Anticholinergics and central nervous system effects: are we confused?

Abstract

The central nervous system (CNS) effects of anticholinergic agents have been documented in various patient populations and to varying degrees in case reports, brain-activity surrogates, and computerized cognitive testing. The older patient population with overactive bladder represents a group at increased risk of cognitive impairment and other CNS side effects associated with antimuscarinic agents. The complexity of the effect of anticholinergic agents on CNS function requires an increased level of careful investigation. Studies need to be performed in the at-risk population with multiple, validated tests at clinically prescribed doses in acute and chronic situations. These studies need to take into account the effect of commonly prescribed dosing regimens, with doses selected to represent with equivalent bladder potency. The alterations in the serum levels and parent/metabolite effects contributed by metabolic issues or drug delivery systems require special attention.

Keywords: Antimuscarinic drugs; CNS adverse events; Cognitive impairment; Elderly; Overactive bladder.

Figure 1

OXY and N-DEO steady-state plasma concentrations. Transdermal delivery provides a more stable serum level and favorably alters the parent compound oxybutynin to the metabolite N-DEO levels. *Extrapolated concentrations from a single OXY-IR dose of 5 mg/d. N-DEO, N-desethyloxybutynin; OXY, oxybutynin. Data from Guay DR and, New K and Appell RA, et al.