Current Pharmacological Management of Premature Ejaculation: A Systematic Review and Meta-analysis.

Premature ejaculation (PE) is the most prevalent male sexual dysfunction. In the last few years, several pharmacologic approaches for oral or topical treatment of PE have been studied. To systematically review the literature on the outcome of pharmacologic interventions for PE on intravaginal ejaculation latency time (IELT) in comparison to placebo. A systematic literature search of PubMed and Scopus using the term "premature ejaculation" was performed on 10 April 2015. Full-text articles on prospective randomized controlled trials (RCTs) investigating pharmacotherapy were included. The main outcome measure was IELT. Out of 266 unique records, a total of 22 were reviewed. The majority of RCTs were of unclear methodological quality because of limited reporting of methods. Pooled evidence suggests that selective serotonin reuptake inhibitors (SSRIs), topical anesthetic creams (TAs), tramadol, and phosphodiesterase type 5 inhibitors (PDE5is) are more effective than placebo at increasing IELT (all p<0.05). However, interpretation of the current meta-analyses may be impaired as a result of frequent heterogeneity in the pooled analyses (all I(2) > 70%). Only pooled analyses for dapoxetine 30mg and 60mg were characterized by homogeneous data (both I(2)<30%) while showing a modest but statistically significant improvement in IELT compared with placebo (mean difference 1.39min, 95% confidence interval 1.23-1.54min; p<0.00001). Meta-analysis revealed that treatment with dapoxetine significantly improves IELT in patients with PE but with modest efficacy. The efficacy of SSRIs, TAs, tramadol, and PDE5is remains unclear owing to high heterogeneity of the available RCT data. There is a persisting need for drug research and development in the field. Premature ejaculation is a condition for which the cause is not well understood. Several types of treatment with medium to low efficacy are available. More research is necessary to identify the ideal treatment.

Castiglione F ，Albersen M ，Hedlund P ，Gratzke C ，Salonia A ，Giuliano F ... -  《-》

Pharmacotherapy of premature ejaculation: a systematic review and network meta-analysis.

Jian Z ，Wei X ，Ye D ，Li H ，Wang K ... -  《-》

Interventions to treat premature ejaculation: a systematic review short report.

Cooper K ，Martyn-St James M ，Kaltenthaler E ，Dickinson K ，Cantrell A ... -  《-》

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.

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. 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. The PubMed database was searched for randomized, double-blind, placebo-controlled studies of oral agents in PE that included stopwatch measurements of IELT. 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. 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. 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.

McMahon CG ，Porst H 《-》

Efficacy and safety of dapoxetine in men with premature ejaculation and concomitant erectile dysfunction treated with a phosphodiesterase type 5 inhibitor: randomized, placebo-controlled, phase III study.

Men with comorbid erectile dysfunction (ED) and premature ejaculation (PE) may be concomitantly prescribed a phosphodiesterase type 5 (PDE5) inhibitor and dapoxetine. Evaluate efficacy and safety of dapoxetine 30 mg and 60 mg on demand (prn) in men with PE and ED who were being treated with PDE5 inhibitors. This randomized, double-blind, placebo-controlled, flexible-dose, multicenter study enrolled men ≥18 years who met diagnostic criteria for PE including intravaginal ejaculatory latency time (IELT) of ≤2 minutes in ≥75% of sexual intercourse episodes; were on stable regimen of a PDE5 inhibitor; and had International Index of Erectile Function-erectile function domain score ≥21. Subjects received placebo, dapoxetine 30 mg, or dapoxetine 60 mg prn (1-3 hours before intercourse) for 12 weeks. Stopwatch-measured average IELT, Clinical Global Impression of Change (CGIC) in PE, Premature Ejaculation Profile (PEP), and treatment-emergent adverse events (TEAEs). Of 495 subjects randomized, 429 completed the study. Arithmetic mean average IELT significantly increased with dapoxetine vs. placebo at end point (5.2 vs. 3.4 minutes) and weeks 4, 8, and 12 (P ≤ 0.002 for all). Men who described their PE at least "better" using the CGIC were significantly greater with dapoxetine vs. placebo at end point (56.5% vs. 35.4%) and weeks 4, 8, and 12 (P ≤ 0.001 for all). Significantly better outcomes were also reported with dapoxetine vs. placebo on PEP measures. Incidence of TEAEs was 20.0% and 29.6% in placebo- and dapoxetine-treated subjects, respectively (P = 0.0135). TEAEs led to discontinuation in 1.6% of subjects in both groups. Most frequent TEAEs were known adverse drug reactions of dapoxetine treatment including nausea (9.2%), headache (4.4%), diarrhea (3.6%), dizziness (2.4%), and dizziness postural (2.4%). In men with PE and comorbid ED on a stable regimen of PDE5 inhibitor, dapoxetine provided meaningful treatment benefit and was generally well tolerated.

McMahon CG ，Giuliano F ，Dean J ，Hellstrom WJ ，Bull S ，Tesfaye F ，Sharma O ，Rivas DA ，Aquilina JW ... -  《-》