Premature Ejaculation: Treatment
Selective Serotonin Reuptake Inhibitor (SSRI) Agents
The AUA panel charged with developing the Guideline could not conclude whether daily dosing or on-demand dosing was superior. The authors also noted that medical therapy only pro-vides symptomatic relief, and not cure of PE. Adverse events are a potential concern when using antidepressant pharmacological agents. While adverse event profiles have not been widely studied in the setting of PE therapy, those associated with the use of SSRIs and TCA agents in patients with depression include: dry mouth, drowsiness, nausea, and decreased libido. The most concerning adverse event is called “serotonergic syndrome.” In mild cases, patients experience headache, dizziness, sweating, and nausea, while in severe cases patients may experience delirium, hyperthermia, and rigidity. Generally, the dosages of these medications used in treating men with PE are lower than dosages used to treat depression; nonetheless, these potential adverse events remain a concern and should be discussed with patients prior to initiating therapy.
Special mention should be made of dapoxetine hydrochloride, another SSRI agent,. Dapoxetine hydrochloride, a short acting SSRI that is being studied for the specific indication for PE. In 2006, Pryor et al. published a manuscript in Lancet summarizing the efficacy of dapoxetine in two identically designed 12-week, randomized, double-blind, placebo-controlled Phase III clinical trials. Both studies evaluated men with moderate to severe PE who received placebo, dapoxetine 30 mg, or dapoxetine 60 mg as needed one to 3 h prior to intercourse. Both dos-ages of dapoxetine resulted in prolonged IELT when compared to placebo (p, 0.0001), and both dosages were associated with only mild side effects. Safarinejad published the results of a double-blind, placebo-controlled, fixed-dose, randomized study of dapoxetine in the treatment of PE in 2007. He reported that daily dapoxetine has moderately better results in terms of IELT and intercourse satisfaction when compared to placebo.
Dapoxetine did not provide men with long-term benefit after withdrawn. In November 2005, the FDA denied the application of dapoxetine in the treatment of PE, and the application for dapoxetine is still pending before the European Medicines Agency. A recent manuscript by Waldinger et al. in the Journal of Sexual Medicine questioned what the authors termed the “statistically significant but clinically small ejaculation-delaying effects of dapoxetine.” The authors also questioned several aspects of the methodology of the Phase III clinical trials, including the importance of patient reported outcomes of perceived control over ejaculation and satisfaction with sexual intercourse, over more objective measures such as IELT. At this time, the manufacturer notes that the clinical development pro-gram is still ongoing and consists of five Phase III placebo-controlled trials.
In summary, both the AUA and ICSD guidelines recommend specific antidepressants and topical anesthetics for the pharmacologic management of PE. Only the ICSD, however, high-lights the benefits of psychological and behavioral interventions.
Miscellaneous Approaches
In closing, some investigators have reported efforts to block nerve receptors for penile tactile stimuli via selective dorsal penile nerve division and hyaluronic acid gel injection. Both of these approaches have been reported to prolong IELT, but clearly need further investigation given their very limited evaluation to date.