Does Amitriptyline Interact With Duloxetine?
Potential for Duloxetine delayed-release capsules to Affect Other Drugs Drugs Metabolized by CYP2D6 — Co-administration of Duloxetine delayed-release capsules with drugs that are extensively metabolized by CYP2D6 and that have a narrow therapeutic index, including certain antidepressants (tricyclic antidepressants [TCAs], such as nortriptyline, amitriptyline, and imipramine), phenothiazines and Type 1C antiarrhythmics (e.g., propafenone, flecainide), should be approached with caution.
Severity: Moderate
Severity basis: warnings section (keywords: caution). Combining Amitriptyline (Tricyclic antidepressant) and Duloxetine (SNRI antidepressant) is classified as a moderate interaction.
What to Do
Use this combination with caution. Your prescriber may monitor you more closely or adjust doses.
How This Interaction Works
Interactions like this one can happen when two medicines have overlapping effects, or when one changes how the other is absorbed, broken down, or cleared from the body. Amitriptyline is a tricyclic antidepressant and Duloxetine is a snri antidepressant; together they are documented as a moderate interaction. How much this matters depends on your dose, your other medications, and your overall health.
If You Take Both Medications
If you have been prescribed both Amitriptyline and Duloxetine, do not start, stop, or change either medication on your own — some medicines are unsafe to stop suddenly. Tell your prescriber and pharmacist that you take both so they can decide whether the combination is right for you, adjust the dose, monitor you more closely, or suggest an alternative.
From the FDA Label
Potential for Duloxetine delayed-release capsules to Affect Other Drugs Drugs Metabolized by CYP2D6 — Co-administration of Duloxetine delayed-release capsules with drugs that are extensively metabolized by CYP2D6 and that have a narrow therapeutic index, including certain antidepressants (tricyclic antidepressants [TCAs], such as nortriptyline, amitriptyline, and imipramine), phenothiazines and Type 1C antiarrhythmics (e.g., propafenone, flecainide), should be approached with caution.
Source: FDA structured product labeling (set_id 00628e5e-4c5b-2573-e063-6294a90a0e3b).
Check these against your full medication list in our free Interaction Checker
Frequently Asked Questions
Can you take Amitriptyline and Duloxetine together?
Amitriptyline and Duloxetine have a documented moderate interaction. Use this combination with caution. Your prescriber may monitor you more closely or adjust doses.
How serious is the Amitriptyline and Duloxetine interaction?
It is classified as a moderate interaction, based on the FDA label's warnings section (keywords: caution). A moderate interaction can be clinically meaningful and usually calls for monitoring or a dose adjustment.
What should I do if I'm taking both Amitriptyline and Duloxetine?
If you have been prescribed both Amitriptyline and Duloxetine, do not start, stop, or change either medication on your own — some medicines are unsafe to stop suddenly. Tell your prescriber and pharmacist that you take both so they can decide whether the combination is right for you, adjust the dose, monitor you more closely, or suggest an alternative.
This information is educational — not medical advice.
This page is provided for general educational purposes and summarizes publicly available data from sources such as the U.S. Food & Drug Administration. It is not a substitute for the judgment of a licensed clinician and should not be used to start, stop, or change any medication. It may be incomplete or out of date, and individual circumstances vary. Always talk with your prescriber or pharmacist about your specific medications and health conditions. If you think you may have a medical emergency, call 911.
Other Amitriptyline Interactions
- Amitriptyline + Risperidone(major)
- Amitriptyline + Carbamazepine(moderate)
- Amitriptyline + Cyclobenzaprine(moderate)
- Amitriptyline + Levothyroxine(moderate)
- Amitriptyline + Liothyronine(moderate)
- Amitriptyline + Valproic Acid(moderate)
- Amitriptyline + Clonidine(minor)
- Amitriptyline + Fluconazole(minor)
- Amitriptyline + Fluoxetine(minor)
- Amitriptyline + Paroxetine(minor)
- Amitriptyline + Sertraline(minor)
- Amitriptyline + Topiramate(minor)
Other Duloxetine Interactions
- Duloxetine + Ciprofloxacin(moderate)
- Duloxetine + Fluoxetine(moderate)
- Duloxetine + Nortriptyline(moderate)
- Duloxetine + Aspirin(minor)
- Duloxetine + Buspirone(minor)
- Duloxetine + Famotidine(minor)
- Duloxetine + Lithium(minor)
- Duloxetine + Lorazepam(minor)
- Duloxetine + Paroxetine(minor)
- Duloxetine + Temazepam(minor)
- Duloxetine + Tramadol(minor)
- Duloxetine + Warfarin(minor)