Clinical Challenges in the Management of Premature Ejaculation


Table 5: Selected Side Effect Profile of Selective Serotonin Re-uptake Inhibitors Taken from the American Urological Association Guidelines Compared with Dapoxetine Data


Drowsiness/ Sleepiness (%)


Clomipramine Paroxetine Fluoxetine Sertraline


Dapoxetine 30mg Dapoxetine 60mg


3–30 0–43 11


0–27 3 5


Nausea (%)


30 3


8–22 3–12 11 20


Dizziness (%)


14 –


3–9


0–12 6


11


Dry Mouth (%)


10–23 6–7 4–8


0–19 2 4


Erectile Dysfunction (%)


20 6 –


0–4 2 3


Anejaculation (%)


–


3–8 –


0–22 0.5 0.5


The data for dapoxetine are taken from the pooled data and from the international study (R096769-PRE-3001). With the exception of dapoxetine, prescription treatments listed are not approved by health authorities for use in premature ejaculation. Where a range of values is given, it either represents findings from a number of studies (American Urological Association [AUA] guidelines) or for a range of doses (30–60mg dapoxetine).51


AUA guidelines, appendix 2, available at: www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines.cfm?sub=pme, accessed 1 November 2010.


A stopwatch and a five-point scale from ‘very poor’ to ‘very good’ were employed to measure IELT, ejaculatory control as well as sexual satisfaction of patients and their partners.


The drug lengthened IELT by three to four times.50 Moreover,


dapoxetine increased their staying power with the first dose and maintained the increases over the whole study period.50


Dapoxetine is the only drug for PE to be effective at the first dose when taken one to three hours before intercourse. The percentage of participants rating their control over ejaculation as ‘fair’ to ‘very good’ increased from 2.5% to nearly 52% and from 3.3% to more than 58% for those taking 30 and 60mg respectively.50


Both patients and their


partners rating sexual satisfaction as ‘good’ to very ‘good’ almost doubled.50


Therefore, on-demand dapoxetine is an effective treatment for men with moderate-to-severe PE.


Other more recent studies substantially confirmed the initial findings. A randomised, double-blind, parallel-group, placebo-controlled, phase III trial conducted in 22 countries enrolled men (n=1,162) aged 18 years of age or older who had met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision criteria for PE for six months or longer. These men had an IELT of two minutes or less in 75% or more intercourse episodes at baseline. Dapoxetine 30mg, 60mg or placebo on-demand (one to three hours before intercourse) were given for 24 weeks.51


Mean average IELT increased


from 0.9 minutes at baseline (across all groups) to 1.9, 3.2 and 3.5 minutes with placebo, dapoxetine 30 and 60mg, respectively, at the study end-point.51


All measures and IELTs improved significantly with


dapoxetine versus placebo at weeks 12 and 24.51 Side Effects


Safety is a very important matter when treating a condition such as PE. The American Urological Association (AUA) guidelines on the treatment of PE note that the safety profiles of SSRIs in patients with PE are similar to those reported for depression. Side effects typically include nausea, dry mouth and dizziness. Table 5 shows a selection of adverse event rates from clinical trials of tricyclic and SSRI antidepressants used off-label in men with PE included in the AUA guidelines compared with information from the dapoxetine clinical dataset.


EUROPEAN UROLOGICAL REVIEW


Evidence of Efficacy in Premature Ejaculation Clinical data from several trials confirm the efficacy of dapoxetine. A phase III clinical trial showed the ability of the drug to alleviate PE. Here, 2,614 men with moderate-to-severe PE were randomised to receive 30 or 60mg dapoxetine (the two available dosages) taken on-demand in two identical, double-blind, placebo-controlled, multicentre trials.50


Practicalities


There are just few practicalities when prescribing dapoxetine. The tablets are indicated for the treatment of PE in men 18 to 64 years of age, but this is just because the clinical and safety studies have been performed in patients within this age group.


The physician should advise the patient that the pill should be taken one to three hours before sexual activity, no more than once a day. The pill can be taken with or without food and it should be taken with at least one full glass of water. Dapoxetine should not be taken with alcohol.


To avoid any risk of syncope or orthostatic hypotension (a class side effect that is very rare in the clinical use of dapoxetine), patients should be advised to perform an orthostatic test before initiating therapy. They should be told not to take dapoxetine if they are dehydrated, to lie down immediately if they feel faint or light headed, not to stand up quickly after sitting or lying down for a long time and not to drive or use any tools or machines if they feel faint. In the clinical practice of the authors, this side effect has not been reported by any patients after one year of prescription.


An Approved Treatment


Approved treatments are, for obvious deontological and ethical reasons, the first therapeutic choice. For this reason, considering efficacy and favourable safety profile, dapoxetine (in countries where it is approved) is to be considered the gold standard of PE therapy.


Other Treatments Topical agents such as anaesthetics52 and herbal products53 can be


used in neurobiological PE due to penile hypersensitivity and have shown limited efficacy. Lidocaine, lidocaine/prilocaine (EMLA, TEMPE spray) have been studied in a few controlled experimental protocols, showing moderate effectiveness in delaying ejaculation. Treatment with anaesthetics carries the potential risk of penile hypo-anaesthesia and for the woman transvaginal absorption, resulting in vaginal numbness and resultant anorgasmia.


Conclusion


Current approaches to treating PE have mixed efficacy and, in all cases, significant drawbacks. The identikit of the Holy Grail for PE treatment is as follows: effective, practical (oral administration), on-demand use, rapid onset, swift elimination and low incidence of adverse effects. The drug that currently most closely fulfils the above-mentioned identikit is, dapoxetine. Despite the fact that it can be successfully treated with powerful and efficacious


53


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