Arver_edit_Layout 1 13/10/2009 12:55 Page 66
Figure 1: Effect of Different Doses of Dapoxetine showed an increase in satisfaction with intercourse from a baseline
on Intravaginal Ejaculatory Latency Time Compared
of 53–58% (fair, good or very good) to 72% in the 30mg group and
78% in the 60mg group, and were unchanged in the placebo group.
10 In the 22-country study the female partner reported a change from
5% (good or very good) at baseline for partner’s control of ejaculation
to 25, 32 and 14.4% in the 30mg, 60mg and placebo groups,
respectively, at the 24-week assessment.
Side Effects of Dapoxetine
The most common side effects of dapoxetine were in line with the side
effect profile of SSRIs in general. The drop-out rate due to side effects
Mean (SD) aver
was 6–8%, with the most frequent adverse events being nausea (16.5,
P 30 60 P 30 60 P 30 60 P 30 60 P 30 60 P 30 60 P 30 60 P 30 60
30.6 and 2.9% for the 30mg, 60mg and placebo groups, respectively)
Baseline First dose Week 4 Week 8 Week 12 Week 16 Week 20 Week 24
and dizziness (7.7, 13.4 and 2.6% for the 30mg, 60mg and placebo
These symptoms were most frequently
P = placebo; 30 = 30mg dapoxetine; 60 = 60mg dapoxetine; SD = standard deviation;
30 reported as being of mild severity. One safety concern was syncope, of
IELT = intravaginal ejaculatory latency time. Source: Buvat et al., 2009.
which half the cases met the strict definition criteria that specify loss
75% of intercourse attempts who were living in stable heterosexual of consciousness. Summarising all phase III studies revealed a syncope
relationships. Study results persistently demonstrate a dose- rate of 0.05% for placebo, 0.06% for 30mg dapoxetine and 0.23% for
dependent increase in IELT (see Figure 1), a significant increase in the 60mg dapoxetine. For syncope, there was no significant difference
sense of control of ejaculation and a lessening of distress, which also between placebo and the 30mg dose of dapoxetine, while the 60mg
included the response from female partners. dose showed a slight increase. Syncope was judged as a vasovagal
reaction (non-cardiac), but any relation to a previous history of
Pooled Data from Four Published Randomised Controlled orthostatic reactions was not assessed. To limit possible problems of
Trials with Dapoxetine/Placebo
syncope or dizziness, it is recommended that men stay hydrated when
Beyond measurement of time to ejaculation (IELT), further efficacy using dapoxetine and sit or lie down when feeling dizzy; men with
evaluation was made using a validated instrument (Premature known orthostasis should avoid using the drug. In a small group of
Ejaculation Profile [PEP]). This is a four-item graded scale related to PE patients taking dapoxetine who reported syncope (30 of 5,929), Holter
(perceived control over ejaculation, personal distress related to electrocardiogram tracking revealed a few instances of bradycardia,
ejaculation, satisfaction with sexual intercourse and interpersonal prolonged R-R interval and, in one patient, sinus arrest lasting for 28
difficulties related to ejaculation).
The evaluation included the seconds.
However, these symptoms were not causally linked with
Clinical Global Impression of Change (CGIC), a seven-point scale (much dapoxetine. Since the phase III trials
excluded men with
worse to much better) that assesses changes in overall condition.
cardiovascular disease and there is little experience of its use in this
There was also a thorough evaluation of sexual side effects, anxiety, group, it was decided that, as a precaution, dapoxetine should be
depression and discontinuation syndrome assessment. contraindicated in individuals with severe congestive heart failure, sick
sinus, AV-bundle delay or severe ischaemic heart disease.
Mean (overall summary) IELT at baseline was 0.9 minutes in all
treatment groups and increased to 1.75 minutes with placebo, 2.78 In summary, dapoxetine, a short-acting SSRI, has been approved for
minutes with 30mg and 3.2 minutes in the 60mg group at 12-week clinical use in Europe. It is the first approved drug for the treatment of
assessment. Changes were highly significant comparing active drug PE, and is likely the forerunner to other therapeutic approaches. The
versus placebo and 30 and 60mg (p<0.0001 for all doses versus mere presence of an approved therapy also highlights the medical
placebo). Furthermore, changes from baseline and from placebo were need for patients with distress related to PE and their need for
seen throughout the study (at four, eight and 12 weeks). CGIC data adequate attention and therapy. Hopefully, this will lead to more men
suggested that an increase in IELT of more than one minute was seeking medical help and the medical community acting with respect
perceived as clinically significant. This was achieved in 47% of men and providing evidence-based diagnosis, counselling and therapy.
receiving 30mg dapoxetine, 51% of men receiving 60mg dapoxetine
and 22% of those in the placebo group.
In a 24-week study conducted Other Pharmacological Approaches to the
in 22 countries in Europe and South America, with a baseline IELT of 0.9 Treatment of Premature Ejaculation
minutes, results were again significantly better at 12 weeks, with an A recent extensive review covered both central (other than 5-HT)
IELT of 3.2 minutes with 30mg, 3.5 minutes with 60mg dapoxetine and and peripheral targets addressed with pharmacological drugs to
1.9 minutes with placebo at week 12; this was maintained after 24 treat PE.
The use of topical therapies with anaesthetics is based on
weeks of therapy. Improvement was seen even after the first dose. an assumption that penile sensitivity is increased in men with PE;
however, this has not been clearly demonstrated and there are
Changes in IELT were also accompanied by increased perceived conflicting results.
Clinical studies of various designs
control over ejaculation, which improved (categories fair, good or demonstrate efficacy with both the Korean SS-cream
very good) from a baseline of 0.3% to 8.7% with placebo, 23.9% with eutectic mixture of lidocain and prilocain (EMLA
or the same in
30mg dapoxetine and 30.2% with 60mg dapoxetine.
Satisfaction an aerosol formulation.
Overall, these studies demonstrate
(good or very good) with sexual intercourse increased from a efficacy, with an increase in IELT from 1.49 to 8.45 minutes,
baseline of <21% to 24.6, 38.7 and 45.5% in the placebo, 30mg and intercourse and satisfaction rates were low in both the placebo and
60mg groups, respectively.
Responses by the female partner active groups and the drop-out rate was 69%. Similar findings were
66 EUROPEAN UROLOGICAL REVIEW