Rasagiline 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
Rasagiline
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) is a tricyclic antidepressant, and rasagiline (Azilect) is a medicine for Parkinson's disease that works as an MAO inhibitor. When these two are taken together, they can rarely cause a serious reaction in the brain and body. Warning signs include confusion or changes in behavior, heavy sweating, stiff muscles, high blood pressure, fainting, and a dangerously high body temperature.
Because this reaction can be severe, doctors usually avoid using these two together. Please don't stop or change either medicine on your own. If you've been prescribed both, reach out to your pharmacist or doctor so they can review your medicines and pick a safer plan for you.
Interaction: Combining amitriptyline (TCA) with rasagiline (MAO-B inhibitor) is associated with severe CNS toxicity, including behavioral/mental status changes, diaphoresis, muscular rigidity, hypertension, syncope, hyperpyrexia, and potential fatality.
- Mechanism: Not fully understood; extrapolated from serious/fatal reactions seen with TCAs plus nonselective MAOIs.
- Direction: Additive/serotonergic-adrenergic CNS toxicity (neither is a relevant prodrug here).
- Evidence: Theoretical; clinical data (n=115) insufficient to exclude the interaction.
- Management: Avoid concurrent use. Allow at least 14 days after discontinuing rasagiline before starting a TCA.
What happens
Severe CNS toxicity
Interaction Deep Dive
Rasagiline should not be taken together with tricyclic antidepressants. Combining or overlapping tricyclic antidepressant therapy with nonselective MAOIs has been associated with serious and occasionally fatal reactions, though the underlying mechanisms remain incompletely understood. Reported manifestations include severe CNS toxicity (changes in behavior and mental status, diaphoresis, muscular rigidity, hypertension, and syncope) occurring alongside hyperpyrexia and death. The clinical study data involving rasagiline-treated patients (n=115) who received concurrent tricyclic antidepressants are not sufficient to exclude an interaction. A minimum of 14 days should pass following discontinuation of rasagiline before starting a tricyclic antidepressant1.
Why it happens (mechanism)
Unknown
How to manage this interaction
Your care team will generally avoid using these two medicines together because of the risk of a serious reaction. If both have been prescribed, keep taking them exactly as directed for now and contact your prescriber or pharmacist promptly so they can review your regimen.
- Your team may switch one medicine or plan a washout period (at least 14 days after stopping rasagiline before starting a tricyclic like amitriptyline).
- Seek urgent care for confusion, agitation, heavy sweating, muscle stiffness, high fever, fainting, or very high blood pressure.
Do not start, stop, or change either medicine on your own.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) The information from clinical studies in which patients receiving rasagiline (n=115) were also given tricyclic antidepressants is not sufficient to exclude an interaction 1.
Common questions
Can I take Rasagiline and Amitriptyline together?
Amitriptyline and rasagiline are generally avoided together because the combination can rarely cause severe, even fatal, CNS toxicity; talk to your prescriber or pharmacist and allow at least a 14-day gap after stopping rasagiline before starting amitriptyline. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Rasagiline 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 Rasagiline and Amitriptyline interaction managed?
Your care team will generally avoid using these two medicines together because of the risk of a serious reaction. If both have been prescribed, keep taking them exactly as directed for now and contact your prescriber or pharmacist promptly so they can review your regimen. Your team may switch one medicine or plan a washout period (at least 14 days after stopping rasagiline before starting a tricyc… 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 Rasagiline 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: AZILECT(R) oral tablets, rasagiline oral tablets. Teva Pharmaceuticals, Kfar Saba, Israel, 2006. DailyMed
Keep reading about Amitriptyline
Keep reading about Rasagiline
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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