title: Adjuvant pioglitazone for unremitted depression: Clinical correlates of treatment response.
abstract: Previous studies suggest that insulin-sensitizing agents could play a significant role in the treatment of major depression, particularly depression in patients with documented insulin resistance or those who are resistant to standard psychopharmacological approaches. This study aimed to assess the effects on depressive symptoms with adjuvant treatment with the PPARγ-agonist pioglitazone. Patients (N=37) with non-psychotic, non-remitting depression receiving standard psychiatric regimens for depression were randomized across an insulin sensitivity spectrum in a 12-week double blind, randomized controlled trial of pioglitazone or placebo. Improvement in depression was associated with improvement in glucose metabolism but only in patients with insulin resistance. An age effect was also shown in that response to pioglitazone was more beneficial in younger aged patients. Study findings suggest differential improvement in depression severity according to both glucose metabolic status and level of depression at baseline. A greater understanding of the reciprocal links between depression and IR may lead to a dramatic shift in the way in which depression is conceptualized and treated, with a greater focus on treating and/or preventing metabolic dysfunction.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA, United States.
authors.forename: Kathleen Watson
authors.initials: KW
authors.lastname: Lin
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA, United States.
authors.forename: Tonita E
authors.initials: TE
authors.lastname: Wroolie
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA, United States.
authors.forename: Thalia
authors.initials: T
authors.lastname: Robakis
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA, United States. Electronic address: nrasgon@stanford.edu.
authors.forename: Natalie L
authors.initials: NL
authors.lastname: Rasgon
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000627:therapeutic use*; D000328:Adult; D000367:Age Factors; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D003865:Major Depressive Disorder / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D000277:Adjuvants, Pharmaceutic; D000928:Antidepressive Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D000077205:Pioglitazone
keywords: Antidepressant response; Clinical trial; Depressive disorders; Insulin resistance; PPAR-γ agonist; Treatment resistant