Amitriptyline and Paroxetine Interaction
Drug interaction information between Amitriptyline and Paroxetine.
Amitriptyline and Paroxetine have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Amitriptyline and Paroxetine. 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
Paroxetine interferes with the liver enzyme that clears amitriptyline from your body. This makes the amitriptyline stay in your blood longer than it should.
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.
Amitriptyline Also Interacts With
- Risperidone major
- Sertraline minor
- Fluoxetine minor
- Disulfiram minor
- Flecainide minor
Paroxetine Also Interacts With
- Linezolid major
- Pimozide major
- Thioridazine major
- Phenelzine moderate
- Tranylcypromine moderate
Frequently Asked Questions
What SPL severity band is on file for Amitriptyline + Paroxetine?
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?
Paroxetine has 51 labeled pairs on file vs Amitriptyline's 21. In the minor band specifically: Amitriptyline has 20 (also Sertraline, Fluoxetine, Disulfiram, Flecainide); Paroxetine has 44 (also Buspirone, Clopidogrel, Aspirin, Venlafaxine).
What mechanism field is on file for Amitriptyline and Paroxetine?
Paroxetine interferes with the liver enzyme that clears amitriptyline from your body. This makes the amitriptyline stay in your blood longer than it should.
Paroxetine 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)); Paroxetine (Selective Serotonin Reuptake Inhibitor (SSRI)).
Paroxetine has 3 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
- Fluoxetine
- Disulfiram
- Flecainide
3 major · 4 moderate · 44 minor · 51 total
- Other minor peers for Paroxetine
- Buspirone
- Clopidogrel
- Aspirin
- Venlafaxine
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.