Advertisement

Drugs

, Volume 67, Issue 4, pp 547–568 | Cite as

Premature Ejaculation

Definition and Drug Treatment
  • Marcel D. Waldinger
Review Article

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.

Keywords

Paroxetine Oxytocin Tramadol Selective Serotonin Reuptake Inhibitor Clomipramine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

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.

References

  1. 1.
    Waldinger MD, Schweitzer DH. Changing paradigms from an historical DSM-III and DSM-IV view towards an evidence based definition of premature ejaculation: part I. Validity of DSM-IV-TR. J Sex Med 2006; 3: 682–92Google Scholar
  2. 2.
    Waldinger MD, Schweitzer DH. Changing paradigms from an historical DSM-III and DSM-IV view towards an evidence-based definition of premature ejaculation: part II. Proposals for DSM-V and ICD-11. J Sex Med 2006; 3: 693–705Google Scholar
  3. 3.
    Waldinger MD. The neurobiological approach to premature ejaculation. J Urol 2002; 168: 2359–67PubMedCrossRefGoogle Scholar
  4. 4.
    Waldinger MD. Lifelong premature ejaculation: from authority based to evidence based medicine. Br J Urol Internat Update Series 2004; 93: 201–7CrossRefGoogle Scholar
  5. 5.
    Waldinger MD. The need for a revival of psychoanalytic investigations into premature ejaculation. J Mens Health Gender 2006; 3: 390–6CrossRefGoogle Scholar
  6. 6.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th edition. Text revision. Washington, DC: American Psychiatric Association, 2000Google Scholar
  7. 7.
    World Health Organization. The ICD-10 classification of mental and behavioural disorders: diagnostic criteria for research. Geneva: World Health Organization, 1993Google Scholar
  8. 8.
    Waldinger MD, Hengeveld MW, Zwinderman AH. Paroxetine treatment of premature ejaculation: a double-blind, randomised, placebo-controlled study. Am J Psychiatry 1994; 151: 1377–9PubMedGoogle Scholar
  9. 9.
    Waldinger MD, Hengeveld MW, Zwinderman AH, et al. An empirical operationalization study of DSM-IV diagnostic criteria for premature ejaculation. Int J Psychiatry Clin Pract 1998; 2: 287–93CrossRefGoogle Scholar
  10. 10.
    Patrick DL, Althof SE, Pryor JL, et al. Premature ejaculation: an observational study of men and their partners. J Sex Med 2005; 2: 358–67PubMedCrossRefGoogle Scholar
  11. 11.
    Schapiro B. Premature ejaculation: a review of 1130 cases. J Urol 1943; 50: 374–9Google Scholar
  12. 12.
    Godpodinoff ML. Premature ejaculation: clinical subgroups and etiology. J Sex Marital Ther 1989; 15: 130–4PubMedCrossRefGoogle Scholar
  13. 13.
    Waldinger MD. Lifelong premature ejaculation: current debate on definition and treatment. J Mens Health Gender 2005; 2: 333–8CrossRefGoogle Scholar
  14. 14.
    Waldinger MD. Overview of premature and retarded ejaculation. Eur Urol Today 2005; 17: 20–2Google Scholar
  15. 15.
    Waldinger MD. Emerging drugs for premature ejaculation. Expert Opin Emerg Drugs 2006; 11: 99–109PubMedCrossRefGoogle Scholar
  16. 16.
    Screponi E, Carosa E, Stasi SM, et al. Prevalence of chronic prostatitis in men with premature ejaculation. Urology 2001; 58: 198–202PubMedCrossRefGoogle Scholar
  17. 17.
    Carani C, Isidori AM, Granata A, et al. Multicenter study on the prevalence of sexual symptoms in male hypo- and hyperthyroid patients. J Clin Endocrinol Metabol 2005; 90: 6472–9CrossRefGoogle Scholar
  18. 18.
    Lawrence JS, Madakasira S. Evaluation and treatment of premature ejaculation: a critical review. Int J Psychiatr Med 1992; 22: 77–97CrossRefGoogle Scholar
  19. 19.
    Althof SE. Psychological treatment strategies for rapid ejaculation: rationale, practical aspects, and outcome. World J Urol 2005; 23: 89–92PubMedCrossRefGoogle Scholar
  20. 20.
    Hartmann U, Schedlowski M, Kruger THC. Cognitive and partner-related factors in rapid ejaculation: differences between dysfunctional and functional men. World J Urol 2005; 23: 93–101PubMedCrossRefGoogle Scholar
  21. 21.
    Waldinger MD. Towards evidence-based drug treatment research on premature ejaculation: a critical evaluation of methodology. Int J Impot Res 2003; 15: 309–13PubMedCrossRefGoogle Scholar
  22. 22.
    Waldinger MD. Relevance of an evidence-based ejaculation time cutoff point for neurobiological research of premature ejaculation. J Comp Neurol 2005; 493: 46–50PubMedCrossRefGoogle Scholar
  23. 23.
    Waldinger MD, Zwinderman AH, Schweitzer DH, et al. Relevance of methodological design for the interpretation of efficacy of drug treatment of premature ejaculation: a systematic review and meta-analysis. Int J Impotence Res 2004; 16: 369–81CrossRefGoogle Scholar
  24. 24.
    Waldinger MD, Hengeveld MW, Zwinderman AH, et al. Effect of SSRI antidepressants on ejaculation: a double-blind, randomized, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine and sertraline. J Clin Psychopharmacol 1998; 18: 274–81PubMedCrossRefGoogle Scholar
  25. 25.
    Pico Costero J, Abreu de la Torre C, Roque Banos YL. Eyacula-cion precoz: tratamiento con tioridacina. Revista del Hospital Psiquiatrico de la Habana 1986; 27: 277–80Google Scholar
  26. 26.
    Hronek J, Kolomaznik M. Farmakoterapie prekotneho prubehu pohlavniho styku. Ceskoslovenska Psychiatrie 1986; 82: 303–6PubMedGoogle Scholar
  27. 27.
    Bartova D, Bouchai M. Thioridazine treatment of ejaculatio praecox. Act Nerv Super [Praha] 1965; 7: 244–5Google Scholar
  28. 28.
    Mellgren A. Treatment of ejaculatio praecox with thioridazine. Psychother Psychosom 1967; 15: 454–60CrossRefGoogle Scholar
  29. 29.
    Falaschi P, Rocco A, De Giorgio G, et al. Brain dopamine and premature ejaculation: results of treatment with dopamine antagonists. In: Gessa GL, Corsini GU, editors. Apomorphine and other dopaminomimetics. Vol. 1. Basic pharmacology. New York: Raven Press, 1981: 117–21Google Scholar
  30. 30.
    Wabrek AJ. Effect of metoclopramine on ejaculatory threshold in a group of premature ejaculators. Neurourol Urodyn 1984; 3: 155–61CrossRefGoogle Scholar
  31. 31.
    Greco E, Polonio-Balbi P, Speranza JC. Levosulpiride: a new solution for premature ejaculation. Int J Impot Res 2002; 14: 308–9PubMedCrossRefGoogle Scholar
  32. 32.
    Nielsen NP. L’ejaculazione precoce e il suo trattamento: nota preliminare sull’attivita’ del caroxazone. Rassegna di Studi Psichiatrici 1981; 70: 1065–80Google Scholar
  33. 33.
    Bennett D. Treatment of ejaculatio praecox with monoamine-oxidase inhibitors [letter]. Lancet 1961 Dec; 9: 1309CrossRefGoogle Scholar
  34. 34.
    Beretta G, Chelo E, Catanzaro F, et al. Trattamento con un alfa-bloccante (fenossibenzamina) della eiaculazione precoce. Minerva Urologica e Nefrologica 1988; 40: 29–32PubMedGoogle Scholar
  35. 35.
    Martinez Hurtado M, Gonzales Menendez R, Idelfonso Alavarez E, et al. La eyaculacion precoz: caracteristicas clinicas y respuesta al tratamiento con guanetidina. Revista del Hospital Psiquiatrico de la Habana 1981; 22: 105–16Google Scholar
  36. 36.
    Shilon M, Paz GF, Hommonai ZT. The use of phenoxybenzamine treatment in premature ejaculation. Fertil Steril 1984; 42: 659–61PubMedGoogle Scholar
  37. 37.
    Beretta G, Chelo E, Fanciullacci F, et al. Effect of an alpha-blocking agent (phenoxybenzamine) in the management of premature ejaculation. Acta Europaea Fertilitatis 1986; 17: 43–5PubMedGoogle Scholar
  38. 38.
    Cavallini G. Alpha-1 blockade pharmacotherapy in primitive psychogenic premature ejaculation resistant to psychotherapy. Eur Urol 1995; 28: 126–30PubMedGoogle Scholar
  39. 39.
    Waldinger MD, Olivier B. Utility of selective serotonin reuptake inhibitors in premature ejaculation. Curr Opin Investig Drugs 2004; 5: 743–7PubMedGoogle Scholar
  40. 40.
    Montague DK, Jarow J, Boderick GA, et al. AUA guidelines on the pharmacologic management of premature ejaculation. J Urol 2004; 172: 290–4PubMedCrossRefGoogle Scholar
  41. 41.
    McMahon CG, McMahon CN, Liang JL, et al. Efficacy of type-5 phosphodiesterase inhibitors in the drug treatment of premature ejaculation: a systematic review. BJU Int 2006; 98: 259–72PubMedCrossRefGoogle Scholar
  42. 42.
    Safarinejad MR, Hosseini SY. Safety and efficacy of tramadol in the treatment of premature ejaculation. J Clin Psychopharmacol 2006; 26: 27–31PubMedCrossRefGoogle Scholar
  43. 43.
    Eaton H. Clomipramine in the treatment of premature ejaculation. J Int Med Res 1973; 1: 432–4Google Scholar
  44. 44.
    Goodman RE. An assessment of clomipramine (Anafranil) in the treatment of premature ejaculation. J Int Med Res 1980; 3 Suppl.: 53–9Google Scholar
  45. 45.
    Porto R. Essai en double aveugle de la clomipramine dans l’ejaculation prematuree. Med Hyg 1981; 39: 1249–53Google Scholar
  46. 46.
    Girgis SM, El-Haggen S, El-Hermouzy S. A double-blind trial of clomipramine in premature ejaculation. Andrologia 1982; 14: 364–8PubMedCrossRefGoogle Scholar
  47. 47.
    Assalian P. Clomipramine in the treatment of premature ejaculation. J Sex Res 1988; 24: 213–5CrossRefGoogle Scholar
  48. 48.
    Althof SE, Levine SB, Corty EW, et al. A double-blind crossover trial of clomipramine for rapid ejaculation in 15 couples. J Clin Psychiatry 1995; 56: 402–7PubMedGoogle Scholar
  49. 49.
    Montorsi F, Guazzoni G, Trimboli F, et al. Clomipramine for premature ejaculation: a randomized, double blind, placebo controlled study. Acta Urol Ital 1995; 1: 5–6Google Scholar
  50. 50.
    Kim SC, Seo KK. Efficacy and safety of fluoxetine, sertraline and clomipramine in patients with premature ejaculation: a double-blind, placebo controlled study. J Urol 1998; 159: 425–7PubMedCrossRefGoogle Scholar
  51. 51.
    Kolomaznik M, Hronek J, Kolomaznik J, et al. Sertralin v leche ejaculatio praecox: Intermitentne nebo kontinualne? Psychiatrie C’slo 1998; 2: 244–6Google Scholar
  52. 52.
    Rowland DL, De Gouveia Brazao CA, Slob AK. Effective daily treatment with clomipramine in men with premature ejaculation when 25mg (as required) is ineffective. BJU Int 2001; 87: 357–60PubMedCrossRefGoogle Scholar
  53. 53.
    Ludovico GM, Corvase A, Pagliarulo G, et al. Paroxetine in the treatment of premature ejaculation. Br J Urol 1996, 2Google Scholar
  54. 54.
    Waldinger MD, Hengeveld MW, Zwinderman AH. Ejaculation retarding properties of paroxetine in patients with primary premature ejaculation: a double-blind, randomised, dose-response study. Br J Urol 1997; 79: 592–5PubMedCrossRefGoogle Scholar
  55. 55.
    Giammusso B, Morgia G, Spampinato A, et al. La paroxetina nel trattamento dell’eiaculazione precoce. Arch Ital Urol Androl 1997; 69: 11–3PubMedGoogle Scholar
  56. 56.
    McMahon CG, Tourna K. Treatment of premature ejaculation with paroxetine hydrochloride. Int J Impot Res 1999; 11: 241–5PubMedCrossRefGoogle Scholar
  57. 57.
    Waldinger MD, Zwinderman AH, Olivier B. Antidepressants and ejaculation: a double-blind, randomized, placebo-controlled, fixed-dose study with paroxetine, sertraline, and nefazodone. J Clin Psychopharmacol 2001; 21: 293–7PubMedCrossRefGoogle Scholar
  58. 58.
    Waldinger MD, Zwinderman AH, Olivier B. SSRIs and ejaculation: a double-blind, randomised, fixed-dose study with paroxetine and citalopram. J Clin Psychopharmacol 2001; 21: 556–60PubMedCrossRefGoogle Scholar
  59. 59.
    Waldinger MD, Zwinderman AH, Olivier B. Antidepressants and ejaculation: a double-blind, randomised, fixed-dose study with mirtazapine and paroxetine. J Clin Psychopharmacol 2003; 23: 467–70PubMedCrossRefGoogle Scholar
  60. 60.
    Waldinger MD, van De Plas A, Pattij T, et al. The SSRIs fluvoxamine and paroxetine differ in sexual inhibitory effects after chronic treatment. Psychopharmacology 2001; 160: 283–9CrossRefGoogle Scholar
  61. 61.
    Mendels J, Camera A, Sikes C. Sertraline treatment for premature ejaculation. J Clin Psychopharmacol 1995; 15: 341–6PubMedCrossRefGoogle Scholar
  62. 62.
    Kery S, Kozma A. Ejaculatio praecox citalopram kezelese. Magyar Urologia 1995; 7: 359–64Google Scholar
  63. 63.
    Kara H, Aydin S, Agargun Y, et al. The efficacy of fluoxetine in the treatment of premature ejaculation: a double-blind, placebo controlled study. J Urol 1996; 156: 1631–2PubMedCrossRefGoogle Scholar
  64. 64.
    Lee HS, Song DH, Kim CH, et al. An open clinical trial of fluoxetine in the treatment of premature ejaculation. J Clin Psychopharmacol 1996; 16: 379–82PubMedCrossRefGoogle Scholar
  65. 65.
    Raju GAR, Rani PU, Naidu MUR, et al. Evaluation of fluoxetine in premature ejaculation. Indian J Pharmacol 1997; 29: 204–5Google Scholar
  66. 66.
    Haensel SM, Klem TMAL, Hop WCJ, et al. Fluoxetine and premature ejaculation: a double-blind, crossover, placebo-controlled study. J Clin Psychopharmacol 1998; 18: 72–7PubMedCrossRefGoogle Scholar
  67. 67.
    Bid H, Isen K, Sinik Z, et al. Sertraline in the treatment of premature ejaculation: a double-blind placebo controlled study. Int Urol Nephrol 1998; 30: 611–5CrossRefGoogle Scholar
  68. 68.
    McMahon CG. Treatment of premature ejaculation with sertraline hydrochloride: a single-blind placebo controlled crossover study. J Urol 1998; 159: 1935–8PubMedCrossRefGoogle Scholar
  69. 69.
    McMahon CG. Treatment of premature ejaculation with sertraline hydrochloride. Int J Impot Res 1998; 10: 181–4PubMedCrossRefGoogle Scholar
  70. 70.
    Balbay MD, Yildiz M, Salvarci A, et al. Treatment of premature ejaculation with sertralin. Int Urol Nephrol 1998; 30: 81–3PubMedCrossRefGoogle Scholar
  71. 71.
    Basar MM, Atan A, Yildiz M, et al. Comparison of sertraline to fluoxetine with regard to their efficacy and side effects in the treatment of premature ejaculation. Arch Esp de Urol 1999; 52: 1008–11Google Scholar
  72. 72.
    Yilmaz U, Tatlisen A, Turan H, et al. The effects of fluoxetine on several neurophysiological variables in patients with premature ejaculation. J Urol 1999; 161: 107–11PubMedCrossRefGoogle Scholar
  73. 73.
    Atan A, Basar MM, Aydoganli L. Comparison of the efficacy of fluoxetine alone vs. fluoxetine plus local lidocaine ointment in the treatment of premature ejaculation. Arch Esp de Urol 2000; 53: 856–8Google Scholar
  74. 74.
    Kolomaznik M, Cervinka L, Kutilek S, et al. Fluoxetin v lecbe ejaculatio praecox. Psychiatrie 2002; 6: 6–9Google Scholar
  75. 75.
    Novaretti JPT, Pompeo ACL, Arap S. Selective serotonin uptake inhibitor in the treatment of premature ejaculation. Braz J Urol 2002; 28: 116–22Google Scholar
  76. 76.
    Atmaca M, Kuloglu M, Tezcan E, et al. The efficacy of citalopram in the treatment of premature ejaculation: a placebo-controlled study. Int J Impot Res 2002; 14: 502–5PubMedCrossRefGoogle Scholar
  77. 77.
    Safarinejad MR, Hosseini SY. Safety and efficacy of citalopram in the treatment of premature ejaculation: a double-blind, placebo-controlled, fixed dose, randomized study. Int J Impot Res 2006; 18: 164–9PubMedCrossRefGoogle Scholar
  78. 78.
    Waldinger MD. Drug treatment of premature ejaculation: pharmacodynamic and pharmacokinetic paradigms. Drug Discov Today 2005; 2: 37–40Google Scholar
  79. 79.
    Weinrieb RM, Auriacombe M, Lynch KG, et al. Selective serotonin re-uptake inhibitors and the risk of bleeding. Expert Opin Drug Saf 2005; 4: 337–44PubMedCrossRefGoogle Scholar
  80. 80.
    Ahmad S. Paroxetine-induced priapism [letter]. Arch Intern Med 1995; 155: 645PubMedCrossRefGoogle Scholar
  81. 81.
    Rand EH. Priapism in a patient taking sertraline [letter]. J Clin Psychiatry 1998; 59: 538PubMedCrossRefGoogle Scholar
  82. 82.
    Fava M, Judge R, Hoog SL, et al. Fluoxetine versus sertraline and paroxetine in major depressive disorder: changes in weight with long-term treatment. J Clin Psychiatry 2000; 61: 863–7PubMedCrossRefGoogle Scholar
  83. 83.
    Ditto KE. SSRI discontinuation syndrome; awareness as an approach to prevention. Postgrad Med 2003; 114: 79–84PubMedCrossRefGoogle Scholar
  84. 84.
    Black K, Shea C, Dursun S, et al. Selective serotonin reuptake inhibitor discontinuation syndrome; proposed diagnostic criteria. J Psychiatry Neurosci 2000; 25: 255–61PubMedGoogle Scholar
  85. 85.
    Borgherini G. The bioequivalence and therapeutic efficacy of generic versus brand-name psychoactive drugs. Clin Ther 2003; 25: 1578–92CrossRefGoogle Scholar
  86. 86.
    Vergouwen AC, Bakker A. Adverse effects after switching to a different generic form of paroxetine: paroxetine mesylate instead of paroxetine HCl hemihydrate [in Dutch]. Ned Tijdschr Geneesk 2002; 146: 811–2Google Scholar
  87. 87.
    Cavallini G. Alpha-1 blockade pharmacotherapy in primitive psychogenic premature ejaculation resistant to psychotherapy. Eur Urol 1995; 28: 126–30PubMedGoogle Scholar
  88. 88.
    Basar MM, Yilmaz E, Ferhat M, et al. Terazosin in the treatment of premature ejaculation: a short-term follow-up. Int Urol Nephrol 2005; 37: 773–7PubMedCrossRefGoogle Scholar
  89. 89.
    Buzelin JM, Fonteyne E, Kontturi MJ, et al. Comparison of tamsulosin with alfuzosin in the treatment of patients with lower urinary tract symptoms suggestive of bladder outlet obstruction (symptomatic benign prostatic hyperplasia). Br J Urol 1997; 80: 597–605PubMedCrossRefGoogle Scholar
  90. 90.
    Berkovitch M, Keresteci AG, Koren G. Efficacy of prilocaine-lidocaine cream in the treatment of premature ejaculation. J Urol 1995; 154: 1360–1PubMedCrossRefGoogle Scholar
  91. 91.
    Busato W, Galindo CC. Topical anaesthetic use for treating premature ejaculation: a double-blind, randomized, placebo-controlled study. BJU Int 2004; 93: 1018–21PubMedCrossRefGoogle Scholar
  92. 92.
    Segraves RT, Saran A, Segraves K, et al. Clomipramine vs placebo in the treatment of premature ejaculation: a pilot study. J Sex Marital Ther 1993; 19: 198–200PubMedCrossRefGoogle Scholar
  93. 93.
    Haensel SM, Rowland DL, Kalian KTHK, et al. Clomipramine and sexual function in men with premature ejaculation and controls. J Urol 1996; 156: 1310–5PubMedCrossRefGoogle Scholar
  94. 94.
    Strassberg DS, de Gouveia Brazao CA, Rowland DL, et al. Clomipramine in the treatment of rapid (premature) ejaculation. J Sex Marital Ther 1999; 25: 89–101PubMedCrossRefGoogle Scholar
  95. 95.
    Abdel-Hamid IA, El Naggar EA, El Gilany AH. Assessment of as needed use of pharmacotherapy and the pause-squeeze technique in premature ejaculation. Int J Impot Res 2001; 13: 41–5PubMedCrossRefGoogle Scholar
  96. 96.
    Waldinger MD, Zwinderman AH, Olivier B. On-demand treatment of premature ejaculation with clomipramine and paroxetine: a randomized, double-blind fixed-dose study with stopwatch assessment. Eur Urol 2004; 46: 510–6PubMedCrossRefGoogle Scholar
  97. 97.
    Kim SW, Paick JS. Short-term analysis of the effects of as needed use of sertraline at 5 PM for the treatment of premature ejaculation. Urology 1999; 54: 544–7PubMedCrossRefGoogle Scholar
  98. 98.
    McMahon C, Tourna K. Treatment of premature ejaculation with paroxetine hydrochloride as needed: 2 single-blind, placebo-controlled, crossover studies. J Urol 1999; 161: 1826–30PubMedCrossRefGoogle Scholar
  99. 99.
    Chia SJ. Management of premature ejaculation: a comparison of treatment outcomes in patients with and without erectile dysfunction. Int J Androl 2002; 25: 301–5PubMedCrossRefGoogle Scholar
  100. 100.
    Salonia A, Maga T, Colombo R, et al. A prospective study comparing paroxetine alone versus paroxetine plus sildenafil in patients with premature ejaculation. J Urol 2002; 168: 2486–9PubMedCrossRefGoogle Scholar
  101. 101.
    Pryor JL, Althof SE, Steidle C, et al. Efficacy and tolerability of dapoxetine in treatment of premature ejaculation: an integrated analysis of two double-blind, randomised controlled trials. Lancet 2006; 368: 929–37PubMedCrossRefGoogle Scholar
  102. 102.
    Waldinger MD, Schweitzer DH, Olivier B. On-demand SSRI treatment of premature ejaculation: pharmacodynamic limitations for relevant ejaculation delay and consequent solutions. J Sex Med 2005; 2: 120–30Google Scholar
  103. 103.
    Waldinger MD, Schweitzer DH, Olivier B. Dapoxetine treatment of premature ejaculation. Lancet. 2006; 368: 1869–70PubMedCrossRefGoogle Scholar
  104. 104.
    Frink MC, Hennies HH, Engelberger W, et al. Influence of tramadol on neurotransmitter systems of the rat brain. Arzneimittelforschung 1996; 46: 1029–36PubMedGoogle Scholar
  105. 105.
    Zhang XS, Wang YX, Huang XY, et al. Comparison between sildenafil plus sertraline and sertraline alone in the treatment of premature ejaculation. Zhanghua Nan Ke Xue 2005; 11: 520–2, 525Google Scholar
  106. 106.
    Chen J, Mabjeesh NJ, Matzkin H, et al. Efficacy of sildenafil as adjuvant therapy to selective serotonin reuptake inhibitor in alleviating premature ejaculation. Urology 2003; 61: 197–200PubMedCrossRefGoogle Scholar
  107. 107.
    Tang W, Ma L, Zhao L, et al. Clinical efficacy of Viagra with behaviour therapy against premature ejaculation. Zhanghua Nan Ke Xue 2004; 10: 366–7, 370Google Scholar
  108. 108.
    McMahon CG, Stuckey B, Andersen ML, et al. Efficacy of Viagra sildenafil citrate in men with premature ejaculation. J Sex Med 2005; 2: 368–75PubMedCrossRefGoogle Scholar
  109. 109.
    Li X, Zhang SX, Cheng HM, et al. Clinical study of sildenafil in the treatment of premature ejaculation complicated by erectile dysfunction. Zhanghua Nan Ke Xue 2003; 9: 266–9Google Scholar
  110. 110.
    Lozano AF. Premature ejaculation: pharmacological treatment. Three years after [abstract no. MP-2-6]. Int J Imp Res 2003; 15 Suppl. 6: S11Google Scholar
  111. 111.
    Sommer F, Klotz T, Mathers MJ. Treatment of premature ejaculation: a comparative vardenafil and SSRI crossover study [abstract no. 741]. J Urol 2005; 173 Suppl.: 202CrossRefGoogle Scholar
  112. 112.
    Mattos RM, Lucon AM. Tadalafil and slow-release fluoxetine in premature ejaculation: a prospective study [abstract no. 880]. J Urol 2005; 173 Suppl.: 239CrossRefGoogle Scholar
  113. 113.
    Erenpreiss J, Zalkalns J. Premature ejaculation: comparison of paroxetine alone, paroxetine plus local lidocaine and paroxetine plus sildenafil [abstract no. PS-7-4]. Int J Imp Res 2002; 14 Suppl. 4: S33Google Scholar
  114. 114.
    Linn R, Ginesin Y, Hardak S, et al. Treatment of sildenafil as part of the treatment in premature ejaculation [abstract no. P-168]. Int J Imp Res 2002; 14 Suppl. 4: S39Google Scholar
  115. 115.
    Atan A, Basar MM, Tuncel A, et al. Comparison of efficacy of sildenafil-only, sildenafil plus topical EMLA cream, and topical EMLA-cream-only in treatment of premature ejaculation. Urology 2006; 67: 388–91PubMedCrossRefGoogle Scholar
  116. 116.
    Fein RL. Intracavernous medication for treatment of premature ejaculation. Urology 1990; 35: 301–3PubMedCrossRefGoogle Scholar
  117. 117.
    Waldinger MD, Berendsen HHG, Blok BFM, et al. Premature ejaculation and SSRI-induced delayed ejaculation: the involvement of the serotonergic system. Behav Brain Res 1998; 92: 111–8PubMedCrossRefGoogle Scholar
  118. 118.
    Olivier B, van Oorschot R, Waldinger MD. Serotonin, serotonergic receptors, selective serotonin reuptake inhibitors and sexual behaviour. Int Clin Psychopharmacol 1998; 13 Suppl. 6: S9–14PubMedCrossRefGoogle Scholar
  119. 119.
    Fuller RW. Uptake inhibitors increase extracellular serotonin concentration measured by brain microdialysis. Life Sci 1994; 55: 163–7PubMedCrossRefGoogle Scholar
  120. 120.
    Mos J, Mollet I, Tolboom JT, et al. A comparison of the effects of different serotonin reuptake blockers on the sexual behaviour of the male rat. Eur Neuropsychopharmacol 1999; 9: 123–35PubMedCrossRefGoogle Scholar
  121. 121.
    Blier P, de Montigny C. Electrophysiological investigations on the effect of repeated zimelidine administration on serotonergic neurotransmission in the rat. J Neurosci 1983; 3: 1270–8PubMedGoogle Scholar
  122. 122.
    Chaput Y, Blier P, de Montigny C. In vivo electrophysiological evidence for the regulatory role of autoreceptors on serotoninergic terminals. J Neurosci 1986; 6: 2796–801PubMedGoogle Scholar
  123. 123.
    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 Schmiedeberg’s Arch Pharmacol 1988; 337: 246–54CrossRefGoogle Scholar
  124. 124.
    Cantor J, Binik I, Pfaus JG. Chronic fluoxetine inhibits sexual behaviour in the male rat: reversal with oxytocin. Psychopharmacology 1999; 144: 355–62PubMedCrossRefGoogle Scholar
  125. 125.
    Frank JL, Hendricks SE, Olson CH. Multiple ejaculations and chronic fluoxetine: effects on male rat copulatory behaviour. Pharmacol Biochem Behav 2000; 66: 337–42PubMedCrossRefGoogle Scholar
  126. 126.
    de Jong TR, Veening JG, Olivier B, et al. Oxytocin involvement in SSRI-induced delayed ejaculation: a review of animal studies. J Sex Med 2007; 4: 14–28PubMedCrossRefGoogle Scholar
  127. 127.
    de Wied D, Diamant M, Fodor M. Central nervous system effects of the neurohypophyseal hormones and related peptides. Front Neuroendocrinol 1993; 14: 251–302PubMedCrossRefGoogle Scholar
  128. 128.
    Hallbeck M, Larhammar D, Blomqvist A. Neuropeptide expression in rat paraventricular hypothalamic neurons that project to the spinal cord. J Comp Neurol 2001; 433: 222–38PubMedCrossRefGoogle Scholar
  129. 129.
    Carter CS. Oxytocin and sexual behavior. Neurosci Biobehav Rev 1992; 16: 131–44PubMedCrossRefGoogle Scholar
  130. 130.
    Benoussaidh A, Maurin Y, Rampin O. Possible neural mediation of the central effects of oxytocin on uterine motility. Am J Physiol Regul Integr Comp Physiol 2005; 289: R798–804PubMedCrossRefGoogle Scholar
  131. 131.
    Carmichael MS, Humbert R, Dixen J, et al. Plasma oxytocin increases in the human sexual response. J Clin Endocrinol Metab 1987; 64: 27–31PubMedCrossRefGoogle Scholar
  132. 132.
    Kruger TH, Haake P, Chereath D, et al. Specificity of the neuroendocrine response to orgasm during sexual arousal in men. J Endocrinol 2003; 177: 57–64PubMedCrossRefGoogle Scholar
  133. 133.
    Murphy MR, Seckl JR, Burton S, et al. Changes in oxytocin and vasopressin secretion during sexual activity in men. J Clin Endocrinol Metab 1987; 65: 738–41PubMedCrossRefGoogle Scholar
  134. 134.
    Uckert S, Becker AJ, Ness BO, et al. Oxytocin plasma levels in the systemic and cavernous blood of healthy males during different penile conditions. World J Urol 2003; 20: 323–6PubMedGoogle Scholar
  135. 135.
    Stoneham MD, Everitt BJ, Hansen S, et al. Oxytocin and sexual behaviour in the male rat and rabbit. J Endocrinol 1985; 107: 97–106PubMedCrossRefGoogle Scholar
  136. 136.
    Hughes AM, Everitt BJ, Lightman SL, et al. Oxytocin in the central nervous system and sexual behaviour in male rats. Brain Res 1987; 414: 133–7PubMedCrossRefGoogle Scholar
  137. 137.
    Honda K, Yanagimoto M, Negoro H, et al. 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: 309–13PubMedCrossRefGoogle Scholar
  138. 138.
    Yanagimoto M, Honda K, Goto Y, et al. Afferents originating from the dorsal penile nerve excite oxytocin cells in the hypothalamic paraventricular nucleus of the rat. Brain Res 1996; 733: 292–6PubMedCrossRefGoogle Scholar
  139. 139.
    Arletti R, Benelli A, Bertolini A. Sexual behavior of aging male rats is stimulated by oxytocin. Eur J Pharmacol 1990; 179: 377–81PubMedCrossRefGoogle Scholar
  140. 140.
    Filippi S, Vannelli GB, Granchi S, et al. Identification, localization and functional activity of oxytocin receptors in epididymis. Mol Cell Endocrinol 2002; 193: 89–100PubMedCrossRefGoogle Scholar
  141. 141.
    Vignozzi L, Filippi S, Luconi M, et al. Oxytocin receptor is expressed in the penis and mediates an estrogen-dependent smooth muscle contractility. Endocrinology 2004; 145: 1823–34PubMedCrossRefGoogle Scholar
  142. 142.
    Mens WB, Witter A, an Wimersma Greidanus TB. Penetration of neurohypophyseal hormones from plasma into cerebrospinal fluid (CSF): half-times of disappearance of these neuropeptides from CSF. Brain Res 1983; 262: 143–9PubMedCrossRefGoogle Scholar
  143. 143.
    Waldinger MD, Rietschel M, Nothen MM, et al. Familial occurrence of primary premature ejaculation. Psychiatr Genet 1998; 8: 37–40PubMedCrossRefGoogle Scholar
  144. 144.
    Waldinger MD. Lifelong premature ejaculation: definition, serotonergic neuro-transmission and drug treatment. World J Urol 2005; 23: 102–8PubMedCrossRefGoogle Scholar
  145. 145.
    Waldinger MD, Quinn P, Dilleen M, et al. A multi-national population survey of intravaginal ejaculation latency time. J Sex Med 2005; 2: 492–7PubMedCrossRefGoogle Scholar
  146. 146.
    Waldinger MD, Zwinderman AH, Olivier B, et al. Proposal for a definition of lifelong premature ejaculation based on epidemiological stopwatch data. J Sex Med 2005; 2: 498–507PubMedCrossRefGoogle Scholar
  147. 147.
    Williamson IJR, Turner L, Woods K, et al. The 5-HT1a receptor antagonist robalzotan enhances SSRI-induced ejaculation delay in the rat [abstract]. Br J Pharmacol 2003; 138 Suppl. 1: PO32Google Scholar
  148. 148.
    de Jong TR, Pattij T, Veening JG, et al. Citalopram combined with WAY 100635 inhibits ejaculation and ejaculation-related Fos immunoreactivity. Eur J Pharmacol 2005; 509: 49–59PubMedCrossRefGoogle Scholar
  149. 149.
    Cremers TIFH, de Boer P, Liao Y, et al. Augmentation with a 5-HT1a, but not a 5-HT1b receptor antagonist, critically depends on the dose of citalopram. Eur J Pharmacol 2000; 397: 63–74PubMedCrossRefGoogle Scholar
  150. 150.
    Johansson L, Sohn D, Thorberg SO, et al. The pharmacological characterization of a novel selective 5-hydroxytryptamine 1A receptor antagonist, NAD-299. J Pharmacol Exp Ther 1997; 283: 216–25PubMedGoogle Scholar
  151. 151.
    de Jong TR, Pattij T, Veening JG, et al. Effects of chronic selective serotonin reuptake inhibitors on 8-OH-DPAT-induced facilitation of ejaculation in rats: comparison of fluvoxamine and paroxetine. Psychopharmacology (Berl) 2005; 179: 509–15CrossRefGoogle Scholar
  152. 152.
    Olivier B, Chan JS, Pattij T, et al. Psychopharmacology of male rat sexual behavior: modeling human sexual dysfunctions? Int J Impot Res. Epub 2005 Apr 21Google Scholar
  153. 153.
    Waldinger MD, Olivier B. Animal models of premature and retarded ejaculation. World J Urol 2005; 23: 115–8PubMedCrossRefGoogle Scholar
  154. 154.
    Pattij T, de Jong T, Uitterdijk A, et al. Individual differences in male rat ejaculatory behavior: searching for models to study ejaculation disorders. Eur J Neurosci 2005; 22: 724–34PubMedCrossRefGoogle Scholar
  155. 155.
    Pattij T, Olivier B, Waldinger MD. Animal models of ejaculatory behaviour. Curr Pharm Des 2005; 11: 4069–77PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  1. 1.Department of Psychiatry and NeurosexologyHagaHospital LeyenburgThe HagueThe Netherlands
  2. 2.Department of Psychopharmacology, Faculty of Pharmaceutical Sciences and Rudolf Magnus Institute for NeurosciencesUtrecht UniversityUtrechtThe Netherlands

Personalised recommendations