Interventions for premature ejaculation: Rapid systematic review and meta-analysis

Background: Premature ejaculation (PE) is commonly defined as ejaculation with minimal sexual stimulation before, on or shortly after penetration and before the person wishes it. PE can be either lifelong and present since first sexual experiences (primary), or acquired (secondary), beginning later (Godpodinoff ML. Premature ejaculation: clinical subgroups and etiology. J Sex Marital Ther 1989;15:130–4). Treatments include behavioural and pharmacological interventions. Objective: To systematically review evidence for clinical effectiveness of behavioural, topical and systemic treatments for PE. Data sources: The following databases were searched from inception to 6 August 2013 for published and unpublished research evidence: MEDLINE; EMBASE; Cumulative Index to Nursing and Allied Health Literature; The Cochrane Library including the Cochrane Systematic Reviews Database, Cochrane Controlled Trials Register, Database of Abstracts of Reviews of Effects and the Health Technology Assessment database; ISI Web of Science, including Science Citation Index, and the Conference Proceedings Citation Index-Science. The US Food and Drug Administration website and the European Medicines Agency (EMA) website were also searched. Methods: Randomised controlled trials (RCTs) in adult men with PE were eligible (or non-RCTs in the absence of RCTs). RCT data were extrapolated from review articles when available. The primary outcome was intravaginal ejaculatory latency time (IELT). Data were meta-analysed when possible. Other outcomes included sexual satisfaction, control over ejaculation, relationship satisfaction, self-esteem, quality of life, treatment acceptability and adverse events (AEs). Results: A total of 103 studies (102 RCTs, 65 from reviews) were included. RCTs were available for all interventions except yoga. The following interventions demonstrated significant improvements (p < 0.05) in arithmetic mean difference in IELT compared with placebo: topical anaesthetics – eutectic mixture of local anaesthetics (EMLA®, AstraZeneca), topical eutectic mixture for PE (Plethora Solutions Ltd) spray; selective serotonin reuptake inhibitors (SSRIs) – citalopram (Cipramil®, Lundbeck), escitalopram (Cipralex®, Lundbeck), fluoxetine, paroxetine, sertraline, dapoxetine (Priligy®, Menarini), 30 mg or 60 mg; serotonin–noradrenaline reuptake inhibitors – duloxetine (Cymbalta®, Eli Lilly & Co Ltd); tricyclic antidepressants – inhaled clomipramine 4 mg; phosphodiesterase-5 (PDE5) inhibitors – vardenafil (Levitra®, Bayer), tadalafil (Cialis®, Eli Lilly & Co Ltd); opioid analgesics – tramadol (Zydol SR®, Grünenthal). Improvements in sexual satisfaction and other outcomes compared with placebo were evident for SSRIs, PDE5 inhibitors and tramadol. Outcomes for interventions not compared with placebo were as follows: behavioural therapies – improvements over wait list control in IELT and other outcomes, behavioural therapy plus pharmacotherapy better than either therapy alone; alpha blockers – terazosin (Hytrin®, AMCO) not significantly different to antidepressants in ejaculation control; acupuncture – improvements over sham acupuncture in IELT, conflicting results for comparisons with SSRIs; Chinese medicine – improvements over treatment as usual; delay device – improvements in IELT when added to stop–start technique; yoga – improved IELT over baseline, fluoxetine better than yoga. Treatment-related AEs were evident with most pharmacological interventions. Limitations: Although data extraction from reviews was optimised when more than one review reported data for the same RCT, the reliability of the data extraction within these reviews cannot be guaranteed by this assessment report. Conclusions: Several interventions significantly improved IELT. Many interventions also improved sexual satisfaction and other outcomes. However, assessment of longer-term safety and effectiveness is required to evaluate whether or not initial treatment effects are maintained long term, whether or not dose escalation is required, how soon treatment effects end following treatment cessation and whether or not treatments can be stopped and resumed at a later time. In addition, assessment of the AEs associated with long-term treatment and whether or not different doses have differing AE profiles is required.