Oral agents for the treatment of premature ejaculation: review of efficacy and safety in the context of the recent International Society for Sexual Medicine criteria for lifelong premature ejaculation.

INTRODUCTION New diagnostic criteria for lifelong premature ejaculation (PE) have been proposed by the International Society of Sexual Medicine (ISSM), including an intravaginal ejaculatory latency time (IELT) of less than about 1 minute, lack of control over ejaculation, and PE-related distress or bother. AIM The aim of this study was to review evidence supporting the efficacy and safety of oral agents for the treatment of PE in the context of the new ISSM criteria. METHODS The PubMed database was searched for randomized, double-blind, placebo-controlled studies of oral agents in PE that included stopwatch measurements of IELT. MAIN OUTCOME MEASURES The main outcome measure used for this study was a review of the efficacy and safety data of oral agents for PE aligned with ISSM criteria. RESULTS Since the latest meta-analyses using similar criteria (conducted in 2004 and 2005 for selective serotonin reuptake inhibitors [SSRIs] and phosphodiesterase type 5 [PDE-5] inhibitors, respectively), eight studies evaluated SSRIs vs. placebo, one compared SSRIs, two evaluated PDE-5 inhibitors, and one evaluated an SSRI/PDE-5 inhibitor combination. New agents included dapoxetine (five studies) and tramadol (one study). Six studies enrolled men who met an approximation of the ISSM criteria. Although evidence suggests that most SSRIs, tramadol, and dapoxetine increase IELT to varying degrees, few studies included control over ejaculation and PE-related distress or bother as enrollment criteria or used validated patient-reported outcome instruments to evaluate these parameters. Among studies that provided comprehensive adverse event data, safety and tolerability observations in men with PE were generally similar to those observed in other populations; however, with the exception of dapoxetine, known SSRI-class effects (e.g., withdrawal syndrome) were not evaluated in men with PE. CONCLUSIONS This systematic review of well-controlled clinical trials in PE has demonstrated that while many oral agents, particularly SSRIs, tramadol, and dapoxetine, have proven effective and safe for the treatment of men with PE, few have been evaluated for their effects on the specific elements of the ISSM criteria.