Background: We performed the network meta-analysis (NMA) and systematic review involved all evidence from relevant trials to compare the efficiency and safety of various types of selective serotonin reuptake inhibitors (SSRI) and phosphodiesterase-5 inhibitors (PDE5i) in patients with premature ejaculation (PE).

Methods: We conducted comprehensive searches of peer-reviewed and grey literature. PubMed, the Cochrane Library Central Register of Controlled Trials, Embase were searched for randomized controlled trials published up to June 1, 2017. The primary outcome was intravaginal ejaculation latency time (IVELT) and adverse effects (AEs). We performed pairwise meta-analyses by random effects model and network meta-analysis by Bayesian model. We used the GRADE framework to assess the quality of evidence contributing to each network estimate.

Results: Of 3046 titles and abstracts initially identified, 17 trials reporting 5739 participants were included. Considering IVELT in the NMA, paroxetine plus sildenafil and sildenafil alone are both superior to placebo (MD: 1.75, 95% CrI: 0.05 to 3.78; MD 1.43, 95% CrI 0.003 to 2.81). Sildenafil is superior to sertraline (MD: 1.63, 95% CrI: 0.10 to 2.79). Considering AEs, placebo demonstrated obviously lower risk comparing to paroxetine, sildenafil and paroxetine plus sildenafil (OR 0.20, 95% CI: 0.05 to 0.52; OR 0.23, 95% CI: 0.04 to 0.80; OR 0.45, 95% CI: 0.01 to 0.92). Compared with tadalafil plus paroxetine, dapoxetine showed significantly less AEs (OR 0.23, 95% CI 0.02 to 0.96).

Conclusions: Our study concluded that although paroxetine plus sildenafil and sildenafil alone both demonstrated significant IVELT benefit compared with placebo, significant increase of AEs risk was also observed. Furthermore, sildenafil alone was superior to sertraline in efficacy with comparable tolerability.