How to manage Extrapyramidal Symptoms (EPS)?

Management of Extrapyramidal Symptoms (EPS)

For drug-induced EPS, immediately initiate anticholinergic therapy with benztropine 1-2 mg orally or parenterally once or twice daily, or trihexyphenidyl 1 mg initially with gradual titration to 5-15 mg daily in divided doses, while simultaneously evaluating whether the offending neuroleptic can be reduced, discontinued, or switched to an atypical antipsychotic. 1, 2

Immediate Assessment and Diagnosis

• Identify the type of EPS present: acute dystonia, parkinsonism, akathisia, or tardive dyskinesia, as these require different management approaches 3, 4
• Document severity using a standardized scale such as the Extrapyramidal Symptoms Rating Scale or Barnes Akathisia Scale to guide treatment intensity and monitor response 4, 5
• Review all current medications including antipsychotics, antiemetics (metoclopramide, prochlorperazine), and any other dopamine-blocking agents that may be causative 1, 3
• Assess for substance abuse (particularly cocaine, alcohol, and cannabis) as these significantly exacerbate EPS and may require concurrent addiction management 5

Acute Management Algorithm

For Acute Dystonic Reactions

• Administer benztropine 1-2 mL (1-2 mg) intramuscularly or intravenously for rapid relief, which typically occurs within minutes 1
• Follow with oral benztropine 1-2 mg twice daily for 1-2 weeks to prevent recurrence 1
• If dystonia develops soon after neuroleptic initiation (likely transient), continue benztropine 1-2 mg two to three times daily for 1-2 weeks, then attempt withdrawal to determine continued need 1

For Drug-Induced Parkinsonism

• Start benztropine 1-4 mg once or twice daily (oral or parenteral), with dosage individualized based on response 1
• Alternatively, use trihexyphenidyl starting at 1 mg daily, increasing by 2 mg increments every 3-5 days until reaching 5-15 mg daily in divided doses 2
• Consider amantadine 100-300 mg daily as an alternative or adjunct, particularly if anticholinergic side effects are problematic 6
• Administer the largest dose at bedtime to improve nighttime mobility and morning function 1, 2

For Akathisia

• Reduce or discontinue the offending neuroleptic if clinically feasible, as akathisia is particularly associated with substance abuse (alcohol, cannabis) 5
• Consider beta-blockers or benzodiazepines as first-line agents, as anticholinergics are less effective for akathisia 3

Medication Adjustment Strategy

• Never abruptly discontinue anticholinergic therapy in patients with parkinsonism, as this can precipitate parkinsonian crisis (sudden marked clinical deterioration) or neuroleptic malignant syndrome 1, 6
• When switching from other antiparkinsonian agents to benztropine or trihexyphenidyl, use partial substitution initially with progressive reduction of the other medication 1, 2
• If using concomitantly with levodopa, reduce doses of both medications and carefully adjust based on side effects and symptom control (typical anticholinergic dose: 3-6 mg daily in divided doses) 2
• Reduce anticholinergic dose if atropine-like effects appear (dry mouth, blurred vision, urinary retention, confusion) 6

Long-Term Management Considerations

• Switch to atypical antipsychotics (if treating psychosis) as first-line strategy, as these have significantly reduced EPS risk compared to conventional antipsychotics at recommended doses 7, 3
• Attempt periodic withdrawal of anticholinergics after EPS have been controlled for several days to weeks, as some patients maintain remission without continued therapy 1, 2
• Monitor for tardive dyskinesia development, which may require different management including dose reduction, switching to atypical antipsychotics, or adjunctive antioxidant therapy 3
• Recognize that EPS predict worse cognitive outcomes, particularly affecting processing speed and visuomotor performance, which should inform treatment decisions 8

Critical Warnings

• Slowly developing drug-induced EPS may not respond to anticholinergics and require neuroleptic dose reduction or discontinuation 1
• Abrupt anticholinergic withdrawal can precipitate delirium, agitation, delusions, hallucinations, paranoid reaction, stupor, anxiety, depression, and slurred speech 6
• Observe patients carefully during dose reduction for signs of neuroleptic malignant syndrome: fever, muscle rigidity, altered consciousness, autonomic dysfunction, elevated creatine phosphokinase 6
• Older patients and thin patients tolerate large anticholinergic doses poorly and require more conservative dosing 1, 2