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Cited by 109Treatment of Major DepressionTryptophan and brain disordersAnxiety, Depression, Psychometrics, Treatment, Cognitive Processes

Use of insulin sensitizers for the treatment of major depressive disorder: A pilot study of pioglitazone for major depression accompanied by abdominal obesity

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Kemp, David E., Ismail-Beigi, Faramarz, Ganocy, Stephen J., Conroy, Carla, Gao, Keming, Obral, Sarah, Fein, Elizabeth, Findling, Robert L. +1 more·2012·Journal of Affective Disorders
DOI 10.1016/j.jad.2011.06.033PMC PMC3225727
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Abstract

Objective This study was conducted to examine the safety and efficacy of pioglitazone, a thiazolidinedione insulin sensitizer, in adult outpatients with major depressive disorder.Method In a 12-week, open-label, flexible-dose study, 23 patients with major depressive disorder received pioglitazone monotherapy or adjunctive therapy initiated at 15 mg daily. Subjects were required to meet criteria for abdominal obesity (waist circumference>35 in. in women and >40 in. in men) or metabolic syndrome. The primary efficacy measure was the change from baseline to Week 12 on the Inventory of Depressive Symptomatology (IDS) total score. Partial responders (≥25% decrease in IDS total score) were eligible to participate in an optional extension phase for an additional three months.Results Pioglitazone decreased depression symptom severity from a total IDS score of 40.3±1.8 to 19.2±1.8 at Week 12 (p<.001). Among partial responders (≥25% decrease in IDS total score), an improvement in depressive symptoms was maintained during an additional 3-month extension phase (total duration=24 weeks) according to IDS total scores (p<.001). Patients experienced a reduction in insulin resistance from baseline to Week 12 according to the log homeostasis model assessment (-0.8±0.75; p<.001) and a significant reduction in inflammation as measured by log highly- sensitive C-reactive protein (-0.87±0.72; p<.001). During the current episode, the majority of participants (74%, n=17), had already failed at least one antidepressant trial. The most common side effects were headache and dizziness; no patient discontinued due to side effects.Limitations These data are limited by a small sample size and an open-label study design with no placebo control.Conclusion Although preliminary, pioglitazone appears to reduce depression severity and improve several markers of cardiometabolic risk, including insulin resistance and inflammation. Larger, placebo-controlled studies are indicated.

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  • A pilot open-label trial involving adult outpatients with major depressive disorder (n = 23) with comorbid abdominal obesity or metabolic syndrome documented that adjunctive pioglitazone significantly improves depressive severity, with a concurrent reduction in insulin resistance and inflammatory markers.

    “A pilot, open-label trial involving adult outpatients with MDD (n = 23) with comorbid abdominal obesity (waist circumference >35 inches in women and >40 inches in men) or metabolic syndrome documented that adjunctive pioglitazone significantly improves depressive severity (assessed by the Inventory of Depressive Symptomatology), with a concurrent reduction in insulin resistance and inflammatory”

    From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [117]

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Authors
Kemp, D. E., Ismail-Beigi, F., Ganocy, S. J., Conroy, C., Gao, K., Obral, S., Fein, E., Findling, R. L., & Calabrese, J. R.
Affiliations
University Hospitals Cleveland Medical Center (US)
Corresponding author
Kemp, David E.
ORCID
Venue
Journal of Affective Disorders
Publisher
Elsevier BV
Published
2012-02
Volume
136
Issue
3
Pages
1164-1173
ISSN
0165-0327 (ISSN-L)
DOI
10.1016/j.jad.2011.06.033
PMC
PMC3225727
OpenAlex
W2160313172
Cited by
109
References
68
Citations by year
2026: 7 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 5 · 2021: 10 · 2020: 8 · 2019: 9 · 2018: 10 · 2017: 7 · 2016: 12 · 2015: 11 · 2014: 3 · 2013: 4 · 2012: 10
FWCI
4.22
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Journal of Affective Disorders (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (5kl2rr024990-05)
  • National Center for Research Resources (KL2-RR-024990, UL1RR024989, 1KL2 RR024990)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007542)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
Keywords
pioglitazone, major depressive disorder, insulin sensitizers, thiazolidinediones, abdominal obesity, metabolic syndrome, insulin resistance, C-reactive protein, inflammation, antidepressant-resistant depression, adjunctive therapy, cardiometabolic risk
MeSH terms
Pioglitazone, Adult, Antidepressive Agents, Major Depressive Disorder, Double-Blind Method, Female, Humans, Hypoglycemic Agents, Male, Middle Aged, Personality Inventory, Pilot Projects, Metabolic Syndrome, Thiazolidinediones, Obesity, Abdominal

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