title: Pioglitazone could induce remission in major depression: a meta-analysis.
abstract: BACKGROUND
  Pioglitazone, a selective agonist of the nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-γ), prescribed for the treatment of type 2 diabetes, could have antidepressant properties. However, its potential to induce remission of major depressive episodes, the optimal clinical target for an antidepressant drug, is a matter of concern. Indeed, only one out of four double-blind randomized controlled trials show higher remission rates with pioglitazone than with control treatments. Hence, the main aim of this study was to perform a meta-analysis of the efficacy of pioglitazone for the treatment of MDE, focusing on remission rates.
  
  
  METHODS
  Four double-blind randomized controlled trials, comprising 161 patients with an MDE, were included in this meta-analysis. Pioglitazone was studied either alone (one study) or as add-on therapy to conventional treatments (antidepressant drugs or lithium salts). It was compared either to placebo (three studies) or to metformin (one study). Remission was defined by a Hamilton Depression Rating Scale score <8 after treatment.
  
  
  RESULTS
  Pioglitazone could induce higher remission rates than control treatments (27% versus 10%,I2=17.3%, fixed-effect model: odds ratio [OR] =3.3, 95% confidence interval [95% CI; 1.4; 7.8],P=0.008). The OR was even higher in the subgroup of patients with major depressive disorder (n=80; 23% versus 8%,I2=0.0%; fixed-effect model: OR =5.9, 95% CI [1.6; 22.4],P=0.009) and in the subgroup of patients without metabolic comorbidities (n=84; 33% versus 10%,I2=0.0%; fixed-effect model: OR =5.1, 95% CI [1.5; 17.9],P=0.01). As compared to control treatments, results suggest six patients would need to be treated with pioglitazone in order to achieve the possibility of one more remission.
  
  
  CONCLUSIONS
  Pioglitazone, either alone or as add-on therapy to conventional treatments, could induce remission of MDE, suggesting that drugs with PPAR-γ agonist properties may be true and clinically relevant antidepressants, even in patients without metabolic comorbidities.
authors.affiliation: Psychiatry Department, Hôpital Bicêtre, INSERM, UMR S1178, University Paris-Sud, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Colle
authors.affiliation: Psychiatry Department, Hôpital Bicêtre, INSERM, UMR S1178, University Paris-Sud, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: de Larminat
authors.affiliation: Psychiatry Department, Hôpital Bicêtre, INSERM, UMR S1178, University Paris-Sud, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France.
authors.forename: Samuel
authors.initials: S
authors.lastname: Rotenberg
authors.affiliation: Psychiatry Department, Hôpital Bicêtre, INSERM, UMR S1178, University Paris-Sud, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France.
authors.forename: Franz
authors.initials: F
authors.lastname: Hozer
authors.affiliation: Psychiatry Department, Hôpital Bicêtre, INSERM, UMR S1178, University Paris-Sud, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Hardy
authors.affiliation: Molecular Genetic, Pharmacogenetics and Hormonology Department, Hôpital Bicêtre, INSERM UMR_S1184, Centre IMVA, University Paris-Sud, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Verstuyft
authors.affiliation: Endocrinology Department, INSERM UMR_S938, Hôpital Saint-Antoine, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire ICAN, Sorbonne Universités, Université Pierre et Marie Curie, Assistance Publique des Hôpitaux de Paris, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Fève
authors.affiliation: Psychiatry Department, Hôpital Bicêtre, INSERM, UMR S1178, University Paris-Sud, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Corruble
keywords: bipolar disorder; major depressive disorder; major depressive episode; meta-analysis; pioglitazone; remission