BERKELEY, CA (UroToday Inc.) - The tricyclic antidepressant clomipramine, and more recently the selective serotonin reuptake inhibitor (SSRI) paroxetine have been increasingly used to treat premature or rapid ejaculation. Most well designed studies, however have focused on daily treatment with these agents and have shown the advantage of paroxetine with a mean 2 fold-increase in ejaculation time of 8.8 minutes versus 4.6 with clomipramine. A recent study was performed to investigate the degree of ejaculation delay induced by on-demand treatment with 20 mg of paroxetine or 25 mg of clomipramine. Investigators also assessed the type and severity of non-sexual side effects of treatment on the day of and the day after treatment with these drugs.

The randomized, double blind, fixed-dose, on-demand study of thirty men with premature ejaculation was performed by M.D. Waldinger and colleagues from the Netherlands and published in the October, 2004 issue of European Urology. During a 1-month baseline period and a 4-week drug treatment period, patients assessed the intravaginal ejaculation latency time (IELT) at home with a stopwatch. Only men with an IELT <1 min were randomly assigned to drug treatment. Patients also recorded the drug-coitus interval time (DCIT) - the time from drug ingestion to coitus and used a side effect scale (the UKU) at baseline, the day of and the day after intercourse.

Analysis of the study group showed a mean age of 37 years and a median IELT of 24 seconds. The median time from drug ingestion to coitus (DDIT) was 5.3 hours for each drug. Treatment results showed that the overall fold-increase in IELT was 1.49 for paroxetine and 3.78 for clomipramine. The greatest increase in the paroxetine group occurred around 5 hours after drug intake, and in the clomipramine group it occurred between 3 and 4 hours after drug ingestion.

When examining side effects, most patients on the day of dosing and intercourse experienced non-sexual side effects such as fatigue, sleepiness, yawning, tremor, nausea, dry mouth, loose stools, dizziness or headache. Paroxetine showed significantly more complaints of sleepiness and yawning than did clomipramine. Both antidepressants exerted similar side effects on the day after drug ingestion. Clomipramine, however, resulted in more nausea than paroxetine, on the day after coitus.

The present study suggests that while the continuous daily treatment of premature ejaculation with paroxetine appears to be more efficacious than clomipramine, on-demand treatment with clomipramine may be superior. Paroxetine relies on serotonin receptor desensitization, which occurs with continuous receptor exposure, and its ability to increase the IELT in men with premature ejaculation may require daily dosing. In men who are willing to withstand the mild yet annoying non-sexual side effects, on-demand treatment with clomipramine taken 3 to 4 hours prior to intercourse may be a good option that results in adequate prolongation of ejaculation.

Eur Urol. 2004 Oct; 46(4):510-5