Premature Ejaculation is a condition in which a man ejaculates earlier that he (or) his partner would like him to. Premature ejaculation is also known as Rapid ejaculation, Rapid climax, premature climax or early ejaculation. Premature ejaculation is one of the most common male sexual disorders.
Many of you suffering from premature ejaculation would have browsed the net to look for a quick remedy and stumbled upon an oral medication (tablet) named Priligy which contains the active medical ingredient ‘Dapoxetine’.
In this blog, we shall discuss in brief the physiology of ejaculation and the role of dapoxetine in treating premature ejaculation along with some of its pharmacokinetic parameters that would enable us to answer the question as to “How safe is Priligy”.
Intravaginal ejaculation latency time (IELT)
The IELT is defined as the time from the moment of vaginal penetration until the moment of intravaginal ejaculation. IELT varies not only from man to man but from one time to the next for the same man and tends to decrease with age.
Recent data suggests that men with an intravaginal ejaculatory latency time (IELT) of less than 1 minute have “definite” premature ejaculation (PE) while men with IELTs between 1 and 1.5 minutes have “probable” PE.
Although there is insufficient evidence to identify the aetiology of premature ejaculation there is limited evidence to suggest that men with premature ejaculation have high levels of sexual anxiety and inherited altered sensitivity of serotonin (5-hydroxytryptamine) receptors.
The role of “Serotonin” in ejaculation
Serotonin, also known as “5-hydroxytryptamine” (5-HT) is a neurotransmitter and is popularly thought to be a contributor to feelings of well-being and happiness.
Human sexual pharmacological studies have shown that serotonin (5-HT) and serotonin receptors (many subtypes) are involved in ejaculation.
In general, it could be stated that
⦁ Activation of the 5-HT2C receptors delays ejaculation, whereas
⦁ Activation of 5-HT1A receptors promotes ejaculation.
Premature ejaculation (PE) has been attributed in part to decreased 5-HT2C receptor hyposensitivity (and/or) 5-HT1A receptor hypersensitivity
Serotonergic antidepressants & Delayed Ejaculation
Clinical studies have shown that the selective serotonin reuptake inhibitors (SSRIs) (e.g. Fluoxetine, Paroxetine, Sertraline, and Citalopram) which comprise a group of medication used to treat depression are safe and effective in delaying ejaculation. In fact, delayed ejaculation was one of the side effects of these agents and therefore have been used “off-label” as the mainstay of pharmacological treatment for lifelong and acquired Premature ejaculation. It should be noted here that none of the above-discussed agents currently used to treat premature ejaculation were developed specifically for the management of PE. The dose used in the treatment of premature ejaculation is lower than those recommended in the treatment of depression. The SSRIs listed above have shown varying benefit toward delaying ejaculation among men with premature ejaculation with Paroxetine showing the greatest benefit
SSRIs (Fluoxetine, Paroxetine, Sertraline, and Citalopram) have long half-lives and therefore require extended lengths of time and repeated dosing to achieve optimal peak concentrations. The clinical effect of the ejaculation delay occurs gradually after 1 to 2 weeks and are therefore not recommended as “on demand” medication to treat premature ejaculation.
The SSRI’s, in general, are well tolerated and side effects, when used on a daily basis, may include dry mouth, fatigue, yawning, diarrhoea, nausea, sleepiness, tremor, dizziness and headache. Other side effects include low sexual desire, anejaculation (absence of ejaculation) and mild erectile dysfunction (ED).
The role of Dapoxetine (Priligy)
Priligy (Dapoxetine) is a novel, well-tolerated, efficacious short-acting SSRI and probably better suited as an ‘on-demand’ treatment for premature ejaculation. Dapoxetine is similar to the other SSRIs in that it exerts its effects through the inhibition of the serotonin reuptake transporter. It is currently the only drug approved (in limited numbers of countries) for premature ejaculation treatment.
Unlike the long-acting SSRIs discussed above (Fluoxetine, Paroxetine, Sertraline, Citalopram) which are prescribed on the basis of daily usage and that take weeks to achieve steady-state concentrations in the plasma, dapoxetine is rapidly absorbed and eliminated after oral administration. Clinical trials have found dapoxetine to be well tolerated and safe, and more suitable for “on-demand” use. It is not yet known whether the effects of dapoxetine are more peripheral, central or both. Nonetheless, the end result of dapoxetine treatment is delayed ejaculation.
Pharmacokinetics of Dapoxetine (Priligy)
The elimination of dapoxetine is rapid, the half-life is 1.3 to 1.4 hours and there appears to be very little accumulation. Less than 5% of the drug is present at 24 hours. This is in contrast to the other SSRI’s that have half-lives in the order of 1 to 4 days and chronic use results in accumulation.
In several clinical trials, dapoxetine has been shown to improve the IELT and is effective from the first dose when taken 1 to 3 hours before intercourse.
Dapoxetine is rapidly absorbed and eliminated, resulting in minimal accumulation, and has dose-proportional pharmacokinetics which is unaffected by multiple dosing. This makes Dapoxetine (Priligy) the drug of choice in the management of premature ejaculation.
The pharmacokinetics of dapoxetine is not altered when administered in combination with food, alcohol or PDE5 inhibitors such as Sildenafil (Viagra) or Tadalafil (Cialis) and this makes it interesting that Dapoxetine could be prescribed with the PDE5 inhibitors used to treat erectile dysfunction.
Clinical trials have demonstrated that both dapoxetine 30 mg and 60 mg were statistically better than placebo (no drug) in terms of improvement in the Intravaginal Ejaculation Latency Time, IELT (time taken to ejaculate after penetration).
Dapoxetine (30 and 60 mg) has been evaluated on demand in men with Premature ejaculation and erectile dysfunction in many studies involving men aged at least 18 years and has shown an increase in IELT. High dose (60 mg) dapoxetine taken 1 to 3 hours before intercourse displayed a higher post-treatment IELT increase compared to 30 mg dapoxetine.
Data suggest that dapoxetine administered 1-2 hours prior to planned intercourse, is effective and well tolerated, superior to placebo and increases IELT 2 to 3 fold over baseline in a dose-dependent fashion. In randomized, controlled studies dapoxetine 30 mg or 60 mg was more effective than placebo (no drug) for all study endpoints. IELT increased from 0.9 minutes at baseline to 2.78 and 3.32 minutes at the end of the study with dapoxetine 30 and 60 mg respectively. Mean patient rating of control-over-ejaculation was fair, good or very good and increased from 3.5% at baseline to 51.8 and 58.4% at the end of the study with dapoxetine 30 and 60 mg respectively.
The improvement in patients’ perception of control over ejaculation and satisfaction with sexual intercourse was achieved with both doses of dapoxetine. Patients who received dapoxetine perceived an overall improvement in symptoms of premature ejaculation, and their partners also had a significant increase in satisfaction with sexual intercourse.
Dapoxetine is a potent selective serotonin reuptake inhibitor, which is administered on-demand 1–3 hours prior to planned sexual contact. The most common treatment-related adverse effects included nausea, dizziness and headache.
Dapoxetine, as the first drug developed for premature ejaculation, allows for flexible “on demand” dosing, is well tolerated and effective and is a safe treatment for premature ejaculation thus representing a major advance in men’s sexual health.
Mens Pharmacy is not liable for the currency or accuracy of the information contained in this blog post. For specific information about your personal medical condition, please contact our doctors or pharmacists for advice on [email protected].