ORIGINAL RESEARCH—EJACULATORY DISORDERS: On-Demand SSRI Treatment of Premature Ejaculation: Pharmacodynamic Limitations for Relevant Ejaculation Delay and Consequent Solutions

Authors

  • Marcel D. Waldinger MD, PhD,

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    1. Department of Psychiatry and Neurosexology, Leyenburg Haga Hospital, The Hague, the Netherlands;
    2. Department of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute for Neurosciences, Utrecht University, Utrecht, the Netherlands;
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  • Dave H. Schweitzer MD, PhD,

    1. Department of Internal Medicine and Endocrinology, Reinier de Graaf Groep Hospital, Delft-Voorburg, the Netherlands;
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  • Berend Olivier PhD

    1. Department of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute for Neurosciences, Utrecht University, Utrecht, the Netherlands;
    2. Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA
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Marcel D. Waldinger, MD, PhD, Department of Psychiatry and Neurosexology, Leyenburg Haga Hospital, The Hague, the Netherlands. Tel: +31 70 3594902; Fax: +31 70 3594902; E-mail: md@waldinger.demon.nl

ABSTRACT

Introduction.  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.

Aim.  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-HT1A receptor antagonists. In addition, we critically reviewed existing on-demand SSRI treatments publications and the current debate on a definition of premature ejaculation.

Main Outcome Measures.  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-HT1A receptor antagonists significantly increases the ejaculation time acutely compared to acute SSRI monoadministration.

Conclusion.  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-HT1A 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.

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