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Elevated Depression Symptoms, Antidepressant Medicine Use, and Risk of Developing Diabetes During the Diabetes Prevention Program Richard R. Rubin , PHD 1 2 , Yong Ma , MS 3 , David G. Marrero , PHD 4 , Mark Peyrot , PHD 1 5 , Elizabeth L. Barrett-Connor , MD 6 , Steven E. Kahn , MD, CHB 7 , Steven M. Haffner , MD, MPH 8 , David W. Price , MD 9 , William C. Knowler , MD, DRPH 10 and for the Diabetes Prevention Program Research Group * 1 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 2 Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 3 Biostatistics Center, George Washington University, Rockville, Maryland 4 Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 5 Department of Sociology, Loyola College in Maryland, Baltimore, Maryland 6 Department of Family and Preventative Medicine, University of California at San Diego, La Jolla, California 7 Department of Medicine, University of Washington, Seattle, Washington 8 Department of Medicine, Clinical Epidemiology, University of Texas Health Science Center, San Antonio, Texas 9 Department of Family Medicine, University of Colorado Denver School of Medicine, Denver, Colorado 10 National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona Address correspondence and reprint requests to Richard R. Rubin, Johns Hopkins University School of Medicine, 946 E. Piney Hill Rd., Monkton, MD 21111. E-mail: rrubin4{at}jhmi.edu Abstract OBJECTIVE —To assess the association between elevated depression symptoms or antidepressant medicine use on entry to the Diabetes Prevention Program (DPP) and during the study and the risk of developing diabetes during the study. RESEARCH DESIGN AND METHODS —DPP participants ( n = 3,187) in three treatment arms (intensive lifestyle [ILS], metformin [MET], and placebo [PLB]) completed the Beck Depression Inventory (BDI) and reported their use of antidepressant medication at randomization and throughout the study (average duration in study 3.2 years). RESULTS —When other factors associated with the risk of developing diabetes were controlled, elevated BDI scores at baseline or during the study were not associated with diabetes risk in any arm. Baseline antidepressant use was associated with diabetes risk in the PLB (hazard ratio 2.25 [95% CI 1.38–3.66]) and ILS (3.48 [1.93–6.28]) arms. Continuous antidepressant use during the study (compared with no use) was also associated with diabetes risk in the same arms (PLB 2.60 [1.37–4.94]; ILS 3.39 [1.61–7.13]), as was intermittent antidepressant use during the study in the ILS arm (2.07 [1.18–3.62]). Among MET arm participants, antidepressant use was not associated with developing diabetes. CONCLUSIONS —A strong and statistically significant association between antidepressant use and diabetes risk in the PLB and ILS arms was not accounted for by measured confounders or mediators. If future research finds that antidepressant use independently predicts diabetes risk, efforts to minimize the negative effects of antidepressant agents on glycemic control should be pursued. BDI, Beck Depression Inventory DPP, Diabetes Prevention Program SSRI, selective serotonin reuptake inhibitor TCA, tricyclic antidepressant Footnotes Published ahead of print at http://care.diabetesjournals.org on 10 December 2007. DOI: 10.2337/dc07-1827. * ↵ * Members of the Diabetes Prevention Program Research Group appear in an online appendix at http://dx.doi.org/10.2337/dc07-1827 . The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted November 30, 2007. Received September 17, 2007. DIABETES CARE