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

Alternative Treatment Options 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 the ditan lasmiditan should be considered as first-line alternatives for acute migraine treatment. 1

First-Line Alternative Treatments

• CGRP Antagonists (Gepants): Consider rimegepant, ubrogepant, or zavegepant for moderate to severe acute episodic migraine headaches 1
• Dihydroergotamine (DHE): Available in intranasal formulation with good evidence for efficacy and safety 1
• Lasmiditan (Ditan): Consider for moderate to severe acute episodic migraine headache when other options are contraindicated or ineffective 1

Second-Line Alternative Treatments

• Acetaminophen-based combinations: While acetaminophen alone is ineffective for migraines, it can be effective when combined with caffeine 1
• Isometheptene combinations: The combination of isometheptene, acetaminophen, and dichloralphenazone (Midrin) has shown effectiveness for milder migraine headaches 1
• Antiemetics: Metoclopramide or prochlorperazine can effectively relieve headache pain in addition to treating nausea 1

Treatment Algorithm Based on Migraine Severity

For Mild to Moderate Migraines:

1. Acetaminophen + caffeine combination 1
2. Isometheptene combinations 1
3. CGRP antagonists if above options fail 1

For Moderate to Severe Migraines:

1. CGRP antagonists (rimegepant, ubrogepant, zavegepant) 1
2. Dihydroergotamine (intranasal formulation preferred) 1
3. Lasmiditan if other options fail 1

For Migraines with Significant Nausea/Vomiting:

1. Non-oral routes of administration (nasal sprays, injections) 1
2. Antiemetics (metoclopramide, prochlorperazine) in addition to migraine treatment 1

Special Considerations

• Avoid opioids and butalbital-containing medications for routine migraine treatment as they can lead to dependency, rebound headaches, and eventual loss of efficacy 1
• Consider intranasal formulations when oral medications are not tolerated due to nausea or vomiting 2
• For status migrainosus (severe, continuous migraine lasting up to one week), systemic steroid therapy may be the treatment of choice 3
• Monitor for medication overuse headache, which can occur with frequent use of acute medications (≥15 days per month with most medications; ≥10 days per month with triptans) 1

Important Cautions

• Cardiovascular safety: While triptans are contraindicated in patients with cardiovascular disease, CGRP antagonists and lasmiditan may be safer alternatives, though long-term studies are still needed 4
• Pregnancy considerations: Acetaminophen is the safest acute migraine drug during pregnancy 5
• Medication overuse: The risk of developing medication overuse headache may differ between different drug classes, but all acute medications should be limited to prevent this complication 4

Treatment Failure Considerations

• If first-line alternatives fail: Consider combination therapy or rescue medications such as antiemetics or corticosteroids 3
• For refractory cases: Evaluate for preventive therapy to reduce frequency and severity of attacks 1
• Non-pharmacological approaches: Lifestyle modifications including hydration, regular meals, sufficient sleep, physical activity, and stress management should be emphasized alongside pharmacological treatment 1