Journal
PHARMACOPSYCHIATRY
Volume 50, Issue 2, Pages 49-55Publisher
GEORG THIEME VERLAG KG
DOI: 10.1055/s-0042-120120
Keywords
major depression; PPAR-gamma agonists; pioglitazone; efficacy; safety
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Funding
- Astra-Zeneca
- Sanofi
- NovoNordisk
- MSD
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Introduction Selective agonists of the nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-gamma) are used for the treatment of type 2 diabetes. We reviewed their efficacy and safety for the treatment of major depression and the association of their potential antidepressant effects with changes in biomarkers of metabolism and inflammation. Methods From 8 studies, 4 open-label trials, and 4 randomized controlled trials (RCT) (3 vs. placebo and 1 vs. metformin), 448 patients with major depression were included, of which 209 patients received PPAR-gamma agonists (pioglitazone or rosiglitazone) for 6-12 weeks, either alone or in add-on therapy to conventional treatments. Results PPAR-gamma agonists have antidepressant effects in the 4 open-label studies and in 3 out of 4 RCT. No major adverse event was reported. Improvement in depression scores was associated with improvement in 3 biomarkers of insulin resistance (homeostatic model assessment [HOMA-IR], oral glucose tolerance test, and fasting plasma glucose) and 1 biomarker of inflammation (interleukin-6) among 21 biomarkers studied. Conclusion PPAR-gamma agonists may have antidepressant properties, which need to be assessed in further studies of major depressive episodes.
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