Beijing Key Laboratory of Mental Disorders, Department of Psychiatry, Beijing Anding Hospital, Capital Medical University, Beijing, China; Center of Schizophrenia, Beijing Institute for Brain Disorders, Laboratory of Brain Disorders (Capital Medical University), Ministry of Science and Technology, Beijing, China.
Bipolar Disord. 2015 May;17(3):235-47. doi: 10.1111/bdi.12272. Epub 2014 Oct 27.
To evaluate the efficacy and safety of clozapine for treatment-resistant bipolar disorder (TRBD).
A systematic review of randomized controlled studies, open-label prospective studies, and retrospective studies of patients with TRBD was carried out. Interventions included clozapine monotherapy or clozapine combined with other medications. Outcome measures were efficacy and adverse drug reactions (ADRs).
Fifteen clinical trials with a total sample of 1,044 patients met the inclusion criteria. Clozapine monotherapy or clozapine combined with other treatments for TRBD was associated with improvement in: (i) symptoms of mania, depression, rapid cycling, and psychotic symptoms, with many patients with TRBD achieving a remission or response; (ii) the number and duration of hospitalizations, the number of psychotropic co-medications, and the number of hospital visits for somatic reasons for intentional self-harm/overdose; (iii) suicidal ideation and aggressive behavior; and (iv) social functioning. In addition, patients with TRBD showed greater clinical improvement in long-term follow-up when compared with published schizophrenia data. Sedation (12%), constipation (5.0%), sialorrhea (5.2%), weight gain (4%), and body ache/pain (2%) were the commonly reported ADRs; however, these symptoms but did not usually require drug discontinuation. The percentage of severe ADRs reported, such as leukopenia (2%), agranulocytosis (0.3%), and seizure (0.5%), appeared to be lower than those reported in the published schizophrenia literature.
The limited current evidence supports the concept that clozapine may be both an effective and a relatively safe medication for TRBD.
评估氯氮平治疗难治性双相障碍（TRBD）的疗效和安全性。
对 TRBD 患者的随机对照研究、开放标签前瞻性研究和回顾性研究进行系统评价。干预措施包括氯氮平单药治疗或氯氮平联合其他药物。结局指标为疗效和药物不良反应（ADRs）。
符合纳入标准的共有 15 项临床试验，共纳入 1044 例患者。氯氮平单药治疗或氯氮平联合其他治疗 TRBD 与以下方面的改善相关：（i）躁狂、抑郁、快速循环和精神病症状的症状，许多 TRBD 患者达到缓解或反应；（ii）住院次数和持续时间、精神药物共用药数量、因故意自残/过量就诊的躯体原因的就诊次数；（iii）自杀意念和攻击行为；（iv）社会功能。此外，与已发表的精神分裂症数据相比，TRBD 患者在长期随访中表现出更大的临床改善。镇静（12%）、便秘（5.0%）、流涎（5.2%）、体重增加（4%）和全身疼痛/疼痛（2%）是常见的不良反应；然而，这些症状通常不需要停药。报告的严重不良反应（如白细胞减少症[2%]、粒细胞缺乏症[0.3%]和癫痫发作[0.5%]）的比例似乎低于已发表的精神分裂症文献报告的比例。
目前有限的证据支持氯氮平可能是治疗 TRBD 既有效又相对安全的药物这一概念。
