Comparative evaluation of safety and efficacy of dapoxetine, silodosin, and citalopram in the management of premature ejaculation: a randomized clinical trial.

backgroundPremature ejaculation (PE) is a prevalent male sexual dysfunction with limited comparative data on pharmacological treatments. This randomized clinical trial aimed to evaluate the efficacy and safety of four active pharmacological interventions for lifelong PE.

methodsA prospective randomized trial was conducted from June 2024 to March 2025 at Beni-Suef University Hospital. Four hundred eligible patients diagnosed with lifelong PE were randomly allocated to one of four active treatment groups (n = 100 per group): (1) citalopram 20 mg/day, (2) silodosin 4 mg/day, (3) dapoxetine 30 mg on-demand (1-3 h before intercourse), or (4) dapoxetine 30 mg daily. The primary outcome was the change in intravaginal ejaculatory latency time (IELT) measured by stopwatch. Secondary outcomes included changes in the Premature Ejaculation Profile Questionnaire (PEPQ) scores and the incidence of treatment-emergent adverse events. Statistical analysis was performed using ANOVA with post-hoc tests for continuous variables and chi-square tests for categorical data.

resultsAll four treatment groups demonstrated significant within-group improvements in IELT from baseline (p < 0.001 for all). The citalopram group exhibited the greatest mean IELT increase (from 110.4 ± 31.5s to 391.2 ± 45.9s; 260% median gain), outperforming the daily dapoxetine (220%), on-demand dapoxetine (197%), and silodosin (149.5%) groups. Improvements in PEPQ scores mirrored the IELT findings, with citalopram showing a 300% improvement compared to 225%, 166.7%, and 175% in the daily dapoxetine, on-demand dapoxetine, and silodosin groups, respectively. In inter-group comparisons, citalopram was superior to silodosin in all PEPQ domains (p < 0.001) and to both dapoxetine regimens in the domain of interpersonal difficulty (p < 0.01). Adverse event profiles differed: silodosin was associated with a higher incidence of ejaculatory dysfunction (23% retrograde ejaculation), while daily dapoxetine led to more systemic effects (18% dizziness).

conclusionIn this direct head-to-head comparison of active treatments for lifelong PE, daily citalopram (20 mg) demonstrated superior efficacy in prolonging IELT and improving psychosocial outcomes compared to daily or on-demand dapoxetine and silodosin. The findings suggest that citalopram is a highly effective first-line option, while the dose-dependent efficacy of dapoxetine and the distinct side-effect profile of silodosin provide alternative considerations for personalized treatment strategies.

trial registrationThis clinical trial was registered at ClinicalTrials.gov (Identifier NCT07113145) on 7 August 2025 after the enrollment of the first participant and is therefore retrospectively registered."