A prescribing cascade involving cholinesterase inhibitors and anticholinergic drugs.

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.

[1]  A. Flint,et al.  Urinary Incontinence Associated with Dementia , 1995, Journal of the American Geriatrics Society.

[2]  E. Antman,et al.  Adherence to national guidelines for drug treatment of suspected acute myocardial infarction: evidence for undertreatment in women and the elderly. , 1996, Archives of internal medicine.

[3]  C. Mackenzie,et al.  A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. , 1987, Journal of chronic diseases.

[4]  J. Ioannidis,et al.  Completeness of safety reporting in randomized trials: an evaluation of 7 medical areas. , 2001, JAMA.

[5]  A. Lerner,et al.  Adverse effects of donepezil in treating Alzheimer's disease associated with Down's syndrome. , 1999, The American journal of psychiatry.

[6]  L. Fried,et al.  Diagnosis of Illness Presentation in the Elderly , 1991, Journal of the American Geriatrics Society.

[7]  H. Petri,et al.  Prescription sequence analysis: a new and fast method for assessing certain adverse reactions of prescription drugs in large populations. , 1988, Statistics in medicine.

[8]  D. Berlowitz,et al.  Geriatric Syndromes as Outcome Measures of Hospital Care: Can Administrative Data Be Used? , 1999, Journal of the American Geriatrics Society.

[9]  J. Tu,et al.  Use of beta-blocker therapy in older patients after acute myocardial infarction in Ontario. , 1999, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[10]  Andreas Laupacis,et al.  Inclusion of drugs in provincial drug benefit programs: who is making these decisions, and are they the right ones? , 2002, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[11]  C Krogh,et al.  "Compendium of pharmaceuticals and specialties". , 1983, Canadian Medical Association journal.

[12]  J. Playfer,et al.  Lesson of the week: Oxybutynin and cognitive dysfunction , 1997 .

[13]  M. Beers,et al.  Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a US consensus panel of experts. , 2003, Archives of internal medicine.

[14]  R. Tamblyn,et al.  Defining inappropriate practices in prescribing for elderly people: a national consensus panel. , 1997, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[15]  D. Redelmeier,et al.  The treatment of unrelated disorders in patients with chronic medical diseases. , 1998, The New England journal of medicine.

[16]  Paula Rochon,et al.  Improving the quality of medication use in elderly patients: a not-so-simple prescription. , 2002, Archives of internal medicine.

[17]  C. Roe,et al.  How Many Patients Complete an Adequate Trial of Donepezil? , 2002, Alzheimer disease and associated disorders.

[18]  M Maclure,et al.  Performance of comorbidity scores to control for confounding in epidemiologic studies using claims data. , 2001, American journal of epidemiology.

[19]  Jerry H Gurwitz,et al.  Optimising drug treatment for elderly people: the prescribing cascade , 1997, BMJ.

[20]  E. Mori,et al.  Urinary incontinence: an unrecognised adverse effect with donepezil , 2000, The Lancet.

[21]  C. Roe,et al.  Use of Anticholinergic Medications by Older Adults with Dementia , 2002, Journal of the American Geriatrics Society.

[22]  P. Herbison,et al.  Effectiveness of anticholinergic drugs compared with placebo in the treatment of overactive bladder: systematic review , 2003, BMJ : British Medical Journal.

[23]  L. Tune,et al.  Chronic exposure to anticholinergic medications adversely affects the course of Alzheimer disease. , 2003, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[24]  L Goldman,et al.  Adverse Outcomes of Underuse of β-Blockers in Elderly Survivors of Acute Myocardial Infarction , 1997 .

[25]  K. Edwards,et al.  RISK OF DELIRIUM WITH CONCOMITANT USE OF TOLTERODINE AND ACETYLCHOLINESTERASE INHIBITORS , 2002, Journal of the American Geriatrics Society.

[26]  S. Stanton,et al.  Regular review: management of urinary incontinence in women. , 2000, BMJ.

[27]  Paul Grootendorst,et al.  Coding accuracy of administrative drug claims in the Ontario Drug Benefit database. , 2003, The Canadian journal of clinical pharmacology = Journal canadien de pharmacologie clinique.

[28]  I. Katz,et al.  Identification of Medications That Cause Cognitive Impairment in Older People: The Case of Oxybutynin Chloride , 1998, Journal of the American Geriatrics Society.

[29]  S. Inouye,et al.  Cognitive and other adverse effects of diphenhydramine use in hospitalized older patients. , 2001, Archives of internal medicine.