Dextroamphetamine 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
Dextroamphetamine
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 dextroamphetamine (Dexedrine) both raise the activity of a brain chemical called serotonin. When you take them together, that combined effect can, in rare cases, build up too much and cause a reaction called serotonin syndrome. Warning signs include feeling agitated or restless, a racing heart, sweating, shaking, muscle twitching, or a high fever.
This risk is mostly theoretical, meaning it is expected from how the drugs work rather than proven to happen often. Many people take these two together safely. Your care team can manage this by starting low and watching you closely, so keep taking both as prescribed and let them know if you feel any of those symptoms.
Effect: Additive serotonergic activity increases the theoretical risk of serotonin syndrome when amitriptyline (a serotonergic TCA) is combined with dextroamphetamine (which promotes monoamine release and reuptake inhibition).
- Mechanism: Additive serotonergic effects; possible sustained increases in central d-amphetamine concentrations and potentiated cardiovascular effects.
- Direction: Increased serotonergic and sympathomimetic effect (neither agent is affected as a prodrug here).
- Severity/Evidence: Major, but theoretical. Onset unspecified.
- Management: If coadministration is required, initiate at lower doses, individualize titration, and monitor closely during initiation and dose changes. Discontinue both if serotonin syndrome is suspected.
What happens
An increased risk of serotonin syndrome
Interaction Deep Dive
When an amphetamine is given together with another serotonergic agent, serotonin syndrome can develop, since both agents act on the serotonergic neurotransmitter system12. The concentration of d-amphetamine in the brain may also remain elevated for a prolonged period, and cardiovascular effects can be intensified1. Should the combined use of an amphetamine and such an agent be clinically necessary, start with reduced doses and observe patients closely, particularly when therapy is begun and when doses are changed. Both medications should be stopped if serotonin syndrome is suspected32.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
Many people use these two medicines together under supervision. Here is how a care team typically handles it:
- They may start at lower doses and adjust gradually, individualized to you.
- They may monitor you more closely, especially when starting or changing a dose.
- Keep taking both medicines as prescribed unless your prescriber tells you otherwise.
Call your pharmacist or doctor promptly if you notice agitation, confusion, a fast heartbeat, heavy sweating, shivering, muscle twitching, or fever, as these can be signs of serotonin syndrome. Bring up any new symptoms at follow-up visits.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Dextroamphetamine and Amitriptyline together?
Combining amitriptyline and dextroamphetamine can theoretically raise serotonin too much, so your care team may start low, monitor you closely, and watch for symptoms like agitation, rapid heartbeat, sweating, or tremor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Dextroamphetamine 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 Dextroamphetamine and Amitriptyline interaction managed?
Many people use these two medicines together under supervision. Here is how a care team typically handles it: They may start at lower doses and adjust gradually, individualized to you. They may monitor you more closely, especially when starting or changing a dose. Keep taking both medicines as prescribed unless your prescriber tells you otherwise. Call your pharmacist or doctor promptly if you not… 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 Dextroamphetamine 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 (3)
- Product Information: VYVANSE(R) oral capsules, oral chewable tablets, lisdexamfetamine dimesylate oral capsules, oral chewable tablets. Shire US Inc (per DailyMed), Lexington, MA, 2018. DailyMed
- Product Information: FETZIMA(R) oral extended-release capsules, levomilnacipran oral extended-release capsules. AbbVie Inc (per FDA), North Chicago, IL, 2023. DailyMed
- Product Information: ADDERALL(R) oral tablets, dextroamphetamine saccharate amphetamine aspartate dextroamphetamine sulfate amphetamine sulfate oral tablets. Teva Select Brands (per FDA), Horsham, PA, 2017. DailyMed
Keep reading about Amitriptyline
Keep reading about Dextroamphetamine
These medications also interact with supplements
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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