Efficacy and safety of a neurokinin-1 receptor antagonist in postmenopausal women with overactive bladder with urge urinary incontinence.

PURPOSE: Urge urinary incontinence is the involuntary leakage of urine commonly occurring in older adults, particularly women. Preclinical evidence suggests that urge urinary incontinence may occur due to up-regulation of tachykinin mediated bladder/spinal reflex signaling. This study tested the hypothesis that aprepitant, a neurokinin-1 receptor antagonist, may be efficacious in the treatment of urge urinary incontinence. MATERIALS AND METHODS: This was a double-blind, randomized, placebo controlled, parallel group pilot study in which postmenopausal women with a history of urge urinary incontinence or mixed incontinence (with predominantly urge urinary incontinence) were assigned to receive a 160 mg capsule of aprepitant (61) or placebo (64) once daily for 8 weeks. The primary end point was percent change from baseline in average daily micturitions assessed by a voiding diary. Secondary end points included average daily total urinary incontinence and urge urinary incontinence episodes, and urgency episodes. RESULTS: Aprepitant significantly decreased the average daily number of micturitions compared with placebo at 8 weeks. The between-group treatment difference expressed as percent change from baseline was -6.8%, 95% CI (-12.5, -1.1) (p = 0.019). The average daily number of urgency episodes was also significantly reduced compared to placebo (p = 0.049). The average daily number of urge urinary incontinence and total urinary incontinence episodes were also reduced, although the difference was not statistically significant. Aprepitant was generally well tolerated and adverse experiences were generally mild. CONCLUSIONS: Results of this initial study suggest that neurokinin-1 receptor antagonism may represent a novel therapeutic approach to treating overactive bladder syndrome.

Measurement characteristics of a voiding diary for use by men and women with overactive bladder.

OBJECTIVES: To examine the test-retest reliability and the validity of a voiding diary designed to assess the symptoms of frequency, urgency, and urge urinary incontinence (UI). METHODS: Voiding diaries serve as the primary tool to assess symptoms of overactive bladder in clinical settings and in clinical trials of treatment for overactive bladder. Despite the widespread use of these instruments, few studies have documented their measurement properties or investigated the number of days required to assess symptoms accurately. Study participants included 21 men and 133 women at least 20 years of age recruited from urogynecology and urology clinics. All had a history of urge incontinence or mixed incontinence with urge as the primary component. Participants completed a 7-day voiding diary on two occasions, separated by at least 1 week. RESULTS: Men and women reported a daily average of approximately 10 micturitions, 7 occurrences of strong urge, and 2 episodes of urge urinary incontinence. The diary exhibited good to excellent reliability, with estimated intraclass correlation coefficients (ICCs) ranging from 0.81 to 0.86 for the symptoms of strong urge, diurnal and nocturnal micturitions, total incontinence, and urge incontinence episodes. Estimates did not differ appreciably between men and women. Moderate correlations with global questions on micturition frequency and UI episodes supported the validity of the diary. Diaries completed for 3 and 4 days were similar, with only slightly lower estimates of reliability (ICC 0.79 to 0.84). CONCLUSIONS: The voiding diary completed for 7 days, following detailed instruction, is reliable and appears to be valid for documenting the change in symptoms of overactive bladder in men and women with predominantly urge incontinence. Because of comparable reliability and reduced patient burden, diaries of shorter duration may also be acceptable to assess the symptoms of overactive bladder, depending on the degree of precision required.