OBJECTIVE This study aimed to reveal the associations between the risk of new-onset type 2 diabetes mellitus and the duration of antidepressant use and the antidepressant dose, and between antidepressant use after diabetes onset and clinical outcomes. RESEARCH DESIGN AND METHODS In this large-scale retrospective cohort study in Japan, new users of antidepressants (exposure group) and nonusers (nonexposure group), aged 20-79 years, were included between 1 April 2006 and 31 May 2015. Patients with a history of diabetes mellitus or receipt of antidiabetes treatment were excluded. Covariates were adjusted by using propensity score matching; the associations were analyzed between risk of new-onset type 2 diabetes and the duration of antidepressant use/dose of antidepressant in the exposure and nonexposure groups by using Cox proportional hazards models. Changes in glycated hemoglobin (HbA1c) level were examined in groups with continuous use, discontinuation, or a reduction in the dose of antidepressants. RESULTS Of 90,530 subjects, 45,265 were in both the exposure and the nonexposure group after propensity score matching; 5,225 patients (5.8%) developed diabetes. Antidepressant use was associated with the risk of diabetes onset in a time- and dose-dependent manner. The adjusted hazard ratio was 1.27 (95% CI 1.16-1.39) for short-term low-dose and 3.95 (95% CI 3.31-4.72) for long-term high-dose antidepressant use. HbA1c levels were lower in patients who discontinued or reduced the dose of antidepressants (F[2,49] = 8.17; P < 0.001). CONCLUSIONS Long-term antidepressant use increased the risk of type 2 diabetes onset in a time- and dose-dependent manner. Glucose tolerance improved when antidepressants were discontinued or the dose was reduced after diabetes onset.

中文翻译：

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抗抑郁药的使用与2型糖尿病风险之间的关联：日本一项基于人群的大型队列研究。

目的本研究旨在揭示新发2型糖尿病的风险与抗抑郁药持续时间和抗抑郁药剂量之间的相关性，以及糖尿病发作后抗抑郁药的使用与临床结局之间的关系。研究设计与方法在日本的一项大规模回顾性队列研究中，纳入了2006年4月1日至2015年5月31日期间年龄在20-79岁之间的抗抑郁药新药使用者（暴露组）和未服用抗抑郁药的使用者（未暴露组）。没有糖尿病史或接受抗糖尿病治疗。通过使用倾向得分匹配来调整协变量。通过使用Cox比例风险模型分析了暴露组和非暴露组新发2型糖尿病的风险与抗抑郁药的持续时间/抗抑郁药的剂量之间的关联。在连续使用，停用或降低抗抑郁药剂量的组中检查了糖化血红蛋白（HbA1c）水平的变化。结果90,530名受试者中，倾向得分匹配后，暴露组和非暴露组分别有45,265名；5,225名患者（5.8％）患有糖尿病。抗抑郁药的使用以时间和剂量依赖的方式与糖尿病发作的风险相关。短期低剂量调整后的危险比为1.27（95％CI 1.16-1.39），长期长期使用大剂量抗抑郁剂的调整后危险比为3.95（95％CI 3.31-4.72）。停用或降低抗抑郁药剂量的患者的HbA1c水平较低（F [2,49] = 8.17； P <0.001）。结论长期服用抗抑郁药会以时间和剂量依赖性方式增加2型糖尿病发作的风险。停用抗抑郁药或在糖尿病发作后降低剂量可改善葡萄糖耐量。