Amphetamine 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
Amphetamine
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 an antidepressant, and amphetamine (like Dexedrine or Adderall-type medicines) treats conditions such as ADHD. Both raise levels of a brain chemical called serotonin. When taken together, they can add up and, in rare cases, cause a reaction called serotonin syndrome.
Signs to watch for include feeling agitated or confused, a fast heartbeat, sweating, shaking, muscle twitching, or a high fever. This is based mostly on how the drugs work in theory, not on lots of real-world cases, so many people take both safely. The good news is your care team can manage this by starting low, watching you closely, and adjusting as needed. Never stop either medicine on your own, but do call your doctor if you feel these symptoms.
Effect: Additive serotonergic activity from amitriptyline (a TCA with serotonin reuptake inhibition) and amphetamine (promotes monoamine release, including serotonin) increases the theoretical risk of serotonin syndrome. Amphetamine CNS concentrations and cardiovascular effects may also be potentiated.
- Mechanism: pharmacodynamic, additive serotonergic effect.
- Direction: increased serotonergic tone; neither agent is metabolically inhibiting the other here.
- Evidence: theoretical; severity rated major.
- Onset: unspecified; risk highest at initiation/dose escalation.
- Management: if required, initiate at lower doses, monitor HR/BP/temperature and neuromuscular status. Discontinue both if serotonin syndrome is suspected.
What happens
An increased risk of serotonin syndrome
Interaction Deep Dive
Giving an amphetamine together with another serotonergic drug can lead to serotonin syndrome, since both agents act on the serotonergic neurotransmitter system12. There may also be prolonged elevations of d-amphetamine levels in the brain, along with potential enhancement of cardiovascular effects1. When using an amphetamine alongside such an agent is clinically necessary, begin with reduced doses and observe patients closely, particularly at the start of therapy and when doses are being changed. Both medications should be stopped if serotonin syndrome is suspected32.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
If your care team has prescribed both, keep taking them as directed unless told otherwise. This combination can be used with care.
- Your doses may be started low and individualized by your care team, with closer monitoring, especially when starting or changing a dose.
- Your team may check your heart rate, blood pressure, and temperature and ask how you are feeling.
- Watch for agitation, confusion, rapid heartbeat, heavy sweating, shivering, muscle twitching, or fever, and report these promptly.
Ask your pharmacist or prescriber before adding any new serotonergic medicine, and get urgent help if the symptoms above appear.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Amphetamine and Amitriptyline together?
Taking amitriptyline and amphetamine together can add up their serotonin effects and, rarely, trigger serotonin syndrome; keep taking both as prescribed, but let your care team monitor you and get help if you notice agitation, fast heartbeat, sweating, shaking, or fever. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amphetamine 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 Amphetamine and Amitriptyline interaction managed?
If your care team has prescribed both, keep taking them as directed unless told otherwise. This combination can be used with care. Your doses may be started low and individualized by your care team, with closer monitoring, especially when starting or changing a dose. Your team may check your heart rate, blood pressure, and temperature and ask how you are feeling. Watch for agitation, confusion, ra… 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:
- Amitriptyline With Passionflower - Interaction Details
- What Dose Of Amitriptyline Is Used For Sleep?
- How Long Does Amitriptyline Take To Work For Headaches?
- Can Allergy Medication Cause A Positive Amphetamine Drug Test?
- Can Vyvanse Cause A Positive Amphetamine Drug Test?
- How Much Amphetamine Do Adderall XR Products Contain?
Questions for your pharmacist
- Does my dose of Amphetamine 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 Amphetamine
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.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist