Preserving cognitive function for patients with overactive bladder: evidence for a differential effect with darifenacin.
BACKGROUND
Antimuscarinic agents used in the treatment of overactive bladder (OAB) differ in their potential to impair cognitive function. It is hypothesised that low brain concentrations and relatively low selectivity for the M(1) muscarinic receptor may reduce the potential for adverse central nervous system (CNS) effects with darifenacin, compared with other antimuscarinics, particularly oxybutynin.


METHODS
Cognitive function studies evaluating darifenacin, oxybutynin, tolterodine, solifenacin and/or trospium were identified from publications databases (Medline, Biosis and Embase) and congress abstracts. Preclinical studies and randomised controlled trials in adults were reviewed.


RESULTS
Five randomised, double-blind, multiple-dose studies of cognitive function were identified. Oxybutynin was consistently associated with cognitive deficit (four studies), whereas darifenacin did not impair cognition (three studies). These findings were supported by data from sleep/attention and EEG studies. Tolterodine data were limited to one small study with each formulation. For solifenacin and trospium, there were no human studies evaluating memory, the cognitive function most vulnerable to CNS anticholinergics.


CONCLUSIONS
There is compelling evidence of cognitive impairment with oxybutynin, whereas darifenacin stands out by demonstrating no impairment of memory or other cognitive functions in three randomised, controlled trials. This may be attributed to the differences in physicochemical properties, efflux mechanisms and relative M(1) muscarinic receptor sparing. The risk of CNS impairment is of particular concern for vulnerable populations such as the elderly (a substantial proportion of the OAB population), and CNS-compromised neurogenic bladder patients such as those with multiple sclerosis or Parkinson's disease.
Kay
G G
GG
Cognitive Research Corporation, Saint Petersburg, FL 33701, USA. gkay@cogres.com
Ebinger
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D000328:Adult; D000368:Aged; D000818:Animals; D001572:Benzofurans / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002490:Central Nervous System / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011759:Pyrrolidines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016032:Randomized Controlled Trials as Topic; D051381:Rats; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000523:psychology
D001572:Benzofurans; D018727:Muscarinic Antagonists; D011759:Pyrrolidines; C101207:darifenacin