The association between antidepressant use and disturbances in glucose homeostasis: evidence from spontaneous reports

Eur J Clin Pharmacol. 2008 May;64(5):531-8. doi: 10.1007/s00228-007-0441-y. Epub 2008 Jan 15.


Objectives: Depression is common in patients with diabetes, and the use of antidepressants may impair glycaemic control. We assessed the association between antidepressant use and hyper- and hypoglycaemia.

Methods: Based on spontaneous reports listed in the World Health Organization (WHO) Adverse Drug Reaction Database, a case-control study was conducted. The study base consisted of all adverse drug reactions (ADRs) ascribed to antidepressants, antipsychotics and benzodiazepines between 1969 and 2005. Cases were defined as reported ADRs classified as hyper- or hypoglycaemia and separated in different study populations. All other reports were considered as controls. Exposure to antidepressants was the primary determinant investigated. Benzodiazepines and antipsychotics were chosen as reference groups. Potential confounding factors, namely, age, gender, use of antidiabetic medication, use of hyper- or hypoglycaemia-inducing comedication and reporting year, were determined on the index date. Multivariate logistic regression was used to evaluate the strength of the association, which was expressed as reporting odds ratios (RORs) with 95% confidence intervals (95% CI).

Results: Overall, the use of antidepressants was associated with hyperglycaemia [ROR 1.52 (95% CI: 1.20-1.93)] and of hypoglycaemia [ROR 1.84 (95% CI: 1.40-2.42)]. The association with hyperglycaemia was most pronounced for antidepressants with affinity for the 5-HT(2c) receptor, histamine-(1) receptor and norepinephrinic (NE) reuptake transporter. The association with hypoglycaemia was most pronounced for antidepressants with affinity for the serotonin reuptake transporter.

Conclusion: The results of this study strengthen the findings in individual case reports that the use of antidepressants is associated with disturbances in glucose homeostasis.

MeSH terms

  • Adolescent
  • Adult
  • Adverse Drug Reaction Reporting Systems
  • Antidepressive Agents / adverse effects*
  • Antidepressive Agents / therapeutic use
  • Blood Glucose / drug effects
  • Case-Control Studies
  • Depression / complications
  • Depression / drug therapy*
  • Diabetes Complications / physiopathology*
  • Female
  • Humans
  • Hyperglycemia / chemically induced*
  • Hypoglycemia / chemically induced*
  • Hypoglycemic Agents / therapeutic use
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Tranquilizing Agents / adverse effects*
  • Tranquilizing Agents / therapeutic use


  • Antidepressive Agents
  • Blood Glucose
  • Hypoglycemic Agents
  • Tranquilizing Agents