What can be given with Benadryl (diphenhydramine) to manage extrapyramidal side effects?

Management of Extrapyramidal Side Effects with Diphenhydramine (Benadryl)

Anticholinergic medications such as benztropine (Cogentin) are the most effective agents to administer with diphenhydramine (Benadryl) for managing extrapyramidal side effects (EPS). 1

First-Line Treatment Options for EPS

Acute Management

• Diphenhydramine (Benadryl)

  • Dosage: 25-50 mg IV/IM/PO
  • Rapidly resolves muscle spasms and abnormal postures
  • Usually effective within minutes when given parenterally 1

• Benztropine (Cogentin)

  • For acute dystonic reactions: 1-2 mg IM/IV 2
  • For ongoing management: 1-4 mg PO once or twice daily 3
  • Maximum daily dose: 6 mg 3

Mechanism of Action

Both medications work through anticholinergic effects that counteract the dopamine blockade caused by antipsychotics, effectively relieving EPS symptoms.

Treatment Algorithm for EPS Management

1. Acute dystonic reaction

   • Administer diphenhydramine 25-50 mg IV/IM/PO immediately 1
   • If inadequate response, add benztropine 1-2 mg IM/IV 2

2. Ongoing EPS management

   • Continue benztropine 1-4 mg once or twice daily 3
   • Adjust dose based on symptom control and side effects
   • Consider maintenance therapy if symptoms recur after discontinuation

3. Alternative options if benztropine is unavailable

   • Trihexyphenidyl 1-5 mg PO three times daily 4
   • Propranolol for akathisia (especially if anticholinergics are ineffective) 5

Special Considerations

Duration of Treatment

• For drug-induced EPS that develops soon after starting antipsychotics, anticholinergic medication may only be needed for 1-2 weeks 3
• After symptom control, attempt to withdraw anticholinergic medication to determine continued need 3
• If EPS symptoms recur, reinstitute anticholinergic therapy 3

Important Cautions

• When discontinuing antipsychotics, maintain anticholinergic medication well after the antipsychotic is discontinued to prevent delayed emergence of EPS 6
• Elderly patients and thin patients generally cannot tolerate large doses of anticholinergics 3
• Monitor for anticholinergic side effects (dry mouth, blurred vision, urinary retention, constipation)

Evidence from Clinical Practice

• Multiple case reports demonstrate successful treatment of EPS with diphenhydramine, including cases involving propofol 7 and aripiprazole 8
• The incidence of EPS with newer antipsychotics is lower but still present, and prompt treatment improves patient outcomes and medication adherence 1
• In a retrospective analysis of perphenazine-induced EPS, diphenhydramine effectively resolved symptoms in most cases 9

Clinical Pearls

• Atypical antipsychotics (quetiapine, olanzapine, low-dose risperidone) have lower risk of EPS than typical antipsychotics 1
• Regular assessment of abnormal movements using standardized scales like AIMS is recommended during prolonged treatment 1
• Some drug-induced extrapyramidal disorders that develop slowly may not respond well to anticholinergic therapy 3

By combining diphenhydramine with benztropine or another anticholinergic agent, you can effectively manage extrapyramidal side effects and improve patient comfort and medication adherence.