title: Use of insulin sensitizers for the treatment of major depressive disorder: a pilot study of pioglitazone for major depression accompanied by abdominal obesity.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  These data are limited by a small sample size and an open-label study design with no placebo control.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Case Western Reserve University, University Hospitals Case Medical Center, Department of Psychiatry, Cleveland, OH 44106, USA. kemp.david@gmail.com
authors.forename: David E
authors.initials: DE
authors.lastname: Kemp
authors.forename: Faramarz
authors.initials: F
authors.lastname: Ismail-Beigi
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ganocy
authors.forename: Carla
authors.initials: C
authors.lastname: Conroy
authors.forename: Keming
authors.initials: K
authors.lastname: Gao
authors.forename: Sarah
authors.initials: S
authors.lastname: Obral
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fein
authors.forename: Robert L
authors.initials: RL
authors.lastname: Findling
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Calabrese
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000188:drug therapy*; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000150:complications*; D010555:Personality Inventory; D010865:Pilot Projects; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D000928:Antidepressive Agents; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone