Green SA et al. (2006) Efficacy and safety of a neurokinin-1 receptor antagonist in postmenopausal women with overactive bladder with urge urinary incontinence. J Urol 176: 2535–2540

Tachykinins such as substance P (an agonist of NK-1, neurokinin receptor 1) are neurotransmitters involved in the micturition reflex, which suggests that NK-1 antagonists might be an effective treatment for urge incontinence. Aprepitant (currently used to treat chemotherapy-induced nausea and vomiting) is a potent NK-1 antagonist that acts in the central nervous system.

Green and colleagues' double-blind, randomized, placebo-controlled pilot study (in 26 US centers) evaluated 125 postmenopausal women (mean age 64.8 years) with overactive bladder syndrome and urge incontinence. After a 1-week run-in period on placebo, patients were randomly allocated to receive either 160 mg aprepitant (n = 61) or placebo (n = 64) as a once-daily tablet for 8 weeks. Patients recorded their symptoms in a validated voiding diary, and were followed up 1, 2, 4 and 8 weeks after randomization. Compared with placebo, aprepitant markedly reduced the mean number of daily micturitions from baseline (by 6.8%) and incidence of urgency episodes (by 13.2%) over the 8-week study. The magnitude of these effects was similar to that previously reported for antimuscarinic agents—the preferred treatment for overactive bladder syndrome. Aprepitant also consistently improved patients' perceived leakage and the bother of their symptoms, and was generally well tolerated; dry mouth occurred in only four aprepitant-treated patients.

The authors speculate that aprepitant acts at the spinal cord to inhibit bladder sensorial input and raise the signal threshold necessary to initiate micturition. This mechanism of action differs from that of antimuscarinic or antispasmodic medications.