What acute treatment options are appropriate for a patient at the peak of a moderate‑to‑severe migraine attack with nausea and photophobia, considering contraindications such as cardiovascular disease, uncontrolled hypertension, stroke history, or monoamine‑oxidase inhibitor use?

Acute Treatment During Peak Migraine

For a patient at the peak of a moderate-to-severe migraine with nausea and photophobia, the optimal treatment is intravenous metoclopramide 10 mg plus intravenous ketorolac 30 mg, which provides rapid pain relief through synergistic mechanisms while minimizing rebound headache risk. 1

First-Line Intravenous Combination Therapy

• Metoclopramide 10 mg IV provides direct analgesic effects through central dopamine receptor antagonism, independent of its antiemetic properties, making it effective for both migraine pain and nausea. 1

• Ketorolac 30 mg IV delivers rapid onset analgesia with approximately 6 hours of duration and carries minimal risk of rebound headache compared to other acute agents. 1

• This combination is specifically recommended by the American Academy of Family Physicians as first-line therapy for severe migraine requiring intravenous treatment. 1

Alternative Parenteral Options When IV Combination Is Unavailable

• Subcutaneous sumatriptan 6 mg provides the highest efficacy among all triptan formulations, achieving complete pain relief in approximately 59% of patients within 2 hours, with onset of action within 15 minutes. 1

• Intranasal sumatriptan 5–20 mg or intranasal zolmitriptan are effective alternatives when IV access is unavailable or the patient prefers non-injectable routes. 1

• Intravenous dihydroergotamine (DHE) 0.5–1.0 mg has good evidence for efficacy as monotherapy and can be repeated hourly up to a maximum of 2 mg per day. 1, 2

Critical Contraindications That Alter Treatment Selection

Cardiovascular Disease & Uncontrolled Hypertension

• Triptans are absolutely contraindicated in patients with ischemic heart disease, previous myocardial infarction, coronary artery vasospasm, uncontrolled hypertension, cerebrovascular disease, history of stroke or TIA, or basilar/hemiplegic migraine. 1

• DHE is contraindicated in patients with uncontrolled hypertension, coronary artery disease, pregnancy, sepsis, and concurrent use of beta-blockers or triptans within the past 24 hours. 1, 2

• For these patients, the metoclopramide 10 mg IV plus ketorolac 30 mg IV combination remains the safest and most effective option, as neither agent causes vasoconstriction. 1

Monoamine Oxidase Inhibitor (MAOI) Use

• Concurrent MAOI therapy does not contraindicate metoclopramide, ketorolac, or DHE, but triptans should be avoided due to potential serotonin syndrome risk when combined with MAOIs. 1

Renal Impairment

• Ketorolac should be avoided in patients with creatinine clearance <30 mL/min or history of GI bleeding. 1

• In this scenario, substitute prochlorperazine 10 mg IV for ketorolac, which provides comparable analgesic efficacy to metoclopramide. 1

Oral Therapy for Patients Who Cannot Receive Parenteral Treatment

• Sumatriptan 50–100 mg PLUS naproxen sodium 500 mg is the strongest oral combination, providing 130 additional patients per 1,000 with sustained pain relief at 48 hours compared to sumatriptan alone. 1

• Rizatriptan 10 mg reaches peak concentration in 60–90 minutes, making it the fastest oral triptan, and is available as an orally disintegrating wafer for patients with nausea. 1, 2

• Eletriptan 40 mg or zolmitriptan 2.5–5 mg are reportedly more effective with fewer adverse reactions than sumatriptan. 1, 2

Adjunctive Antiemetic Therapy

• When nausea is prominent but IV access is unavailable, metoclopramide 10 mg oral or rectal or prochlorperazine 25 mg rectal suppository should be administered 20–30 minutes before oral analgesics to enhance absorption and provide synergistic analgesia. 1

Newer CGRP Antagonists for Patients With Triptan Contraindications

• Ubrogepant 50–100 mg or rimegepant are third-line oral alternatives for patients with cardiovascular contraindications to triptans, as they have no vasoconstrictor activity. 1

• Lasmiditan (Reyvow) 50–200 mg is a 5-HT1F receptor agonist without vasoconstriction, but patients must not drive or operate machinery for at least 8 hours due to CNS effects (dizziness, somnolence). 1

Critical Medication-Overuse Prevention

• All acute migraine medications must be 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

• If the patient requires acute treatment more than twice weekly, preventive therapy must be initiated immediately rather than increasing acute medication frequency. 1

Absolutely Contraindicated Therapies

• Opioids (hydromorphone, morphine, codeine, tramadol) are absolutely contraindicated for migraine treatment because they provide questionable efficacy, carry high risk of dependence, precipitate rebound headaches, and worsen overall migraine outcomes. 1

• Butalbital-containing compounds should be avoided due to high risk of medication-overuse headache and should be reserved only when all other evidence-based treatments are contraindicated. 1

Common Pitfalls to Avoid

• Do not delay treatment until pain becomes severe; treating early (when pain is mild) results in 50% pain-free response at 2 hours versus only 28% when treatment is delayed. 1

• Do not substitute another acute medication during medication-overuse headache withdrawal, as this merely transfers the overuse to a different agent. 1

• Do not use triptans and DHE within 24 hours of each other due to additive vasoconstrictive effects. 1, 2

• Metoclopramide is contraindicated in patients with pheochromocytoma, seizure disorder, GI bleeding, or GI obstruction. 1

• Prochlorperazine is contraindicated in CNS depression and concurrent use of adrenergic blockers, and carries additional risks of tardive dyskinesia, hypotension, tachycardia, and arrhythmias. 1