A Possible Role for Pioglitazone in the Management of Depressive Symptoms in Metabolic Syndrome Patients (EPICAMP Study): A Double Blind, Randomized Clinical Trial

The present trial aimed to evaluate the effects of pioglitazone on the mental status of nondiabetic metabolic syndrome patients. From 145 patients screened, 104 eligible volunteers (57% female; age 20-70 years) were enrolled and randomly assigned to receive either pioglitazone (uptitrated to 30 mg/day; P = 53) or matching placebo (P = 51) for 24 weeks. Depression and anxiety were quantified using the hospital anxiety and depression scale and stress level using the general health questionnaire 12 at baseline, week 12, and endpoint. Homeostasis model assessment was used to estimate insulin resistance. At week 24, pioglitazone was superior in mitigating depression score (P = 0.011). In trend analysis, the effect of time (P < 0.001) and group (P = 0.023) as well as the time by group interaction (P = 0.032) on the mean depression score was considerable. In contrast, significant decrements in anxiety and stress levels (P < 0.001 and P = 0.012, resp.) were comparable between two groups. With respect to our findings, alterations in depression severity were not correlated with changes in insulin resistance level (P = 0.145). In conclusion, our findings suggest that pioglitazone might be able to improve mood in nondiabetic insulin resistant patients. (Registered at Australian New Zealand Clinical Trials Registry; ACTRN12611000351910.).