Objective— To examine antidepressant medication use as a risk factor for type 2 diabetes and weight gain.

Research design and methods— A series of nested studies within a prospective cohort of 151,347 working-aged men and women including 9197 participants with continuing antidepressant medication, 224 with severe depression, and 851 with incident type 2 diabetes mellitus during a mean follow-up of 4.8 years, as indicated by national health and prescription registers (the Public Sector study, Finland 1995-2005).

Results— In the first analysis, the cases were individuals with incident type 2 diabetes compared with matched diabetes-free controls. Antidepressant use of ≥200 defined daily doses was associated with a doubling of diabetes risk in both participants with no indication of severe depression (odds ratio 1.93, 95% CI 1.48-2.51) and participants with severe depression (odds ratio 2.65 95% CI 1.31-5.39). In the further analyses, exposed group was antidepressant users and reference group non-users matched for depression-related characteristics. The 5-year absolute risk of diabetes was 1.1% for non-users, 1.7% for individuals treated with 200-399 defined daily doses a year, and 2.3% for those with ≥400 defined daily doses (p_trend<0.0001). An average self-reported weight gain, based on repeated surveys, was 1.4 kg (2.5%) among non-users and 2.5 kg (4.3%) among users of ≥200 defined daily doses (p_trend<0.0001). Separate analyses for tricyclic antidepressants and selective-serotonin-re-uptake inhibitors replicated these findings.

Conclusions— In these data, continuing use of antidepressant medication was associated with an increased relative risk of type 2 diabetes, although the elevation in absolute risk was modest.