Skip to main content Skip to main navigation menu Skip to site footer

A network meta-analysis on comparative efficacy and tolerability of on-demand therapy for premature ejaculation



Abstract

Introduction: The use of pharmacotherapy as a first-line treatment for premature ejaculation (PE) is recommended by EAU guidelines. However, no study had analyzed multiple treatment comparisons among available on-demand therapy. Therefore, we aimed to perform a network meta-analysis (NMA) to characterize the comparative efficacy and tolerability of on-demand therapy for PE.

Methods: We systematically searched randomized controlled trials (RCTs) in several databases at any period up to November 2019. NMA was performed to estimate efficacy and tolerability outcomes using intravaginal ejaculation latency time (IELT) and overall adverse effects (AEs), respectively. We ranked each outcome using the surface under the cumulative ranking curve (SUCRA) and presented the two outcomes as a clustered ranking plot.

Results: A total of 19 RCTs comprising 5950 patients were included in this NMA. All active treatments showed significant improvement compared to placebo. Among the available on-demand treatment, the combination of SSRI plus PDE5i showed the highest efficacy (MD: 3.06; 95%CI 1.84-4.29) followed by tramadol 100 mg and vardenafil 10 mg (MD 2.9, 95%CI 1.63-4.16; MD 2.36, 95%CI 1.2-3.52; respectively). Based on the SUCRA, the combination of SSRI plus PDE5i had the highest score (91.7%) in efficacy, while dapoxetine 30 mg had the highest score (73.3%) in terms of tolerability.

Conclusion: The combination of SSRI plus PDE5i was the treatment of choice for individuals who prioritize efficacy. For those who prioritize tolerability, dapoxetine 30 mg and vardenafil 10 mg became alternative treatments. Various on-demand therapy options require careful discussion with patient expectations of treatment effects.

Keywords: premature ejaculation sexual dysfunction on-demand therapy phosphodiesterase type 5 inhibitor selective serotonin reuptake inhibitor

References

  1. Porst, H. et al. The Premature Ejaculation Prevalence and Attitudes (PEPA) Survey: Prevalence, Comorbidities, and Professional Help-Seeking. Eur. Urol. 2007 (51) :816–824 doi:10.1016/j.eururo.2006.07.004.
  2. Serefoglu, E. C. et al. An evidence-based unified definition of lifelong and acquired premature ejaculation: Report of the second international society for sexual medicine Ad Hoc committee for the definition of premature ejaculation. J. Sex. Med. 2014 (11) :1423–1441 doi:10.1111/jsm.12524.
  3. Limoncin, E. et al. Premature ejaculation results in female sexual distress: Standardization and validation of a new diagnostic tool for sexual distress. J. Urol. 2013 (189) :1830–1835 doi:10.1016/j.juro.2012.11.007.
  4. EAU Guidelines: Non-Oncology Guidelines | Uroweb. https://uroweb.org/individual-guidelines/non-oncology-guidelines/.
  5. Mohee, A. & Eardley, I. Medical therapy for premature ejaculation. Ther. Adv. Urol. 2011 (3) :211–22 doi:10.1177/1756287211424172.
  6. Cormio, L. et al. The Combination of Dapoxetine and Behavioral Treatment Provides Better Results than Dapoxetine Alone in the Management of Patients with Lifelong Premature Ejaculation. J. Sex. Med. 2015 (12) :1609–1615 doi:10.1111/jsm.12925.
  7. Freeman, S. C., Fisher, D., White, I. R., Auperin, A. & Carpenter, J. R. Identifying inconsistency in network metaâ€analysis: Is the net heat plot a reliable method? Stat. Med. 2019 (38) :5547–5564 doi:10.1002/sim.8383.
  8. Book Series, C., Higgins, J. P. & Green, S. Cochrane Handbook for Systematic Reviews of Interventions THE COCHRANE COLLABORATION ®.
  9. Salanti, G. Indirect and mixed-treatment comparison, network, or multiple-treatments meta-analysis: many names, many benefits, many concerns for the next generation evidence synthesis tool. Res. Synth. Methods 2012 (3) :80–97 doi:10.1002/jrsm.1037.
  10. Rücker, G. & Schwarzer, G. Ranking treatments in frequentist network meta-analysis works without resampling methods. BMC Med. Res. Methodol. 2015 (15) :58 doi:10.1186/s12874-015-0060-8.
  11. Higgins, J. P. T. et al. Consistency and inconsistency in network meta-analysis: concepts and models for multi-arm studies. Res. Synth. Methods 2012 (3) :98–110 doi:10.1002/jrsm.1044.
  12. Salanti, G., Ades, A. E. & Ioannidis, J. P. A. Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: An overview and tutorial. J. Clin. Epidemiol. 2011 (64) :163–171 doi:10.1016/j.jclinepi.2010.03.016.
  13. McMahon, C. G. et al. Efficacy of sildenafil citrate (viagra) in men with premature ejaculation. J. Sex. Med. 2005 (2) :368–375 doi:10.1111/j.1743-6109.2005.20351.x.
  14. Pryor, J. L. et al. Efficacy and tolerability of dapoxetine in treatment of premature ejaculation: an integrated analysis of two double-blind, randomised controlled trials. Lancet 2006 (368) :929–937 doi:10.1016/S0140-6736(06)69373-2.
  15. Mattos, R. M., Marmo Lucon, A. & Srougi, M. Tadalafil and fluoxetine in premature ejaculation: Prospective, randomized, double-blind, placebo-controlled study. Urol. Int. 2008 (80) :162–165 doi:10.1159/000112607.
  16. Buvat, J., Tesfaye, F., Rothman, M., Rivas, D. A. & Giuliano, F. Dapoxetine for the Treatment of Premature Ejaculation: Results from a Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial in 22 Countries. Eur. Urol. 2009 (55) :957–968 doi:10.1016/j.eururo.2009.01.025.
  17. Mathers, M. J., Klotz, T., Roth, S., Lümmen, G. & Sommer, F. Safety and efficacy of vardenafil versus sertraline in the treatment of premature ejaculation: A randomised, prospective and crossover study. Andrologia 2009 (41) :169–175 doi:10.1111/j.1439-0272.2008.00910.x.
  18. Aversa, A. et al. Effects of vardenafil administration on intravaginal ejaculatory latency time in men with lifelong premature ejaculation. Int. J. Impot. Res. 2009 (21) :221–227 doi:10.1038/ijir.2009.21.
  19. McMahon, C. G. et al. Efficacy and Safety of Dapoxetine for the Treatment of Premature Ejaculation: Integrated Analysis of Results from Five Phase 3 Trials. J. Sex. Med. 2011 (8) :524–539 doi:10.1111/j.1743-6109.2010.02097.x.
  20. Gökçe, A. & Ekmekcioglu, O. The Relationship between Lifelong Premature Ejaculation and Monosymptomatic Enuresis. J. Sex. Med. 2010 (7) :2868–2872 doi:10.1111/j.1743-6109.2010.01754.x.
  21. Gökçe, A., Halis, F., Demirtas, A. & Ekmekcioglu, O. The effects of three phosphodiesterase type 5 inhibitors on ejaculation latency time in lifelong premature ejaculators: a double-blind laboratory setting study. BJU Int. 2011 (107) :1274–1277 doi:10.1111/j.1464-410X.2010.09646.x.
  22. Pastore, A. L. et al. A prospective randomized study to compare pelvic floor rehabilitation and dapoxetine for treatment of lifelong premature ejaculation. Int. J. Androl. 2012 (35) :528–533 doi:10.1111/j.1365-2605.2011.01243.x.
  23. Kaynar, M., Kilic, O. & Yurdakul, T. On-demand tramadol hydrochloride use in premature ejaculation treatment. Urology 2012 (79) :145–149 doi:10.1016/j.urology.2011.09.031.
  24. Gameel, T. A. et al. On-demand use of tramadol, sildenafil, paroxetine and local anaesthetics for the management of premature ejaculation: A randomised placebo-controlled clinical trial. Arab J. Urol. 2013 (11) :392–397 doi:10.1016/j.aju.2013.05.003.
  25. Lee, W. K. et al. Comparison between on-demand dosing of dapoxetine alone and dapoxetine plus mirodenafil in patients with lifelong premature ejaculation: Prospective, randomized, double-blind, placebo-controlled, multicenter study. J. Sex. Med. 2013 (10) :2832–2841 doi:10.1111/jsm.12287.
  26. Mcmahon, C. G. et al. 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. J. Sex. Med. 2013 (10) :2312–2325 doi:10.1111/jsm.12236.
  27. Khan, A. & Rasaily, D. Tramadol use in premature ejaculation: Daily versus sporadic treatment. Indian J. Psychol. Med. 2013 (35) :256 doi:10.4103/0253-7176.119477.
  28. Kurkar, A. et al. A randomized, double-blind, placebo-controlled, crossover trial of «on-demand» tramadol for treatment of premature ejaculation. Urol. Ann. 2015 (7) :205–210 doi:10.4103/0974-7796.150481.
  29. Polat, E. C., Ozbek, E., Otunctemur, A., Ozcan, L. & Simsek, A. Combination therapy with selective serotonin reuptake inhibitors and phosphodiesterase-5 inhibitors in the treatment of premature ejaculation. Andrologia 2015 (47) :487–492 doi:10.1111/and.12289.
  30. Abu El-Hamd, M. & Abdelhamed, A. Comparison of the clinical efficacy and safety of the on-demand use of paroxetine, dapoxetine, sildenafil and combined dapoxetine with sildenafil in treatment of patients with premature ejaculation: A randomised placebo-controlled clinical trial. Andrologia 2018 (50) doi:10.1111/and.12829.
  31. Hamidi-Madani, A. et al. The Efficacy and Safety of On-demand Tramadol and Paroxetine Use in Treatment of Life Long Premature Ejaculation: A Randomized Double-blind Placebo-controlled Clinical Trial. J. Reprod. Infertil. 2018 (19) :10–15.
  32. Althof, S. E. et al. International Society for Sexual Medicine’s Guidelines for the Diagnosis and Treatment of Premature Ejaculation. J. Sex. Med. 2010 (7) :2947–2969 doi:10.1111/j.1743-6109.2010.01975.x.
  33. Qin, Z. et al. Safety and efficacy characteristics of oral drugs in patients with premature ejaculation: a Bayesian network meta-analysis of randomized controlled trials. Int. J. Impot. Res. 2019 (31) :356–368 doi:10.1038/s41443-019-0146-7.
  34. Wu, T. et al. Efficacy and safety of tramadol for premature ejaculation: A systematic review and meta-analysis. Urology 2012 (80) :618–624 doi:10.1016/j.urology.2012.05.035.
  35. Gur, S., Kadowitz, P. J. & Sikka, S. C. Current therapies for premature ejaculation. Drug Discovery Today 2016 vol. 21 :1147–1154 doi:10.1016/j.drudis.2016.05.004.
  36. MALE SEXUAL DYSFUNCTION : pathophysiology and treatment. 2019 (CRC PRESS, 2019).
  37. Jin, K. et al. Comparative efficacy and safety of phosphodiesterase-5 inhibitors with selective serotonin reuptake inhibitors in men with premature ejaculation: A systematic review and Bayesian network meta-analysis. Medicine (United States) 2018 vol. 97 :e13342 doi:10.1097/MD.0000000000013342.

How to Cite

Yogiswara, N., Azmi, Y., & Azmi, Y. A. (2020). A network meta-analysis on comparative efficacy and tolerability of on-demand therapy for premature ejaculation. Bali Medical Journal, 9(3), 591–598. https://doi.org/10.15562/bmj.v9i3.1792
ACM ACS APA ABNT Chicago Harvard IEEE MLA Turabian Vancouver
Download Citation
Endnote/Zotero/Mendeley (RIS) BibTeX

HTML
1

Total
13

Share

Search Panel

Niwanda Yogiswara
Google Scholar
Pubmed
BMJ Journal

Yusuf Azmi
Google Scholar
Pubmed
BMJ Journal

Yufi Aulia Azmi
Google Scholar
Pubmed
BMJ Journal