Original Research

International Journal of Impotence Research (2004) 16, 369–381. doi:10.1038/sj.ijir.3901172 Published online 12 February 2004

Relevance of methodological design for the interpretation of efficacy of drug treatment of premature ejaculation: a systematic review and meta-analysis

M D Waldinger1,2, A H Zwinderman3, D H Schweitzer4 and B Olivier2,5

  1. 1Department of Psychiatry and Neurosexology, Leyenburg Hospital, The Hague, The Netherlands
  2. 2Department of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute for Neurosciences, Faculty of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
  3. 3Department of Medical Statistics, Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  4. 4Department of Internal Medicine and Endocrinology, Reinier de Graaf Groep, Delft-Voorburg, The Netherlands
  5. 5Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA

Correspondence: MD Waldinger, MD, PhD, Leyenburg Hospital, Psychiatry and Neurosexology, Leyweg 275, The Hague 2545 CH, The Netherlands. E-mail: md@waldinger.demon.nl

Received 16 May 2003; Revised 15 October 2003; Accepted 27 October 2003; Published online 12 February 2004.



The aim of this systematic review and meta-analysis is to evaluate whether the design and methodology of drug-treatment studies of premature ejaculation affect the efficacy outcome differently. Therefore, methodological, design and efficacy data from 79 studies (3034 males), published between 1943 and 2003, are reviewed. A meta-analysis is performed on 43 selective serotonin reuptake inhibitors (SSRIs) and clomipramine studies (1514 males), published between 1973 and 2003; these studies were pooled to provide a summary variance-weighted effect size. The antidepressant-induced percentage increase of the intravaginal ejaculation latency time (IELT) was calculated and examined against various methodological items. A significant difference in efficacy between SSRIs was observed. Using daily treatment, paroxetine appeared more effective than the other SSRIs. Retrospective use of a questionnaire, subjective reports, single-blind and open study designs generate far greater variability of ejaculation time both at baseline and during active drug treatment than real time assessment by stopwatch. In conclusion, at daily treatment, the overall efficacy of paroxetine, clomipramine, sertraline and fluoxetine is comparable, but paroxetine exerts the strongest ejaculation delay. Only eight (18.5%) studies on antidepressant treatment fulfilled all criteria used in evidence-based medicine, for example, randomised, double-blind studies with prospective real time (stopwatch) assessment of the IELT at each intercourse. Single-blind studies, open designs, retrospective reporting, or the use of a questionnaire to assess ejaculation time should be avoided.


premature ejaculation, meta-analysis, paroxetine, SSRI, serotonin



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