Chang Daniel, See Yuen Mei, Yee Jie Yin, Law Claire, Lee Jimmy
Central Region, Institute of Mental Health, Singapore.
North Region, Institute of Mental Health, Singapore.
J Clin Psychopharmacol. 2025;45(5):484-487. doi: 10.1097/JCP.0000000000002048. Epub 2025 Aug 11.
Clozapine, indicated for use in treatment-resistant schizophrenia (TRS), comes with notable weight gain and metabolic side effects. Prior studies have suggested a link between weight gain and antipsychotic efficacy in schizophrenia. In this study, we seek to explore the relationship between obesity and clinical outcome in TRS on clozapine treatment.
This study was conducted at a tertiary mental health institution on patients with TRS on clozapine for at least 12 weeks. Data were collected through a research interview and review of medical records. Symptoms were assessed on the Positive and Negative Syndrome Scale. Anthropometric measures, including weight, height, waist circumference and blood pressure, were measured during the visit. A blood sample for lipids and glucose was obtained after an 8-hour fast.
One hundred Fifty-four patients on clozapine were identified and included in the final analysis. Thirty-seven patients (24.0%) achieved symptomatic remission. The remitter group had a significantly higher body mass index (BMI) compared with the nonremitter group (26.6 vs 24.2 kg/m 2 , P = 0.007). Univariate analyses identified BMI, waist circumference and blood pressure as possible metabolic factors associated with remission. In the multivariate model, BMI was the only statistically significant predictor of remission status (OR = 1.147, P = 0.020).
Our study found that obesity was associated with remission in TRS patients on clozapine. This lends support to the metabolic threshold for clozapine. Further investigations are needed to study the mechanisms underpinning weight gain and clozapine efficacy.
氯氮平用于治疗难治性精神分裂症（TRS），但会带来显著的体重增加和代谢副作用。先前的研究表明精神分裂症患者体重增加与抗精神病药物疗效之间存在联系。在本研究中，我们旨在探讨肥胖与接受氯氮平治疗的TRS患者临床结局之间的关系。
本研究在一家三级精神卫生机构对接受氯氮平治疗至少12周的TRS患者进行。通过研究访谈和病历审查收集数据。使用阳性和阴性症状量表评估症状。在就诊期间测量人体测量指标，包括体重、身高、腰围和血压。禁食8小时后采集血液样本检测血脂和血糖。
确定了154例接受氯氮平治疗的患者并纳入最终分析。37例患者（24.0%）实现症状缓解。缓解组的体重指数（BMI）显著高于未缓解组（26.6 vs 24.2kg/m²，P = 0.007）。单因素分析确定BMI、腰围和血压可能是与缓解相关的代谢因素。在多变量模型中，BMI是缓解状态唯一具有统计学意义的预测因素（OR = 1.147，P = 0.020）。
我们的研究发现肥胖与接受氯氮平治疗的TRS患者缓解相关。这支持了氯氮平的代谢阈值。需要进一步研究以探讨体重增加和氯氮平疗效背后的机制。
