What is the role of lesmiditan in treating acute migraine attacks?

Role of Lasmiditan in Treating Acute Migraine Attacks

Lasmiditan is a third-line medication for acute migraine treatment, recommended for patients who have failed or cannot use triptans due to contraindications, particularly those with cardiovascular risk factors. 1

Mechanism and Classification

• Lasmiditan (Reyvow) is the first and only approved "ditan" - a selective serotonin 5-HT1F receptor agonist that does not cause vasoconstriction, unlike triptans 2
• Its mechanism provides a therapeutic option for migraine patients with cardiovascular conditions where triptans are contraindicated 2

Treatment Algorithm for Acute Migraine

First-Line Treatment

• NSAIDs (acetylsalicylic acid, ibuprofen, diclofenac potassium) should be used as first-line medications for mild to moderate migraine attacks 1
• These should be administered early in the headache phase for maximum effectiveness 1

Second-Line Treatment

• Triptans are recommended as second-line medications when NSAIDs provide inadequate relief 1
• Triptans are most effective when taken early in an attack while headache pain is still mild 1
• If one triptan is ineffective, others might still provide relief 1

Third-Line Treatment

• Lasmiditan should be considered as a third-line medication when:
  • All available triptans have failed after adequate trials (no/insufficient response in at least three consecutive attacks) 1
  • Triptans are contraindicated (particularly in patients with cardiovascular risk factors) 2

Efficacy of Lasmiditan

• Randomized controlled trials show that lasmiditan at doses of 50mg, 100mg, and 200mg is superior to placebo for:

  • Pain freedom at 2 hours post-dose 3, 4
  • Relief from most bothersome migraine symptoms 4
  • Global impression improvement 5
  • Reduced need for rescue medication 3

• Efficacy appears comparable to triptans based on indirect comparisons of clinical trials 1

• Lasmiditan demonstrates efficacy in both triptan-responsive patients and those with insufficient response to triptans 6

Safety Considerations and Limitations

• Lasmiditan is associated with significant central nervous system (CNS) side effects that may limit its use 1:

  • Dizziness (most common adverse effect) 3, 5
  • Somnolence 4
  • Paresthesia 5
  • Fatigue 5

• Important safety warning: Lasmiditan causes temporary driving impairment - patients should not operate machinery for at least 8 hours after taking the medication 1

• Unlike triptans, lasmiditan does not appear to cause vasoconstriction, making it potentially safer for patients with cardiovascular risk factors 2

Practical Recommendations

• Consider lasmiditan particularly for patients with:

  • Cardiovascular conditions that contraindicate triptan use 2
  • History of inadequate response to multiple triptans 6
  • Intolerance to triptans 1

• When prescribing lasmiditan:

  • Start with lower doses (50mg or 100mg) to minimize adverse effects 3
  • Warn patients about driving restrictions (no driving for 8 hours after dosing) 1
  • Monitor for CNS-related side effects 5

• For optimal migraine management, combine with:

  • Prokinetic antiemetics (domperidone or metoclopramide) if nausea/vomiting is present 1
  • Preventive therapy if migraine attacks occur frequently (≥2 days/month) 1

Common Pitfalls to Avoid

• Do not use lasmiditan as first-line therapy - NSAIDs should be tried first for most patients 1
• Do not expect immediate driving ability after lasmiditan use - the 8-hour restriction is critical for safety 1
• Do not underestimate the potential for CNS side effects, which occur in approximately 25-39% of patients depending on dose 4
• Do not use in combination with other CNS depressants without careful consideration of additive effects 4