Amitriptyline and Sertraline Interaction
Drug interaction information between Amitriptyline and Sertraline.
Amitriptyline and Sertraline have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Amitriptyline and Sertraline. 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
Sertraline slows down the liver's ability to process amitriptyline. This can cause amitriptyline to build up to higher levels in your body.
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
- Fluoxetine minor
- Paroxetine minor
- Disulfiram minor
- Flecainide minor
Sertraline Also Interacts With
- Clonazepam major
- Aspirin moderate
- Phenelzine moderate
- Fluoxetine minor
- Citalopram minor
Frequently Asked Questions
What SPL severity band is on file for Amitriptyline + Sertraline?
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?
Sertraline has 34 labeled pairs on file vs Amitriptyline's 21. In the minor band specifically: Amitriptyline has 20 (also Fluoxetine, Paroxetine, Disulfiram, Flecainide); Sertraline has 31 (also Fluoxetine, Citalopram, Paroxetine, Atenolol).
What mechanism field is on file for Amitriptyline and Sertraline?
Sertraline slows down the liver's ability to process amitriptyline. This can cause amitriptyline to build up to higher levels in your body.
Sertraline's labeled portfolio outnumbers Amitriptyline
SPL source-record counts only. This page's band is minor · classes on file: Amitriptyline (Tricyclic Antidepressant (TCA)); Sertraline (Selective Serotonin Reuptake Inhibitor (SSRI)).
1 major · 0 moderate · 20 minor · 21 total
- Other minor peers for Amitriptyline
- Fluoxetine
- Paroxetine
- Disulfiram
- Flecainide
1 major · 2 moderate · 31 minor · 34 total
- Other minor peers for Sertraline
- Fluoxetine
- Citalopram
- Paroxetine
- Atenolol
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.