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

David E. Kemp, Faramarz Ismail-Beigi, Stephen J. Ganocy, Carla Conroy, Keming Gao, Sarah Obral, Elizabeth Fein, Robert L. Findling, Joseph R. Calabrese

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1164-1173
Number of pages10
JournalJournal of Affective Disorders
Volume136
Issue number3
DOIs
StatePublished - Feb 2012
Externally publishedYes

Keywords

  • Insulin resistance
  • Major depressive disorder
  • Metabolic syndrome
  • Pioglitazone

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health

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