Pioglitazone could induce remission in major depression: a meta-analysis

Background: Pioglitazone, a selective agonist of the nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-gamma), prescribed for the treatment of type 2 diabetes, could have antidepressant properties. However, its potential to induce remission of major depressive episodes, the optimal clinical target for an antidepressant drug, is a matter of concern. Indeed, only one out of four double-blind randomized controlled trials show higher remission rates with pioglitazone than with control treatments. Hence, the main aim of this study was to perform a meta-analysis of the efficacy of pioglitazone for the treatment of MDE, focusing on remission rates. Methods: Four double-blind randomized controlled trials, comprising 161 patients with an MDE, were included in this meta-analysis. Pioglitazone was studied either alone (one study) or as add-on therapy to conventional treatments (antidepressant drugs or lithium salts). It was compared either to placebo (three studies) or to metformin (one study). Remission was defined by a Hamilton Depression Rating Scale score <8 after treatment. Results: Pioglitazone could induce higher remission rates than control treatments (27% versus 10%, I-2= 17.3%, fixed-effect model: odds ratio [OR]=3.3, 95% confidence interval [95% CI; 1.4; 7.8], P=0.008). The OR was even higher in the subgroup of patients with major depressive disorder (n= 80; 23% versus 8%, I-2= 0.0%; fixed-effect model: OR=5.9, 95% CI [1.6; 22.4], P= 0.009) and in the subgroup of patients without metabolic comorbidities (n= 84; 33% versus 10%, I-2= 0.0%; fixed-effect model: OR=5.1, 95% CI [1.5; 17.9], P=0.01). As compared to control treatments, results suggest six patients would need to be treated with pioglitazone in order to achieve the possibility of one more remission. Conclusion: Pioglitazone, either alone or as add-on therapy to conventional treatments, could induce remission of MDE, suggesting that drugs with PPAR-gamma agonist properties may be true and clinically relevant antidepressants, even in patients without metabolic comorbidities.