Pioglitazone Versus Metformin In The Treatment Of Obese Patients With Concomitant Polycystic Ovarian Syndrome And Major Depressive Disorder: A Double Blind, Randomized Clinical Trial

Shahin Akhondzadeh1, Ladan Kashani2. 1Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Tehran, Iran, 2Arash Hospital, Tehran University of Medical Sciences, Tehran, Iran

Background: 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. In addition, a recent trial by our group has provided evidence for adjunctive effect of pioglitazone in treatment of patients with MDD who did not have metabolic syndrome (Sepanjnia et al., 2012). 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).

Methods: In a six-week double-blind study, 50 patients with PCOS and MDD ( based on Diagnostic and Statistical Manual of Mental Disorders-IV Text Revised criteria) with Hamilton depression rating scale (HDRS) score of <20, randomly received pioglitazone (15 mg twice daily) or metformin (750 mg twice daily). Assessment was done using HDRS (week 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 (week 0 and 6). The trial was performed in accordance with the Declaration of Helsinki and subsequent revisions and approved by the ethics committee at Tehran University of Medical Sciences. Written informed consents were obtained from the parents of patients before entering into the study. One-sample Kolmogorov-Smirnov test was used to assess normality. One and two-way repeated measure analysis of variance (ANOVA) was used for comparison of the effect of the two groups (within and between-group effects respectively) on depression during the course of the study.

Results: 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 six 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).

Conclusion: We showed that pioglitazone improved depression with mechanisms largely unrelated to its insulin-sensitizing action.

Sepanjnia K, Modabbernia A, Ashrafi M, Modabbernia MJ, Akhondzadeh S. (2012). Neuropsychopharmacology 3, 2093-100