What alternative medications can be used to treat migraine headaches when triptans (5-hydroxytryptamine receptor agonists) are ineffective?

Alternative Medications for Migraine Headaches When Triptans Are Ineffective

When triptans fail to provide relief for migraine headaches, dihydroergotamine (DHE) should be used as the first alternative medication due to its effectiveness in treating severe migraines that are unresponsive to other treatments. 1

First-Line Alternatives to Triptans

Dihydroergotamine (DHE)

• DHE is a semisynthetic ergot alkaloid and nonselective 5-HT1 receptor agonist that is particularly effective for severe migraines unresponsive to triptans 1
• Available in multiple formulations:
  • Intranasal spray: One 0.5-mg spray in each nostril, followed by one spray in each nostril 15 minutes later; maximum 4 sprays (2 mg) per day 1
  • Parenteral preparations: Initial dose 0.5-1.0 mg, can be repeated hourly to maximum 3 mg IM or 2 mg IV per day 1
• Evidence for efficacy and safety is particularly good for the intranasal formulation 1
• Contraindications include use with triptans, beta blockers, certain antihypertensives, pregnancy, and cardiovascular disease 1

Ergotamine Derivatives

• Traditional ergotamine preparations can be considered when DHE is unavailable 1
• Dosage: 1-2 mg orally every hour, maximum three doses in 24 hours 1
• Caffeine plus ergotamine (Cafergot): Two tablets at onset, then one tablet every 30 minutes, up to six tablets per attack 1
• Caution: Ergotamine has more limited use due to potential for medication-overuse headaches and peripheral vasoconstriction 1
• Contraindications include concurrent use of triptans, pregnancy, and lactation 2

Second-Line Alternatives

Butorphanol Nasal Spray

• Evidence supports efficacy for migraine attacks unresponsive to first-line treatments 1
• Particularly useful when rapid relief is needed and other options have failed 1

Opioids

• May be considered when other medications cannot be used 1
• Should only be used after addressing risk of abuse and when sedation is not a concern 1
• Best used as a rescue medication for severe migraine attacks unresponsive to other treatments 1

Route of Administration Considerations

• When nausea or vomiting are significant components of migraine attacks, non-oral routes should be selected 1
• Options include:
  • Intranasal DHE or butorphanol 1
  • Rectal suppositories (ergotamine derivatives) 1
  • Injectable preparations (DHE) 1

Important Clinical Considerations

• Antiemetics should be administered when nausea is present 1
• To prevent medication-overuse headaches, limit acute treatments to no more than twice a week 1
• Consider preventive therapy if acute treatments consistently fail or if medication overuse is a risk 1
• First-line preventive agents include propranolol, timolol, amitriptyline, divalproex sodium, and sodium valproate 1

Cautions and Contraindications

• Ergot derivatives should not be used with triptans due to risk of severe vasoconstriction 2, 3
• DHE and ergotamine are contraindicated in pregnancy, cardiovascular disease, and uncontrolled hypertension 1, 2
• Ergot alkaloids should not be used chronically due to risk of peripheral vasoconstriction 1
• Watch for signs of ergotism: numbness, coldness, and pallor of digits, which can progress to gangrene if untreated 2

Treatment Algorithm for Triptan Failures

1. First try DHE (preferably intranasal or parenteral) for fastest and most reliable relief 1
2. If DHE is contraindicated or unavailable, consider ergotamine derivatives 1
3. For patients with significant nausea/vomiting, use non-oral routes of administration 1
4. Add antiemetics when nausea is present 1
5. Consider butorphanol nasal spray or opioids only when other options have failed 1
6. Evaluate for preventive therapy if acute treatments consistently fail 1

Remember that patients should try a medication for two to three headache episodes before abandoning that line of therapy, and if one triptan is ineffective, a different triptan should be tried before moving to non-triptan alternatives 1.