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Cited by 116Ovarian function and disordersTreatment of Major DepressionSchizophrenia research and treatment

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

Kashani, Ladan, Omidvar, Targol, Farazmand, Behnoud, Modabbernia, Amirhossein, Ramzanzadeh, Fatemeh, Tehraninejad, Ensiyeh Shahrokh, Ashrafi, Mandana, Tabrizi, Mina +1 more·2013·Psychoneuroendocrinology
DOI 10.1016/j.psyneuen.2012.08.010
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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).

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  • The antidepressant properties of pioglitazone appeared to be largely independent of insulin-sensitizing action and possibly mediated by anti-inflammatory and antioxidant actions, including inhibition of the nuclear factor kappa B cascade and cytokine production, as well as quinolinic acid-induced neurotoxicity.

    “Importantly, the authors of this study underscored that antidepressant properties appeared to be largely independent of insulin-sensitizing action and are possibly mediated by anti-inflammatory and antioxidant”

    From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [118]

  • A subsequent 6-week RCT confirmed the antidepressant efficacy of pioglitazone in obese patients with concomitant polycystic ovarian syndrome and major depressive disorder (n = 50), reporting significant reductions in HDRS scores.

    “In accord, a subsequent 6-week RCT confirmed the antidepressant efficacy of pioglitazone in obese patients with concomitant polycystic ovarian syndrome and MDD (n = 50), reporting significant reductions in HDRS scores [118].”

    From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [118]

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Authors
Kashani, L., Omidvar, T., Farazmand, B., Modabbernia, A., Ramzanzadeh, F., Tehraninejad, E. S., Ashrafi, M., Tabrizi, M., & Akhondzadeh, S.
Affiliations
  • Tehran University of Medical Sciences (IR)
  • Roozbeh Hospital (IR)
Corresponding author
Akhondzadeh, Shahin
ORCID
Venue
Psychoneuroendocrinology
Publisher
Elsevier BV
Published
2013-06
Volume
38
Issue
6
Pages
767-776
ISSN
0306-4530 (ISSN-L)
DOI
10.1016/j.psyneuen.2012.08.010
OpenAlex
W2130194207
Cited by
116
References
69
Citations by year
2026: 4 · 2025: 7 · 2024: 7 · 2023: 13 · 2022: 10 · 2021: 12 · 2020: 13 · 2019: 5 · 2018: 7 · 2017: 12 · 2016: 11 · 2015: 9 · 2014: 3 · 2013: 3
FWCI
5.61
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Psychoneuroendocrinology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords
pioglitazone, metformin, major depressive disorder, polycystic ovary syndrome, insulin sensitizers, thiazolidinediones, antidepressant efficacy, insulin resistance, HOMA-IR, obesity, gastrointestinal adverse effects, androgens
MeSH terms
Pioglitazone, Adolescent, Adult, Antidepressive Agents, Depressive Disorder, Major, Major Depressive Disorder, Double-Blind Method, Female, Humans, Hypoglycemic Agents, Insulin Resistance, Metformin, Obesity, Polycystic Ovary Syndrome, Biomarkers, Thiazolidinediones

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