Emerging treatments for premature ejaculation: focus on dapoxetine

Neuropsychiatric Disease and Treatment downloaded from https://www.dovepress.com/ by 180.226.29.66 on 11-Jul-2020 For personal use only. E X P E RT O P I N I O N Emerging treatments for premature ejaculation: focus on dapoxetine Wayne JG Hellstrom Chief, Section of Andrology, Department of Urology, Tulane University School of Medicine, New Orleans, LA, USA Abstract: Premature ejaculation (PE) is a common problem in men worldwide. It has a significant impact on affected men and their partners in terms of self-esteem, dissatisfaction with their sexual relationships, personal distress, and interpersonal difficulty. Psychological therapies may achieve short-term improvements, but there are limited data on the long-term success of these methods. Oral therapy with long-acting selective serotonin reuptake inhibitors (SSRIs) improves intravaginal ejaculatory latency time (IELT), but these agents are designed to be administered daily and may be associated with unwanted sexual side effects and withdrawal symptoms upon abrupt discontinuation. Dapoxetine is a short-acting SSRI that can be taken as needed (prn) by men with PE. It has been studied in five separate multicenter, randomized, double-blind, placebo-controlled trials involving more than 6000 men with PE. In four studies that evaluated IELT as an endpoint (N = 4843), dapoxetine 30 and 60 mg prn achieved statistically significant increases in IELT versus placebo. Dapoxetine also showed statistically significant improvements in perceived control over ejaculation, PE-related personal distress, and other patient-reported outcomes in all five trials. Dapoxetine treatment is generally well-tolerated, with low incidences of discontinuation syndrome, sexual dysfunction, and treatment-emergent mood symptoms. The most common adverse events with dapoxetine included nausea, diarrhea, headache, dizziness, and somnolence. Keywords: dapoxetine, discontinuation syndrome, premature ejaculation, selective serotonin reuptake inhibitor Introduction Correspondence: Wayne JG Hellstrom Chief, Section of Andrology, Tulane University School of Medicine, Department of Urology, 1430 Tulane Avenue, SL 42, New Orleans, LA 70112, USA Tel +1 504 988 7308 Fax +1 504 988 5059 Email Premature ejaculation (PE) is the most common form of male sexual dysfunction.1 Globally, between 20% and 40% of men, at some point in their lives, have reported symptoms of PE or a complaint of PE,1–3 which may be classified as lifelong or acquired.4 Lifelong PE is characterized by early ejaculation in the majority of intercourse attempts with nearly every partner from the first sexual encounter onwards, whereas acquired PE develops at some point in a man’s life after he has previously experienced normal ejaculation and may be linked to urological or psychological problems.4 Some have also suggested that 2 additional forms of PE be considered, including natural-variable PE and premature-like ejaculatory dysfunction. Naturalvariable PE is characterized by early ejaculations that occur sporadically and should be regarded as a normal variation in sexual performance.4 Premature-like ejaculatory dysfunction is characterized by a false perception of PE even though these men have normal to very long ejaculation times.4 In clinical practice and for the purposes of clinical trials, the most commonly used definition of PE has been the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR), definition, which describes PE as “persistent or recurrent ejaculation with minimal sexual stimulation before, on, or shortly after penetration and before the person wishes it” that “causes marked distress or interpersonal Neuropsychiatric Disease and Treatment 2009:5 37–46 © 2009 Hellstrom, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. Powered by TCPDF (www.tcpdf.org) 37 Neuropsychiatric Disease and Treatment downloaded from https://www.dovepress.com/ by 180.226.29.66 on 11-Jul-2020 For personal use only. Hellstrom difficulty” and “is not due exclusively to the direct effects of a substance.”5 More recently, the International Society for Sexual Medicine (ISSM) has more precisely defined lifelong PE as “a male sexual dysfunction characterized by ejaculation which always or nearly always occurs prior to or within about 1 minute of vaginal penetration; 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.”6 The negative impact of PE on both the man and his female partner can be significant. The man may often feel ashamed and embarrassed at not being able to satisfy his partner; subsequently, low self-esteem, anxiety, and feelings of inferiority are common.7–10 Satisfaction with sexual intercourse and the sexual relationship may be reduced while personal distress and interpersonal difficulty may be increased in men with PE.8,10–12 Overall, many aspects of quality of life, including social functioning and emotional well-being, are significantly decreased.10 In two surveys of the female partners of men with PE, sexual satisfaction was “poor” or “very poor” in approximately 25% of respondents, personal distress related to PE was reported as at least “moderate” by approximately 50% of respondents, and interpersonal difficulty was at least “moderate” in up to 32% of respondents.11,13 The level of personal distress, perceived lack of control over ejaculation, satisfaction with sexual intercourse, and degree of interpersonal difficulty is comparable for men with PE and their female partners.12 Despite the high prevalence of PE, very few men seek treatment.14,15 In the Premature Ejaculation Prevalence and Attitudes (PEPA) survey of more than 12,000 men, only 9% of men with self-reported PE sought help from a physician.2 Factors discouraging men from seeking treatment included doubts regarding the effectiveness of medication, concerns about becoming reliant on medication to perform sexually, and discomfort or embarrassment in discussing their PE. Of the men who had sought treatment for their PE, 92% reported little or no improvement in their condition. Further, physicians rarely inquire about sexual health. In a separate international survey of 27,500 men and women aged 40 to 80 years, only 9% of respondents said they had been asked about their sexual health at routine visits within the previous 3 years, but more than 40% felt this should have occurred.15 These findings emphasize the need for an effective, well-tolerated, and acceptable treatment for PE. The physiology of ejaculation and the role of serotonin Ejaculation is a biphasic process consisting of emission, which involves the secretion of seminal fluid from the 38 Powered by TCPDF (www.tcpdf.org) prostate and seminal vesicle, contraction of the smooth mus (...truncated)