New Drug for Overactive Bladder Lacks Cognitive Side Effects


ORLANDO, FLA. — Darifenacin, a selective muscarinic M3 receptor antagonist approved last month for the treatment of overactive bladder, doesn't affect cognition in the elderly at clinically effective doses, Richard B. Lipton, M.D., reported at Wonca 2004, the conference of the World Organization of Family Doctors.

Darifenacin (Enablex) thus stands in marked contrast to traditional antimuscarinic agents, which are effective for overactive bladder but have a high rate of limiting cognitive side effects due to their broad spectrum of action. Older antimuscarinic drugs lack selectivity for the M3 receptor, which regulates detrusor muscle function, and often cause collateral blockade of central muscarinic M1 receptors, with resultant cognitive impairment and sleepiness, explained Dr. Lipton, professor and vice chair of neurology and professor of psychiatry at Albert Einstein College of Medicine, New York.

The Food and Drug Administration approved darifenacin extended-release tablets at once daily doses of 7.5 mg and 15 mg last month The drug, which is being marketed by Novartis, is indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency.

At the meeting Dr. Lipton presented a Novartis-sponsored randomized controlled trial of darifenacin that focused on the drug's cognitive impact rather than on clinical efficacy, which has already been established in numerous clinical trials totaling more than 10,000 subjects.

He reported on 129 subjects aged 65-84 years who participated in a randomized, double-blind, placebo-controlled crossover study in which they received 2-week courses of three of four regimens: darifenacin at 3.75, 7.5, or 15 mg once daily, or placebo.

The primary study end points consisted of scores on a battery of cognitive function tests assessing memory scanning sensitivity, speed-of-choice reaction time, and delayed word recognition sensitivity.

There was no change from baseline in mean scores on any of the cognitive tests over the course of 14 days of darifenacin at any of the studied dosages. Nor were test scores while on darifenacin significantly different than with placebo.

The most common darifenacin-related adverse events were mild to moderate non-treatment-limiting constipation and dry mouth, each of which was reported in 4%-12% of patients on various dosages.

There were no ECG abnormalities, which can occur with blockade of the muscarinic M2 receptor.

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