Urodynamic Measurement of Urethral Closure Function in Women with Stress Urinary Incontinence: A Randomized, Double-Blind, Single-Dose, Two-Period Crossover Study of Duloxetine

Objectives: Duloxetine, a serotonin and noradrenaline reuptake inhibitor, has been approved for the treatment of stress urinary incontinence (SUI) in women in the European Union, but not in the United States or Japan where newer drugs are under development. The present urodynamic study in women with SUI was performed to evaluate the effect of duloxetine on urethral function and to determine an appropriate method for making go/no-go decisions in early clinical studies of new drugs under development for SUI treatment.Methods: A randomized, double-blind, single-dose, two-period crossover study of 40 mg duloxetine was conducted in 10 women with SUI (≥1 episode/wk). The urethral pressure profiles at rest and during coughing, Valsalva leak point pressure, and leakage in a 20-min pad test were measured before and 6 hr after administration of duloxetine or placebo.Results: Although a single oral dose of duloxetine did not affect Valsalva leak point pressure or leakage in a pad test, this drug significantly increased the mean and maximal urethral closure pressures at rest calculated over the entire urethra, compared with placebo. During coughing, duloxetine significantly increased the mean closure pressure and the change from baseline in maximal amplitude of negative closure pressure spike in the distal third of the urethra, compared with placebo.Conclusions: The facilitatory effect of duloxetine on urethral closure function was confirmed in women with SUI, suggesting the usefulness of the method used in this urodynamic study. Thus, the proposed method is potentially useful to reduce attrition rate by providing decision-making data in early clinical studies of new drugs being developed for treating SUI.