Examining the safety profile of clozapine versus other antipsychotics: systematic review and meta-analysis

作者：Elisavet Pinioti, Eleni Glarou, Andreas S. Lappas, Iwo Fober, Bartosz Helfer, Spyridon Siafis, George N. Christodoulou, Adriani Nikolakopoulou, Stefan Leucht, Myrto Samara · 发表于：The British Journal of Psychiatry · 年份：2025 · DOI：10.1192/bjp.2025.10421 · 被引用次数：7 · 研究领域：Schizophrenia research and treatment、Healthcare Decision-Making and Restraints、Mental Health and Psychiatry

Background Antipsychotics are first-line treatments for schizophrenia, yet many patients show inadequate response. Clozapine, the gold standard for treatment-resistant schizophrenia, remains underutilised due to safety and monitoring concerns. Aims To evaluate the adverse effects of clozapine in schizophrenia through a meta-analysis of randomised controlled trials (RCTs). Method We systematically searched MEDLINE, CENTRAL, Embase, PsycINFO, ClinicalTrials.gov and WHO ICTRP up to 10 October 2024 for RCTs comparing clozapine (as either monotherapy or combination therapy) with other antipsychotics. We assessed 37 distinct adverse outcomes. Risk ratios were calculated for dichotomous outcomes and standardised mean differences for continuous outcomes, with confidence intervals. Results A total of 116 RCTs ( n = 8431) were included. In 69 monotherapy RCTs ( n = 6281), clozapine showed no difference in either mortality (risk ratio 1.01, 95% CI: 0.50, 2.01, prevalence 0.1%) or discontinuation due to adverse effects (risk ratio 1.18, 95% CI: 0.91, 1.53, prevalence 7.2%). Agranulocytosis risk was nearly tripled (risk ratio 2.81, 95% CI: 0.97, 8.12, prevalence 0.7%), although with wide confidence intervals. Clozapine increased the risk of seizures (risk ratio 3.61, 95% CI: 1.80, 7.95, prevalence 3.1%) and orthostatic hypotension/bradycardia/syncope (risk ratio 1.66, 95% CI: 1.00, 2.77, prevalence 11%). No difference was found for myocarditis/cardiomyopathy (risk ratio 0.33, 95% CI: 0.01...