New Insights in Premature Ejaculation

A meta-analysis of 35 clomipramine(Drug information on clomipramine) and SSRI daily treatment studies that were conducted between 1973 and 2003 revealed that the use of placebo may delay ejaculation to some extent.¹⁷ It was also shown that of all SSRIs, daily treatment with 20 mg of paroxetine(Drug information on paroxetine) exerts the strongest ejaculation delay. Expressed in fold-increase compared with baseline values and using the geometric mean IELT, it was shown that placebo exerts a geometric mean 1.4-fold IELT increase (95% CI, 1.2-1.7) and that SSRIs differ in their ability to delay ejaculation. The rank order (geometric mean fold-increase of IELT) was paroxetine, clomipramine, sertraline, and fluoxetine(Drug information on fluoxetine) (Table).

Recommended daily treatment is 20 to 40 mg of paroxetine, 10 to 50 mg of clomipramine, 50 to 100 mg of sertraline(Drug information on sertraline), 20 to 40 mg of fluoxetine, 20 to 40 mg of citalopram(Drug information on citalopram), or 10 to 20 mg of escitalopram(Drug information on escitalopram). Ejaculation delay usually starts a few days after drug intake; however, a clinically relevant effect only gradually occurs after 1 to 2 weeks. Most often the delay continues to exist for years as long as treatment is continued, but in some cases it may diminish after 6 to 12 months. The cause of this tachyphylaxis of SSRIs has not yet been clarified.

Patients should be informed about the short-term and long-term adverse effects of SSRIs. The short-term effects include fatigue, yawning, mild nausea, loose stools, and perspiration. These adverse effects are usually mild, start within the first 1 to 2 weeks of treatment, and most often gradually disappear within 2 to 3 weeks.

Although a comparative study has not yet been performed, drug treatment studies seem to indicate that in contrast to the adverse effects in patients with depression, diminished libido and erectile dysfunction are reported less often by healthy men who have lifelong PE and are not depressed. A rather rare adverse effect of SSRIs is bleeding.²⁰ Clinicians should caution patients about combining SSRIs with aspirin(Drug information on aspirin) or NSAIDs because this may increase the risk of bleeding. A very rare adverse effect is priapism,²¹ and all patients using SSRIs should be advised about the risk for priapism and the need for immediate medical treatment.

One should not prescribe these drugs for the treatment of PE in men who are younger than 18 years. These drugs should be used with caution in young men who have a depressive disorder and who are at risk for developing suicidal thoughts. Long-term adverse effects include weight gain with an associated risk for type 2 diabetes mellitus.²² To prevent the occurrence of SSRI discontinuation syndrome, patients should be advised not to stop taking the medication abruptly.²³

The aim of on-demand treatment strategies is to delay ejaculation, preferably within 1 to 2 hours after drug intake. A disadvantage of on-demand drug treatment is that it may negatively interfere with the spontaneity of having sex and that adverse effects may occur a few hours after drug intake, which is usually during the hours of intimacy and coitus. A recent study showed that the majority (81%) of a sample of men with lifelong PE actually favored daily SSRI treatment to on-demand treatment with clomipramine and the use of topical anesthetics.²⁴ In general, on-demand use of SSRIs exerts much less ejaculation delay than daily SSRI treatment. On- demand use of 20 to 40 mg of clomipramine may delay ejaculation after 4 to 6 hours²⁵; however, this may lead to nausea on the same day or the following day.

Another on-demand treatment option is the use of topical local anesthetics such as lidocaine and/or prilocaine(Drug information on prilocaine) in the form of a cream or spray that reduce the sensitivity of the glans penis.²⁶ Although topical anesthetics lack systemic adverse effects, their use may lead to erectile difficulties because of too strong anesthesia of the penis. It may also lead to vaginal numbness, but this may be prevented with the use of a condom.

Recently, it has been suggested that dapoxetine, an SSRI with a short half-life, would be a breakthrough drug for on-demand treatment of PE.²⁷ However, in 2005 the FDA did not approve dapoxetine for this indication. In recent years, a few studies suggested efficacy of on-demand use of phosphodiesterase type-5 (PDE-5) inhibitors to delay ejaculation. However, a recent review of 14 studies found that the majority did not fulfill the current criteria of evidence-based research.²⁸ It was concluded that there is no convincing evidence that PDE-5 inhibitors are effective in delaying ejaculation. Yet, they may be useful to treat PE in men with comorbid erectile dysfunction.

A definitive cure for lifelong PE does not exist. After cessation of drug treatment, PE returns within a few days.

DSM-IV-TR definition of PE has been based on authoritative opinions. Recently, a new classification of 4 PE syndromes that is based on evidence-based clinical and epidemiological data has been proposed for the pending DSM-V. For about a decade, SSRIs have been increasingly used to treat PE. However, to date, there is no information on the percentage of men that use SSRIs to delay ejaculation. For that purpose, pharmaco-epidemiological research is needed. The very high prevalence rates of PE of 20% to 30% probably do not reflect the real percentage of men who are in need of drug treatment for PE. Drug treatment should be confined only to men who have lifelong PE and acquired PE. Men with normal and even long durations of IELT should not be treated a priori with medication but with counseling and psychoeducation.

Apart from the topical use of anesthetics and on-demand use of clomipramine, daily treatment with some SSRIs has been shown to be an effective way to treat lifelong PE. Despite their adverse effects, daily treatment with SSRIs is currently one of the best options to treat PE.