Type of antidepressant therapy and risk of type 2 diabetes in people with depression Lauren C. Brown a,b , Sumit R. Majumdar a,b,c , Jeffrey A. Johnson a,b, * a School of Public Health, University of Alberta, Edmonton, Alberta, Canada b Institute of Health Economics, Edmonton, Alberta, Canada c Department of Medicine, University of Alberta, Edmonton, Alberta, Canada 1. Introduction Recent literature suggests that having depression (or high depressive symptoms) is associated with an increased risk of developing type 2 diabetes [1–9]. Although the studies varied considerably in populations studied, methods of identifying depression or depressive symptoms, and control for potential confounding variables, the results are relatively consistent, demonstrating 1.2–2.6 times the risk of diabetes in people with depression or depressive symptoms compared to people without depression [1–9]. This literature is relatively silent, however, regarding the mechanisms behind this relationship. A number of theories have been postulated regarding the mechanism associated with the increased risk of diabetes in people with depression [10,11]. One possibility is the bio- chemical changes seen with depression, stimulation of the hypothalamic–pituitary–adrenal (HPA) axis, resulting in increased cortisol levels and a resulting increase in blood glucose, eventually progressing to diabetes [11]. Another mechanism may be the behavioural changes seen in people with depression. Depression is associated with decreased self- care activities and an increase in potentially damaging behaviours such as smoking and alcohol consumption [12]. Each of these changes can also potentially contribute to diabetes research and clinical practice 79 (2008) 61–67 article info Article history: Received 18 May 2007 Accepted 10 July 2007 Published on line 21 August 2007 Keywords: Depression Type 2 diabetes Antidepressant therapy abstract Objective: The objective of this study was to evaluate the differential risk of diabetes among people with depression taking antidepressant therapy. Methods: A nested case control design was used to investigate the study objective. Data from the Canadian province of Saskatchewan was available from January 1, 1991 to December 31, 2001; the average length of follow-up was 4.07 years. Type 2 diabetes was identified based on ICD-9 diagnostic codes and antidiabetic medication prescriptions; prior depression was ascertained based on ICD-9 diagnostic codes and antidepressant prescriptions. Results: Multivariate logistic regression analysis was used to estimate the odds ratio (OR) and 95% confidence intervals (CI). We identified 2391 individuals with incident depression treated with antidepressant therapy. The mean age was 53.6 (S.D.: 16.4) and 68% were female. After multivariate adjustment, the concurrent use of selective serotonin reuptake inhibitors (SSRI) and tricyclic antidepressants (TCA) was associated with a significantly increased risk of type 2 diabetes (adjusted OR: 1.89; 95% CI: 1.35–2.65). Conclusions: Concurrent use of TCA and SSRI was associated with an increased risk of developing type 2 diabetes compared to using TCA alone. Individuals taking combination TCA and SSRI therapy should be closely monitored for development of type 2 diabetes. # 2007 Elsevier Ireland Ltd. All rights reserved. * Corresponding author at: #1200-10405 Jasper Avenue, Edmonton, Alberta, Canada T5J 3N4. Tel.: +1 780 448 4881; fax: +1 780 448 0018. E-mail address: jeff.johnson@ualberta.ca (J.A. Johnson). available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/diabres 0168-8227/$ – see front matter # 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.diabres.2007.07.009