Premature Ejaculation: Definition and Drug Treatment

Overview

Journal Drugs

Specialty Pharmacology

Date 2007 Mar 14

PMID 17352514

Citations 28

Authors

Marcel D Waldinger

Affiliations

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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-HT(1A) 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.

Citing Articles

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References

Arletti R, Benelli A, Bertolini A . Sexual behavior of aging male rats is stimulated by oxytocin. Eur J Pharmacol. 1990; 179(3):377-81. DOI: 10.1016/0014-2999(90)90178-9. View

Mos J, Mollet I, Tolboom J, Waldinger M, Olivier B . A comparison of the effects of different serotonin reuptake blockers on sexual behaviour of the male rat. Eur Neuropsychopharmacol. 1999; 9(1-2):123-35. DOI: 10.1016/s0924-977x(98)00015-7. View

Fuller R . Uptake inhibitors increase extracellular serotonin concentration measured by brain microdialysis. Life Sci. 1994; 55(3):163-7. DOI: 10.1016/0024-3205(94)00876-0. View

Olivier B, Chan J, Pattij T, de Jong T, Oosting R, Veening J . Psychopharmacology of male rat sexual behavior: modeling human sexual dysfunctions?. Int J Impot Res. 2005; 18 Suppl 1:S14-23. DOI: 10.1038/sj.ijir.3901330. View

Balbay M, Yildiz M, Salvarci A, Ozsan O, Ozbek E . Treatment of premature ejaculation with sertralin. Int Urol Nephrol. 1998; 30(1):81-3. DOI: 10.1007/BF02550283. View

Waldinger M, Schweitzer D . Changing paradigms from a historical DSM-III and DSM-IV view toward an evidence-based definition of premature ejaculation. Part II--proposals for DSM-V and ICD-11. J Sex Med. 2006; 3(4):693-705. DOI: 10.1111/j.1743-6109.2006.00276.x. View

Rowland D, de Gouveia Brazao C, Slob A . Effective daily treatment with clomipramine in men with premature ejaculation when 25 mg (as required) is ineffective. BJU Int. 2001; 87(4):357-60. DOI: 10.1046/j.1464-410x.2001.00112.x. View

Waldinger M . Relevance of an evidence-based ejaculation time cutoff point for neurobiological research of premature ejaculation. J Comp Neurol. 2005; 493(1):46-50. DOI: 10.1002/cne.20718. View

Salonia A, Maga T, Colombo R, Scattoni V, Briganti A, Cestari A . A prospective study comparing paroxetine alone versus paroxetine plus sildenafil in patients with premature ejaculation. J Urol. 2002; 168(6):2486-9. DOI: 10.1016/S0022-5347(05)64174-2. View

10.

Honda K, Yanagimoto M, Negoro H, Narita K, Murata T, Higuchi T . Excitation of oxytocin cells in the hypothalamic supraoptic nucleus by electrical stimulation of the dorsal penile nerve and tactile stimulation of the penis in the rat. Brain Res Bull. 1999; 48(3):309-13. DOI: 10.1016/s0361-9230(98)00180-4. View

11.

Cavallini G . Alpha-1 blockade pharmacotherapy in primitive psychogenic premature ejaculation resistant to psychotherapy. Eur Urol. 1995; 28(2):126-30. DOI: 10.1159/000475036. View

12.

Waldinger M, Zwinderman A, Olivier B . Antidepressants and ejaculation: a double-blind, randomized, placebo-controlled, fixed-dose study with paroxetine, sertraline, and nefazodone. J Clin Psychopharmacol. 2001; 21(3):293-7. DOI: 10.1097/00004714-200106000-00007. View

13.

McMahon C, Touma K . Treatment of premature ejaculation with paroxetine hydrochloride as needed: 2 single-blind placebo controlled crossover studies. J Urol. 1999; 161(6):1826-30. View

14.

Johansson L, Sohn D, Thorberg S, Jackson D, Kelder D, Larsson L . The pharmacological characterization of a novel selective 5-hydroxytryptamine1A receptor antagonist, NAD-299. J Pharmacol Exp Ther. 1997; 283(1):216-25. View

15.

CHAPUT Y, Blier P, De Montigny C . In vivo electrophysiological evidence for the regulatory role of autoreceptors on serotonergic terminals. J Neurosci. 1986; 6(10):2796-801. PMC: 6568801. View

16.

Ahmad S . Paroxetine-induced priapism. Arch Intern Med. 1995; 155(6):645. View

17.

Greco E, Polonio-Balbi P, Speranza J . Levosulpiride: a new solution for premature ejaculation?. Int J Impot Res. 2002; 14(4):308-9. DOI: 10.1038/sj.ijir.3900901. View

18.

Godpodinoff M . Premature ejaculation: clinical subgroups and etiology. J Sex Marital Ther. 1989; 15(2):130-4. DOI: 10.1080/00926238908403817. View

19.

Blier P, CHAPUT Y, De Montigny C . Long-term 5-HT reuptake blockade, but not monoamine oxidase inhibition, decreases the function of terminal 5-HT autoreceptors: an electrophysiological study in the rat brain. Naunyn Schmiedebergs Arch Pharmacol. 1988; 337(3):246-54. DOI: 10.1007/BF00168834. View

20.

Atan A, Basar M, Tuncel A, Ferhat M, Agras K, Tekdogan U . Comparison of efficacy of sildenafil-only, sildenafil plus topical EMLA cream, and topical EMLA-cream-only in treatment of premature ejaculation. Urology. 2006; 67(2):388-91. DOI: 10.1016/j.urology.2005.09.002. View