Tolerability and Optimal Therapeutic Dosage of Clomipramine for Premature Ejaculation: A Systematic Review and Meta-Analysis

Abstract

Introduction Clomipramine is effective in treating premature ejaculation, a common form of male sexual dysfunction that affects individual's mental health and quality of life, but its optimal dosage remains controversial. Aim In this systematic review and meta-analysis, we aimed to evaluate the efficacy, safety, and optimal dose of clomipramine for treating premature ejaculation among men. Methods Eligible studies of PubMed, Embase, and Web of Science were identified from the date of inception to June 21, 2020. We conducted the study according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data of the study characteristics, intravaginal latency ejaculatory time (IELT), adverse events, success rate, and satisfaction rate of clomipramine vs placebo were extracted and analyzed. The risk ratio and mean difference were used for quantitatively analyzing binary outcomes and continuous outcomes. The standardized mean difference was applied to the outcome of satisfaction rate. The Mantel–Haenszel method was used for meta-analysis under random-effects model. To assess dose effect of clomipramine, a meta-regression analysis was performed. Main Outcome Measures The primary outcomes were the IELT and adverse events, and the secondary outcomes were the success rate and satisfaction rate of clomipramine treatment relative to the placebo. Results A total 14 randomized controlled trials with 710 patients were included for quantitative analysis. Clomipramine significantly increased the IELT compared with the placebo (mean difference: 1.47, 95% CI: 0.73–2.21). However, clomipramine was associated with higher risks of overall adverse events and adverse events in the nervous and respiratory systems. Significant dosage effects on the IELT (estimate: 0.0637, 95% CI: 0.0074–0.12) and a slightly increasing slope on adverse events were revealed. Conclusion Clomipramine increased the IELT and yielded greater satisfaction than the placebo, and the higher dose results in a superior IELT without leading to higher risk of adverse events under a dosage of 50-mg clomipramine.

European Association of Urology Guidelines on Sexual and Reproductive Health—2021 Update: Male Sexual Dysfunction

“…Of all, several systematic reviews and meta-analyses of drug treatment studies showed that, despite methodological problems in most studies, daily SSRIs are significantly effective for PE [3,176,182]. Paroxetine was found to be superior to fluoxetine, clomipramine, and sertraline [3,[183][184][185][186]. Likewise, tramadol, a mild opioid receptor agonist that also promotes reuptake inhibition of serotonin and noradrenaline, has been demonstrated to be effective as an off-label on-demand oral therapy in men with a history of lifelong PE [3,187,188].…”

Ocular Abnormalities in Patients with Vitiligo: A Systematic Review and Meta-Analysis

“…The types of eligible studies included cross-sectional, case-control, and cohort studies. Two experienced reviewers (S.-H. Ma and P.-C. Wu) independently performed the literature search, data extraction, and quality assessment [9, 17, 18]. Any disagreement was resolved by consensus among the reviewers or referred to a third reviewer (Y.-X.…”

Comparison of fluoxetine with other selective serotonin reuptake inhibitors in the treatment of premature ejaculation: A systematic review and meta‐analysis

“…Our clinical findings and literature analysis suggest that not all patients respond to dapoxetine and experience varying degrees of withdrawal (Mondaini et al, 2013). Sertraline, paroxetine, citalopram and clomipramine all can prevent central serotonin uptake and are used to treat premature ejaculation (Arafa et al, 2006; Rezakhaniha et al, 2014; Salonia et al, 2009; Wu et al, 2021). Fluoxetine is a serotonin reuptake inhibitor that induces delayed ejaculation by reducing vasoconstriction while simultaneously increasing central serotonin levels (Giuliano, 2007).…”