Rosiglitazone Adjunct to Sertraline for Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial

Why clinicians should know about it

• Picked for Psychiatry and Mental Health (paper of the day, 24 July 2026).

Abstract

Insufficient responses to available treatments for major depressive disorder (MDD) underscores the necessity for innovative therapeutic strategies. This study investigated the efficacy of adjunctive rosiglitazone, an antidiabetic agent with neuroprotective and anti-inflammatory effects, for MDD. In this 6-week randomized, parallel-group, double-blind, placebo-controlled clinical trial, patients with MDD were assigned to receive sertraline along with either rosiglitazone 2 mg or a matched placebo q12 h. Participants were evaluated using the Hamilton depression rating scale (HDRS) at baseline and weeks 2, 4, and 6. The difference in its score changes to the endpoint was the primary outcome. Side effects were documented as well. The participants had comparable baseline characteristics. A significant time -treatment interaction effect was observed for HDRS scores ( η P 2  = 0.052), with the rosiglitazone group experiencing significantly greater reductions at weeks 2 (Cohen's d = 0.507), 4 (Cohen's d = 0.556), and 6 (Cohen's d = 0.541) compared to the placebo group. Additionally, the rosiglitazone group demonstrated significantly higher response rates until weeks 4 (50.0% vs. 24.2%) and 6 (84.4% versus 51.5%). By week 6, the remission rate was nonsignificantly higher in the rosiglitazone group (18.8%) than in the placebo group (9.1%). Side effect frequencies were comparable. In conclusion, rosiglitazone was beneficial for depressive symptoms of patients with MDD safely and tolerably. Further long-term, large-scale studies are recommended to confirm this evidence. Trial Registration: ClinicalTrials.gov identifier: IRCT20090117001556N152.

Abstract as published, via PubMed.