Emerging and investigational drugs for premature ejaculation

Abstract

Over the past 20−30 years, the premature ejaculation (PE) treatment paradigm, previously limited to behavioural psychotherapy, has expanded to include drug treatment. Pharmacotherapy for PE predominantly targets the multiple neurotransmitters and receptors involved in the control of ejaculation which include serotonin, dopamine, oxytocin, norepinephrine, gamma amino-butyric acid (GABA) and nitric oxide (NO). The objective of this article is to review emerging PE interventions contemporary data on the treatment of PE was reviewed and critiqued using the principles of evidence-based medicine. Multiple well-controlled evidence-based studies have demonstrated the efficacy and safety of selective serotonin reuptake inhibitors (SSRIs) in delaying ejaculation, confirming their role as first-line agents for the medical treatment of lifelong and acquired PE. Daily dosing of SSRIs is likely to be associated with superior fold increases in IELT compared to on-demand SSRIs. On-demand SSRIs are less effective but may fulfill the treatment goals of many patients. Integrated pharmacotherapy and CBT may achieve superior treatment outcomes in some patients. PDE-5 inhibitors alone or in combination with SSRIs should be limited to men with acquired PE secondary to co-morbid ED. New on-demand rapid acting SSRIs, oxytocin receptor antagonists, or single agents that target multiple receptors may form the foundation of more effective future on-demand medication. Current evidence confirms the efficacy and safety of dapoxetine, off-label SSRI drugs, tramadol and topical anaesthetics drugs. Treatment with α1-adrenoceptor antagonists cannot be recommended until the results of large well-designed RCTs are published in major international peer-reviewed medical journals. As our understanding of the neurochemical control of ejaculation improves, new therapeutic targets and candidate molecules will be identified which may increase our pharmacotherapeutic armamentarium.

Premature ejaculation: challenging new and the old concepts

“…Topical local anaesthetic agents are the oldest treatments for PE. However, they are often criticised for not being specifically optimised for PE, for being slow-acting, and for requiring the use of condoms to prevent partner transference and resultant partner hypoanaesthesia 64 , 65 . Topical eutectic mixture for PE (TEMPE, Plethora Solutions Ltd, Chalgrove, UK) was designed specifically for PE.…”

“…This is a drug used in the treatment of narcolepsy. Its mechanism of action is poorly understood but is thought to be via activation of central dopaminergic and serotonin pathways 65 , 96 . A sexual study in male rats has shown that the administration of D-modafinil resulted in a significant delay in ejaculation latency times 97 .…”

Lidocaine/prilocaine spray for premature ejaculation

“…For primary premature ejaculation, drugs may be used alongside psychosexual therapy 18,19. However, there are few studies on long-term efficacy,20 and in the UK, dapoxetine is the only drug other than lidocaine/prilocaine spray licensed for premature ejaculation 2…”

Introductory Chapter: Sexual Dysfunction - Introduction and Perspective

“…Treatment by selective serotonin reuptake inhibitors (SSRIs) has really led to a paradigm shift in the understanding and treatment of PE as all SSRIs exert ejaculation delaying effects in men with PE [8,9]. Although the treatment of PE by SSRIs is "off-label," it is the present therapy used for PE, notwithstanding the nonsexual side effects and the need to take the medication daily and permanently [10]. An ideal anti-PE medication would be "on demand," that can be taken shortly (hours) before sexual activity.…”

“…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]. Several other approaches for treatment of PE are used or are in development, including local anesthetics (e.g., lidocaine) used as cream, gel, or spray, and are moderately effective in delaying ejaculation [10]. Several other compounds with various mechanisms of action (tramadol, α 1 -adrenoceptor antagonists, oxytocin antagonists, modafinil, and botulin-A toxin) have been proposed in the treatment of PE but need extensive testing and will not reach the market soon.…”