title: On-demand SSRI treatment of premature ejaculation: pharmacodynamic limitations for relevant ejaculation delay and consequent solutions.
abstract: BACKGROUND
  Recently, the idea has emerged that on-demand use of serotonin reuptake inhibitors (SSRIs), particularly short half-life, should be equally effective in delaying ejaculation as daily SSRI treatment of premature ejaculation.
  
  
  OBJECTIVE
  To provide evidence that SSRI-induced ejaculation delay is mainly dependent on pharmacodynamic properties of the drug and hardly on pharmacokinetic factors, and that combined SSRI administration with specific 5-hydroxytryptamine (5-HT) receptor antagonism leads acutely to stronger ejaculation delay than acute SSRI monoadministration.
  
  
  METHODS
  We performed a detailed analysis of serotonin neurotransmission and reviewed animal studies with 5-HT(1A) receptor antagonists. In addition, we critically reviewed existing on-demand SSRI treatments publications and the current debate on a definition of premature ejaculation.
  
  
  METHODS
  Intravaginal ejaculation latency time (IELT).
  
  
  RESULTS
  Acute SSRI administration leads to only a mild or no increase of 5-HT neurotransmission and concomitant stimulation of postsynaptic 5-HT receptors. Existing on-demand SSRI treatment studies suffer from methodological insufficiencies, and the reported high-fold increases of ejaculation time contradict with neuropharmacological insights from serotonin metabolism. Animal studies show that SSRI coadministration with 5-HT(1A) receptor antagonists significantly increases the ejaculation time acutely compared to acute SSRI monoadministration.
  
  
  CONCLUSIONS
  On-demand SSRI treatment has less ejaculation-delaying effects than daily SSRI treatment. SSRIs with a short half-life are likely leading to much less ejaculation delay than current registered SSRIs. Combined use of SSRIs with 5-HT(1A) receptor antagonists increases the likelihood of clinically relevant ejaculation delay after on-demand treatment. On-demand SSRIs with short half-life that insufficiently delay ejaculation in men with IELTs less than 1 minute should be called ejaculation-delaying drugs rather than drugs against premature ejaculation.
authors.affiliation: Department of Psychiatry and Neurosexology, Leyenburg Haga Hospital, The Hague, the Netherlands. md@waldinger.demon.nl
authors.forename: Marcel D
authors.initials: MD
authors.lastname: Waldinger
authors.forename: Dave H
authors.initials: DH
authors.lastname: Schweitzer
authors.forename: Berend
authors.initials: B
authors.lastname: Olivier
mesh_terms: D000818:Animals; D004334:Drug Administration Schedule; D004542:Ejaculation / Q000187:drug effects*; D006207:Half-Life; D006801:Humans; D008297:Male; D008959:Models, Neurological; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D012735:Sexual Dysfunction, Physiological / Q000188:drug therapy*
chemical_list: D011985:Receptors, Serotonin; D017367:Selective Serotonin Reuptake Inhibitors