Phosphodiesterase inhibitor and selective serotonin reuptake inhibitor combination therapy versus monotherapy for the treatment of major depressive disorder: a systematic review and meta-analysis

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.