Frequently Prescribed Medications Linked to Increased Dementia Risk

FEBRUARY 01, 2015

Medications with strong anticholinergic activity can increase the risk of developing dementia, according to the results of a prospective cohort study published in JAMA Internal Medicine.


Medications with anticholinergic activity, including diphenhydramineoxybutynin, tolterodine, and doxepin, are commonly prescribed to older adults for conditions such as seasonal allergies, insomnia, overactive bladder, and depression. Although the American Geriatric Society does not recommend the regular use of anticholinergic medications in the elderly, their prevalence ranges from 8% to 37%. 


Researchers enrolled a total of 3434 participants aged 65 years or older with no dementia at study initiation. The objective of the study was to examine the association between 10-year cumulative anticholinergic use and the risk for dementia.


Dementia was screened at study entry and each biennial study visit using the Cognitive Abilities Screening Instrument. Anticholinergic exposure was defined as the total standardized daily doses (TSDDs) dispensed in the past 10 years. Cumulative exposure was updated as participants were followed up over time.


After analysis of the data, an increased risk for dementia and Alzheimer disease (AD) was seen in patients with higher use of anticholinergics. During a mean follow-up of 7.3 years, 797 participants (23.2%) developed dementia, while 637 (79.9%) were considered to have possible or probable AD.


Individuals in the highest anticholinergic exposure group had a statistically increased risk for dementia (adjusted HR=1.54; 95% CI=1.21-1.96) or AD (adjusted HR=1.63; 95% CI=1.24-2.14) compared with those with no use. Participants in the next 2 highest exposure levels had slightly elevated risks for dementia or AD compared with no use; however, the results were not statistically significant.


Additionally, it was found that participants with past anticholinergic use had a dementia risk similar to those with greater recent or continuous use. This suggests that the risk for dementia associated with these drugs may not be reversible after patients stop taking them.


The most common anticholinergic classes used in the study were tricyclic antidepressants, first-generation antihistamines, and bladder antimuscarinics, which comprised >90% of all anticholinergic exposure. The most common drugs prescribed from these 3 classes were doxepin, chlorpheniramine, and oxybutynin.


"Prescribers should be aware of this potential association when considering anticholinergics for their older patients and should consider alternatives when possible," the authors wrote. "For conditions with no therapeutic alternatives, prescribers should use the lowest effective dose and discontinue therapy if ineffective.” 


The authors also emphasized the importance of counseling older adults about the safety risk of OTC products with anticholinergic activity, such as diphenhydramine, the active ingredient in Benadryl. Instead of taking these medications, older adults should work with their health care professionals to find alternatives to minimize overall anticholinergic use.

Timothy O'Shea, PharmD
Timothy O'Shea, PharmD
Timothy O'Shea, PharmD, is a Clinical Pharmacist working at a large health insurance plan on the east coast. Additionally he works per diem at a retail pharmacy chain. He graduated from MCPHS University - Boston in 2015 and subsequently completed a PGY-1 Managed Care Pharmacy Residency. His professional interests include pharmacy legislation and managed care pharmacy. He can be followed on Twitter at @toshea125.
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