Pharmacologic treatment of premature ejaculation represents a new approach to the treatment of PE and a radical departure from the psychosexual model of treatment. There have been many papers discussing this topic. I chose to write a clinical paper, in the form of Questions and Answers, which is an innovative way of writing an article (with several citations) to help clinicians in the management of premature ejaculation.

PIERRE ASSALIAN , M.D., C.S.P.Q.

Dipl. Psych. (McGill)
Associate Professor, Department of Psychiatry
McGill University, Montreal, Canada
Director, Human Sexuality Unit
McGill University Health Centre, MGH site
Executive Director, Canadian Sex Research Forum

August 2007

Introduction

Pharmacologic treatment of premature ejaculation represents a new approach to the treatment of PE and a radical departure from the psychosexual model of treatment. There have been many papers discussing this topic. I chose to write a clinical paper, in the form of Questions and Answers, which is an innovative way of writing an article (with several citations) to help clinicians in the management of premature ejaculation.

Q: What is the basis for the pharmacological treatment of Premature Ejaculation?

A: To understand this, we have to talk about the neuropharmacology of ejaculation. Ejaculation is centrally mediated by both the serotonergic (5-hydroxytryptamine; 5-HT) and dopaminergic systems. Animal studies have clearly demonstrated that activation of the 5-HT1A receptor facilitates ejaculation. Other animal studies suggest involvement of 5-HT2C and 5-HT1B receptors. It is assumed that in men these receptors have similar functions, but evidence-based data about their role in men is still lacking.

On the other hand the mechanism of action of serotonergic neurons is well known. Interference of these mechanisms by daily use of selective serotonin re-uptake inhibitor (SSRIs) drugs initially leads to only mild changes in the serotonergic content of their synapses. It is only after desensitization of 5-HT receptors, usually occurring within one to two weeks, that the 5-HT content of the synapse increases in a non-natural way, hereby stimulating various post-synaptic 5-HT receptors. The timing of interference may have consequences for the extent of clinical efficacy of on-demand and chronic use of SSRI drugs.

Q: So what are the medications used?

A: Before the introduction of SSRIs Clomipramine was used. Doses were ranging from 25 mg to 50 mg, taken once a day, preferable at nighttime. At times, I started with 10 mg and went up to 75 mg daily if needed. After 48 hours of taking Clomipramine patients reported better control over their ejaculation. The most common complaints of patients were sedation, headaches, constipation and very rarely weak erections. Most of the side effects will disappear after one week.

Later SSRIs were used. Most common are Fluoxetine in the dose of 20 mg daily, Paroxetine 10-20 mg daily and Sertraline 50-100 mg every day. Paroxetine appears to exert the strongest ejaculation delay. Ejaculation delay usually occurs within 5-10 days, but may occur earlier.

Adverse effects include fatigue, mild nausea especially if taken on an empty stomach, loose stools or perspiration. Patients may report diminished sexual desire and/or weak erections.

Q: Can we combine two medications?

A: Yes – In my opinion this is indicated in 2 conditions! If a patient is on Clomipramine 50 mg daily and has severe side effects, I would lower the dose to 25 mg and add Paroxetine 10 mg daily.
OR
If the patient is on 75 mg or 100 mg of Clomipramine and still has no, or minimal, control over his ejaculation I would add Paroxetine 10-20 mg daily.

Once the patient achieves good ejaculation control, one can think of lowering one of the medications.

Always remember to ask the patient which he prefers.

Q: Do we prescribe daily treatment or on-demand?

A: I always favored daily dosing and this is for many reasons. When the patient takes the medication daily, side effects will disappear within one week. If they take the medication on demand, they will always experience side effects that can be unpleasant.

Also taking medications daily promotes spontaneity in the sexual relation and takes away the performance pressure. All my patients, prefer the daily use of medications

Recently Waldinger conducted a preference study with the aim to investigate how men with life-long PE feel about the use of serotonergic antidepressants, and which option they would prefer for themselves; either a daily drug or a drug to be used on-demand, – 81% of men preferred a drug for daily use, while 16 % a drug on-demand. The most frequently reported argument to prefer daily drug treatment was that this strategy would possibly have the least effect towards the spontaneity of having sex.

Q: Are there any guidelines for the use of medications in the treatment of PE?

A: I have published a paper, in which I have outlined the Guidelines for the Pharmacotherapy of Premature Ejaculation. There are the set of guidelines:

• Etiology is indicative of biological origin
• Patient’s choice
• Loss of beneficial effect of traditional sex therapy
• Life saving measures
• In failing relations where PE has been an important factor
• When the female partner refuses to participate in sex therapy
• In certain cultures or religions
• The “exciting vagina”
  To know more about this set of guidelines I invite you to read the article.

Q: Are there any other pharmacological treatments?

A: Yes – The use of topical local anesthetics such a lidocaine and/or prilocaine as a cream, gel or spray is well established and is moderately effective in retarding ejaculation. They may be associated with significant penile hypo-anesthesia and possible transvaginal absorption, resulting in vaginal numbness and female anorgasmia unless a condom is used.

Q: Can one use a PDE-5 inhibitor?

Several authors have reported their experience with PDE5 inhibitors alone or in combination with SSRIs as a treatment for PE. The proposed mechanisms for the effect of sildenafil on ejaculatory latencies include a central effect involving increased NO and reduced sympathetic tone, smooth muscle dilatation of the vas deferens and seminal vesicles, which may oppose sympathetic vasoconstriction and delay ejaculation, reduced performance anxiety due to better erections, and down-regulation of the erectile threshold to a lower level of arousal so that increased levels of arousal are required to achieve the ejaculation threshold. Most of these studies are uncontrolled and the results are confusing and difficult to interpret. The only double-blind placebo-controlled and the results are confusing and difficult to interpret. The only double-blind placebo-controlled and the results are confusing and difficult to interpret. The only double-blind placebo-controlled multicenter study showed no significant difference in the IELT of sildenafil-treated subjects compared to placebo, but did demonstrate significant improvements in the ejaculatory control domain and the ejaculatory function global efficacy question. The latter is possibly consistent with the erectile response of sildenafil.

It is unlikely that PDE inhibitors significantly delay ejaculation in men with PE without erectile dysfunction. However, it may well be that PDE inhibitors may beneficial in men with erectile dysfunction and secondary PE.

References:

• Assalian P. Clomipramine in the treatment of premature ejaculation. J Sex Res 1988; 24 : 213-215.
• Assalian P. Guidelines for the pharmacotherapy of premature ejaculation. World J Urol 2005;12: 12.
• Waldinger MD.. Majority of men with lifelong premature ejaculation prefer daily drug treatment: an observational study in a consecutive group of dutch men. J Sex Medecine 2007 ( in press).
• Waldinger MD. Lifelong premature ejaculation: definition, serotonergic neurotransmission and drug treatment. World J Urology 2005; 23: 102-108. Standard Practice in Sexual Medecine, Chapter 16: ejaculatory disorders; Blackwell publishing 2006.