A recent increase in the literature regarding the evidence base for clozapine has made it increasingly difficult for clinicians to judge “best evidence” for clozapine use. As such, we aimed at elucidating the state-of-the-art for clozapine with regard to efficacy, effectiveness, tolerability, and management of clozapine and clozapine-related adverse events in neuropsychiatric disorders. We conducted a systematic PRISMA-conforming quantitative meta-review of available meta-analytic evidence regarding clozapine use. Primary outcome effect sizes were extracted and transformed into relative risk ratios (RR) and standardized mean differences (SMD). The methodological quality of meta-analyses was assessed using the AMSTAR-2 checklist. Of the 112 meta-analyses included in our review, 61 (54.5%) had an overall high methodological quality according to AMSTAR-2. Clozapine appears to have superior effects on positive, negative, and overall symptoms and relapse rates in schizophrenia (treatment-resistant and non-treatment-resistant subpopulations) compared to first-generation antipsychotics (FGAs) and to pooled FGAs/second-generation antipsychotics (SGAs) in treatment-resistant schizophrenia (TRS). Despite an unfavorable metabolic and hematological adverse-event profile compared to other antipsychotics, hospitalization, mortality and all-cause discontinuation (ACD) rates of clozapine surprisingly show a pattern of superiority. Our meta-review outlines the superior overall efficacy of clozapine compared to FGAs and most other SGAs in schizophrenia and suggests beneficial efficacy outcomes in bipolar disorder and Parkinson’s disease psychosis (PDP). More clinical studies and subsequent meta-analyses are needed beyond the application of clozapine in schizophrenia-spectrum disorders and future studies should be directed into multidimensional clozapine side-effect management to foster evidence and to inform future guidelines.

最近有关氯氮平证据基础的文献增多，使得临床医生越来越难以判断氯氮平使用的“最佳证据”。因此，我们旨在阐明氯氮平在疗效、有效性、耐受性和神经精神疾病中氯氮平和氯氮平相关不良事件管理方面的最新技术。我们对有关氯氮平使用的可用荟萃分析证据进行了系统的符合 PRISMA 的定量荟萃审查。提取主要结果效应量并将其转化为相对风险比 (RR) 和标准化均值差 (SMD)。使用AMSTAR-2评估荟萃分析的方法学质量清单。根据AMSTAR-2，在我们审查的 112 项荟萃分析中，61 项 (54.5%) 具有总体较高的方法学质量. 与第一代抗精神病药物 (FGA) 和混合 FGA/第二代抗精神病药物相比，氯氮平似乎对精神分裂症（治疗耐药和非治疗耐药亚群）的阳性、阴性和总体症状以及复发率有更好的影响。 SGAs）治疗难治性精神分裂症（TRS）。尽管与其他抗精神病药相比，氯氮平的代谢和血液学不良事件不佳，但氯氮平的住院率、死亡率和全因停药 (ACD) 率令人惊讶地显示出一种优势模式。我们的荟萃综述概述了与 FGA 和大多数其他 SGA 相比，氯氮平在精神分裂症中的总体疗效优越，并表明在双相情感障碍和帕金森病精神病 (PDP) 中的有益疗效结果。