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Item Elevated Depression Symptoms, Antidepressant Medicine Use, and Risk of Developing Diabetes During the Diabetes Prevention Program(2008-03) Rubin, Richard R.; Ma, Yong; Marrero, David G.; Peyrot, Mark; Barrett-Connor, Elizabeth L.; Kahn, Steven E.; Haffner, Steven M.; Price, David W.; Knowler, William C.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.