Lasmiditan and Amitriptyline: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Amitriptyline
Lasmiditan
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Amitriptyline (Elavil) and lasmiditan (Reyvow) can each raise serotonin, a natural chemical in your brain. When you take them together, that serotonin can add up, and in rare cases this can lead to a condition called serotonin syndrome.
Warning signs to watch for include agitation or confusion, a fast heartbeat, high fever, heavy sweating, shivering, muscle twitching or stiffness, and shakiness. This is considered a possible (theoretical) risk rather than something proven to happen often. The good news is your care team can manage this safely by watching for symptoms. If any of those signs show up, get medical help right away, and always let your pharmacist or doctor know you take both.
Interaction: Additive serotonergic effects. Both agents increase central serotonin (amitriptyline via serotonin reuptake inhibition; lasmiditan as a 5-HT1F receptor agonist), raising the theoretical risk of serotonin syndrome (hypertension, hyperthermia, myoclonus, autonomic instability, altered mental status).
- Direction: Pharmacodynamic (PD), additive; not a metabolic/prodrug interaction.
- Severity: Major. Evidence: Theoretical. Onset: Unspecified.
- Management: Use lasmiditan with caution in patients on serotonergic agents. Monitor for signs of serotonin syndrome; discontinue lasmiditan if suspected and provide supportive care.
What happens
Increased risk of serotonin syndrome (hypertension, hyperthermia, myoclonus, mental status changes)
Interaction Deep Dive
As a serotonin agonist, lasmiditan carries a heightened potential for serotonin syndrome when given together with a second serotonergic drug. Exercise caution when prescribing lasmiditan to patients receiving agents that elevate serotonin levels, and stop lasmiditan should serotonin syndrome be suspected1.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
Both medicines can raise serotonin, so together they slightly increase the chance of serotonin syndrome. This is a possible, not proven, risk, and your care team can manage it.
- Keep taking both exactly as prescribed unless your doctor or pharmacist tells you otherwise.
- Your team may monitor you more closely and use lasmiditan with caution.
- Watch for confusion, fever, sweating, fast heartbeat, muscle twitching, or shivering, especially after a lasmiditan dose.
- Get medical help right away if these symptoms appear; lasmiditan may be stopped if serotonin syndrome is suspected.
- Tell any prescriber that you take both drugs.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Lasmiditan and Amitriptyline together?
Taking amitriptyline with lasmiditan can add up serotonin and, rarely, cause serotonin syndrome. Keep taking both as prescribed, watch for confusion, fever, sweating, fast heartbeat, or muscle twitching, and seek care right away if they occur. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lasmiditan and Amitriptyline interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Lasmiditan and Amitriptyline interaction managed?
Both medicines can raise serotonin, so together they slightly increase the chance of serotonin syndrome. This is a possible, not proven, risk, and your care team can manage it. Keep taking both exactly as prescribed unless your doctor or pharmacist tells you otherwise. Your team may monitor you more closely and use lasmiditan with caution. Watch for confusion, fever, sweating, fast heartbeat, musc… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Lasmiditan or Amitriptyline need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (1)
- Product Information: REYVOW(TM) oral tablets, lasmiditan oral tablets. Lilly USA LLC (per manufacturer), Indianapolis, IN, 2019. DailyMed
Keep reading about Amitriptyline
Keep reading about Lasmiditan
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