Moncada_A4_template_04 16/03/2010 10:43 Page 68
Premature Ejaculation
Dapoxetine – A New Pharmacological Treatment for Premature Ejaculation
Juan Ignacio Martinez-Salamanca
1
and Ignacio Moncada
2
1. Attending Urologist, Hospital Puerta de Hierro, Madrid; 2. Urologist, Hospital Sanitas-La Zarzuela, Madrid
Abstract
The International Society for Sexual Medicine (ISSM) definition of lifelong premature ejaculation (PE) states “it is a male sexual dysfunction
characterised by ejaculation which always or nearly always occurs before or within about one minute of vaginal penetration, and the inability
to delay ejaculation on all or nearly all vaginal penetrations, and negative personal consequences, such as distress, bother, frustration and/or
the avoidance of sexual intimacy”. The triggers for ejaculation include tactile stimulation of the glans penis and various supraspinal stimuli. The
neural control network for ejaculation involves specific spinal, supraspinal and peripheral neural pathways. The management of PE is shifting
from a traditional diagnostic and treatment pattern based on expert opinion to a more experimental, evidence-based approach. Continuous
daily dosing of selective serotonin re-uptake inhibitors (SSRIs) is effective in delaying ejaculation. However, this approach increases exposure to
medication, thereby increasing the likelihood of side effects. Considering the shortcomings of chronic SSRI treatment, an optimal therapy for PE
would have a short duration of activity with clinical efficacy after each dose for on-demand treatment with no need for lead-in dosing.
Dapoxetine, a short-acting SSRI, is the first oral agent approved for the treatment of PE. Dapoxetine has recently been approved in several
European countries. In contrast to the longer-acting SSRI antidepressants, the pharmacokinetic profile of dapoxetine is better suited to the on-
demand treatment of PE.
Keywords
Premature ejaculation, selective serotonin reuptake inhibitors (SRIs), sexual side effects, dapoxetine
Disclosure: Juan Ignacio Martinez-Salamanca has no conflicts of interest to declare. Ignacio Moncada is a clinical investigator, advisory board member and speaker for
Janssen Cilag.
Received: 31 January 2010 Accepted: 26 February 2010
ignacio@moncada.name
There are several definitions of premature ejaculation (PE). The most lifelong PE who engage in vaginal intercourse. The panel concluded that
commonly quoted – the American Psychiatric Association’s there are insufficient published objective data to propose an evidence-
Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, based definition of acquired PE. The ISSM definition of lifelong PE
Text Revision (DSM-IV-TR) – and other definitions of PE are all represents the first evidence-based definition of PE.
1
authority-based rather than evidence-based, and have no support
from controlled clinical and/or epidemiological studies. Thus, in Neurophysiology of Ejaculation
August 2007 the International Society for Sexual Medicine (ISSM) Normal ejaculation
2
involves the processes of emission and expulsion
appointed several international experts in PE to an Ad Hoc Committee of semen, which are co-ordinated by a network of afferent and
for the Definition of PE. The committee met in Amsterdam in October efferent neural pathways.
3,4
The triggers for ejaculation include tactile
2007 to evaluate the strengths and weaknesses of current definitions stimulation of the glans penis and various supraspinal stimuli. The
of PE; to critically assess the evidence in support of the constructs of neural control network for ejaculation involves specific spinal,
ejaculatory latency, ejaculatory control, sexual satisfaction and supraspinal and peripheral neural pathways.
5
Ejaculatory control
personal/interpersonal distress; and to propose a new evidence- centres within the spinal cord are responsive to peripheral afferents
based definition of PE. and supraspinal influences, and function to co-ordinate, in a timely
fashion, the sympathetic, parasympathetic and somatic outputs to
The Committee unanimously agreed that the constructs necessary to the pelviperineal anatomical structures participating in the emission
define PE are rapidity of ejaculation, perceived self-efficacy, control and and expulsion phases. Inhibitory and excitatory controls are exerted
negative personal consequences from PE. The Committee proposed from supraspinal sites. Certain brain structures have been identified
that “lifelong PE be defined as a male sexual dysfunction characterised as specifically related to ejaculation and are activated during
by ejaculation which always or nearly always occurs before or within sexual activity.
6,7
These include discrete regions lying within the
about one minute of vaginal penetration, and the inability to delay posteromedial bed nucleus of the stria terminalis, the posterodorsal
ejaculation on all or nearly all vaginal penetrations, and negative medial amygdaloid nucleus, the posterodorsal preoptic nucleus and
personal consequences, such as distress, bother, frustration and/or the the parvicellular part of the subparafascicular thalamus.
8
In the
avoidance of sexual intimacy”. This definition is limited to men with brainstem, the nucleus paragigantocellularis, which contains a high
68
© TOUCH BRIEFINGS 2009
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89  |  Page 90  |  Page 91  |  Page 92  |  Page 93  |  Page 94  |  Page 95  |  Page 96  |  Page 97  |  Page 98  |  Page 99  |  Page 100