Can Benadryl (diphenhydramine) be used to treat akathisia?

Benadryl for Akathisia

Benadryl (diphenhydramine) is effective for treating new-onset akathisia, particularly when caused by antidopaminergic agents like prochlorperazine (Compazine) or metoclopramide, but it is not recommended as prophylaxis or first-line treatment for antipsychotic-induced akathisia. 1, 2

Context-Dependent Effectiveness

The utility of diphenhydramine varies significantly based on the causative agent and timing:

For Antiemetic-Induced Akathisia (Compazine, Metoclopramide)

• Diphenhydramine 25-50 mg parenterally is often effective for new-onset akathisia from antidopaminergic antiemetics like prochlorperazine, working through anticholinergic and antihistaminic properties to counteract dopamine blockade. 1, 2
• For pediatric patients, use 1-2 mg/kg per dose (maximum 50 mg) administered parenterally. 3
• The American Academy of Child and Adolescent Psychiatry recommends diphenhydramine as an effective treatment for new-onset Compazine-induced akathisia, though it should be considered alongside dose reduction as first-line management. 1

For Antipsychotic-Induced Akathisia

• Diphenhydramine is NOT recommended as first-line treatment for antipsychotic-induced akathisia. 4, 5
• Beta-blockers (propranolol 10-30 mg two to three times daily) and mirtazapine (7.5-15 mg once daily) have the strongest evidence for antipsychotic-induced akathisia. 1, 4, 5
• Anticholinergic agents like diphenhydramine may provide symptomatic relief but are considered inferior to beta-blockers or mirtazapine. 4, 6

Critical Distinction: Treatment vs. Prophylaxis

Diphenhydramine should NOT be used routinely as prophylaxis against metoclopramide-induced akathisia. 7

• A randomized trial demonstrated that prophylactic diphenhydramine 25 mg provided no benefit in preventing akathisia when metoclopramide was administered intravenously over 15 minutes (12% akathisia rate in both diphenhydramine and placebo groups). 7
• The ASCO guideline update explicitly removed diphenhydramine from antiemetic regimens, noting that with high-dose metoclopramide rarely used, the rationale for prophylactic diphenhydramine no longer exists. 8

Practical Treatment Algorithm

When akathisia develops:

1. First priority: Reduce or discontinue the offending agent if clinically feasible, as this addresses the root cause most reliably. 1

2. For antiemetic-induced akathisia (Compazine, metoclopramide):

   • Administer diphenhydramine 25-50 mg IV/IM for adults 1, 2
   • For children: 1-2 mg/kg per dose (maximum 50 mg) 3
   • Expect onset within several minutes with effects lasting 4-6 hours 3

3. For antipsychotic-induced akathisia:

   • First-line: Propranolol 10-30 mg two to three times daily 1, 5
   • Alternative: Mirtazapine 7.5-15 mg once daily 4, 5
   • Benzodiazepines (clonazepam) for symptomatic relief 1, 5
   • Anticholinergics like diphenhydramine only if other options fail or are contraindicated 6

Important Caveats

• Monitor for excessive sedation when combining diphenhydramine with other sedating medications like prochlorperazine, requiring careful assessment of respiratory status and consciousness level. 3
• Other adverse effects include hypotension, dizziness, blurred vision, dry mouth, and urinary retention. 3
• For patients with contraindications to beta-blockers (asthma, bradycardia, hypotension), consider alternative antiemetics like ondansetron rather than relying on diphenhydramine for akathisia management. 3, 4
• Diphenhydramine is most effective when akathisia is recognized and treated early in its course. 2