Pôle Universitaire de Psychiatrie - Solaris, Hôpital Sainte Marguerite, Marseille, France.
Expert Opin Pharmacother. 2012 Sep;13(13):1923-35. doi: 10.1517/14656566.2012.709235. Epub 2012 Jul 18.
Despite considerable progress in the pharmacological treatment of schizophrenia, about 30% of patients are minimally responsive to antipsychotics and there is still an excessively high rate of mortality in schizophrenia patients. Clozapine , a D(2)-5HT(2) antagonist, was the first antipsychotic to demonstrate efficacy in treatment-resistant patients, and to be associated with the lowest risk of death.
The pharmacodynamics, pharmacokinetics, clinical efficacy, safety and cost-effectiveness of clozapine are covered in this article, based on a literature review (PubMed) from 1975 to 2012. Pivotal, as well as supporting, randomized controlled trials are reviewed, along with observational and/or naturalistic safety studies. This review of clozapine will allow the reader to determine the place for clozapine in the schizophrenia treatment landscape.
Studies conducted so far suggest that clozapine is the treatment of choice for schizophrenic patients who are refractory to treatment, display violent behaviors, or who are at high risk of suicide. However, it is also the antipsychotic with the worst side effect profile, the highest risk of complications, and the most difficult to prescribe. Experience with clozapine should therefore be included in the education of future physicians.
尽管精神分裂症的药物治疗已经取得了相当大的进展，但仍有约 30%的患者对抗精神病药物反应不佳，精神分裂症患者的死亡率仍然过高。氯氮平是一种 D2-5HT2 拮抗剂，是第一种在治疗抵抗患者中显示疗效的抗精神病药物，与最低的死亡风险相关。
本文基于 1975 年至 2012 年的文献回顾（PubMed），介绍了氯氮平的药效学、药代动力学、临床疗效、安全性和成本效益。关键性和支持性随机对照试验，以及观察性和/或自然安全性研究都进行了回顾。对氯氮平的回顾将使读者能够确定氯氮平在精神分裂症治疗领域的地位。
迄今为止的研究表明，氯氮平是治疗对治疗有抗药性、表现出暴力行为或有自杀高风险的精神分裂症患者的首选药物。然而，它也是副作用最严重、并发症风险最高、最难开处方的抗精神病药物。因此，氯氮平的经验应纳入未来医生的教育中。
