Use of insulin sensitizers for the treatment of major depressive disorder: A pilot study of pioglitazone for major depression accompanied by abdominal obesity

Objective: This study was conducted to examine the safety and efficacy of pioglitazone, a thiazolidinedione insulin sensitizer, in adult outpatients with major depressive disorder. Method: In a 12-week, open-label, flexible-dose study, 23 patients with major depressive disorder received pioglitazone monotherapy or adjunctive therapy initiated at 15 mg daily. Subjects were required to meet criteria for abdominal obesity (waist circumference >35 in. in women and >40 in. in men) or metabolic syndrome. The primary efficacy measure was the change from baseline to Week 12 on the Inventory of Depressive Symptomatology (IDS) total score. Partial responders (>= 25% decrease in IDS total score) were eligible to participate in an optional extension phase for an additional three months. Results: Pioglitazone decreased depression symptom severity from a total IDS score of 40.3 +/- 1.8 to 19.2 +/- 1.8 at Week 12 (p<.001). Among partial responders (>= 25% decrease in IDS total score), an improvement in depressive symptoms was maintained during an additional 3-month extension phase (total duration = 24 weeks) according to IDS total scores (p<.001). Patients experienced a reduction in insulin resistance from baseline to Week 12 according to the log homeostasis model assessment (- 0.8 +/- 0.75; p<.001) and a significant reduction in inflammation as measured by log highly- sensitive C-reactive protein (- 0.87 +/- 0.72; p<.001). During the current episode, the majority of participants (74%, n = 17), had already failed at least one antidepressant trial. The most common side effects were headache and dizziness; no patient discontinued due to side effects. Limitations: These data are limited by a small sample size and an open-label study design with no placebo control. Conclusion: Although preliminary, pioglitazone appears to reduce depression severity and improve several markers of cardiometabolic risk, including insulin resistance and inflammation. larger. placebo-controlled studies are indicated. (C) 2011 Elsevier B.V. All rights reserved.