Why is lasmitidan (likely a misspelling of a medication, possibly lasmiditan, a serotonin receptor agonist) considered a second-line agent for migraine abortive care?

Why Lasmiditan is a Third-Line Agent for Migraine Abortive Care

Lasmiditan is classified as a third-line agent for migraine abortive care because it is reserved for patients who have failed or cannot use first-line NSAIDs and second-line triptans, and its use is associated with significant driving impairment despite comparable efficacy to triptans. 1

Treatment Algorithm for Migraine Abortive Care

The stepped care approach for migraine abortive treatment follows this evidence-based sequence:

First-Line Therapy

• NSAIDs with strongest evidence: acetylsalicylic acid, ibuprofen, and diclofenac potassium
• Combination therapy: aspirin-acetaminophen-caffeine (strong recommendation) 1
• Paracetamol (acetaminophen) only for those intolerant to NSAIDs

Second-Line Therapy

• Triptans (all have well-documented effectiveness)
• Most effective when taken early in attack while headache is still mild
• Options include oral triptans or sumatriptan subcutaneous injection for rapid onset or when vomiting prevents oral administration
• Can be combined with fast-acting NSAIDs for relapse prevention 1

Third-Line Therapy (including Lasmiditan)

Indicated when:

1. All available triptans have failed after adequate trial (no/insufficient response in at least three consecutive attacks)
2. Triptans are contraindicated (e.g., cardiovascular conditions)

Third-line options include:

• Lasmiditan (ditan class)
• Gepants (ubrogepant and rimegepant) 1

Why Lasmiditan is Third-Line Rather Than Second-Line

Several factors contribute to lasmiditan's third-line positioning:

1. Significant Driving Impairment: Lasmiditan causes temporary driving impairment requiring patients to avoid operating machinery for at least 8 hours after intake. This significant limitation affects daily functioning and discourages widespread use. 1

2. Self-Assessment Concerns: Patients taking lasmiditan may be unable to accurately self-assess their driving competence, creating safety concerns. 1

3. Central Nervous System Side Effects: While lasmiditan offers comparable efficacy to triptans, it has a higher rate of CNS-related adverse effects, with a low number needed to harm of 4 for treatment-emergent adverse effects. 1

4. Newer Medication with Limited Real-World Data: As a newer agent, long-term safety data is still accumulating compared to the well-established safety profiles of NSAIDs and triptans.

Clinical Advantages of Lasmiditan

Despite being third-line, lasmiditan offers important advantages for specific patient populations:

• No Vasoconstriction: Unlike triptans, lasmiditan acts selectively on 5-HT1F receptors and does not cause vasoconstriction, making it suitable for patients with cardiovascular conditions where triptans are contraindicated. 2, 3

• Efficacy in Triptan Failures: Can be effective for patients who have not responded to multiple triptan trials. 4

Practical Considerations When Prescribing Lasmiditan

When using lasmiditan as a third-line agent:

• Warn patients about driving restrictions: Emphasize the need to avoid driving or operating machinery for at least 8 hours after taking the medication.

• Consider scheduling: Patients may need to plan medication use around work or other activities due to the driving restrictions.

• Monitor for CNS effects: Common side effects include dizziness, paresthesias, and vertigo. 5

• Assess cardiovascular risk: While lasmiditan lacks the vasoconstrictive effects of triptans, the overall benefit-risk profile should still be evaluated for each patient.

Avoiding Common Pitfalls

• Don't use as first or second-line: Despite its efficacy, lasmiditan should not replace NSAIDs or triptans in patients who can safely use and respond to these medications.

• Don't ignore driving restrictions: Failure to emphasize the 8-hour driving restriction could lead to safety issues.

• Don't overlook medication overuse headache risk: As with all acute migraine medications, frequent use (more than twice weekly) can lead to medication overuse headache. 1

• Don't use with other CNS depressants: The sedating effects may be potentiated by other medications with CNS depressant properties.

By following this evidence-based approach to migraine treatment, clinicians can appropriately position lasmiditan as a valuable third-line option for patients who cannot use or have failed standard first and second-line therapies.