What is the treatment for anticholinergic (anticholinergic syndrome) effects?

Treatment of Anticholinergic Effects

For severe anticholinergic toxicity, immediately discontinue all offending medications and administer physostigmine 0.5-1 mg IV in adults (0.01-0.02 mg/kg in children), which reverses both central and peripheral anticholinergic effects within minutes. 1, 2, 3

Immediate Management of Acute Anticholinergic Syndrome

Recognition of the Syndrome

• Look for the classic presentation: "Red as a beet, dry as a bone, hot as a hare, blind as a bat, mad as a hatter, full as a flask" 1
• Central manifestations include agitated delirium, confusion, hallucinations, disorientation, anxiety, and seizures 1, 2
• Peripheral manifestations include tachycardia, mild hyperthermia, mydriasis, dry mucous membranes, hot/dry/erythematous skin, hypoactive bowel sounds, and urinary retention 1, 2

Acute Treatment Protocol

• Stop all anticholinergic medications immediately including first-generation antihistamines (diphenhydramine), muscle relaxants (cyclobenzaprine), overactive bladder agents (oxybutynin), tricyclic antidepressants, phenothiazines, and anticholinergics used for antipsychotic side effects 2, 3
• Provide supportive care with benzodiazepines for agitation 1
• Administer physostigmine as the antidote of choice: 0.5-1 mg IV in adults, 0.01-0.02 mg/kg in children 2, 3
• Expect dramatic reversal within minutes if the diagnosis is correct and no anoxic injury has occurred 3
• Important caveat: The duration of physostigmine action is only 45-60 minutes, so repeated dosing may be necessary 3

Management of Chronic Anticholinergic Burden

Stepwise Deprescribing Algorithm

Step 1: Prioritize which medications to discontinue first

• Discontinue anticholinergic medications used solely to manage side effects of other drugs (e.g., benztropine for antipsychotic-induced extrapyramidal symptoms) before stopping medications treating primary conditions 1

Step 2: For medications treating primary conditions

• Reduce doses to the minimum effective level 1
• Switch to alternatives with lower anticholinergic activity 1
• Use gradual tapering rather than abrupt discontinuation to avoid withdrawal symptoms or rebound worsening 1

Step 3: Medication-specific substitutions

• For antipsychotics: Switch from high anticholinergic agents to those with lower anticholinergic burden while remaining within therapeutic range 1
• For antidepressants: Switch from tertiary amine tricyclics (amitriptyline, imipramine) to secondary amines (nortriptyline, desipramine) which have reduced anticholinergic effects 1
• For overactive bladder: Switch from anticholinergic agents to beta-3 adrenergic receptor agonists, which carry less risk of urinary retention 1

Special Population Considerations

Elderly Patients

• Older adults are particularly vulnerable to anticholinergic adverse effects due to baseline cognitive impairment and reduced physiologic reserve 4, 2, 5
• Strongly anticholinergic medications (diphenhydramine, cyclobenzaprine, oxybutynin) are usually poorly tolerated and should be avoided entirely 4, 2
• In elderly patients with Alzheimer's disease receiving antipsychotics, avoid benztropine or trihexyphenidyl entirely 1, 2
• Deprescribing anticholinergic medications can prevent falls, reverse cognitive decline, and improve functional status and activities of daily living scores 4

Anticholinergic Burden Assessment

• Multiple anticholinergic drugs create cumulative "anticholinergic burden" that adversely affects cognition and functionality 4, 5
• Use validated tools like the Anticholinergic Drug Scale or Drug Burden Index to assess cumulative risk 5, 6
• Regularly assess the continued need for all anticholinergic medications through periodic medication reviews 1

Common Pitfalls to Avoid

• Do not use the AM/PM dosing strategy (second-generation antihistamine in morning, first-generation at bedtime) as first-generation antihistamines dosed at bedtime still cause significant daytime drowsiness and performance impairment due to prolonged half-lives 4
• Do not assume physostigmine provides lasting protection—its short duration of action (45-60 minutes) means symptoms may recur and repeat dosing may be needed 3
• Do not overlook over-the-counter medications—educate patients about avoiding OTC anticholinergic medications like diphenhydramine 1
• Be aware that anticholinergic effects persist longer than plasma levels of the parent compound, so symptoms may continue even after drug levels decline 4

Long-term Prevention

• Conduct regular medication reviews to identify and minimize anticholinergic burden 1, 6
• Educate patients about the risks of anticholinergic medications, particularly regarding cognitive impairment, falls, and functional decline 4, 1
• Consider deprescribing as a therapeutic intervention with potential benefits including reversal of adverse effects and prevention of falls 6