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

Abstract

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.

Deleterious effects of selective serotonin reuptake inhibitor treatment on semen parameters in patients with lifelong premature ejaculation

“…15 A systematic review and meta-analysis of all drug treatment studies confirmed the therapeutic benefits of SSRIs on PE. 16 On the basis of this meta-analysis, SSRIs increase geometric mean intravaginal ejaculatory latency times 2.6-to 13.2-fold. 16 On the basis of animal and human studies, Waldinger et al 17--19 postulated that lifelong PE is a neurobiological disorder related to decreased central serotonergic neurotransmission, 5-HT 2C receptor hyposensitivity and/or 5-HT 1A hypersensitivity.…”

“…16 On the basis of this meta-analysis, SSRIs increase geometric mean intravaginal ejaculatory latency times 2.6-to 13.2-fold. 16 On the basis of animal and human studies, Waldinger et al 17--19 postulated that lifelong PE is a neurobiological disorder related to decreased central serotonergic neurotransmission, 5-HT 2C receptor hyposensitivity and/or 5-HT 1A hypersensitivity. At least three serotonin receptor subtypes have been identified as having a role in ejaculation, where activation of the 5-HT 1A receptor has a proejaculatory effect but activation of the 5-HT 1B and 5-HT 2C receptors delay ejaculation.…”

Current therapeutic strategies for premature ejaculation and future perspectives

“…The rank order of efficacy, as defined by the increase in IELT, was as follows: paroxetine, sertraline, clomipramine, fluoxetine and placebo. 15 However, the author has highlighted the unreliability of IELT and the absence of patient-reported outcomes as clear weaknesses of this meta-analysis.…”

“…A meta-analysis has shown that daily use of clomipramine increases intravaginal ejaculatory latency time (IELT) by 4.6-fold, which is not statistically different from the effect of sertraline or fluoxetine. 15 In three double-blind, placebo-controlled crossover studies, [22][23][24] on-demand use of clomipramine (25 mg; 12-24 h before intercourse) significantly increased the IELT by approximately fourfold in PE patients. However, only the smallest of these three trials used an objective stopwatch technique for measuring the IELT.…”

“…A systematic review and meta-analysis revealed 79 publications on drug treatment for PE involving 3034 men between 1943 14 and 2003. 15 A recent meta-analysis showed that, in spite of a trend towards more evidence-based research on drug treatments, the majority of studies for PE still lack adequate design and methodology. 16 Current and widely accepted pharmacological treatment options for PE include antidepressive agents, topical desensitizing agents, phosphodiesterase type 5 inhibitors (PDE-5Is) and a-receptor blockers.…”