Meta-AnalysisPhosphodiesterase inhibitor and selective serotonin reuptake inhibitor combination therapy versus monotherapy for the treatment of major depressive disorder: a systematic review and meta-analysisNawras, Mohamada; Beran, Azizullahb; Yazdi, Vahida; Hecht, Mordechaia; Lewis, Chandania,c Author Information aCollege of Medicine and Life Sciences, University of Toledo, Toledo, Ohio bDivision of Gastroenterology & Hepatology, Indiana University, Indianapolis, Indiana cDepartment of Psychiatry, University of Toledo, Toledo, Ohio, USA Received 1 October 2022 Accepted 11 December 2022. Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.intclinpsychopharm.com. Correspondence to Mohamad Nawras, BS, College of Medicine and Life Sciences, University of Toledo, 3000 Arlington Ave, Toledo, OH 43614, USA, E-mail: [email protected] International Clinical Psychopharmacology 38(4):p 261-268, July 2023. | DOI: 10.1097/YIC.0000000000000457 Buy SDC Metrics Abstract Selective serotonin reuptakeinhibitors (SSRIs) are the gold standard treatment for major depressive disorder (MDD). However, the use of phosphodiesterase (PDE) inhibitors in the treatment of MDD remains unclear. Our study aims to compare the effect of PDE inhibitor combination therapy to SSRI monotherapy for the treatment of MDD. We performed a comprehensive literature search using PubMed, EMBASE, and Web of Science databases, for studies that assess the impact of PDE inhibitor therapy on MDD patients. The primary outcome of our study was treatment response rate at the end of study time. Pooled odds ratio (OR) and corresponding 95% confidence intervals (CIs) were calculated using the random-effects model. A P-value <0.05 was considered statistically significant. A total of four randomized control trials (RCTs), including 270 patients with MDD, were included in the analysis. Follow-up periods ranged from 6 to 12 weeks. The PDE inhibitor group was associated with a significantly higher treatment response rate (OR, 4.77; 95% CI, 2.05–11.12; P = 0.0003). Our meta-analysis demonstrated that MDD patients receiving PDE inhibitor combination therapy had a higher treatment response rate than MDD patients receiving SSRI monotherapy. Further large-scale RCTs with long-term follow-ups are necessary to validate our findings. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.