Does pioglitazone improve depression through insulin-sensitization? Results of a randomized double-blind metformin-controlled trial in patients with polycystic ovarian syndrome and comorbid depression

Ladan Kashani, Targol Omidvar, Behnoud Farazmand, Amirhossein Modabbernia, Fatemeh Ramzanzadeh, Ensiyeh Shahrokh Tehraninejad, Mandana Ashrafi, Mina Tabrizi, Shahin Akhondzadeh

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

Thiazolidinediones have shown beneficial effects in short-term treatment of depression. However, it is unclear whether the antidepressant efficacy of these agents is related to their insulin-sensitizing action. We conducted the present study to compare the antidepressant efficacy of pioglitazone with another insulin-sensitizer, metformin, in obese patients with concomitant polycystic ovarian syndrome (PCOS) and major depressive disorder (MDD). In a six-week double-blind study, 50 patients with PCOS and MDD (DSM-IV-TR criteria) with Hamilton depression rating scale (HDRS) score of <20, randomly received pioglitazone (15. mg twice daily; PO) or metformin (750. mg twice daily; PO). Assessment was done using HDRS (weeks 0, 3, 6) together with fasting Insulin, glucose, and lipid profile, liver enzymes, homeostatic model assessment of insulin resistance (HOMA-IR), anthropometric measures, and serum androgens (weeks 0 and 6). Pioglitazone was superior to metformin in reducing HDRS scores at the end of the study [38.3% versus 8.3% reduction from baseline scores, F(1, 37) = 73.513, P<0.001]. Changes from baseline in HOMA-IR values at week 6 were not significantly different between the two groups (P=0.888). Baseline (but not follow-up) HDRS and HOMA-IR values were significantly correlated (r=0.393, P=0.012). In multiple regression analysis, treatment with pioglitazone independent of HOMA-IR values predicted greater score reduction on HDRS at week 6 (standardized beta = 0.801, P<0.001). Biochemical and hormonal profile did not differ between the two groups at week 6. Metformin was associated with higher frequency of gastrointestinal side effects (P=0.014). In summary, we showed that pioglitazone improved depression with mechanisms largely unrelated to its insulin-sensitizing action (registration number: IRCT201106081556N23).

Original languageEnglish
Pages (from-to)767-776
Number of pages10
JournalPsychoneuroendocrinology
Volume38
Issue number6
DOIs
StatePublished - Jun 2013
Externally publishedYes

Keywords

  • Insulin resistance
  • Major depressive disorder
  • Metformin
  • PPAR-gamma
  • Pioglitazone
  • Polycystic ovarian syndrome
  • Thiazolidinediones

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