Association Between the Use of Antidepressants and the Risk of Type 2 Diabetes Mellitus: A Large, Population-Based Cohort Study in Japan

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 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.