Long-term use of antidepressants for depressive disorders and the risk of diabetes mellitus

Am J Psychiatry. 2009 May;166(5):591-8. doi: 10.1176/appi.ajp.2008.08071065. Epub 2009 Apr 1.


Objective: Use of antidepressants has been reported to cause considerable weight gain. The aim of this study was to assess the risk of diabetes mellitus associated with antidepressant treatment and to examine whether the risk is influenced by treatment duration or daily dose.

Method: This was a nested case-control study in a cohort of 165,958 patients with depression who received at least one new prescription for an antidepressant between January 1, 1990, and June 30, 2005. Data were from from the U.K. General Practice Research Database. Patients were at least 30 years of age and without diabetes at cohort entry.

Results: A total of 2,243 cases of incident diabetes mellitus and 8,963 matched comparison subjects were identified. Compared with no use of antidepressants during the past 2 years, recent long-term use (>24 months) of antidepressants in moderate to high daily doses was associated with an increased risk of diabetes (incidence rate ratio=1.84, 95% CI=1.35-2.52). The magnitude of the risk was similar for long-term use of moderate to high daily doses of tricyclic antidepressants (incidence rate ratio=1.77, 95% CI=1.21-2.59) and selective serotonin reuptake inhibitors (incidence rate ratio=2.06, 95% CI=1.20-3.52). Treatment for shorter periods or with lower daily doses was not associated with an increased risk.

Conclusions: Long-term use of antidepressants in at least moderate daily doses was associated with an increased risk of diabetes. This association was observed for both tricyclic antidepressants and selective serotonin reuptake inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amitriptyline / adverse effects
  • Antidepressive Agents, Tricyclic / adverse effects*
  • Body Mass Index
  • Case-Control Studies
  • Cyclohexanols / adverse effects
  • Depressive Disorder / drug therapy*
  • Diabetes Mellitus / chemically induced*
  • Diabetes Mellitus / epidemiology*
  • Female
  • Fluvoxamine / adverse effects
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Paroxetine / adverse effects
  • Risk Factors
  • Serotonin Uptake Inhibitors / adverse effects*
  • Time Factors
  • United Kingdom / epidemiology
  • Venlafaxine Hydrochloride


  • Antidepressive Agents, Tricyclic
  • Cyclohexanols
  • Serotonin Uptake Inhibitors
  • Amitriptyline
  • Paroxetine
  • Venlafaxine Hydrochloride
  • Fluvoxamine