Clozapine induces metformin-resistant prediabetes/diabetes that is associated with poor clinical efficacy in patients with early treatment-resistant schizophrenia.

IF 4.9 2区医学 Q1 CLINICAL NEUROLOGY

Journal of affective disorders Pub Date : 2021-02-25 DOI:10.2139/SSRN.3787457

C. Zhuo, Yong Xu, Haibo Wang, Chuanhua Zhou, Jian Liu, Xiaocui Yu, Hailin Shao, H. Tian, T. Fang, Qianchen Li, Jiayue Chen, Shuli Xu, Xiaoyan Ma, Weiliang Yang, Cong Yao, Bo Li, Anqu Yang, Yuhui Chen, Gongyong Huang, Chong-guang Lin

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引用次数: 7

Abstract

BACKGROUND Two distinct subtypes of treatment-resistant schizophrenia (TRS) have been recently reported, including early-treatment resistance (E-TR) and late-treatment resistance (L-TR). This study was to assess clozapine-induced metformin-resistant prediabetes/diabetes and its correlation with clinical efficacy in schizophrenia E-TR subtype. METHODS This prospective cohort study enrolled 230 patients with schizophrenia E-TR subtype and they were treated with adequate doses of clozapine for 16 weeks, during which patients with prediabetes/diabetes were assigned to receive add-on metformin. The main outcomes and measures included incidence of clozapine-induced prediabetes/diabetes and metformin-resistant prediabetes/diabetes, and the efficacy of clozapine as assessed by the Positive and Negative Syndrome Scale (PANSS) score. RESULTS Clozapine-induced prediabetes/diabetes occurred in 76.52% of patients (170 prediabetes and 6 diabetes), of which the blood sugar of 43 (24.43%) patients was controlled with metformin. Despite add-on metformin, 47.06% (74/170) of prediabetes patients progressed to diabetes. In total, the incidence of clozapine-induced metformin-resistant prediabetes/diabetes was 75.57% (133/176). On completion of 16-week clozapine treatment, 16.52% (38/230) patients showed clinical improvement with PANSS scores of ≥50% declining. Furthermore, clozapine-induced prediabetes/diabetes was significantly correlated with the poor clinical efficacy of clozapine for schizophrenia E-TR subtype. CONCLUSIONS The incidence of clozapine-induced metformin-resistant prediabetes/diabetes was considerably high in the schizophrenia E-TR subtype. Clozapine-induced metformin-resistant prediabetes/diabetes represents an independent risk factor that adversely affects the clinical efficacy of clozapine for the schizophrenia E-TR subtype. This study provided new evidence for re-evaluating the use of clozapine for TRS, especially E-TR subtype, and the use of metformin for the glycemic control of clozapine-induced prediabetes/diabetes.

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氯氮平诱导二甲双胍抵抗性前驱糖尿病/糖尿病与早期治疗抵抗性精神分裂症患者临床疗效差相关。

背景最近报道了两种不同的耐治疗精神分裂症亚型，包括早期治疗耐药性（E-TR）和晚期治疗耐药性（L-TR）。本研究旨在评估氯氮平诱导的二甲双胍耐药性糖尿病前期/糖尿病及其与精神分裂症E-TR亚型临床疗效的相关性。方法本前瞻性队列研究纳入了230名精神分裂症E-TR亚型患者，他们接受了为期16周的足够剂量的氯氮平治疗，在此期间，糖尿病前期/糖尿病患者被分配接受额外的二甲双胍治疗。主要结果和指标包括氯氮平诱导的糖尿病前期/糖尿病和二甲双胍耐药性糖尿病前期/患者的发生率，以及通过阳性和阴性综合征量表（PANSS）评分评估的氯氮平疗效。结果76.52%的患者（170例糖尿病前期和6例糖尿病）发生氯氮平诱导的糖尿病前期/糖尿病，其中43例（24.43%）患者的血糖得到二甲双胍控制。尽管添加了二甲双胍，但47.06%（74/170）的糖尿病前期患者进展为糖尿病。总的来说，氯氮平诱导的二甲双胍耐药性糖尿病前期/糖尿病的发生率为75.57%（133/176）。在完成16周氯氮平治疗后，16.52%（38/230）的患者表现出临床改善，PANSS评分下降≥50%。此外，氯氮平诱导的糖尿病前期/糖尿病与氯氮平治疗精神分裂症E-TR亚型的不良临床疗效显著相关。结论在精神分裂症E-TR亚型中，氯氮平诱导的二甲双胍耐药性糖尿病前期/糖尿病的发生率相当高。氯氮平诱导的二甲双胍耐药性糖尿病前期/糖尿病是一个独立的风险因素，对氯氮平治疗精神分裂症E-TR亚型的临床疗效产生不利影响。本研究为重新评估氯氮平治疗TRS，特别是E-TR亚型的使用，以及二甲双胍用于氯氮平诱导的糖尿病前期/糖尿病的血糖控制提供了新的证据。

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来源期刊

Journal of affective disorders 医学-精神病学

CiteScore

10.90

自引率

6.10%

发文量

1319

审稿时长

9.3 weeks

期刊介绍： The Journal of Affective Disorders publishes papers concerned with affective disorders in the widest sense: depression, mania, mood spectrum, emotions and personality, anxiety and stress. It is interdisciplinary and aims to bring together different approaches for a diverse readership. Top quality papers will be accepted dealing with any aspect of affective disorders, including neuroimaging, cognitive neurosciences, genetics, molecular biology, experimental and clinical neurosciences, pharmacology, neuroimmunoendocrinology, intervention and treatment trials.