Tehran University of Medical Sciences The Research in Heart Yield and Translational Medicine (RHYTHM) 3115-7270 21 3 2026 07 05 231 242 Parisa Rajabi Tehran University of Medical Sciences Fateme TaghaviZanjani Tehran University of Medical Sciences Mohamadjavad Ershadmanesh Tehran University of Medical Sciences Faezeh Mokhtari Tehran University of Medical Sciences Zahra Haji Faraj Tabrizi Tehran University of Medical Sciences Melika Jameie Tehran University of Medical Sciences Saeed Nateghi Tehran University of Medical Sciences Mayam Mehrpooya Tehran University of Medical Sciences Sara Hashempour Tehran University of Medical Sciences Sayedeh Elham Sharafi Tehran University of Medical Sciences Hamed Vahidi Tehran University of Medical Sciences Ahmad Shamabadi Tehran University of Medical Sciences Ahmad Ali Noorbala Tehran University of Medical Sciences Shahin Akhondzadeh Tehran University of Medical Sciences 2026 06 02 2026 07 05 Background: Major depressive disorder (MDD) frequently occurs alongside coronary artery disease (CAD), worsening cardiovascular outcomes. Cilostazol is a phosphodiesterase 3 inhibitor used as an antiplatelet agent with potential antidepressant effects. This study evaluated the efficacy of cilostazol for treating depressive symptoms in participants with CAD. Methods: This 6-week, double-blind, placebo-controlled clinical trial enrolled individuals with MDD and Hamilton Depression Rating Scale (HDRS) scores of 14 to 17 who had undergone percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Participants were randomly assigned to receive cilostazol (100 mg/d) or placebo. Outcomes included HDRS scores and adverse events. Results: Baseline characteristics were similar between the groups (all P>.05). A significant time × treatment interaction effect on HDRS scores was observed (P=.037; partial η2=0.055). The cilostazol group showed greater reductions in HDRS scores through weeks 4 and 6 (P=.012 and P=.054, respectively). Adverse effects were not serious and were comparable between the groups (all P>.05). Conclusion: Cilostazol was beneficial and safe for treating depressive symptoms in individuals who had recently undergone PCI or CABG. Further studies are needed to support broader clinical application. https://jthc.tums.ac.ir/index.php/jthc/article/view/2481 https://jthc.tums.ac.ir/index.php/jthc/article/download/2481/1277