Pioglitazone Adjunctive Therapy for Moderate-to-Severe Major Depressive Disorder: Randomized Double-Blind Placebo-Controlled Trial
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Thiazolidinediones have shown antidepressant effect in animal studies, as well as in some uncontrolled studies evaluating human subjects with concurrent major depressive disorder (MDD) and metabolic syndrome. Although these drugs are insulin sensitizers, they also have important anti-inflammatory, neuroprotective, and anti-excitotoxic properties. Thus, we hypothesized that they would show antidepressant effect in patients with MDD even if it was not accompanied by metabolic disturbances. In this double-blind placebo-controlled study, 40 patients with MDD (DSM-IV-TR) and Hamilton depression rating scale-17 (Ham-D) score ≥ 22 were randomized to citalopram plus pioglitazone (15 mg every 12 h) (n=20) or citalopram plus placebo (n=20) for 6 weeks. Patients were evaluated using Ham-D (weeks 0, 2, 4, 6). Repeated-measure analysis of variance (ANOVA) and analysis of covariance were used for comparison of scores between the two groups. Treatment response (≥ 50% reduction in Ham-D score), remission (Ham-D score ≤ 7), and early improvement (≥ 20% reduction in Ham-D score within the first 2 weeks) were compared between the two groups using Fisher's exact test. Pioglitazone showed superiority over placebo during the course of the trial (F(1, 38)=9.483, p=0.004). Patients in the pioglitazone group had significantly lower scores at all time points than the placebo group (P<0.01). Frequency of early improvement, response (week 6), and remission was significantly higher in the pioglitazone group (95%, 95%, 45%, respectively) than in the placebo (30%, 40%, 15% respectively) group (P<0.001, <0.001, 0.04, respectively). Frequency of side effects was similar between the two groups. Pioglitazone is a safe and effective adjunctive short-term treatment in patients with moderate-to-severe MDD even in the absence of metabolic syndrome and diabetes.
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In a 6-week RCT on individuals with moderate-to-severe major depressive disorder (n = 40) without diabetes or metabolic syndrome, adjunctive treatment with pioglitazone was associated with greater decrements in HDRS compared with a placebo group.
“In a 6-week RCT on individuals with moderate-to-severe MDD (n = 40) without diabetes or metabolic syndrome, adjunctive treatment with pioglitazone was associated with greater decrements in HDRS compared with a placebo group, in line with the hypothesis that antidepressant effects are mediated by anti-inflammatory, anti-excitotoxic, and neuroprotective properties [120].”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [120]
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“Other drugs, such as thiazolidinediones with anti-inflammatory effects, are being re-examined for their potential role in the treatment of mood disorders (105).”
BackgroundAnti-inflammatory treatments for mood disorders: Systematic review and meta-analysis
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- Authors
- Sepanjnia, K., Modabbernia, A., Ashrafi, M., Modabbernia, M.-J., & Akhondzadeh, S.
- Affiliations
- Roozbeh Hospital (IR)
- Guilan University of Medical Sciences (IR)
- Corresponding author
- Akhondzadeh, Shahin
- Venue
- Neuropsychopharmacology
- Published
- 2012-05-02
- Volume
- 37
- Issue
- 9
- Pages
- 2093-2100
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3398722
- OpenAlex
- W2079344641
- Cited by
- 153
- References
- 46
- Citations by year
- 2026: 13 · 2025: 9 · 2024: 7 · 2023: 13 · 2022: 11 · 2021: 13 · 2020: 9 · 2019: 10 · 2018: 9 · 2017: 12 · 2016: 13 · 2015: 14 · 2014: 7 · 2013: 7 · 2012: 6
- FWCI
- 8.00
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Tehran University of Medical Sciences and Health Services
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- pioglitazone, major depressive disorder, thiazolidinediones, adjunctive therapy, antidepressant effects, citalopram, insulin sensitizers, anti-inflammatory activity, neuroprotection, treatment response and remission, adverse effects
- MeSH terms
- Pioglitazone, Adult, Major Depressive Disorder, Double-Blind Method, Drug Therapy, Combination, Female, Follow-Up Studies, Humans, Male, Severity of Illness Index, Citalopram, Treatment Outcome, Chemotherapy, Adjuvant, Thiazolidinediones
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