re: david bar-or, kristin m. salottolo, alessandro orlando, james v. winkler. a randomized...

E U R O P E A N U R O L O G Y 6 1 ( 2 0 1 2 ) e 2 3 – e 2 4

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Letter to the Editor

Re: David Bar-Or, Kristin M. Salottolo, Alessandro

Orlando, James V. Winkler. A Randomized Double-Blind,

Placebo-Controlled Multicenter Study to Evaluate the

Efficacy and Safety of Two Doses of the Tramadol Orally

Disintegrating Tablet for the Treatment of Premature

Ejaculation Within Less Than 2 Minutes. Eur Urol

2012;61:736–43

The International Society of Sexual Medicine recently

published an evidence-based definition of lifelong prema-

ture ejaculation (PE) as ‘‘a male sexual dysfunction

characterized by ejaculation which always or nearly always

occurs prior to or within about one minute of vaginal

penetration, and the inability to delay ejaculation on all or

nearly all vaginal penetrations, and negative personal

consequences, such as distress, bother, frustration and/or

the avoidance of sexual intimacy’’ [1]. To date, the only

approved oral drug to treat premature ejaculation is

dapoxetine.

Tramadol has been shown to be effective for on-demand

treatment of PE in two placebo-controlled studies (one

single blind, one double blind) [2,3]. In these trials, tramadol

50 mg significantly increased intravaginal ejaculatory

latency time (IELT), and measures of sexual satisfaction

and ejaculatory control compared with placebo ( p < 0.05

for all). However, the sample sizes for both studies were

small (about 60 subjects). Therefore, the results of the large,

randomized, double-blind, placebo-controlled multicenter

study by Bar-Or et al are welcomed [4]. In this study, the on-

demand 62 mg tramadol orally disintegrating tablet (ODT)

was shown to be an effective treatment for PE, in the

improvement of both IELT and Premature Ejaculation

Profile scores, at a low and safe therapeutic dose. This

treatment provides a new option for managing mild to

severe PE.

I would like to raise a few pertinent issues. The results

published were the end results after 12 wk of treatment.

The authors mentioned that the subjects were assessed

every 3 wk. It would be interesting to elucidate the

results at these intervals because it would give us an idea

of the efficacy of this drug at these intervals. This

information would be important for patient counseling

later.

DOI of original article: 10.1016/j.eururo.2011.08.039

0302-2838/$ – see back matter # 2011 European Association of Urology. Publis

The other issue about which most of us worry is the long-

term effect of drug dependence, for which opioids are

notorious. It would be of great help if these patients can be

followed up for a longer period to assess the safety of

tramadol ODT. A long follow-up would also enable us to

assess for the development of drug tolerance.

It is interesting to note that patients with erectile

dysfunction (ED) were excluded from this study. It has been

reported that ED and PE can co-occur in up to 30% of

patients [5]. There may be patients with ED who are

effectively treated with phosphodiesterase type 5 inhibitors

(PDE5-Is) but who may have PE. Therefore, it is important to

assess this group of patients because the interaction

between PDE5-Is and tramadol ODT is not known.

It is heartening to know that tramadol ODT is as

efficacious and safe as dapoxetine. It is hoped that cost

would not be an issue and that patients are not deprived of

the opportunity to receive treatment.

This excellent publication by Bar-Or et al is much

appreciated because it gives us an option besides

dapoxetine for the treatment of PE. The editor should

also be applauded for publishing such clinically important

articles.

Conflicts of interest: The author has nothing to disclose.

References

[1] Althof SE, Abdo CH, Dean J, et al. International Society for Sexual

Medicine’s guidelines for the diagnosis and treatment of premature

ejaculation. J Sex Med 2010;7:2947–69.

[2] Safarinejad MR, Hosseini SY. Safety and efficacy of tramadol in

the treatment of premature ejaculation: a double-blind, placebo-

controlled, fixed-dose, randomized study. J Clin Psychopharmacol

2006;26:27–31.

[3] Salem EA, Wilson SK, Bissada NK, Delk JR, Hellstrom WJ, Cleves MA.

Tramadol HCl has promise in on-demand use to treat premature

ejaculation. J Sex Med 2008;5:188–93.

[4] Bar-Or D, Salottolo KM, Orlando A, Winkler JV. A randomized

double-blind, placebo-controlled multicenter study to evaluate

the efcacy and safety of two doses of the tramadol orally disin-

tegrating tablet for the treatment of premature ejaculation within

less than 2 minutes. Eur Urol 2012;61:736–43.

hed by Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2011.09.007

E U R O P E A N U R O L O G Y 6 1 ( 2 0 1 2 ) e 2 3 – e 2 4e24

[5] Payne RE, Sadovsky R. Identifying and treating premature ejacula-

tion: importance of the sexual history. Cleve Clin J Med 2007;

74(Suppl 3):S47–53.

Christopher C.K. Ho*

Department of Surgery, Universiti Kebangsaan Malaysia

Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak,

56000 Cheras, Kuala Lumpur,

Malaysia

*Department of Surgery, Universiti Kebangsaan Malaysia

Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak,

56000 Cheras, Kuala Lumpur, Malaysia.

Tel. +6 03 91546202;

Fax: +6 03 91456684

E-mail address: chrisckho2002@yahoo.com (C.C.K. Ho)

September 6, 2011

Published online on September 15, 2011