IV Prochlorperazine + Diphenhydramine for Acute Migraine in the Emergency Department

Indications for Use

• The emergency department should administer IV prochlorperazine 10 mg together with diphenhydramine 25–50 mg for patients with moderate‑to‑severe acute migraine; the combination is highly effective and diphenhydramine also prevents akathisia. 1
• This regimen is indicated when patients present with severe nausea or vomiting that makes oral medication impractical, providing both antimigraine and anti‑emetic effects. 1, 2
• Patients who have failed or cannot tolerate oral triptan + NSAID therapy should receive the IV prochlorperazine/diphenhydramine combination. 1, 3

Post‑Discharge Outpatient Management

• After ED discharge, clinicians should prescribe an oral triptan + NSAID combination as the first‑line outpatient treatment for future migraine attacks. 1, 3
• The IV prochlorperazine/diphenhydramine regimen should not replace oral triptan + NSAID therapy in patients who can tolerate oral medications and are not in the emergency setting. 1, 3

Initiation of Preventive Therapy

• For patients experiencing ≥ 2 migraine attacks per month that cause ≥ 3 days of disability, clinicians should initiate preventive therapy (e.g., propranolol, topiramate, CGRP monoclonal antibodies, or other evidence‑based agents). 2, 4

Medication‑Overuse Headache Counseling

• Patients should be counseled to limit use of prochlorperazine to no more than 10 days per month to avoid medication‑overuse headache. 1, 3