Amitriptyline and Fluoxetine Interaction
Drug interaction information between Amitriptyline and Fluoxetine.
Amitriptyline and Fluoxetine have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Amitriptyline and Fluoxetine. This page displays the available source-record category and label text. The category is not an individual risk estimate or medication-combination direction.
How They Interact
Fluoxetine blocks the liver from breaking down amitriptyline and stays in the body for a very long time. This can cause amitriptyline levels to become too high even after you stop taking fluoxetine.
FDA Label Information
While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).
Amitriptyline Also Interacts With
- Risperidone major
- Sertraline minor
- Paroxetine minor
- Disulfiram minor
- Flecainide minor
Fluoxetine Also Interacts With
- Aspirin major
- Warfarin major
- Olanzapine major
- Pimozide major
- Thioridazine major
Frequently Asked Questions
What SPL severity band is on file for Amitriptyline + Fluoxetine?
Compiled FDA labeling labels this pair minor. That is a source-record field, not an individual medication-combination decision.
Which drug in this pair has the larger labeled-interaction portfolio?
Fluoxetine has 68 labeled pairs on file vs Amitriptyline's 21. In the minor band specifically: Amitriptyline has 20 (also Sertraline, Paroxetine, Disulfiram, Flecainide); Fluoxetine has 43 (also Ketoconazole, Lithium, Moxifloxacin, Erythromycin).
What mechanism field is on file for Amitriptyline and Fluoxetine?
Fluoxetine blocks the liver from breaking down amitriptyline and stays in the body for a very long time. This can cause amitriptyline levels to become too high even after you stop taking fluoxetine.
Fluoxetine carries more major-labeled pairs than Amitriptyline
SPL source-record counts only. This page's band is minor · classes on file: Amitriptyline (Tricyclic Antidepressant (TCA)); Fluoxetine (Selective Serotonin Reuptake Inhibitor (SSRI)).
Fluoxetine has 6 major-labeled pairs vs Amitriptyline's 1. This page itself is in the minor band, not the major band.
1 major · 0 moderate · 20 minor · 21 total
- Other minor peers for Amitriptyline
- Sertraline
- Paroxetine
- Disulfiram
- Flecainide
6 major · 19 moderate · 43 minor · 68 total
- Other minor peers for Fluoxetine
- Ketoconazole
- Lithium
- Moxifloxacin
- Erythromycin
Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. This registry does not provide individual medication-combination directions.
Read our methodology - how this data is sourced, computed, and verified.