Anticholinergics for overactive bladder therapy: central nervous system effects

CNS Neurosci Ther. 2012 Feb;18(2):167-74. doi: 10.1111/j.1755-5949.2011.00248.x. Epub 2011 Feb 16.


The mainstay of pharmacological treatment of overactive bladder (OAB) is anticholinergic therapy using muscarinic receptor antagonists (tertiary or quaternary amines). Muscarinic receptors in the brain play an important role in cognitive function, and there is growing awareness that antimuscarinic OAB drugs may have adverse central nervous system (CNS) effects, ranging from headache to cognitive impairment and episodes of psychosis. This review discusses the physicochemical and pharmacokinetic properties of OAB antimuscarinics that affect their propensity to cause adverse CNS effects, as observed in phase III clinical trials and in specific investigations on cognitive function and sleep architecture. PubMed/MEDLINE was searched for "OAB" plus "muscarinic antagonists" or "anticholinergic drug." Additional relevant literature was identified by examining the reference lists of papers identified through the search. Preclinical and clinical trials in adults were assessed, focusing on the OAB antimuscarinics approved in the United States. The blood-brain barrier (BBB) plays a key role in protecting the CNS, but it is penetrable. The lipophilic tertiary amines, particularly oxybutynin, are more likely to cross the BBB than the hydrophilic quaternary amine trospium chloride, for which there are very few reports of adverse CNS effects. In fact, in 2008 the US product labels for oral oxybutynin were modified to include the potential for anticholinergic CNS events and a warning to monitor patients for adverse CNS effects. Even modest cognitive impairment in the elderly may negatively affect independence; therefore, selection of an antimuscarinic OAB drug with reduced potential for CNS effects is advisable.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism
  • Central Nervous System / drug effects*
  • Central Nervous System / metabolism
  • Cholinergic Antagonists / adverse effects*
  • Cholinergic Antagonists / metabolism
  • Cholinergic Antagonists / therapeutic use
  • Cognition Disorders / chemically induced
  • Cognition Disorders / metabolism
  • Humans
  • Sleep Wake Disorders / chemically induced
  • Sleep Wake Disorders / metabolism
  • Urinary Bladder, Overactive / drug therapy*
  • Urinary Bladder, Overactive / metabolism


  • Cholinergic Antagonists