Extra dry or up with a twist? A take on the ‘migraine cocktail’

You’re seeing a patient in the community emergency department with a primary headache disorder. Based on your history & physical examination skills, you have considered and ruled out all dangerous secondary headache causes such as intracranial hemorrhage, sentinel bleed, meningoencephalitis, abscess, tumor, temporal arteritis, hypertensive encephalopathy, acute angle closure glaucoma, etc. With many classes of treatments available, providers have typically used some form of a ‘migraine cocktail’ including IV prochlorperazine, IV ketorolac, IV diphenhydramine, IV dexamethasone, and/or IV normal saline.[1]

There are several considerations with the above typical ‘headache cocktail’ that I would like to discuss. Ideally, the treatment regimen implemented in the ED will be efficacious in providing modest headache relief, while also being safe (few side effects) and fast. Depending on other considerations for the department at that time, the nurse may be limited with time and unable to obtain IV access and initiate the typical multimodal intravenous components of the ‘migraine cocktail’. Furthermore, most headache patients will not need labs drawn. While not advocating for a one-size fits all approach, my goal is to discuss the evidence on the utility of commonly used therapeutics as well as providing you with additional time-efficient modalities to add to your armamentarium in effectively treating patients with primary headache disorder.


Any of the typical medications, whatever available readily, will work, including: metoclopramide 10 mg IM, prochlorperazine 10 mg IM, or promethazine 25 mg IM. The onset of action of all three medications via the IM route is between 10-20 minutes.[2-4]


Routine co-administration with metoclopramide has not been shown to improve migraine outcomes or prevent metoclopramide-induced akathasia.[5,6] Additionally, the sedative side effects will potentially keep the patient in the ED for a lengthier time frame.

IV Fluids:

In a post hoc analysis of 4 ED-based migraine clinical trials utilizing IV metoclopramide as well as IV fluids at the discretion of the treating physician, the patients receiving IV fluids had a lower improvement in pain scale after one hour and their use was not associated with sustained headache freedom.[7] Universal addition of this modality to patients with primary headache disorder similarly will likely add to a lengthier ED visit as the fluids trickle in.


Typical treatment is with ketorolac 60 mg IM, and has been proven to be effective for migraine treatment in comparison to many antidopaminergics.[8] It may also be fruitful to maximize the patient’s appropriate use of acetaminophen and ibuprofen/naproxen upon discharge.


Dexamethasone 10-25 mg IM can be administered to help prevent headache recurrence.[9]


Frequently forgotten are triptains and anecdotally do not seem to be the go-to for many ED providers, but 6 mg subcutaneous has shown benefit in treating patient with primary headache disorder.[10]

For patients with primary headache disorder, it is vitally important to do several things:

  • Rule out dangerous secondary causes, as above, first and foremost

  • Set expectations with the patient, that their headache may not be completely resolved, but we hope to be aggressive up front

  • Delineate return precautions to the ED and close Neurology followup or referral

Faculty Reviewer: Dr. Kristina McAteer


  1. Long B, Koyfman A. Headache management in the ED. emDocs Cases. http://www.emdocs.net/emdocs-cases-headache-management-ed/. Accessed June 2019.

  2. Promethazine: drug information. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com/contents/promethazine-drug-information?search=promethazine&source=panel_search_result&selectedTitle=1~79&usage_type=panel&kp_tab=drug_general&display_rank=1#F214058. Accessed June 2019.

  3. Metoclopramide: drug information. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com/contents/metoclopramide-drug-information?search=metoclopramide&source=panel_search_result&selectedTitle=1~149&usage_type=panel&kp_tab=drug_general&display_rank=1. Accessed June 2019.

  4. Prochlorperazine: drug information. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com/contents/prochlorperazine-drug-information?search=prochlorperazine&source=panel_search_result&selectedTitle=1~72&usage_type=panel&kp_tab=drug_general&display_rank=1. Accessed June 2019.

  5. Friedman BW, Cabral L, Adewunmi V, et al. Diphenhydramine as adjuvant therapy for acute migraine: an emergency department-based randomized clinical trial. Ann Emerg Med. 2016 Jan:67(1):32-39.

  6. Erdur B, Tura P, Aydin B, et al. A trial of midazolam vs diphenhydramine in prophylaxis of metoclopramide-induced akathisia. Am J Emerg Med. 2012 Jan;30(1):84-91.

  7. Balbin JE, Nerenberg R, Baratloo A, et al. Intravenous fluids for migraine: a post hoc analysis of clinical trial data. Am J Emerg Med. 2016 Apr;34(4):713-6.

  8. Taggart E, Doran S, Kokotillo A, et al. Ketorolac in the treatment of acute migraine: a systematic review. Headache 2013;53:277.'

  9. Does the addition of dexamethasone to standard therapy for acute migraine headache decrease the incidence of recurrent headache for patients treated in the emergency department? A meta-analysis and systematic review of the literature. Acad Emerg Med. 2008 Dec;15(12):1223-33.

  10. Sumatriptan (subcutaneous route of administration) for acute migraine attacks in adults. Cochrane Database Syst Rev. 2012 Feb 15;(2):CD009665.