Amitriptyline and Atomoxetine: 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
Atomoxetine
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.
Taking amitriptyline (Elavil) and atomoxetine (Strattera) together can cause more atomoxetine to build up in your body. That is because amitriptyline slows down the liver enzyme that normally breaks atomoxetine down, so the levels can rise quite a bit.
When atomoxetine levels climb, you may notice more of its side effects, like a faster heartbeat, higher blood pressure, trouble sleeping, dry mouth, or feeling jittery. This does not mean you cannot use both. Your care team can manage this safely by tailoring your atomoxetine dose and keeping an eye on how you feel. Keep taking both as prescribed, and let your pharmacist or doctor know about any new symptoms.
Effect: Amitriptyline inhibits CYP2D6, the primary pathway that metabolizes atomoxetine to 4-hydroxyatomoxetine. This raises atomoxetine exposure.
- Direction/magnitude: In CYP2D6 extensive metabolizers, atomoxetine AUC increases roughly 6- to 8-fold and Cmax 3- to 4-fold, approaching levels seen in poor metabolizers.
- Onset: Unspecified; relevant at steady state.
- Evidence: Probable.
- Management: Atomoxetine dose may need to be adjusted and individualized. Monitor for dose-related effects (tachycardia, elevated BP, insomnia, GI upset, appetite loss).
What happens
An increase in atomoxetine steady-state plasma concentrations
Interaction Deep Dive
The main metabolic route for atomoxetine involves the cytochrome P450 2D6 (CYP 2D6) enzyme, which converts it to 4-hydroxyatomoxetine. When extensive metabolizers receive selective CYP2D6 inhibitors, for example amitriptyline, atomoxetine steady-state plasma levels rise, reaching exposures comparable to those seen in poor metabolizers. Specifically, extensive metabolizers who are given amitriptyline show an atomoxetine area under the concentration-time curve that is roughly 6- to 8-fold higher, along with a steady-state maximum plasma concentration that is about 3- to 4-fold higher, relative to atomoxetine given by itself1.
Why it happens (mechanism)
Inhibition of cytochrome P450 2D6-mediated metabolism of atomoxetine by amitriptyline
How to manage this interaction
This interaction is manageable with the right oversight. Here is what typically happens and what you can do:
- Dose tailoring: Your atomoxetine dose may need to be adjusted and individualized by your care team when it is used with amitriptyline.
- Closer monitoring: Your team may watch you more closely for signs the atomoxetine level is running high, such as a fast heartbeat, raised blood pressure, trouble sleeping, or reduced appetite.
- Keep both going: Do not start, stop, or change either medicine on your own. Take them exactly as prescribed.
- Speak up: Tell your pharmacist or prescriber about any new or bothersome symptoms so they can fine-tune your plan.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Amitriptyline and Atomoxetine together?
Amitriptyline can substantially raise atomoxetine levels, so your care team may adjust the atomoxetine dose and monitor you more closely. Keep taking both as prescribed and report any new side effects. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Atomoxetine interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Amitriptyline and Atomoxetine interaction managed?
This interaction is manageable with the right oversight. Here is what typically happens and what you can do: Dose tailoring: Your atomoxetine dose may need to be adjusted and individualized by your care team when it is used with amitriptyline. Closer monitoring: Your team may watch you more closely for signs the atomoxetine level is running high, such as a fast heartbeat, raised blood pressure, tr… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Amitriptyline or Atomoxetine 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 anything you'd monitor while I'm on both?
References (1)
- Product Information: Strattera(TM), atomoxetine. Eli Lilly and Company, Indianapolis, IN, 2002. DailyMed
Keep reading about Amitriptyline
Keep reading about Atomoxetine
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