A network meta-analysis on comparative efficacy and tolerability of on-demand therapy for premature ejaculation

Introduction: The use of pharmacotherapy as a first-line treatment for premature ejaculation (PE) is recommended by EAU guidelines. However, no study had analyzed multiple treatment comparisons among available on-demand therapy. Therefore, we aimed to perform a network meta-analysis (NMA) to characterize the comparative efficacy and tolerability of on-demand therapy for PE. Methods: We systematically searched randomized controlled trials (RCTs) in several databases at any period up to November 2019. NMA was performed to estimate efficacy and tolerability outcomes using intravaginal ejaculation latency time (IELT) and overall adverse effects (AEs), respectively. We ranked each outcome using the surface under the cumulative ranking curve (SUCRA) and presented the two outcomes as a clustered ranking plot. Results: A total of 19 RCTs comprising 5950 patients were included in this NMA. All active treatments showed significant improvement compared to placebo. Among the available on-demand treatment, the combination of SSRI plus PDE5i showed the highest efficacy (MD: 3.06; 95%CI 1.84-4.29) followed by tramadol 100 mg and vardenafil 10 mg (MD 2.9, 95%CI 1.63-4.16; MD 2.36, 95%CI 1.2-3.52; respectively). Based on the SUCRA, the combination of SSRI plus PDE5i had the highest score (91.7%) in efficacy, while dapoxetine 30 mg had the highest score (73.3%) in terms of tolerability. Conclusion: The combination of SSRI plus PDE5i was the treatment of choice for individuals who prioritize efficacy. For those who prioritize tolerability, dapoxetine 30 mg and vardenafil 10 mg became alternative treatments. Various on-demand therapy options require careful discussion with patient expectations of treatment effects.