Spokes Jessica, Hollingworth Samantha, Winckel Karl, Kisely Steve, Baker Andrea, Cosgrove Peter, Siskind Dan
School of Pharmacy, The University of Queensland, Woolloongabba, Australia.
School of Pharmacy, The University of Queensland, Woolloongabba, Australia Pharmacy Department, Princess Alexandra Hospital, Brisbane, Australia.
Ther Adv Psychopharmacol. 2021 Mar 16;11:20451253211000609. doi: 10.1177/20451253211000609. eCollection 2021.
People with schizophrenia have a 15-20-year reduction in life expectancy, driven in part by the metabolic effects of antipsychotics. Clozapine is associated with the highest rates of weight gain. As clozapine remains the most effective antipsychotic for treatment-resistant schizophrenia (TRS), identifying treatments to ameliorate clozapine-induced weight gain (CIWG) is urgently needed to reduce this morality gap.
We retrospectively analysed digital health records of patients with TRS aged 18-65 newly initiated on clozapine at four tertiary hospitals in south-east Queensland from 1 March 2017 to 30 June 2019. Our primary outcome was the effect of metformin on change in percentage bodyweight at 12 months after clozapine initiation, with secondary outcome being proportion with >5% or >7% bodyweight change. We also explored impact on bodyweight change of other variables including sex, tobacco smoking, type 2 diabetes (T2DM), age, clozapine level and dose and clozapine/norclozapine ratio.
Among 90 patients initiated on clozapine, metformin use ( = 48) was associated with a smaller increase in percentage bodyweight (1.32% 5.95%, = 0.031), lower rates of >7% gain in bodyweight (37.8% 63.0%, = 0.025) but not >5% gain in bodyweight. Age below the median (32.0 years) was associated with greater bodyweight gain (5.55% 1.22%, = 0.046). Sex, tobacco smoking, T2DM, clozapine dose and level and clozapine/norclozapine ratio were not associated with differences in change in bodyweight.
In this small retrospective cohort study, use of metformin within 12-months of clozapine initiation was associated with a statistically and clinically significant reduction in CIWG. Although there is increasing evidence for the role of metformin to ameliorate bodyweight gain at time of clozapine initiation, our findings need replication and testing in a randomised controlled trial before recommending metformin co-commencement with clozapine as standard clinical practice.
精神分裂症患者的预期寿命缩短15 - 20年，部分原因是抗精神病药物的代谢作用。氯氮平与体重增加率最高相关。由于氯氮平仍是治疗难治性精神分裂症（TRS）最有效的抗精神病药物，因此迫切需要确定改善氯氮平所致体重增加（CIWG）的治疗方法，以缩小这种死亡率差距。
我们回顾性分析了2017年3月1日至2019年6月30日在昆士兰东南部四家三级医院新开始使用氯氮平的18 - 65岁TRS患者的数字健康记录。我们的主要结局是二甲双胍对氯氮平开始使用后12个月体重百分比变化的影响，次要结局是体重变化>5%或>7%的比例。我们还探讨了其他变量对体重变化的影响，包括性别、吸烟、2型糖尿病（T2DM）、年龄、氯氮平水平和剂量以及氯氮平/去甲氯氮平比率。
在90例开始使用氯氮平的患者中，使用二甲双胍（n = 48）与体重百分比增加较小（1.32% ± 5.95%，P = 0.031）、体重增加>7%的发生率较低（37.8% ± 63.0%，P = 0.025）相关，但与体重增加>5%无关。年龄低于中位数（32.0岁）与更大的体重增加相关（5.55% ± 1.22%，P = 0.046）。性别、吸烟、T2DM、氯氮平剂量和水平以及氯氮平/去甲氯氮平比率与体重变化差异无关。
在这项小型回顾性队列研究中，氯氮平开始使用后一年内使用二甲双胍与CIWG在统计学和临床上有显著降低相关。尽管越来越多的证据表明二甲双胍在氯氮平开始使用时对改善体重增加有作用，但在推荐二甲双胍与氯氮平同时开始作为标准临床实践之前，我们的研究结果需要在随机对照试验中进行重复和验证。
