Premature Ejaculation and Pharmaceutical Company-Based Medicine: The Dapoxetine Case

Abstract

Introduction The manufacturer of dapoxetine funded randomized clinical trials to study its effect in premature ejaculation (PE). Financial support by pharmaceutical companies, however, may jeopardize the neutrality of clinical research. Aim To investigate the scientific process that has been followed in dapoxetine treatment trials and reviews as compared to daily drug treatment trials and reviews with selective serotonin reuptake inhibitors (SSRIs) in men with PE. Methods A search of Medline and Embase was conducted using the search terms “dapoxetine” or “SSRI.” References of retrieved articles were searched. Only studies describing the use of these drugs in men with PE were included. Main Outcome Measures Compared fold-increase intravaginal ejaculation latency time (IELT), geometric mean IELT, and adverse effect profiles between dapoxetine and SSRIs in PE. Results Preclinical studies on dapoxetine, including a multicenter study (category A) and reviews (category B), were compared with clinical studies with daily conventional SSRIs in PE (category C). Categories A/B focused on patient-reported outcomes with less attention for the IELT. The ejaculation-delaying effect of dapoxetine was expressed as natural mean IELT rather than as geometrical mean IELT. Dapoxetine side effects were monthly scored. In contrast, a significant part of category C articles focused on IELT data, used geometric mean IELT outcomes, and one study reported the side effects measured 24–48 hours after drug intake using a validated questionnaire. Without the Food and Drug Administration approval, dapoxetine, as well as other SSRIs in PE, is an off-label drug for PE. However, the off-label use of dapoxetine has never been criticized by clinical investigators in contrast to commentaries against the off-label use of daily SSRI treatment in PE. Conclusions Manufacturer-funded drug treatment research (categories A and B) is advantageously treated by some authors as compared with nonfunded trials with daily conventional SSRIs (category C). PE drug treatment research is a young and dynamic field, and its development deserves transparency to its development.

Distress, disease, desire: perspectives on the medicalisation of premature ejaculation

“…In 2004, Johnson & Johnson filed an unsuccessful application for Food and Drug Administration (FDA) approval of dapoxetine for on-demand treatment of PE. However, the drug has since been approved in several other countries 3. Our aim here is not to criticise the evidence for treating PE with dapoxetine or to compare it with other approaches such as counselling or manual techniques.…”

“…Critics within the field of sexual medicine argue that the second and third aspects have been constructed in order to make up for the rather limited increase in IELT 3. Both sides in the debate, however, argue from the position of the coital imperative, and the main goal remains to prolong vaginal penetration 19…”

‘Up and coming’ treatments for premature ejaculation: progress towards an approved therapy

“…The involvement of pharmaceutical companies in the sponsorship of clinical trials for PE has been endorsed by some, 9 but has not been universally welcomed, as demonstrated by the recent publication of a controversial article regarding the selective serotonin reuptake inhibitor (SSRI) dapoxetine. 10 However, the unusual number of detailed comments by leading workers in the field following the article gives a flavour of the differing, but clearly emotive views on the subject.…”

Introductory Chapter: Sexual Dysfunction - Introduction and Perspective

“…An ideal anti-PE medication would be "on demand," that can be taken shortly (hours) before sexual activity. Although it still would come with side effects, it is assumed that many men may prefer the convenience of "on demand" dosing compared to daily and long-term dosing [11]. The search for an "on demand" treatment for PE has led to the development of dapoxetine, which has received approval for treatment of PE in many countries, although it has not been approved by the US Food and Drug Administration (FDA).…”

“…Dapoxetine is a potent SSRI, and it is postulated that its rapid absorption and rapid appearance of peak plasma concentration combined with a relatively short half-life lead to an ideal pharmacokinetic profile for such an "on demand" profile. Dapoxetine has some minor "on demand" efficacy but clearly is not a breakthrough medicine in the treatment of PE [11]. Another SSRI, with a comparable profile as dapoxetine, DA-8031 is in development for PE, but efficacy data have not yet been elucidated [12,13].…”