The Zucker Hillside Hospital, North Shore - Long Island Jewish Health System, Glen Oaks, New York, United States.
Schizophr Res. 2012 Feb;134(2-3):180-6. doi: 10.1016/j.schres.2011.10.014. Epub 2011 Nov 22.
Clozapine is widely prescribed for treatment refractory patients with schizophrenia, but its use is limited by potentially life threatening adverse effects. Rechallenge after these complications has been occasionally attempted in patients with severe psychotic symptoms.
To review the outcome of clozapine rechallenge after potentially life threatening adverse effects.
Electronic, all-language, literature search (1972-2011) followed by demographic and clinical data extraction. The outcome of rechallenge was considered favorable when the lower bound of the 95% confidence interval (CI) of the proportion of patients who could continue clozapine was >50%.
Altogether, 138 patients (mean age: 36.3years, 65.7% male, 57.6% Caucasian, virtually all with schizophrenia spectrum diagnosis) underwent clozapine rechallenge after developing neutropenia (n=112), agranulocytosis (n=15), neuroleptic malignant syndrome (NMS) (n=5), myocarditis (n=4), pericarditis (n=1) and lupus erythematosus (n=1). Rechallenge strategies were heterogeneous and not systematically evaluated. Clozapine rechallenge was successful in 78/112 patients (69.6%, CI: 60.6-77.4) after neutropenia, 3/15 (20%, CI: 7.1-45.2) after agranulocytosis, 5/5 (100%, CI: 56-100) after NMS, 3/4 (75%, CI: 30-95) after myocarditis, 1/1 after pericarditis, and 0/1 after clozapine-induced lupus. Successfully rechallenged patients were followed for 16-96weeks. None of the rechallenged patients died.
Although controlled studies are clearly needed, using a priori, confidence interval-based criteria, case reports/series suggest that in refractory patients who benefited from clozapine, careful rechallenge can be considered after neutropenia and NMS, but not after agranulocytosis and myocarditis.
氯氮平被广泛用于治疗治疗抵抗的精神分裂症患者，但由于其潜在的致命不良反应，其使用受到限制。在出现严重精神病症状的患者中，偶尔会尝试在这些并发症后重新使用氯氮平。
回顾潜在危及生命的不良反应后氯氮平重新使用的结果。
电子、所有语言的文献检索（1972-2011 年），随后进行人口统计学和临床数据提取。当置信区间（CI）下限>50%的患者继续使用氯氮平的比例时，重新使用的结果被认为是有利的。
共有 138 名患者（平均年龄：36.3 岁，65.7%为男性，57.6%为白种人，几乎所有患者均为精神分裂症谱系诊断）在发生中性粒细胞减少症（n=112）、粒细胞缺乏症（n=15）、恶性神经阻滞剂综合征（NMS）（n=5）、心肌炎（n=4）、心包炎（n=1）和红斑狼疮（n=1）后重新使用氯氮平。重新使用的策略是不同的，没有进行系统评估。中性粒细胞减少症后，112 名患者中有 78 名（69.6%，CI：60.6-77.4）、粒细胞缺乏症后 15 名患者中有 3 名（20%，CI：7.1-45.2）、NMS 后 5 名患者中有 5 名（100%，CI：56-100）、心肌炎后 4 名患者中有 3 名（75%，CI：30-95）、心包炎后 1 名患者中有 1 名（100%，CI：56-100）、红斑狼疮后 1 名患者中有 0 名（0%，CI：0-100）成功重新使用氯氮平。成功重新使用的患者随访时间为 16-96 周。重新使用的患者无一例死亡。
尽管显然需要对照研究，但根据预先设定的置信区间基于标准，病例报告/系列表明，在受益于氯氮平的难治性患者中，在中性粒细胞减少症和 NMS 后可以考虑谨慎重新使用，但粒细胞缺乏症和心肌炎后不可以。
