How are anticholinergic side effects managed?

Management of Anticholinergic Side Effects

The primary management strategy for anticholinergic side effects is to minimize anticholinergic burden by reviewing all medications, discontinuing or reducing doses of anticholinergic agents (particularly those used to manage side effects of other drugs rather than treating primary conditions), and switching to medications with lower anticholinergic activity when clinically feasible. 1, 2

Immediate Assessment and Identification

Recognize the Anticholinergic Syndrome

• Central effects: Agitated delirium, confusion, hallucinations, disorientation, anxiety, and seizures 1
• Peripheral effects: Tachycardia, mild hyperthermia (<38.8°C), mydriasis (dilated pupils), dry mucous membranes, hot/dry/erythematous skin, hypoactive or absent bowel sounds, and urinary retention 1
• The classic mnemonic describes the syndrome as "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

Identify All Contributing Medications

• Review the complete medication list for drugs with anticholinergic properties, including antipsychotics (especially clozapine, olanzapine, quetiapine), tricyclic antidepressants, antihistamines, sleep aids, cold preparations, diphenhydramine, and medications for urinary incontinence 1, 3, 4
• Many patients experience cumulative anticholinergic burden from multiple medications with modest antimuscarinic activity rather than a single agent 4, 5

Stepwise Management Algorithm

Step 1: Discontinue or Reduce Offending Agents

• Prioritize discontinuation of anticholinergic medications used to manage side effects of other drugs (such as benztropine for extrapyramidal symptoms) while maintaining those treating primary conditions 2
• For medications treating primary conditions, reduce doses to the minimum effective level or switch to alternatives with lower anticholinergic activity 1, 6
• Use gradual tapering rather than abrupt discontinuation to avoid withdrawal symptoms or rebound worsening 2

Step 2: Switch to Lower Anticholinergic Alternatives

• For antipsychotics: If positive symptoms are controlled, switch from high anticholinergic agents (clozapine, olanzapine, quetiapine) to those with lower anticholinergic burden while remaining within therapeutic range 1
• For antidepressants: Switch from tertiary amine tricyclics to secondary amines (nortriptyline or desipramine) which have reduced anticholinergic effects 1
• For overactive bladder: Consider switching from anticholinergic agents to beta-3 adrenergic receptor agonists which carry less risk of urinary retention 2

Step 3: Manage Specific Anticholinergic Side Effects

Cognitive Impairment

• Review and minimize total anticholinergic burden, as this is particularly important in elderly patients and those with baseline cognitive impairment 1, 3, 4
• Reducing anticholinergic burden has been shown to improve memory and quality of life 6

Urinary Retention

• Discontinue or reduce anticholinergic medications used for managing side effects while maintaining those essential for primary disorders 2
• Monitor post-void residual urine volume to assess improvement after medication adjustments 2
• Exclude or treat constipation, which can exacerbate urinary retention 2

Peripheral Effects (Dry Mouth, Constipation)

• These effects can be reduced by starting with low doses administered at bedtime and using slow titration 1
• Consider symptomatic management while working to reduce anticholinergic burden 3

Severe Anticholinergic Toxicity

Emergency Treatment

• Discontinue the precipitating drug immediately and provide supportive care 1
• Benzodiazepines for agitation 1
• Physostigmine (a reversible anticholinesterase) can reverse both central and peripheral anticholinergic effects, with dramatic reversal expected within minutes of intravenous administration 7
  • Physostigmine is FDA-approved to reverse CNS effects caused by drugs producing anticholinergic syndrome 7
  • Duration of action is relatively short (45-60 minutes), so repeat dosing may be necessary 7
• Treat hyperthermia by terminating extreme muscle activity; antipyretics are typically not efficacious as fever is not due to hypothalamic thermoregulation changes 1

Special Populations and Considerations

Elderly Patients

• Older patients are particularly vulnerable to anticholinergic adverse effects due to baseline cognitive impairment and reduced physiologic reserve 4, 5
• Deprescribing anticholinergic medications in elderly patients can prevent falls and reverse cognitive decline 3
• In elderly patients with Alzheimer's disease receiving typical antipsychotics, avoid benztropine or trihexyphenidyl entirely 8

Patients on Antipsychotics

• Do not use anticholinergics routinely or prophylactically when starting antipsychotics 8
• Only prescribe anticholinergics short-term if significant extrapyramidal symptoms develop after dose reduction or switching strategies have failed 8
• Reevaluate the need for antiparkinsonian agents after the acute phase or if antipsychotic doses are lowered, as many patients no longer need them during long-term therapy 8

Common Pitfalls to Avoid

• Avoid prophylactic anticholinergics: Do not routinely prescribe benztropine or similar agents when starting antipsychotics unless the patient has documented history of severe dystonic reactions 8
• Avoid antipsychotics with anticholinergic properties in patients presenting with anticholinergic delirium or intoxication 9
• Do not overlook cumulative burden: Many patients develop toxicity from multiple medications with modest anticholinergic activity rather than a single high-potency agent 4, 5
• Monitor for reemergence: When reducing anticholinergic burden, monitor closely during the first 4-6 weeks for reemergence of the symptoms being treated 8

Long-term Monitoring and Prevention

• Regularly assess the continued need for all anticholinergic medications through periodic medication reviews 1, 2
• Use anticholinergic burden assessment tools (such as the Anticholinergic Drug Scale) to guide clinical decision-making 4
• Educate patients about avoiding over-the-counter anticholinergic medications 1
• Benefits of reducing anticholinergic burden include improvements in side effects, memory, and quality of life 6