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Development of new serotonergic drugs seems inevitable in light of the high incidence and the need for effective treatment of premature ejaculationThusthe development of an in vivo experimental model for objectively assessing the efficacy of these new drugs is mandatoryHsieh et al1998previously established a rat model involving electrical stimulation of the lesser splanchnic nerve to induce changes in the intraluminal pressure of the seminal vesicleThese investigators evaluated the impact of various agentssuch as prazosin5-hydroxy tryptamineclomipraminefluoxetineimipramineand indatralineon seminal vesicle pressure induced by electrical stimulationThey documented concentration-dependent effects with prazosin and all serotonergic agentsbut not with imipramine or indatralineFluoxetine was reported to have the highest efficacyOn the other handKim et al2000studied the effects of serotonergic drugs including clomipraminesertralineparoxetineand fluoxetine on the vasal pressure induced by electrical stimulation of the hypogastric nerveKim et al 2000All these serotonergic drugs were documented to cause concentration-dependent inhibition of intraluminal pressure elevation in the vas deferensThese investigators reported clomipramine as having the strongest inhibitory effect followed by sertralineparoxetineand fluoxetineKim et al 2000

In a double-blind stopwatch study in men with lifelong PE associated with an IELT of less than 1 minuteWaldinger et al2004afound that on-demand treatment with 20 mg paroxetine exerted only a 1.41-fold increase in IELT at a drug coitus interval timeDCITof 5.30 hoursWaldinger et al 2004aThe calculated 1.41-fold increase means that on-demand treatment with 20 mg paroxetine induced only a 40ejaculation delayThe degree of ejaculation delay in this study was considered as clinically insignificant by the men and their female partnersOn the other handon-demand treatment with 25 mg clomipramine with a mean DCIT of 5.15 hours led to a 4.05-fold increase in the IELTwhich was considered as clinically relevant by the couplesand confirmed earlier reports on the efficacy of on-demand clomipramine treatmentSegraves et al 1993Haensel et al 1996Waldinger et al 2004a

Recentlyin a well-designed studySalonia et al2002compared paroxetine alone with paroxetine and sildenafil as an oral therapy for men reporting PEIn the combination groupparoxetine was given as 10 mg once daily for 20 daysfollowed by 20 mg as needed and sildenafil 50 mg 1 hour before sexual activityThis study demonstrated that the combination of paroxetine and sildenafil obtained better results in regards to IELT and intercourse satisfaction than paroxetine aloneThe combination treatment was associated with a mild increase in drug-related adverse eventssuch as headache20nausea15and flushing15Despite the higher incidence of adverse effects associated with the combined therapymost patients90were willing to continue this treatment on an as-needed basis.

Patient is in a stablemonogamous sexual relationship with the same woman for at least 6 months and plans to maintain this relationship for the duration of the study history of premature ejaculation in the 6 months before study initiation not due to distressinterpersonal difficulty or medication withdrawal history of intravaginal ejaculatory latency timeIELTof.

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it should also be mentioned that dapoxetine rarely causes erectile dysfunction as a side effect compared to antidepressants from the same ssri group.