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

J Affect Disord. 2012 Feb;136(3):1164-73. doi: 10.1016/j.jad.2011.06.033. Epub 2011 Jul 22.

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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antidepressive Agents / therapeutic use*
  • Depressive Disorder, Major / complications
  • Depressive Disorder, Major / drug therapy*
  • Double-Blind Method
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Metabolic Syndrome / complications
  • Metabolic Syndrome / drug therapy*
  • Middle Aged
  • Obesity, Abdominal / complications*
  • Personality Inventory
  • Pilot Projects
  • Pioglitazone
  • Thiazolidinediones / therapeutic use*

Substances

  • Antidepressive Agents
  • Hypoglycemic Agents
  • Thiazolidinediones
  • Pioglitazone