Rosiglitazone Add-On in Treatment of Depressed Patients With Insulin Resistance: a Pilot Study

An association between insulin resistance (IR) and affective disorders has been postulated in a number of cross-sectional studies. Limited data exist on potential changes in IR associated with improvement in depressive symptoms and/or depression remission resolution - two studies reported decreased IR after successful antidepressant treatment, while another study reported persisting IR even after successful treatment.

We have postulated that IR is a part of the pathophysiology of affective disorders, and its improvement (via pharmacological or nonpharmacological treatments) may significantly reduce the severity of depressive symptoms. In support of this hypothesis, we previously reported increased IR in women with bipolar disorder, as well as a significant association between IR and depressive symptoms in women with primary IR syndrome (polycystic ovary syndrome [PCOS]). In the current pilot study, we attempted a more direct testing of the hypothesis that improvement of IR will result in improvement in mood in patients with depressive disorders. The aim of the study was to evaluate whether addition of the peroxisome proliferator-activated receptor-γ (PPAR) agonist rosiglitazone to the treatment as usual (TAU) of nondiabetic patients with unipolar or bipolar depression would result in improvement in depression severity and clinical global impression (CGI). Insulin sensitizing agents have proven efficacious in nondiabetic IR, or "prediabetic", individuals. All subjects in this pilot study had elevated fasting plasma glucose (FPG) and ratios of high density lipoproteins (HDL) to triglycerides (TG), which are established surrogate markers of IR.

In the current pilot study, we attempted a more direct testing of the hypothesis that improvement of IR will result in improvement in mood in patients with depressive disorders. The aim of the study was to evaluate whether addition of the peroxisome proliferator-activated receptor-γ (PPAR) agonist rosiglitazone to the treatment as usual (TAU) of nondiabetic patients with unipolar or bipolar depression would result in improvement in depression severity and clinical global impression (CGI). Insulin sensitizing agents have proven efficacious in nondiabetic IR, or "prediabetic", individuals. All subjects in this pilot study had elevated fasting plasma glucose (FPG) and ratios of high density lipoproteins (HDL) to triglycerides (TG), which are established surrogate markers of IR.