What is the recommended treatment for a patient with migraine attacks, considering the use of Reyvow (lasmiditan)?

Reyvow (Lasmiditan) for Acute Migraine Treatment

Reyvow (lasmiditan) should be reserved as a third-line option for acute migraine treatment, used only when all available triptans have failed after adequate trials (no response in at least three consecutive attacks) or when triptans are contraindicated due to cardiovascular disease. 1

Position in Treatment Algorithm

First-Line Treatment

• Start with NSAIDs (aspirin, ibuprofen, or diclofenac potassium) for initial acute migraine management 1
• These medications should be taken early in the attack when headache is still mild 1

Second-Line Treatment

• Escalate to triptans when NSAIDs provide inadequate relief 1
• Consider combining triptans with fast-acting NSAIDs to prevent relapse 1
• If one triptan fails, trial other triptans as response varies between agents 1

Third-Line Treatment: Lasmiditan

• Consider lasmiditan only after all available triptans have been tried without success in at least three consecutive attacks 1
• Lasmiditan efficacy is comparable to triptans based on indirect comparisons from randomized controlled trials 1
• The 2024 VA/DoD guidelines note insufficient evidence to make a definitive recommendation for or against lasmiditan, reflecting its uncertain position in therapy 1

Critical Safety Considerations

Driving Impairment Warning

• Patients taking lasmiditan cannot self-assess their driving competence and must not operate machinery for at least 8 hours after intake 1
• This temporary driving impairment will likely discourage widespread use 1
• The high incidence of CNS-related adverse events may adversely limit clinical utility 2

Adverse Event Profile

• CNS-related adverse events are common and often moderate to severe 2, 3
• Treatment-emergent adverse events occurred in 65-87% of patients receiving lasmiditan 50-400 mg compared to 22% with placebo 3

Dosing Considerations

Available Doses

• Lasmiditan is available in 50 mg, 100 mg, and 200 mg tablets 4, 5
• Higher doses (100-200 mg) demonstrate greater efficacy but also increased adverse events 5

Dose Optimization

• Patients starting on 50 mg who increase to 100 or 200 mg show improved efficacy despite increased adverse events, providing a positive efficacy-tolerability balance 5
• Patients starting on 100 mg who increase to 200 mg also demonstrate a positive efficacy-tolerability balance 5
• Decreasing from 200 to 100 mg reduces both efficacy and adverse events, resulting in a neutral balance 5

Efficacy Timeline

Onset of Action

• Pain relief can occur as early as 30 minutes with 100-200 mg doses 6
• Pain freedom rates become significantly higher than placebo at 60 minutes for 100-200 mg doses (10.0% and 15.5% vs 7.0% placebo) 6
• Most bothersome symptom freedom occurs as early as 30 minutes with 100-200 mg doses 6

Specific Clinical Scenarios

Cardiovascular Contraindications to Triptans

• Lasmiditan lacks vasoconstrictive activity, making it theoretically suitable for patients with cardiovascular risk factors where triptans are contraindicated 2, 3
• However, the cardiovascular benefit must be weighed against increased CNS risks 2

Difficult-to-Treat Populations

• Lasmiditan 100-200 mg demonstrates efficacy in patients with ≥24 headache days per month, migraine history ≥20 years, severe disability, obesity, and psychiatric comorbidities 7
• Efficacy is maintained in patients with severe headache, co-existent nausea, or delayed treatment ≥2 hours from onset 7

Critical Pitfalls to Avoid

Medication Overuse Headache

• Limit lasmiditan use to no more than 2 days per week to prevent medication overuse headache 1
• Frequent use of any acute medication (≥10 days/month for triptans, ≥15 days/month for NSAIDs) can lead to medication overuse headache 1

Premature Use

• Do not use lasmiditan before adequately trialing multiple triptans 1
• The 2025 American College of Physicians guidelines note that comparative evidence for lasmiditan monotherapy remains inconclusive 1

Adjunctive Therapy

• For nausea and vomiting, add prokinetic antiemetics (domperidone or metoclopramide) rather than relying solely on lasmiditan 1

When to Consider Preventive Therapy

• If acute medications (including lasmiditan) are needed more than twice weekly, initiate preventive therapy immediately 1
• Preventive therapy is indicated for patients with ≥2 migraine attacks per month producing disability lasting ≥3 days 1, 8