title: PPAR-γ Agonists for the Treatment of Major Depression: A Review.
abstract: Introduction:Selective agonists of the nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-γ) are used for the treatment of type 2 diabetes. We reviewed their efficacy and safety for the treatment of major depression and the association of their potential antidepressant effects with changes in biomarkers of metabolism and inflammation.Methods:From 8 studies, 4 open-label trials, and 4 randomized controlled trials (RCT) (3 vs. placebo and 1 vs. metformin), 448 patients with major depression were included, of which 209 patients received PPAR-γ agonists (pioglitazone or rosiglitazone) for 6-12 weeks, either alone or in add-on therapy to conventional treatments.Results:PPAR-γ agonists have antidepressant effects in the 4 open-label studies and in 3 out of 4 RCT. No major adverse event was reported. Improvement in depression scores was associated with improvement in 3 biomarkers of insulin resistance (homeostatic model assessment [HOMA-IR], oral glucose tolerance test, and fasting plasma glucose) and 1 biomarker of inflammation (interleukin-6) among 21 biomarkers studied.Conclusion:PPAR-γ agonists may have antidepressant properties, which need to be assessed in further studies of major depressive episodes.
authors.affiliation: University Paris-Sud, Le Kremlin Bicêtre, France.
authors.forename: R
authors.initials: R
authors.lastname: Colle
authors.affiliation: University Paris-Sud, Le Kremlin Bicêtre, France.
authors.forename: D
authors.initials: D
authors.lastname: de Larminat
authors.affiliation: University Paris-Sud, Le Kremlin Bicêtre, France.
authors.forename: S
authors.initials: S
authors.lastname: Rotenberg
authors.affiliation: University Paris-Sud, Le Kremlin Bicêtre, France.
authors.forename: F
authors.initials: F
authors.lastname: Hozer
authors.affiliation: University Paris-Sud, Le Kremlin Bicêtre, France.
authors.forename: P
authors.initials: P
authors.lastname: Hardy
authors.affiliation: University Paris-Sud, Le Kremlin Bicêtre, France.
authors.forename: C
authors.initials: C
authors.lastname: Verstuyft
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie, Centre de Recherche Saint-Antoine, INSERM UMR_S938, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Fève
authors.affiliation: University Paris-Sud, Le Kremlin Bicêtre, France.
authors.forename: E
authors.initials: E
authors.lastname: Corruble
mesh_terms: D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D005215:Fasting; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000928:Antidepressive Agents; D015415:Biomarkers; D001786:Blood Glucose; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077205:Pioglitazone