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Eutectic Mixture of Local Anaesthetics (EMLA) is recommended for use off-label as a treatment for premature ejaculation (PE). Other topical anaesthetics are available, some of which have been evaluated against oral treatments. The purpose of this systematic review was to evaluate the evidence from randomised controlled trials (RCTs) for topical anaesthetics in the management of PE. Bibliographic databases including MEDLINE were searched to August 2014. The primary outcome was intra-vaginal ejaculatory latency time (IELT).Methodological quality of RCTs was assessed. IELT and other outcomes were pooled across RCTs in a metaanalysis. Between-trial heterogeneity was assessed. Nine RCTs were included. Seven were of unclear methodological quality. Pooled evidence (two RCTs, 43 participants) suggests that EMLA is significantly more effective than placebo at increasing IELT (P < 0.00001). Individual RCT evidence also suggests that Topical Eutectic-like Mixture for Premature Ejaculation (TEMPE) spray and lidocaine gel are both significantly more effective than placebo (P = 0.003; P < 0.00001); and lidocaine gel is significantly more effective than sildenafil or paroxetine (P = 0.01; P = 0.0001). TEMPE spray is associated with significantly more adverse events than placebo (P = 0.003). More systemic adverse events are reported with tramadol, sildenafil and paroxetine than with lidocaine gel. Diverse methods of assessing sexual satisfaction and ejaculatory control with topical anaesthetics are reported and evidence is conflicting. Topical anaesthetics appear more effective than placebo, paroxetine and sildenafil at increasing IELT in men with PE. However, the methodological quality of the existing RCT evidence base is uncertain.Topical anaesthetics were compared with placebo and oral agents for the treatment of premature ejaculation in a systematic review and meta-analysis. Topical anaesthetics are significantly more effective than placebo, sildenafil or paroxetine at increasing intra-vaginal ejaculatory latency time. Topical Eutectic-like Mixture for Premature Ejaculation spray is associated with erectile dysfunction, numbness and burning. More systemic adverse events are reported with tramadol, sildenafil and paroxetine than with lidocaine gel.
Eutectic Mixture of Local Anaesthetics (EMLA) is recommended for use off-label as a treatment for premature ejaculation (PE). Other topical anaesthetics are available, some of which have been evaluated against oral treatments. The purpose of this systematic review was to evaluate the evidence from randomised controlled trials (RCTs) for topical anaesthetics in the management of PE. Bibliographic databases including MEDLINE were searched to August 2014. The primary outcome was intra-vaginal ejaculatory latency time (IELT).Methodological quality of RCTs was assessed. IELT and other outcomes were pooled across RCTs in a metaanalysis. Between-trial heterogeneity was assessed. Nine RCTs were included. Seven were of unclear methodological quality. Pooled evidence (two RCTs, 43 participants) suggests that EMLA is significantly more effective than placebo at increasing IELT (P < 0.00001). Individual RCT evidence also suggests that Topical Eutectic-like Mixture for Premature Ejaculation (TEMPE) spray and lidocaine gel are both significantly more effective than placebo (P = 0.003; P < 0.00001); and lidocaine gel is significantly more effective than sildenafil or paroxetine (P = 0.01; P = 0.0001). TEMPE spray is associated with significantly more adverse events than placebo (P = 0.003). More systemic adverse events are reported with tramadol, sildenafil and paroxetine than with lidocaine gel. Diverse methods of assessing sexual satisfaction and ejaculatory control with topical anaesthetics are reported and evidence is conflicting. Topical anaesthetics appear more effective than placebo, paroxetine and sildenafil at increasing IELT in men with PE. However, the methodological quality of the existing RCT evidence base is uncertain.Topical anaesthetics were compared with placebo and oral agents for the treatment of premature ejaculation in a systematic review and meta-analysis. Topical anaesthetics are significantly more effective than placebo, sildenafil or paroxetine at increasing intra-vaginal ejaculatory latency time. Topical Eutectic-like Mixture for Premature Ejaculation spray is associated with erectile dysfunction, numbness and burning. More systemic adverse events are reported with tramadol, sildenafil and paroxetine than with lidocaine gel.
BackgroundPremature 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 Ther1989;15:130–4). Treatments include behavioural and pharmacological interventions.ObjectiveTo systematically review evidence for clinical effectiveness of behavioural, topical and systemic treatments for PE.Data sourcesThe 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 theHealth Technology Assessmentdatabase; 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.MethodsRandomised 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).ResultsA 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.LimitationsAlthough 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.ConclusionsSeveral 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.Study registrationThis study is registered as PROSPERO CRD42013005289.FundingThe National Institute for Health Research Health Technology Assessment programme.
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