A Systematic Review and Narrative Synthesis Comparing the Efficacy of Dapoxetine and Clomipramine in the Management of Premature Ejaculation

ABSTRACT Dapoxetine (on‐demand SSRI) and clomipramine (daily TCA) are commonly used for premature ejaculation (PE), yet direct comparative evidence remains limited and heterogeneous, particularly because dapoxetine is administered on‐demand while clomipramine requires daily dosing. To systematically review evidence comparing dapoxetine and clomipramine with emphasis on intravaginal ejaculatory latency time (IELT) and patient‐reported outcomes (PROMs). A narrative synthesis following PRISMA guidelines was conducted, evaluating randomized controlled trials assessing either drug. Owing to heterogeneity in dosing regimens, outcome definitions, and study designs, and to the absence of PROSPERO preregistration, findings were analyzed descriptively. Nineteen RCTs met inclusion criteria, including five studying dapoxetine (30–60 mg on‐demand) and 14 studying clomipramine (15–50 mg daily). Dapoxetine increased IELT 2.5–3.0‐fold, while clomipramine increased IELT 2.5–5.2‐fold. Improvements in PROMs were reported for both drugs. Only one RCT directly compared dapoxetine with clomipramine; all other trials compared each drug with placebo. The limited number of head‐to‐head trials and heterogeneity across studies restrict the strength of comparative conclusions. Both medications demonstrate meaningful improvements in IELT and patient satisfaction. Clomipramine shows greater short‐term efficacy, while dapoxetine offers superior tolerability and long‐term adherence. Given the heterogeneity in dosing regimens and limited direct comparative trials, treatment selection should be individualized. These findings align with EAU and ISSM guideline recommendations for PE management.