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Premature Ejaculation

Definition and Drug Treatment

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Abstract

Premature ejaculation (PE) is a frequent male sexual complaint that is mediated mainly by disturbances of serotonergic neurotransmission and certain serotonin (5-HT) receptors and, to a lesser extent, oxytocinergic neurotransmission in the CNS.

The current Diagnostic Manual of Mental Disorders (fourth edition, revised text) [DSM-IV-TR] definition of PE has a low positive predictive value and is inadequate for clinical, epidemiological and drug treatment research. Categorisation of PE into four well defined syndromes has recently been proposed for the pending DSM (fifth edition) definition of PE.

Over the last decade, an increasing number of studies of drug treatment of PE have been published. A meta-analysis of those studies, conducted in accordance with current standards of evidence-based medicine, demonstrated similar efficacies for daily treatment with the serotonergic antidepressants paroxetine hemihydrate, clomipramine, sertraline and fluoxetine, with paroxetine (hydrochloride) hemihydrate exerting the strongest effect on ejaculation. On the basis of fundamental insights into serotonergic neurotransmission, it has been suggested that on-demand selective serotonin reuptake inhibitor (SSRI) treatment will not lead to similarly impressive delays in ejaculation as has been observed with daily SSRI treatment. Indeed, some on-demand studies with SSRIs and studies with the new SSRI dapoxetine have shown a weak ejaculation-delaying effect after 1–2 hours of drug intake. Apart from daily treatment with SSRIs, PE can be delayed by on-demand use of topical anaesthetics and tramadol. Treatment with phosphodiesterase type 5 inhibitors should not be prescribed to men with PE with normal erectile function, but may be used if PE is accompanied by erectile difficulties. There is no scientific support for treatment of PE with intracavernous injection of vasoactive drugs.

Animal studies have shown that strong immediate ejaculation delay may be induced by administration of a combination of an SSRI with a serotonin 5-HT1A receptor antagonist. The combination of an SSRI and any other compound that immediately and potently raises serotonin neurotransmission and/or use of oxytocin receptor antagonists may form the basis for the development of new on-demand and/or daily drugs for the treatment of PE.

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Acknowledgements

No sources of funding were used to assist in the preparation of this review. The author has no conflicts of interest that are directly relevant to the content of this review.

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  1. Department of Psychiatry and Neurosexology, HagaHospital Leyenburg, Leyweg 275, 2545 CH, The Hague, The Netherlands

    Marcel D. Waldinger

  2. Department of Psychopharmacology, Faculty of Pharmaceutical Sciences and Rudolf Magnus Institute for Neurosciences, Utrecht University, Utrecht, The Netherlands

    Marcel D. Waldinger

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Waldinger, M.D. Premature Ejaculation. Drugs 67, 547–568 (2007). https://doi.org/10.2165/00003495-200767040-00005

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