Amitriptyline and Desipramine: 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
Desipramine
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 desipramine (Norpramin) are both tricyclic antidepressants. Each one can slightly affect the heart's electrical rhythm, a change doctors call QT prolongation. When you take both together, those effects can add up, which may raise the chance of an irregular heartbeat.
It's actually pretty unusual to be on two of these medicines at the same time. If you are, don't worry, this is something your care team can manage. Keep taking both exactly as prescribed, and check in with your pharmacist or doctor so they can watch your heart rhythm and make sure the combination is right for you.
Effect: Additive QT-interval prolongation and increased risk of serious cardiovascular events (including torsades de pointes).
Mechanism: Both are tricyclic antidepressants with intrinsic effects on cardiac repolarization; combined use produces additive pharmacodynamic QT prolongation. Neither is a prodrug in a way that alters direction.
- Direction: Additive PD effect, increased cardiac risk
- Onset: Unspecified
- Evidence: Theoretical
- Management: Concurrent TCA use is uncommon; if unavoidable, use caution, obtain baseline/periodic ECG, monitor electrolytes (K+, Mg2+), and review other QT-prolonging agents. Dose should be individualized by the care team.
What happens
An increased risk of QT interval prolongation
Interaction Deep Dive
Prescribing amitriptyline together with desipramine is not typically encountered in clinical settings. If these two agents are administered concurrently, however, exercise caution because they may produce additive QT interval effects and heighten the likelihood of serious cardiovascular events1.
Why it happens (mechanism)
Additive effects on the QT interval
How to manage this interaction
Using two tricyclic antidepressants together is uncommon, but if your care team has prescribed both, here is how they typically handle it:
- Keep taking both medicines exactly as prescribed, do not stop or change doses on your own.
- Your team may check your heart rhythm with an ECG and may monitor you more closely.
- They may review your other medicines and correct electrolytes like potassium and magnesium.
- Your doses may need to be adjusted and individualized by your care team.
Tell your pharmacist or doctor right away if you feel a fast, pounding, or irregular heartbeat, dizziness, or fainting.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Amitriptyline and Desipramine together?
Taking amitriptyline and desipramine together can add up their effects on your heart rhythm, so keep taking both as prescribed and let your care team monitor you and tailor your doses. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Desipramine 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 Amitriptyline and Desipramine interaction managed?
Using two tricyclic antidepressants together is uncommon, but if your care team has prescribed both, here is how they typically handle it: Keep taking both medicines exactly as prescribed, do not stop or change doses on your own. Your team may check your heart rhythm with an ECG and may monitor you more closely. They may review your other medicines and correct electrolytes like potassium and magne… 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 Amitriptyline or Desipramine 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: amitriptyline HCl oral tablet, amitriptyline HCl oral tablet. RemedyRepack Inc. (per DailyMed), Indiana, PA, 2010. DailyMed
Keep reading about Amitriptyline
Keep reading about Desipramine
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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