Risks Associated with Long-Term Anticholinergic Medication Use

Cognitive and Neurological Risks

Anticholinergic medications can cause significant cognitive impairment, including memory problems, confusion, and delirium, especially in older adults due to age-related decline in acetylcholine physiology 1, 2
The cognitive effects of anticholinergic burden are more pronounced in patients over 75 years of age 1, 3

Anticholinergic medications commonly cause physical adverse effects including dry mouth and eyes 4, 5
These medications can cause constipation and gastrointestinal disturbances 1, 5
Anticholinergic medications can cause urinary retention and bladder dysfunction 1, 5
These medications significantly increase fall risk in older adults, which can lead to fractures and subdural hematomas 4, 5
Functional decline is common with long-term use, with decreased activities of daily living (ADL) scores documented in multiple studies 1, 3

These medications may worsen hypertension and complicate blood pressure management 6, 3
When combined with other CNS-active substances, anticholinergics can cause enhanced performance impairment and sedation 4, 7
In men, anticholinergics can exacerbate benign prostatic hyperplasia symptoms 5

The cumulative effect of multiple anticholinergic medications significantly increases risk of adverse outcomes 1, 2
Studies show that approximately one-third of independent living older adults and half of those in long-term care facilities take medications with anticholinergic properties that may be unnecessary 2
Specific medication classes with strong anticholinergic effects include older antihistamines (e.g., diphenhydramine, hydroxyzine) 1, 4
Muscle relaxants (e.g., cyclobenzaprine) have strong anticholinergic effects 1, 6

Older adults are more sensitive to anticholinergic effects due to physiological changes in aging 1, 5
The Beers Criteria and STOPP/START criteria identify many anticholinergic medications as potentially inappropriate for older adults 1, 2
Anticholinergic medications in older adults are associated with increased emergency department visits 1
These medications are associated with higher hospitalization rates in older adults 1, 3
Anticholinergic medications are associated with greater healthcare costs in older adults 1

Avoid anticholinergic medications in older adults whenever possible, particularly those with existing cognitive impairment, dementia risk factors, or narrow-angle glaucoma 1, 2
When treating allergic conditions, second-generation antihistamines are preferred over first-generation antihistamines due to reduced anticholinergic effects 4, 5
For patients requiring anticholinergic medications, use the lowest effective dose for the shortest duration possible 8
Regularly review medication regimens to identify and reduce anticholinergic burden, particularly in older adults 2
For patients with overactive bladder, consider topical anticholinergic agents rather than systemic ones to minimize cognitive side effects 5

The American Geriatrics Society recommends avoiding oxybutynin in adults aged 65 years and older due to significant risk of cognitive impairment, delirium, and dementia 9
The 2019 American Geriatrics Society Beers Criteria specifically identifies anticholinergic medications as potentially inappropriate for older adults due to drug-disease interactions 9
Older adults are more susceptible to anticholinergic effects due to reduced renal function and medication clearance, with a higher likelihood of polypharmacy and potential drug interactions 10

The American Diabetes Association recommends annual screening for cognitive impairment in adults 65 years of age or older, using validated screening tools such as the Mini-Mental State Examination or the Montreal Cognitive Assessment 11
Patients with diabetes and older adults are at particularly high risk for cognitive impairment when using anticholinergic medications 12, 13

The Canadian Consensus Conference on Dementia (2020) recommends that exposure to highly anticholinergic medications, including diphenhydramine, be minimized in older persons, with alternative agents used instead (Grade 1B, 100 % consensus). [14][15]
The Mayo Clinic Polypharmacy Guidelines (2021) identify diphenhydramine (and hydroxyzine) as first‑generation antihistamines that cause central nervous system impairment—delirium, slowed comprehension, sedation, and increased fall risk—in older adults. 16
The American Academy of Allergy, Asthma & Immunology (AAAI) Guidelines on Mast Cell Disorders (2019) warn that H1‑blocking antihistamines with anticholinergic activity have been associated with cognitive decline, especially in elderly populations. 17

Immediate discontinuation of diphenhydramine is advised for all adults ≥ 65 years and for anyone with existing cognitive impairment, mild cognitive impairment, or dementia. (Evidence: strong consensus from the Canadian Consensus Conference.) 14
Substitution with second‑generation antihistamines such as fexofenadine or cetirizine is recommended for allergic conditions, as these agents lack anticholinergic effects and do not cross the blood‑brain barrier. (AAAI guideline) 17
Annual cognitive screening of adults ≥ 65 years using validated tools (e.g., Mini‑Mental State Examination or Montreal Cognitive Assessment) is advised to detect early impairment. (Diabetes Care recommendation) 18

Adults ≥ 65 years should avoid diphenhydramine because of the documented increased risk of dementia, accelerated cognitive decline, and delirium. (Canadian Consensus + Mayo Clinic evidence) [14][16]
Patients with diabetes are at heightened baseline risk for cognitive decline and should also avoid diphenhydramine. (Diabetes Care) 18

Using diphenhydramine as a sleep aid in older adults is discouraged due to its sedating properties and the associated unacceptable risk of cognitive impairment; safer non‑anticholinergic alternatives are available. (Mayo Clinic guideline) 16