Over the past 20-30 years, the Premature Ejaculation (PE) treatment paradigm, previously limited to behavioural psychotherapy, has expanded to include drug treatment. Animal and human sexual psychopharmacological studies have demonstrated that serotonin and 5-HT receptors are involved in ejaculation and confirm a role for SSRIs in the treatment of PE. Multiple well-controlled evidence-based studies have demonstrated the efficacy and safety of 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 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. Drug combinations of on-demand rapid acting SSRIs and 5-HT1A receptor antagonists and/or oxytocin receptor antagonists, or single agents that target multiple receptors may form the foundation of more effective future on-demand medication.