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



Shamabadi A ; Karami R ; Sadati S ; Farahmand K ; Ershadmanesh M ; Moosavi R ; Rahiminejad F ; Khodaei Ardakani M R ; Akhondzadeh S
Source: Depression and Anxiety Published: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 ((Formula presented.) = 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. Copyright © 2026 Ahmad Shamabadi et al. Depression and Anxiety published by John Wiley & Sons Ltd.