Treatment of Premature Ejaculation

A. Riley; R. T. Segraves

Int J Clin Pract. 2006;60(6):694-697. 

Summary and Introduction

Premature ejaculation (PE) is a common problem, the treatment of which has received an increasing interest in recent years. Traditional management continues to be psychotherapy, with techniques such as the 'squeeze' and 'stop-start' most commonly employed. The application of local anaesthetics to the glans to delay ejaculation, first described over 60 years ago, continues to be used both in medical practice and as an 'over-the-counter' remedy. Over the years, a variety of psychopharmacological agents, especially antidepressants, have been described as treatments for PE. At the present time, the selective serotonin re-uptake inhibitors, licensed for other indications, emerge as the most effective agents to delay ejaculation, but none are licensed for the treatment of PE. There appears to be a high relapse rate irrespective of the mode of therapy used.

It is axiomatic that a man presenting with premature ejaculation (PE) requires proper psychosexual, relationship and medical assessment. As there is comorbidity of PE with female sexual dysfunction,[1,2] the patient's partner should be involved in the assessment process. Both partners' reasons for seeking treatment for PE and what they hope to get out of the treatment should also be elucidated. The physician should ascertain whether these expectations are attainable; if not, initial treatment should address the couple's unrealistic expectations.

It is important to hear a description of the problem from both partners and to listen for similarities and discrepancies in their reports. When rapid ejaculation becomes a problem, it depends not only on ejaculatory latency after vaginal penetration but also on the sexual attitudes of both partners, which vary with the sociocultural background of each. There may be differences in distress levels in the male as compared with his partner. A survey of representative population samples in Sweden, Finland, Estonia and St Petersberg, Russia, found that females stated that PE was a problem in their male partners more often than those men who reported this as a problem. Later cohorts of females reported this problem in their male partners far more commonly than earlier cohorts, suggesting a societal change in female expectations of male sexual performance.[3]

Current Treatments

By the time many men with PE present for treatment, they will have tried self-help remedies. Most commonly, men use distracting thoughts[4] and other behavioural processes including short foreplay, gentle thrusting, interrupting thrusting and withdrawing for a few moments. Other self-help remedies include taking alcohol, applying an over-the-counter purchased anaesthetic preparation to the penis and using thick condoms. Condoms are available that contain within them a local anaesthetic. The effectiveness of such self-help remedies is unknown, as only treatment failures are seen in clinics.

Behavioural approaches to the management of PE have been far less well researched than pharmacotherapy; nevertheless, they are well established. The two most widely used retraining methods are the 'stop-start' programme[5] and the squeeze technique.[6] These re-training processes are based on two premises. First is the hypothesis that PE occurs because the man fails to appreciate the sensations of heightened arousal and recognise the feelings of ejaculatory inevitability. The retraining process familiarises him with these sensations. Second, the procedures may act to attenuate stimulus-response connections by gradually exposing the patient to progressively more intense and more prolonged stimulation but maintaining the intensity and duration of the stimulus just below the threshold for triggering the response.[7]

A different psychotherapeutic approach for the treatment of PE involves training the man to recognise the signs of increased sexual arousal and then teaching him how to keep his level of sexual excitement below the level of intensity that elicits the ejaculatory reflex. Preliminary studies indicate that this approach is superior to a waiting list control and equivalent to the efficacy of the start-stop technique.[8]

Therapists tend to develop their own preferred methods of employing these procedures.

Local anaesthetics. Application of local anaesthetics to the penis as a treatment for PE has been advocated for more than 60 years.[9] The FDA considered a product that delivers lignocaine (lidocaine) 10% as a spray to be safe and effective for use as a 'male genital desensitiser' for the management of PE.[10] A cream containing lignocaine (lidocaine) and prilocaine is used.[11]

An herbal local anaesthetic preparation, SS cream, when applied to the glans 1 h before sexual intercourse, has been reported to delay ejaculation and enhance sexual satisfaction in a high proportion of patients.[12] Local irritation and sensitisation can occur with local anaesthetics. There are reports that these preparations can reduce sexual arousal and cause erectile dysfunction in the patient.[13] There is also the risk of transfer to the female partner, unless a condom is used.

Psychopharmacotherapy for PE started when delayed ejaculation was encountered as a side-effect of antidepressants over 40 years ago.[14] Since then, successful treatment of PE by a number of different psychotherapeutic agents have been reported, based mainly on single-case histories or small, poorly designed studies. As a consequence of the renewed interest in psychopharmacological approaches to PE, better clinical trial methodologies are being developed.

Until recently, drugs already licensed for the treatment of depression were evaluated in PE. Clomipramine was one of the first antidepressants to be evaluated in placebo-controlled studies.[15,16] It showed therapeutic promise in these and subsequent trials. It has been dosed at 25-50 mg as required 4 h prior to coitus. The treatment of PE by the selective serotonin re-uptake inhibitors (SSRIs) has been evaluated. Fluoxetine, paroxetine and sertraline taken daily significantly delay ejaculation relative to placebo.[17] Doses employed, respectively, have been 20-40, 20-40 and 50-100 mg. During daily treatment with antidepressants, the delay of ejaculation usually occurs within 5-10 days but may occur earlier.

Studies have also been undertaken of antidepressants when used to treat PE on an as-required basis. Efficacy in terms of ejaculatory delay has been demonstrated with clomipramine, sertraline and paroxetine.[18-22] In these studies, the drug was either taken 4-6 h before sexual intercourse, at a specified time of the day when intercourse was anticipated later that day (e.g. at 17:00 h[21]) or between 12 and 24 h before anticipated sexual activity.

Dapoxetine, an SSRI that is not licensed as an antidepressant, is under development as treatment for PE.[23] Early observations are that 30 and 60 mg of this drug administered 4 h before anticipated sexual intercourse are effective for the on-demand treatment of PE, but results from controlled clinical trials have not yet been published. The acceptability of a treatment that has to be taken 4 h before anticipated sexual activity requires evaluation.

Dapoxetine did not receive approval from the FDA. A major concern was the safety of an SSRI prescribed by general practitioners without psychiatric training. Recent data suggest that SSRIs may increase suicidality in some patients. This suggests that regulatory authorities may impose extremely high safety standards on 'life style' drugs.

There are several reports of phosphodiesterase-5 (PDE-5) inhibitors used alone or as an adjunct to SSRIs in the treatment of PE. The best study so far undertaken failed to demonstrate a significant effect of as-required sildenafil on ejaculatory latency time in PE.[24] However, in this study, sildenafil treatment was associated with increases in confidence, perception of ejaculatory control and overall sexual satisfaction. It also decreased the refractory time to achieve a second erection after ejaculation.

Perhaps the real value of PDE-5 inhibitors will be in those men whose PE is associated with erectile dysfunction.

An Ideal Pharmacological Agent for Treating PE

Adverse effects occurring with clomipramine and the SSIRs, although usually described as mild, can lead to treatment withdrawal. However, the most important consideration is the dosing regimen used. Whilst daily dosing appears to be associated with better ejaculatory control than as-required dosing, it leads to considerable drug exposure for events that usually do not occur every day. By contrast, daily dosing removes the need to anticipate the occurrence of sexual intercourse 4 or 6 h before it is likely to occur. The need to do this may put undue pressure on the couple at a time when there may already be some degree of relationship difficulty resulting from PE. The ideal drug for treating PE would have a predictable therapeutic effect within a few minutes of administration so that it could be taken once sexual foreplay has commenced. No such drug is currently available.

Choice of Treatment

The choice of treatment is essentially between behavioural and pharmacological approaches. Whilst recognising that combination treatment is an option, some authorities advocate different first-line treatment according to whether the patient has life-long or acquired PE.[25] For life-long PE, they advocate pharmacotherapy as the first-line treatment with behavioural therapy and relationship counselling as second-line treatment. For acquired PE, they suggest behavioural therapy and relationship counselling as first line, with pharmacotherapy as second-line treatment. Evidence for such treatment allocation has not been found. Perhaps a better recommendation is the adoption of a more 'goal-oriented' approach in which the patient, his partner (if he has one) and the physician agree on the most appropriate treatment after taking into account patient's and partner's expected outcome of treatment (which may not be just ejaculatory delay), their treatment preferences and the physician's guidance. Considerations to be taken into account include the following:

For successful outcome, behavioural approaches require the participation of a well-motivated and co-operative partner and adequate time together available for the retraining process. Although men can practice the 'stop-start' process on their own and gain some degree of ejaculatory control, many find it difficult to extend their improvement to partner-involved sexual activity. Hence, single men, especially those whose PE prevents them from entering sexual relationships, are probably candidates for pharmacological treatment.

Behavioural therapy generally involves masturbation, which is unacceptable in some Asian cultures. Replacing the word 'masturbation' with 'pleasuring' may occasionally make the process more acceptable.[26] However, Asian men with PE generally have a host of associated psychosomatic symptoms and are not receptive to long-term home therapy assignments in which their wives may not be willing to participate, leading to a high drop-out rate from behavioural therapy programmes.[26]

There is a high degree of comorbidity of PE with other sexual problems and relationship difficulties.[2] Some patients, and their partners, expect that once they have overcome the problem of PE, all other sexual and relationship difficulties will disappear without any additional therapy. Except where all the concomitant problems arise directly from the PE, rarely is this expectation met. When concomitant sexual and/or relationship difficulties exist, patients should be guided to sex and/or relationship therapy in the first instance.

Couples have to devote substantial amounts of time each week undertaking homework exercises in behaviour therapy programmes over several months. Many find such a commitment difficult to entertain. Both partners working long hours, babies and children to care for limit the amount of intimate time they can spend together. The situation may be complicated by poor social conditions with the lack of privacy. For some of these people, PE is a consequence of such a rushed life. There is the temptation to give these couples a 'quick pharmacological fix' to delay ejaculation, but they are the very people who can benefit from sex and relationship therapy. The use of an hourly activity diary can often demonstrate how by rearranging their occupational and domestic activities then can gain precious time for unrushed lovemaking.

Pharmacotherapy may be considered first-line therapy in those couples where one or both partners have a disability that limits their ability to use behavioural approaches.

Outcome of PE Treatments

In the short term, both behavioural and pharmacological approaches to the treatment of PE are generally effective if prior treatment assessment of the patient and his partner is properly made and appropriate choice of first-line therapy used. Few studies have compared behavioural therapy and pharmacotherapy. In an early double-blind, randomised study that compared the combination amitriptyline-perphenazine against placebo in patients with PE who were all taught the squeeze technique, those on the active medication plus squeeze technique gained ejaculatory control more quickly than those on placebo plus squeeze technique.[27] However, there was no difference in outcome at the end of the 12-week treatment period. More recently, Abdel-Mamid et al.[28] reported a double-blind, randomised, five-way cross-over study comparing squeeze technique and clomipramine, sertraline, paroxetine and sildenafil. All treatments significantly prolonged median ejaculatory latency time. The three antidepressants were comparable in terms of efficacy but only paroxetine was superior to the pause-squeeze technique. There are, however, methodological problems with this study.

Long-term outcome must be considered, but regrettably there is only limited information about the patient's progress after the initial treatment is discontinued. The available information suggests that relapse rates are high and that strategies to prevent this need to be developed.

Conclusion

There is an increased interest in all aspects of PE but especially in the search for effective treatments. Whilst behavioural approaches have been the therapeutic mainstay over the past 50 years or so, many clinicians now consider pharmacotherapy as a viable first-line treatment, especially in life-long PE.[25] There is no doubt that pharmacotherapy has a role to play in the treatment of this common problem, but none of the currently available drugs is an ideal candidate and optimum dose regimens have not been established. The treatment of PE should not be solely to prolong ejaculatory latency time in the short term, but to provide the patient and couple with strategies to prevent relapse and enhance relationship satisfaction in the long term. These objectives cannot always be achieved by the 'quick fix' of a pharmacological agent but require sex and couple therapy. Pharmacotherapy can only be considered first-line treatment when all concomitant sexual and relationship issues have been properly addressed. However, the management of PE is not evidence based, as not all treatments have been adequately evaluated.


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