Management of Anticholinergic Burden in Older Adults

Epidemiology and Clinical Impact

The Mayo Clinic recommends immediate deprescribing of strongly anticholinergic medications in older adults because they are linked to cognitive decline, delirium, falls, and functional impairment. 1
Anticholinergic use in the elderly is associated with measurable declines in activities of daily living (ADL) scores. 1
Injurious falls are more frequent in older patients with a high anticholinergic burden. 1
Episodes of confusion or delirium increase proportionally with cumulative anticholinergic exposure. 1
Higher anticholinergic burden leads to more emergency‑department visits and hospital admissions. 1
Age‑related decline in central acetylcholine activity is further suppressed by anticholinergic drugs, worsening cognitive outcomes. 1
Comorbid conditions such as elevated intra‑ocular pressure, benign prostatic hypertrophy, and pre‑existing cognitive impairment raise the risk of anticholinergic complications. 2
Older adults with anticholinergic exposure have a greater incidence of falls, fractures, and subdural hematomas. 2

First‑generation antihistamines (e.g., diphenhydramine) and muscle relaxants (e.g., cyclobenzaprine) are among the strongest anticholinergic agents and should be targeted first for deprescribing. [1][3]
Diphenhydramine is frequently abused for its sedative and hallucinogenic effects at high doses. [1][3]
Hydroxyzine impairs driving performance, an effect that is amplified when using a cellular phone. [2][3]
Cyclobenzaprine possesses potent anticholinergic properties and is sometimes misused. [1][3]
Oxybutynin adds substantially to anticholinergic load and worsens cognition, particularly in elderly women with overactive bladder. [1][3]

The Mayo Clinic advises using the Anticholinergic Drug Scale or the Anticholinergic Cognitive Burden Scale (updated 2012) to quantify each patient’s anticholinergic load. 1
Calculation of a Drug Burden Index provides a composite measure of cumulative effects on cognition, functional status, and ADL performance. 1

Immediate supportive care with continuous cardiorespiratory monitoring is essential in anticholinergic toxidrome. 4
Continuous cardiac monitoring for dysrhythmias, core‑temperature surveillance, and serial ECGs (to detect QRS widening from possible tricyclic co‑ingestion) are required. 4
Benzodiazepines are the first‑line agents for agitation; antipsychotics should be avoided because they exacerbate anticholinergic effects. [5][4]
Aggressive external cooling should be instituted if the patient develops hyperthermia. 4
Intravenous fluid resuscitation is indicated for hypotension. 4
Activated charcoal may be administered when the airway is protected and the patient can safely swallow. 4
Physostigmine is the specific antidote for life‑threatening anticholinergic toxicity and should be reserved for severe cases. [5][4]
Physical restraints must be avoided, as they worsen hyperthermia and lactic acidosis. [5][4]

Identify all anticholinergic agents using the scales above, then prioritize discontinuation of those with the strongest anticholinergic activity (e.g., diphenhydramine, cyclobenzaprine, oxybutynin). [1][3]
Tailor deprescribing decisions to individual functional status, support needs, living environment, and overall care plan. 1
For allergic rhinitis, replace first‑generation antihistamines with second‑generation agents (fexofenadine, loratadine, desloratadine) that do not cause sedation at recommended doses. 2
Behavioral symptoms should be managed with non‑pharmacologic interventions such as redirection. 3
Avoid “AM/PM” regimens that pair a second‑generation antihistamine in the morning with a first‑generation agent at night, because the latter’s long half‑life produces significant daytime drowsiness and performance impairment. 2

The overall anticholinergic drug burden—not just a single agent—determines the risk of cognitive impairment, delirium, falls, and functional decline in patients. 6, 7
Polypharmacy in advanced disease states raises the anticholinergic burden, and the cumulative effect of multiple anticholinergic agents amplifies the risk of cognitive adverse outcomes. 6, 7
Patients with high Drug Burden Index (DBI) scores are roughly three times more likely to be admitted for delirium compared with those without anticholinergic exposure. 6, 7

Clinicians should calculate total anticholinergic burden (e.g., using the Anticholinergic Drug Scale or Anticholinergic Cognitive Burden Scale) before initiating or continuing anticholinergic therapy to reduce the risk of delirium and falls. 6, 7

The Canadian Consensus Conference advises that exposure to highly anticholinergic medications should be minimized in older adults, with alternative agents preferred for indications such as depression, neuropathic pain, and urge‑type urinary incontinence (Grade 1B recommendation). 8

The 2020 Canadian Consensus Conference achieved 100 % consensus on the recommendation to reduce anticholinergic exposure in this population, reflecting strong expert agreement and moderate‑to‑high quality evidence. 8