Central nervous system safety of anticholinergic drugs for the treatment of overactive bladder in the elderly.
BACKGROUND
Overactive bladder (OAB) is characterized by urgency and increased frequency of micturition, with or without urinary urge incontinence. Anticholinergic agents are important in the treatment of OAB. However, concerns have emerged about their central nervous system (CNS) safety and the associated risk of cognitive impairment.


OBJECTIVE
This article describes the CNS adverse effects of anticholinergic drugs used for the treatment of OAB, with particular emphasis on their use in the elderly. Its objective is to help physicians make optimal choices when selecting anticholinergic treatment for OAB.


METHODS
: Relevant data from the literature were identified primarily through a MEDLINE search of articles published through December 2003. The search terms included overactive bladder, central nervous system, anticholinergic, and antimuscarinic. This was not intended to be a systematic review, and articles were chosen for inclusion based on their pertinence to the focus on treatment of OAB in the elderly.


RESULTS
Several anticholinergic drugs are available for the treatment of OAB, including oxybutymn, tolterodine, trospium chloride, and propiverine (not available in the United States). Among the agents reviewed, penetration of the blood-brain barrier (as predicted by lipophilicity, polarity, and molecular size and structure) is highest for oxybutymn, lower for tolterodine, and lowest for trospium chloride; limited data are available for propiverine. The total anticholinergic drug burden may also be important in determining the potential for CNS adverse effects. The spectrum of anticholinergic CNS adverse effects ranges from drowsiness to hallucinations, severe cognitive impairment, and even coma. The immediate-release (IR) and extended-release (ER) formulations of oxybutynin have been associated with cognitive impairment. In the only published clinical trial that was identified, no significant differences in CNS adverse effects were observed between the IR and ER formulations of tolterodine. There were few clinical data on the use of propiverine in patients with OAB. Trospium chloride has shown favorable CNS tolerability in postmarketing surveillance studies.


CONCLUSIONS
When considering treatment choices for patients with OAB, particularly the elderly, the potential CNS adverse effects of each anticholinergic agent must be weighed against the severity of OAB symptoms.
Scheife
Richard
R
Department of Neurology, Tufts University School of Medicine, Boston, Massachusetts, USA. rtsbmw@aol.com
Takeda
Masayuki
M
D000368:Aged; D001812:Blood-Brain Barrier / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects*; D018680:Cholinergic Antagonists / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003692:Delayed-Action Preparations; D006801:Humans; D009422:Nervous System Diseases / Q000139:chemically induced*; D014549:Urinary Incontinence / Q000188:drug therapy*
D018680:Cholinergic Antagonists; D003692:Delayed-Action Preparations