Use of antidepressants and the risk of type 2 diabetes mellitus: a nested case-control study.

Background: Recent evidence from case reports, observational studies, and randomized trials suggests that long-term use of antidepressants increases the risk of developing diabetes. However, the nature of the relationship between antidepressants and diabetes remains unclear.

Objective: To determine whether there is an association between antidepressant use and the risk of developing type 2 diabetes mellitus.

Methods: A nested case-control study using the Texas Medicaid prescription claims database was conducted. Data were extracted for new users of either antidepressant agents (exposed) or benzodiazepines (unexposed) from January 1, 2002 through December 31, 2009. Patients aged 18-64 years without a history of diabetes were included in the cohort. The adjusted odds ratio (OR) and 95% confidence interval (CI) for the risk of diabetes associated with antidepressant exposure was computed using conditional logistic regression, controlling for demographic and clinical covariates.

Main Outcome Measure: Development of type 2 diabetes mellitus.

Results: Among the total sample (N = 44,715), the majority were in the exposed (N = 35,552) vs. the unexposed (N = 9,163) group. A total of 2,943 cases of type 2 diabetes mellitus and 11,748 matched controls (1:4) were identified using risk-set sampling. Cases and controls were matched using age and gender. Antidepressant use was associated with an increase in the risk of (type-2) diabetes when compared to benzodiazepine use [Adjusted Odds Ratio (OR) = 1.512; 95% CI 1.345-1.700]. The association was observed with serotonin-norepinephrine reuptake inhibitors (OR = 1.742; 95% CI 1.472-2.060), tricyclic antidepressants (OR = 1.533; 95% CI 1.295-1.814), selective serotonin reuptake inhibitors (OR = 1.457; 95% CI 1.279-1.659), "Other" antidepressants (OR = 1.318; 95% CI 1.129-1.540).

Conclusions: Antidepressant use was associated with an increased risk of (type-2) diabetes. This association was observed for tricyclic antidepressants, serotonin-reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and other antidepressants.