Association Between the Use of Antidepressants and the Risk
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 or receipt of antidiabetes treatment were excluded. Covariates were adjusted by using propensity score matching; the associations were analyzed between the 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 for short-term low-dose and 3.95 for long-term high-dose antidepressant use. HbA1c levels were lower in patients who discontinued or reduced the dose of antidepressants.

Conclusively, Long-term antidepressant use might increase the risk of type 2 diabetes in a time- and dose-dependent manner. Moreover, discontinuation of antidepressant therapy and reduction of the antidepressant dose after type 2 diabetes onset improved glucose tolerance. Accordingly, the HbA1c level should be regularly monitored in patients taking antidepressants in order to inform the decision to reduce or discontinue antidepressant use, if possible, when impaired glucose tolerance is observed.