高了1.6±0.3分，而接受安慰剂治疗的患者为0.5±0.2分（P<0.001）。接受氯氮平治疗的患者简明精神病评定量表评分提高了9.3±1.5分，接受安慰剂治疗的患者为2.6±1.3分（P=0.002）。接受氯氮平治疗的患者阳性症状评估量表评分提高了11.8±2.0分，接受安慰剂治疗的患者为3.8±1.9分（P=0.01）。接受氯氮平治疗的7例患者在七点临床总体印象量表上的改善至少为三分，而接受安慰剂治疗的患者只有1例。氯氮平治疗改善了震颤，且对帕金森综合征的严重程度没有有害影响。有1例患者因白细胞减少而停用氯氮平。
氯氮平每日剂量50毫克或更低时是安全的，可显著改善药物性精神病，且不会加重帕金森综合征。
