little guy pictured to the left is href="http://en.wikipedia.org/wiki/Dapoxetine" rel="tag">dapoxetine,
a drug under development for the treatment of href="http://en.wikipedia.org/wiki/Premature_ejaculation"
I wrote about this href="http://trots.blogspot.com/2005/05/cns-pipeline-updatewas-dr-angell-right.html">before,
in the context of recent criticism of the pharmaceutical industry.
Some have argued that the industry spends too much time and
money developing drugs that we no not really need.
That is not too much of a problem, except that it might divert
resources away from developing things that are more important, from a
public health standpoint.
One thing that I did not mention in my prior post, is that it is likely
that Eli Lilly (the company that originally produced the compound) did
not originally produce this compound with the intent of finding a drug
for premature ejaculation. It is impossible to know for sure,
but it seems likely that they were looking for another antidepressant.
After I wrote the old post, the href="http://www.fdanews.com/dailies/drugdaily/2_218/news/48111-1.html">FDA
decided to href="http://dapoxetineapproval.com/2006/04/jj_not_giving_up_hope_on_dapox.html">
not approve the drug. But, such decisions are not
final. The company has the opportunity to do new studies to
address whatever concerns the FDA had.
In this case, the reason for the non-approvable status were not
released publicly. Often, companies are tight-lipped about
Now, we see that that ALZA (which now has the license for dapoxetine)
has done additional href="http://en.wikipedia.org/wiki/Clinical_trial#Phase_III">phase
III studies. The results were published in href="http://www.thelancet.com/journals/lancet/article/PIIS0140673606693732/fulltext">The
Lancet . (subscription required)
The authors disclosed financial connections to ALZA, so the report has
to be interpreted accordingly.
Efficacy and tolerability of dapoxetine in
treatment of premature ejaculation: an integrated analysis of two
double-blind, randomised controlled trials
Volume 368, Issue 9539 , 9 September 2006-15 September
2006, Pages 929-937
No drugs are approved for treatment of premature ejaculation. Our aim
was to determine the efficacy and tolerability of on-demand dapoxetine
in patients with severe premature ejaculation.
We determined the efficacy of dapoxetine in a prospectively predefined
integrated analysis of two 12-week randomised, double-blind,
placebo-controlled, phase III trials of identical design done
independently, in parallel, at 121 sites in the USA. Men with
moderate-to-severe premature ejaculation in stable, heterosexual
relationships took placebo (n=870), 30 mg dapoxetine (874), or 60 mg
dapoxetine (870) on-demand (as needed, 1–3 h before
anticipated sexual activity). The primary endpoint was intravaginal
ejaculatory latency time (IELT) measured by stopwatch. Safety and
tolerability were assessed. All analyses were done on an
intention-to-treat basis. The trials are registered at
ClinicalTrials.gov, numbers NCT00211107 and NCT00211094.
672, 676, and 610 patients completed in the placebo, 30 mg dapoxetine,
and 60 mg dapoxetine groups, respectively. Dapoxetine significantly
prolonged IELT (p<0·0001, all doses vs placebo). Mean
IELT at baseline was 0·90 (SD 0·47) minute,
0·92 (0·50) minute, and 0·91
(0·48) minute, and at study endpoint (week 12 or final
visit) was 1·75 (2·21) minutes for placebo,
2·78 (3·48) minutes for 30 mg dapoxetine, and
3·32 (3·68) minutes for 60 mg dapoxetine. Both
dapoxetine doses were effective on the first dose. Common adverse
events (30 mg and 60 mg dapoxetine, respectively) were nausea
(8·7%, 20·1%), diarrhoea (3·9%,
6·8%), headache (5·9%, 6·8%), and
dizziness (3·0%, 6·2%).
On-demand dapoxetine is an effective and generally well tolerated
treatment for men with moderate-to-severe premature ejaculation.
Some limitations of the studies were noted:
One should note that the study population was
restricted to patients with title="intravaginal ejaculatory latency time">IELT
consistently 2 minutes or less and who described their premature
ejaculation as moderate to severe. Therefore, the results cannot be
generalised to men with milder forms of premature ejaculation.
Additionally, the effects of dapoxetine on patient types excluded from
these trials—those with coexisting erectile dysfunction or
premature ejaculation of other cause—are not known. Finally,
because of the predominance of caucasian and young patients, robust
conclusions in other ethnic groups and older men could not be
Dapoxetine has a time-to-maximum-concentration (Tmax) of 1 hour, and a
half-life of 1.2 hours, on average. That means that it would
not accumulate in the body even if taken every day. That
could be a good thing, but not necessarily:
Accidental injuries—eg, sprained ankle, car
accident—were reported in 17 (1·9%) patients
receiving placebo, in 28 (3·2%) patients receiving 30 mg
dapoxetine, and in 26 (3·0%) on 60 mg dapoxetine...
...Accidental injury is a recognised adverse event reported with many
drug classes, especially with agents that modulate the central nervous
system. Accidental injury is reported with some SSRIs and
phosphodiesterase-5 inhibitors. Events should be examined
qualitatively for details of circumstances surrounding the reported
accidental injury. Such an assessment of the accidental injuries in
these trials showed that there was no clinical signal to suggest that
the accidental injuries were masking any other important adverse
events—eg, syncope and suicidality. Neurocognitive adverse
events—eg, dizziness and somnolence—seemed to be
dose dependent. Both accidental injuries and neurocognitive adverse
events could be drug related. The relation between the occurrence of
these two types of adverse events needs further investigation. The
discontinuation rate due to adverse events with dapoxetine (about 7%)
was much the same as or less than that of other SSRI compounds when
used in men with premature ejaculation.
Clinical experience with other SSRIs shows that rapid changes in
concentration are more likely to produce certain adverse effects, such
as dizziness. I doubt that dapoxetine is really dangerous,
but perhaps users should be cautioned about driving, climbing trees, or
using dangerous equipment (e.g. chainsaws) after taking the drug.
My biggest frustration with this drug is that the company website takes extra effort to define PE as an exclusively psychologic disease, and yet wants to treat PE with a psychologic drug that doesn't even address the psychologic disease. It seems difficult for me to define PE as a PRIMARY psych illness when it makes siginificant better sense as a feature of depression, anxiety, etc. And of course we have no head-to-head trials with current SSRIs, which have been studied fairly well in conjunction with PDE5 inhibiotrs for delaying ejaculation. When all but Lexapro are finally going off patent, I don't think the FDA would be doing us any favors by putting more SSRIs on the market whose benefits are purely theoretical and absent in situ.
Is premature ejaculation a disease, i.e., a type of pathology? I can imagine that some people might actually have a pathological condition underlying PE, but I seriously doubt that's the case for the majority of people for whom this is a problem.
Please understand that I have no objection to people using drugs to help them prolong pleasure. But I do object quite strongly to inappropriate medicalization.
One of the peculiar and sometimes-unfortunate consequences of the way our drug-approval process works, is that drugs have to be approved to diagnose or treat an illness: no illness, no approval.
I suppose we could say that a disease is any condition that doctors take it upon themselves to try to do something about.
Granted, there is a risk in applying labels too quickly. Part of the risk comes from the risks inherent in any visit to a doctor. There is always a chance that you'll walk out sicker than when you walked in. Plus, there are sociological implications to medicalizing something; those implications are not always valid.