What Will They Give Me in the Emergency Department for My Migraine Attack?: Migraine Cocktail Explained

In the United States, emergency physicians rely on guidelines from the American Headache Society (AHS) to assist in deciding which medications to use when treating migraine attacks. The AHS guidelines uses research to provide recommendations for maximum efficacy while avoiding medications that are ineffective or potentially harmful. This evidence-based guidance assists ED physicians in tailoring treatment, or, creating a "migraine cocktail" based on the options available.

The AHS graded the evidence quality and strength of their recommendations on a 3-level scale:

Level A means the recommendation is based on two or more relevant high-quality randomized controlled trials.

Level B means it is based on one relevant high-quality randomized trial or two or more relevant moderate or low-quality randomized trials.

Level C refers to expert opinion or studies that do not meet Level A or B criteria.

Level U means there is not enough evidence to make a recommendation.

Due to these many options, the term “migraine cocktail” is used to refer to a combination of different medications depending on the hospital, the treating physician, contraindications, what has previously been effective for the patient, any comorbidities, pregnancy, etc.

In this article, we will list all the possible options with their level of evidence. It’s important to note that this is relevant to emergency departments in the US and may be different in other countries (although some of the listed medications by the AHS are not available in the US and this will be noted). Lastly, there is no Level A evidence for the treatment of acute migraine in the emergency department.

First-Line Treatment Options (Level B)

For first-line treatment, the AHS recommends the following intravenous (IV) medications with a Level B evidence grade:

• Metoclopramide 10-20 mg IV
• Prochlorperazine 10 mg IV
• Sumatriptan 6 mg injected subcutaneously (should be avoided if the patient has taken ergotamine, dihydroergotamine, or a triptan in the past 24 hours due to risk of serotonin syndrome)

The AHS also recommends IV dexamethasone to reduce the risk of recurrence, again with a Level B grade, but it did not find sufficient evidence (Level U) to recommend dexamethasone specifically for acute migraine relief. This is important because it is falsely believed that there is evidence suggesting that IV corticosteroids abate a migraine attack. This is not the case, but there is evidence that it does prevent RECURRENCE of a migraine attack.

Second-Line Treatment Options (Level C)

As second-line options, the AHS suggests considering the following medications with a Level C evidence grade:

• Acetaminophen 1 g IV
• Aspirin 0.5-1.8 g IV (not available in the United States)
• Chlorpromazine up to 25 mg IV (patients should be warned about adverse effects which include orthostatic hypotension, drowsiness, and akathisia)
• Dexketoprofen 50 mg IV (not available in the United States)
• Diclofenac 75 mg intramuscularly (not available in the United States)
• Droperidol 2.5-8.25 mg intramuscularly (drowsiness and akathisia risk with a small risk of life-threatening cardiac dysrhythmias)
• Haloperidol 5 mg IV (drowsiness and akathisia risk among others)
• Ketorolac 30-60 mg IV or intramuscularly
• Valproate 500-1,000 mg IV

The AHS noted that intravenous dipyrone has some efficacy evidence but is not available in the United States or many other countries due to rare but potentially fatal adverse effects.

Recommended Against (Level C)

Conversely, the AHS recommends against using the following medications with a Level C grade:

• IV diphenhydramine (While this may come as a surprise, we must follow the science: https://linkinghub.elsevier.com/retrieve/pii/S0196064415010859) Diphenhydramine may still be given for the possible prevention of extra-pyramidal symptoms when administered with other medications.
• IV hydromorphone
• IV lidocaine
• IV morphine
• IV octreotide

Insufficient Evidence (Level U)

For several other medications, the AHS found insufficient evidence (Level U) to make any recommendations for or against their use:

• Injectable dihydroergotamine
• Injectable ergotamine
• Injectable ketamine
• Injectable lysine clonixinate
• IV magnesium
• IV meperidine
• IV nalbuphine
• IV propofol
• Parenteral promethazine
• IV tramadol
• Intramuscular trimethobenzamide

Finally, while not part of the AHS guidelines, the use of IV saline, while ubiquitous for migraine treatment, has no good evidence for the effective treatment of a migraine attack. This randomized controlled trial showed that there was no statistically significant treatment effect from fluid administration, but does not exclude the possibility of a clinically meaningful effect:  https://pubmed.ncbi.nlm.nih.gov/30665504/. Moreover, fluid administration may be used for symptoms of migraine such a vomiting. 

The AHS guidelines provide a useful framework for emergency physicians to choose wisely from available pharmacological options when treating acute migraine. Following these evidence-based recommendations result in a “migraine cocktail” that helps maximize the chances of effective relief while avoiding medications that are ineffective, unavailable, or potentially harmful.