Acute Migraine Cocktail for Moderate-to-Severe Attack with Nausea
Intravenous "Migraine Cocktail" for Emergency/Urgent Care Settings
For an adult presenting with moderate-to-severe migraine accompanied by nausea, photophobia, and phonophobia, the optimal IV cocktail is metoclopramide 10 mg IV plus ketorolac 30 mg IV, administered together as first-line therapy. 1
Components and Rationale
Metoclopramide 10 mg IV provides direct analgesic effects through central dopamine receptor antagonism—independent of its antiemetic properties—while simultaneously treating nausea and enhancing absorption of co-administered medications through prokinetic effects. 1
Ketorolac 30 mg IV (60 mg IM for patients <65 years) delivers rapid onset analgesia with approximately 6 hours of duration and carries minimal risk of rebound headache compared to other analgesics. 1
This combination is superior to either agent alone and avoids opioids, which should never be used for migraine due to dependency risk, rebound headaches, and eventual loss of efficacy. 1
Alternative IV Options When First-Line Fails
Prochlorperazine 10 mg IV is comparable in efficacy to metoclopramide and may be substituted, though it carries higher rates of adverse events (21% vs. metoclopramide's lower profile) and additional risks of tardive dyskinesia, hypotension, and QT prolongation. 1
Dihydroergotamine (DHE) 0.5–1.0 mg IV has good evidence as monotherapy for acute migraine when NSAIDs are contraindicated, but is contraindicated with concurrent triptan use (within 24 hours), beta-blockers, uncontrolled hypertension, coronary artery disease, pregnancy, and sepsis. 1
Critical Contraindications to Screen Before Administration
Metoclopramide is contraindicated in pheochromocytoma, seizure disorders, active GI bleeding, and GI obstruction. 1
Ketorolac must be avoided in renal impairment (CrCl <30 mL/min), history of GI bleeding, aspirin/NSAID-induced asthma, and active GI bleeding. 1
Prochlorperazine is contraindicated in CNS depression, concurrent adrenergic blockers, baseline QTc >500 ms, and history of torsades de pointes. 1
Oral Outpatient "Migraine Cocktail" for Home Treatment
For patients treating at home, the evidence-based oral cocktail is sumatriptan 50–100 mg PLUS naproxen sodium 500 mg, taken together at headache onset while pain is still mild. 1, 2
Superiority of Combination Therapy
This combination achieves 130 more patients per 1,000 with sustained pain relief at 48 hours and 90 more patients per 1,000 with pain relief at 2 hours compared to either agent alone (high-certainty evidence). 1
The number-needed-to-treat for headache relief at 2 hours is 3.5, making this the strongest-rated intervention in current guidelines. 1
Early administration (when pain is mild) results in ≈50% pain-free at 2 hours versus only ≈28% when delayed until pain is moderate-to-severe. 1
Adding an Antiemetic for Nausea
Metoclopramide 10 mg oral or prochlorperazine 25 mg oral should be added 20–30 minutes before the triptan-NSAID combination when nausea is present, providing synergistic analgesia beyond antiemetic effects alone. 1
Promethazine (rectal suppository or IV) is an alternative when oral routes are not tolerated due to severe nausea or vomiting. 1
Alternative Oral Regimens
For patients with contraindications to triptans (ischemic heart disease, uncontrolled hypertension, cerebrovascular disease, basilar or hemiplegic migraine), use naproxen 500–825 mg PLUS metoclopramide 10 mg as first-line. 1
For patients with contraindications to NSAIDs (renal impairment, GI bleeding history), substitute acetaminophen 1,000 mg for the NSAID component, though efficacy is lower. 1, 3
CGRP antagonists (gepants) such as ubrogepant 50–100 mg or rimegepant are third-line options reserved for patients who fail triptan-NSAID combinations or have cardiovascular contraindications to triptans. 1
Non-Oral Routes for Severe Nausea/Vomiting
Subcutaneous sumatriptan 6 mg provides the highest efficacy among all triptan formulations, with 59% achieving complete pain relief by 2 hours and onset within 15 minutes—ideal when oral routes are not tolerated. 1
Intranasal sumatriptan 5–20 mg or intranasal zolmitriptan are effective alternatives when IV access is unavailable and oral medication cannot be retained. 1
Critical Frequency Limitation to Prevent Medication-Overuse Headache
All acute migraine medications—including NSAIDs, triptans, antiemetics, and combination therapies—must be strictly limited to ≤2 days per week (≤10 days per month) to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches. 1, 2
If a patient requires acute treatment more than twice weekly, initiate preventive therapy immediately rather than increasing acute medication frequency. 1, 2
Medication-overuse headache occurs with NSAIDs at ≥15 days/month and with triptans at ≥10 days/month. 1, 2
Medications to Absolutely Avoid
Opioids (hydromorphone, oxycodone, codeine, meperidine) should never be used for migraine due to questionable efficacy, high risk of dependency, rebound headaches, and loss of efficacy over time. 1, 3
Butalbital-containing compounds carry substantial risk of medication-overuse headache and should be reserved only for cases where all other evidence-based treatments are contraindicated. 1
Intravenous ketamine lacks proven efficacy for acute migraine and carries safety concerns. 1
When to Escalate or Refer
If the patient fails two different triptans after adequate trials (2–3 headache episodes each), escalate to CGRP antagonists (ubrogepant, rimegepant) or consider subcutaneous sumatriptan if oral formulations were used. 1
Immediate referral to a neurologist or headache specialist is required for patients with refractory migraine despite optimized acute therapy, those requiring acute treatment >2 days/week, or those with red-flag features (thunderclap headache, progressive worsening, new neurological deficits, fever with neck stiffness). 1