Centre for Schizophrenia, Aalborg Psychiatric Hospital, Aarhus University Hospital, Denmark.
Schizophr Res. 2012 Sep;140(1-3):204-13. doi: 10.1016/j.schres.2012.06.020. Epub 2012 Jul 23.
Clozapine remains the drug of choice for treatment resistant schizophrenia, but is associated with potentially life threatening side effects, including agranulocytosis and myocarditis. Immunological mechanisms may be involved in the development of these side effects or in the unique antipsychotic efficacy in subgroups of schizophrenia patients. This systematic review presents the immunomodulatory effects of clozapine from human in vitro and in vivo studies and relates these findings to the developments of adverse and therapeutic effects of clozapine. Several studies confirm the immunomodulatory actions of clozapine, but only few studies investigated their relationship to the unique adverse and therapeutic effects of clozapine. During the first month of clozapine treatment, up to 50% of patients develop fever and flu like symptoms, which is seemingly driven by increased cytokines. Within the same time period, the risk of side-effects with a suspected immunological mechanism peaks. Patients developing fever during the first weeks of treatment should have a thorough physical examination, and measurements of white blood cell count, absolute neutrophil count, ECG, C-reactive protein, creatinine kinase, and troponin to exclude infection, agranulocytosis, myocarditis and neuroleptic malignant syndrome. To what degree the unique antipsychotic efficacy of clozapine in subgroups of schizophrenia patients is related to its immunomodulatory effects has not been studied. Research relating the immunomodulatory actions of clozapine and its early markers to clinically relevant adverse and therapeutic outcomes is hoped to provide new leads for the understanding of the pathophysiology of schizophrenia and aid the development of novel treatment targets.
氯氮平仍然是治疗耐药性精神分裂症的首选药物，但它与潜在的危及生命的副作用有关，包括粒细胞缺乏症和心肌炎。免疫机制可能参与这些副作用的发展，或参与精神分裂症患者亚组中氯氮平独特的抗精神病疗效。本系统评价从人体体外和体内研究中呈现了氯氮平的免疫调节作用，并将这些发现与氯氮平不良和治疗效果的发展联系起来。几项研究证实了氯氮平的免疫调节作用，但只有少数研究调查了它们与氯氮平独特的不良和治疗效果之间的关系。在氯氮平治疗的第一个月，多达 50%的患者出现发热和流感样症状，这似乎是由细胞因子增加引起的。在同一时期，具有疑似免疫机制的副作用风险达到高峰。在治疗的最初几周内出现发热的患者应进行彻底的体格检查，并测量白细胞计数、绝对中性粒细胞计数、心电图、C 反应蛋白、肌酸激酶和肌钙蛋白，以排除感染、粒细胞缺乏症、心肌炎和神经阻滞剂恶性综合征。氯氮平在精神分裂症患者亚组中独特的抗精神病疗效与其免疫调节作用有多大关系尚未研究。将氯氮平的免疫调节作用及其早期标志物与临床相关的不良和治疗结果联系起来的研究有望为理解精神分裂症的病理生理学提供新的线索，并有助于开发新的治疗靶点。
