Dapoxetine: a new option in the medical management of premature ejaculation

Abstract

Premature ejaculation (PE) is a common male sexual disorder which is associated with substantial personal and interpersonal negative psychological consequences. Pharmacotherapy of PE with off-label antidepressant selective serotonin reuptake inhibitors (SSRIs) is common, effective and safe. Development and regulatory approval of drugs specifically for the treatment of PE will reduce reliance on off-label treatments and serve to fill an unmet treatment need. The objective of this article is to review evidence supporting the efficacy and safety of dapoxetine in the treatment of PE. MEDLINE, Web of Science, PICA, EMBASE and the proceedings of major international and regional scientific meetings were searched for publications or abstracts published during the period 1993-2012 that used the word 'dapoxetine' in the title, abstract or keywords. This search was then manually cross referenced for all papers. This review encompasses studies of dapoxetine pharmacokinetics, animal studies, human phase I, II and III studies, independent postmarketing and pharmacovigilance efficacy and safety studies and drug-interaction studies. Dapoxetine is a potent SSRI which is administered on demand 1-3 h prior to planned sexual contact. It is rapidly absorbed and eliminated, resulting in minimal accumulation, and has doseproportional pharmacokinetics which are unaffected by multiple dosing. Dapoxetine 30 mg and 60 mg has been evaluated in five industry-sponsored randomized, double-blind, placebo-controlled studies in 6081 men aged at least 18 years. Outcome measures included stopwatch-measured intravaginal ejaculatory latency time (IELT), Premature Ejaculation Profile (PEP) inventory items, Clinical Global Impression of Change (CGIC) in PE, and adverse events. Mean IELT, all PEP items and CGIC improved significantly with both doses of dapoxetine versus placebo (all p <0.001). The most common treatment-related adverse effects included nausea (11.0% for 30 mg, 22.2% for 60 mg), dizziness (5.9% for 30 mg, 10.9% for 60 mg), and headache (5.6% for 30 mg, 8.8% for 60 mg), and evaluation of validated rated scales demonstrated no SSRI class-related effects with dapoxetine use. Dapoxetine, as the first drug developed for PE, is an effective and safe treatment for PE and represents a major advance in sexual medicine.

Results from a Prospective Observational Study of Men with Premature Ejaculation Treated with Dapoxetine or Alternative Care: The PAUSE Study

“…In phase 3 studies, several well-recognized side effects of SSRIs (ie, akathisia, withdrawal syndrome, and mood-related changes) were not reported for dapoxetine use [2]. A low rate of vasovagal syncope was reported in phase 3 studies, and the premarketing safety profile did not show evidence of serious cardiovascular (CV) events or arrhythmias [4,5]. The primary objectives of this study were to characterize the safety profile of dapoxetine when used to treat men with PE in routine clinical practice, and to report the incidence, severity, and type of adverse events (serious adverse events and/or adverse events of special clinical interest).…”

Methods for a rapid systematic review and metaanalysis in evaluating selective serotonin reuptake inhibitors for premature ejaculation

“…For SSRIs, eleven existing reviews were identified and it was possible to check the data across these reviews for concordance (Cong et al 2012;Huang et al 2009;Luo et al 2012;McCarty and Dinsmore 2012;McMahon 2012;McMahon and Porst 2011;Moreland and Makela 2005;Richardson et al 2005;Waldinger et al 2004a;Wang et al 2007;Wang et al 2010). Outcome data from RCTs not reported in reviews was extracted from the RCT publication.…”

Interventions to treat premature ejaculation: a systematic review short report

“…Dapoxetine as the primary treatment of investigation was evaluated by four systematic reviews of effectiveness, [108][109][110]169 two of which pooled data in a meta-analysis. 108,110 One systematic review evaluated the risk-benefit assessment of dapoxetine including withdrawal data from Phase III trials, 111 one review evaluated dapoxetine Phase II trials including pharmacokinetic and safety data 112 and two further effectiveness reviews of SSRIs included studies of dapoxetine and other SSRIs.…”