The Headache Cocktail with Depakote, Benadryl, and Reglan
The headache cocktail combining Depakote (valproate sodium), Benadryl (diphenhydramine), and Reglan (metoclopramide) is an intravenous treatment option for acute severe migraine attacks, particularly when other treatments have failed or are contraindicated.
Composition and Dosing
The standard components of this headache cocktail include:
- Depakote (IV valproate sodium): 500-1000mg administered intravenously over 60 minutes 1, 2
- Benadryl (diphenhydramine): 50mg administered intravenously 3
- Reglan (metoclopramide): 10mg administered intravenously 4, 1
Mechanism and Evidence Base
Depakote (Valproate Sodium)
- Functions as both an acute treatment and potential preventive therapy for migraine
- Studies show 50-75% of patients experience significant pain relief within 60 minutes of administration 1, 2
- The loading dose typically ranges from 900-1200mg, with average response time of about 50 minutes 2
- Particularly useful for patients with chronic daily headache/transformed migraine who have failed other treatments 5
Reglan (Metoclopramide)
- Fair evidence supports its use as monotherapy for acute migraine attacks 4
- Particularly beneficial for patients with nausea and vomiting
- Provides both antiemetic effects and direct pain relief 4
Benadryl (Diphenhydramine)
- Often added to prevent or treat extrapyramidal side effects from metoclopramide
- Research shows mixed results on its efficacy as an adjuvant therapy for migraine 3
- May provide sedative effects that can be beneficial during acute attacks
Clinical Applications
This cocktail is typically used in:
- Emergency department settings for severe, refractory migraine attacks
- Patients who have failed oral medications or cannot tolerate them due to nausea/vomiting
- Situations where triptans or ergotamines are contraindicated
- Breaking the cycle of medication-overuse headache
Important Considerations and Cautions
- Medication Overuse: Acute therapy should be limited to no more than twice weekly to prevent medication-overuse headache 4
- Monitoring Requirements: Patients should be monitored for sedation, hypotension, and cardiac effects
- Infusion Rate: Valproate sodium should be administered over at least 60 minutes to minimize side effects; may need to be extended to 120 minutes in sensitive patients 6
- Contraindications:
- Valproate is contraindicated in pregnancy
- Use caution with metoclopramide in patients with Parkinson's disease or history of tardive dyskinesia
- Consider cardiac status before administering the full cocktail
Treatment Outcomes
- In studies of IV valproate, 60% of patients reported significant headache improvement at 2-4 hours 1
- For refractory chronic migraine, a protocol of repeated IV valproate doses showed improvement in 69% of patients 6
- The combination may provide faster relief than single agents alone
- The cocktail is generally well-tolerated with minimal side effects when properly administered
Alternative Approaches
If this cocktail is ineffective or contraindicated, consider:
- Sumatriptan (if not already tried and no contraindications)
- Dihydroergotamine with metoclopramide
- NSAID-based protocols
- Neuroleptics such as chlorpromazine or prochlorperazine
This headache cocktail represents one approach to managing severe migraine attacks, particularly in emergency settings when standard outpatient treatments have failed.