What are alternative treatments for migraine relief in patients who cannot take Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) or triptans?

Alternative Treatments for Migraine Relief in Patients Who Cannot Take NSAIDs or Triptans

For patients who cannot take NSAIDs or triptans, CGRP antagonists (gepants), dihydroergotamine (DHE), or lasmiditan should be considered as first-line alternatives for acute migraine treatment. 1

First-Line Alternative Treatments

• CGRP antagonists (rimegepant, ubrogepant, zavegepant) are effective for moderate to severe acute episodic migraine headaches and have a favorable safety profile for patients with contraindications to NSAIDs or triptans 1
• Dihydroergotamine (DHE), particularly in intranasal formulation, provides good efficacy and safety for acute migraine relief 1
• Lasmiditan (a ditan) is recommended for moderate to severe acute episodic migraine headaches when NSAIDs and triptans are contraindicated 1

Second-Line Alternative Treatments

• Acetaminophen-based combinations (acetaminophen with caffeine) can effectively treat mild to moderate migraines and are generally well-tolerated 1, 2
• Isometheptene combinations (such as Midrin) have demonstrated effectiveness for milder migraine headaches 1
• Antiemetics (metoclopramide, prochlorperazine) can provide dual benefits by relieving both headache pain and accompanying nausea 1, 3

Treatment Algorithm Based on Migraine Severity

For Mild to Moderate Migraines:

• First choice: Acetaminophen + caffeine combination 1, 2
• Second choice: Isometheptene combinations 1
• Third choice: CGRP antagonists if above options fail 1

For Moderate to Severe Migraines:

• First choice: CGRP antagonists (rimegepant, ubrogepant, zavegepant) 1
• Second choice: Dihydroergotamine (intranasal formulation preferred) 1
• Third choice: Lasmiditan 1

For Status Migrainosus (severe, continuous migraine lasting up to one week):

• Systemic steroid therapy is the treatment of choice 1, 3
• Antiemetics should be administered concurrently to treat accompanying nausea 3
• IV fluids for hydration are recommended as part of initial management 3

Important Considerations and Cautions

• Avoid opioids and butalbital-containing medications for routine migraine treatment as they can lead to dependency, rebound headaches, and eventual loss of efficacy 1, 3
• Monitor for medication overuse headache, which can occur with frequent use of acute medications (≥15 days per month with most medications) 1
• Non-oral routes of administration are preferred when significant nausea or vomiting is present 3
• For refractory cases, consider combination therapy or rescue medications such as antiemetics or corticosteroids 1
• Evaluate for preventive therapy to reduce frequency and severity of attacks in patients with frequent migraines 1, 3

Special Populations

• For pregnant patients, acetaminophen is the preferred option 2, 4
• In patients with cardiovascular disease who cannot take triptans or NSAIDs, antiemetics may be a safer alternative 3
• For children, acetaminophen remains a first-choice option 4