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A Computerized Test Battery to Study Pharmacodynamic Effects on the Central Nervous System of Cholinergic Drugs in Early Phase Drug Development
Published on: February 11, 2019
A prescribing cascade involving cholinesterase inhibitors and anticholinergic drugs
Sudeep S Gill1, Muhammad Mamdani, Gary Naglie
1Institute for Clinical Evaluative Sciences, Toronto, Ontario. gills@pccchealth.org
Background:
The prescribing cascade model involves the misinterpretation of an adverse reaction to 1 drug and the subsequent, potentially inappropriate prescription of a second drug. We present a new example of the prescribing cascade involving cholinesterase inhibitors and anticholinergic drugs used to manage urinary incontinence.
Methods:
A population-based retrospective cohort study was carried out in Ontario, Canada. Participants included 44,884 older adults with dementia (20,491 were dispensed a cholinesterase inhibitor and 24,393 were not), enrolled between June 1, 1999, and March 31, 2002. Subjects were observed until they received an anticholinergic drug, stopped the cholinesterase inhibitor treatment, died, or the study period ended (March 31, 2003). The main outcome measure was receipt of an anticholinergic drug to manage urinary incontinence.
Results:
After adjusting for potential confounding factors, we observed that older adults with dementia who were dispensed cholinesterase inhibitors had an increased risk of subsequently receiving an anticholinergic drug (4.5% vs 3.1%; P<.001; adjusted hazard ratio, 1.55; 95% confidence interval, 1.39-1.72), relative to those not receiving cholinesterase inhibitors. This finding was consistent in a series of subgroup analyses.
Conclusions:
Use of cholinesterase inhibitors is associated with an increased risk of receiving an anticholinergic drug to manage urinary incontinence. The use of an anticholinergic drug in this setting may represent a clinically important prescribing cascade. Clinicians should consider the possible contributing role of cholinesterase inhibitors in new-onset or worsening urinary incontinence and the potential risk of coprescribing cholinesterase inhibitors and anticholinergic drugs to patients with dementia.
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