What are the risks associated with long-term use of anticholinergic (anticholinergic) medications?

Risks Associated with Long-Term Anticholinergic Medication Use

Long-term use of anticholinergic medications is associated with significant adverse effects including cognitive decline, increased risk of dementia, falls, and decreased functional status, particularly in older adults, and should be avoided whenever possible or used at the lowest effective dose for the shortest duration.

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
• Long-term exposure to anticholinergic drugs is associated with a 1.5-fold increased risk of developing dementia, with higher cumulative doses carrying greater risk 2, 3
• The risk of dementia appears dose-dependent, with those receiving the highest cumulative exposure (>1095 total standardized daily doses) showing the greatest risk 2
• Recent research shows anticholinergic medications may contribute to dementia development through a mediating relationship with delirium, with one study finding delirium explained approximately 58% of the association between anticholinergic use and subsequent dementia 4
• The cognitive effects of anticholinergic burden are more pronounced in patients over 75 years of age 1

Physical and Functional Risks

• Anticholinergic medications commonly cause physical adverse effects including:
  • Dry mouth and eyes 1
  • Constipation and gastrointestinal disturbances 1
  • Urinary retention and bladder dysfunction 1
  • Blurred vision 1
  • Increased risk of narrow-angle glaucoma 1
• These medications significantly increase fall risk in older adults, which can lead to fractures and subdural hematomas 1
• Functional decline is common with long-term use, with decreased activities of daily living (ADL) scores documented in multiple studies 1
• The Drug Burden Index shows that medications with strong anticholinergic properties are associated with decline in functional status 1

Cardiovascular and Other Systemic Risks

• Anticholinergic drugs can cause tachycardia and cardiac rhythm disturbances 5
• These medications may worsen hypertension and complicate blood pressure management 1
• When combined with other CNS-active substances (alcohol, sedatives, hypnotics, or antidepressants), anticholinergics can cause enhanced performance impairment and sedation 1
• In men, anticholinergics can exacerbate benign prostatic hyperplasia symptoms 1

Anticholinergic Burden and Polypharmacy

• The cumulative effect of multiple anticholinergic medications ("anticholinergic burden") significantly increases risk of adverse outcomes 1
• 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 1
• The risk of adverse events increases with the number of anticholinergic medications and the duration of use 5, 3
• Specific medication classes with strong anticholinergic effects include:
  • Older antihistamines (e.g., diphenhydramine, hydroxyzine) 1
  • Muscle relaxants (e.g., cyclobenzaprine) 1
  • Bladder antimuscarinic agents (e.g., oxybutynin) 1, 2
  • Certain antidepressants, particularly tricyclics 2, 3
  • Some antipsychotics 1, 2

Special Considerations for Older Adults

• Older adults are more sensitive to anticholinergic effects due to physiological changes in aging 1
• The Beers Criteria and STOPP/START criteria identify many anticholinergic medications as potentially inappropriate for older adults 1
• Anticholinergic medications in older adults are associated with:
  • Increased emergency department visits 1
  • Higher hospitalization rates 1
  • Greater healthcare costs 1
  • Increased mortality risk 5
• Deprescribing anticholinergic medications in hospitalized older adults has been shown to effectively reduce anticholinergic burden 6

Recommendations for Clinical Practice

• Avoid anticholinergic medications in older adults whenever possible, particularly those with existing cognitive impairment, dementia risk factors, or narrow-angle glaucoma 1
• When treating allergic conditions, second-generation antihistamines are preferred over first-generation antihistamines due to reduced anticholinergic effects 1
• For patients requiring anticholinergic medications, use the lowest effective dose for the shortest duration possible 1
• Regularly review medication regimens to identify and reduce anticholinergic burden, particularly in older adults 1, 6
• Consider deprescribing anticholinergic medications during hospital stays as this provides an opportunity to reduce anticholinergic burden 6
• For patients with overactive bladder, consider topical anticholinergic agents rather than systemic ones to minimize cognitive side effects 1