On-Demand SSRI Called Effective for Premature Ejaculation
- By Judith Groch, Senior Writer, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine. September 08, 2006
- Explain to interested patients that the FDA issued a "not-approvable" letter on this SSRI a year ago, and the drug company said as late as yesterday it was still "exploring its options."
Review
MINNEAPOLIS, Sept. 8 -- For prevention of premature ejaculation, a investigational drug that can be used when the need arises, rather than round-the-clock, has checked out as safe and effective, according to the combined results of two large studies.
The drug is dapoxetine, a short-acting selective serotonin reuptake inhibitor that has been in regulatory limbo since the FDA issued a "not-approvable" letter last Oct. 26.
At the time, the Alza Corporation, a division of Johnson & Johnson, said it "continues to believe that dapoxetine provides important benefits for men who suffer from premature ejaculation." As of yesterday, Alza said it was still exploring its options.
If approved, the short-acting SSRI could replace chronic continuous-dose off-label treatment with an SSRI, or non-drug therapy approaches. Dapoxetine is the first on-demand agent for premature ejaculation, Jon Pryor, M.D., of the University of Minnesota here, and colleagues, reported in the Sept. 9 issue of The Lancet.
In addition to inconvenience, these continuous-dose compounds, Dr. Pryor said, are associated with drawbacks, such as psychiatric and neurologic issues, anticholinergic side-effects, and sexual side effects such as erectile dysfunction.
To determine the safety and efficacy of on-demand dapoxetine, the researchers did a prospectively predefned integrated analysis of two 12-week randomized, double-blind, placebo-controlled, phase III trials.
The trials were identical in design and were done in parallel at 121 sites in the U.S. The analysis included 2,614 men in stable heterosexual relationships with moderate to severe premature ejaculation and their partners.
Of 2,614 men (mean age 40.5, range 18 to 77) with moderate-to-severe premature ejaculation, 870 were given a placebo, 874 took 30 mg of dapoxetine, and 870 took 60 mg of dapoxetine as needed, one to three hours before anticipated sexual activity.
At baseline, 1,623 (62%) of the men ejaculated under a minute after penetration, with mean values much the same across the groups. according to the intravaginal ejaculatory latency time as measured by stopwatch. Mean intravaginal ejaculatory latency time at baseline for the three groups was 0.90 minute (SD 0·47), 0.92 minute (0.50), and 0.91 minute (0.48).
At week 12, both dapoxetine doses were more effective than placebo. (P<0.0001, for all doses versus placebo). Intravaginal ejaculatory latency time was 1.75 (SD 2.21) minutes for placebo, 2.78 (3.48) minutes for 30 mg dapoxetine, and 3.32 (3.68) minutes for 60 mg dapoxetine.
Only 14% of the placebo patients had an intravaginal ejaculatory latency time of three minutes or more, compared with 29% for the 30 mg dose and 34% for the 60 mg dose. Both dapoxetine doses were effective on the first dose, the researchers reported.
Dapoxetine improved patients' perception of control over ejaculation and overall satisfaction with sexual intercourse, a benefit shred by their partners, Dr. Pryor said. Although a placebo effect was apparent in terms of intravaginal ejaculatory latency time, a corresponding improvement in satisfaction with sexual intercourse with placebo treatment was not, he said.
The drug was generally well tolerated, the researchers said. Common adverse events, usually mild and transient, for 30 mg and 60 mg dapoxetine, respectively, were nausea (8.7%, 20.1%), diarrhea (3.9%, 6.8%), headache (5.9%, 6.8%), and dizziness (3.0%, 6.2%).
Among the study's limitations, the researchers noted that the study population was restricted to patients with intravaginal ejaculatory latency time under two minutes with moderate to severe premature ejaculation. Therefore, they said, the results cannot be generalized to men with milder forms of the disorder.
The study, they said, also failed to assess patients excluded from the trial (those with coexisting erectile dysfunction, for example). Finally, they noted that because of the predominance of Caucasian and young patients, the results cannot be extended to other ethnic or age groups.
In conclusion, Dr. Pryor said that in view of the distress and interpersonal difficulties generally associated with this condition, availability of effective treatment "might encourage men with premature ejaculation to seek a physician diagnosis, and could provide a substantial benefit for men and their partners."
Several study authors served as consultants for Johnson & Johnson, and two said they were Alza employees. Dr. Pryor and another author reported having served on advisory boards for Alza.
In a commentary in the same Lancet issue, Francesco Montorsi, M.D., and Andrea Salonia, M.D., wrote that a main limitation of chronic administration of an SSRI is the need to continue it, lest premature ejaculation recur.
On the other hand, they wrote, dapoxetine with its short duration makes it appealing for on-demand use. Although its three- to four-fold increase in intravaginal ejaculatory latency time is less than that typically seen with chronic SSRIs, "in our experience, most patients would clearly prefer on-demand treatment compared with being placed on a drug long-term," they wrote.
"Our hope is that on-demand dapoxetine will become an important drug to offer patients with premature ejaculation," they concluded.
Primary source: The Lancet
Source reference:
Pryor, J.L. "Efficacy and tolerability of dapoxetine in treatment of premature ejaculation: an integrated analysis of two double-blind, randomized trials" The Lancet 2006; 368: 929-937.
Additional source: The Lancet
Source reference:
Montorsi, F., Salonia, A. "Medical therapy for premature ejaculation" The Lancet 2006, 368: 894-896.
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