Lau Sue Lynn, Muir Christopher, Assur Yolinda, Beach Rhonda, Tran Bich, Bartrop Roger, McLean Mark, Caetano Dorgival
From the *Blacktown Clinical School and Research Centre, University of Western Sydney, Parramatta; †St Vincent's Hospital, Darlinghurst; ‡Blacktown City Mental Health Service, Blacktown Hospital, Blacktown; and §Centre for Big Data Research in Health, University of New South Wales, Kensington, New South Wales, Australia.
J Clin Psychopharmacol. 2016 Apr;36(2):120-4. doi: 10.1097/JCP.0000000000000476.
Weight gain on clozapine is highly variable and poorly predictable. Its mechanisms are not well understood. This study explores the factors that predict weight gain between 3 and 12 months of clozapine therapy in community-dwelling patients.
We conducted a retrospective audit of patients attending an outpatient clozapine clinic. Weight change from 3 to 12 months of therapy was recorded, expressed as a percentage of the 3-month weight. Univariate analyses compared percent weight change according to sex, smoking status, country of birth, and baseline body mass index. Correlations between weight gain, age, and clozapine dose were explored. A general linear model identified independent predictors of weight gain.
The mean weight change from 3 to 12 months in 117 patients was +3.1% (range, -17% to +30%). Females gained more weight than males (+5.5% vs +1.3%, P = 0.01), smokers gained more than nonsmokers (+5.1% vs +1.2%, P = 0.02), and obese patients gained less than normal or overweight individuals (0.15% vs 4.6% and 5.2%, respectively, P = 0.01). Age and clozapine dose had no relation to weight change. On multivariate analysis, baseline BMI and smoking status remained independent predictors of percent weight change in females. These 2 predictors explained 25% of weight change in females in the first 3 to 12 months of therapy. These associations were not observed in males.
We hypothesize that smoking affects weight change by promoting clozapine metabolism to norclozapine via cytochrome P450 enzymes. Verifying this hypothesis and exploring the mechanisms underpinning the sex dichotomy are areas for further research.
氯氮平治疗期间体重增加情况高度可变且难以预测。其机制尚不清楚。本研究探讨了社区居住患者在氯氮平治疗3至12个月期间体重增加的预测因素。
我们对一家门诊氯氮平诊所的患者进行了回顾性审计。记录治疗3至12个月期间的体重变化，以3个月时体重的百分比表示。单因素分析根据性别、吸烟状况、出生国家和基线体重指数比较体重变化百分比。探讨了体重增加、年龄和氯氮平剂量之间的相关性。一个通用线性模型确定了体重增加的独立预测因素。
117例患者在3至12个月期间的平均体重变化为+3.1%（范围为-17%至+30%）。女性比男性体重增加更多（+5.5%对+1.3%，P = 0.01），吸烟者比不吸烟者体重增加更多（+5.1%对+1.2%，P = 0.02），肥胖患者比正常或超重个体体重增加更少（分别为0.15%对4.6%和5.2%，P = 0.01）。年龄和氯氮平剂量与体重变化无关。多因素分析显示，基线BMI和吸烟状况仍然是女性体重变化百分比的独立预测因素。这两个预测因素解释了治疗前3至12个月女性体重变化的25%。在男性中未观察到这些关联。
我们假设吸烟通过细胞色素P450酶将氯氮平代谢为去甲氯氮平来影响体重变化。验证这一假设并探索性别差异背后的机制是进一步研究的领域。
