Methadone and Trazodone Interaction
Drug interaction information between Methadone and Trazodone.
Methadone and Trazodone have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Methadone and Trazodone. 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
These drugs both increase a chemical called serotonin in your body, which can cause a dangerous reaction if levels get too high.
FDA Label Information
Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that effect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).
Methadone Also Interacts With
- Itraconazole major
- Safinamide major
- Phenobarbital moderate
- Tranylcypromine moderate
- Gabapentin minor
Trazodone Also Interacts With
- Linezolid major
- Aspirin moderate
- Phenelzine moderate
- Tranylcypromine moderate
- Selegiline moderate
Frequently Asked Questions
What SPL severity band is on file for Methadone + Trazodone?
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?
Methadone has 41 labeled pairs on file vs Trazodone's 40. In the minor band specifically: Methadone has 37 (also Gabapentin, Sertraline, Tramadol, Cyclobenzaprine); Trazodone has 35 (also Tramadol, Buspirone, Clopidogrel, Rivaroxaban).
What mechanism field is on file for Methadone and Trazodone?
These drugs both increase a chemical called serotonin in your body, which can cause a dangerous reaction if levels get too high.
Methadone carries more major-labeled pairs than Trazodone
SPL source-record counts only. This page's band is minor · classes on file: Methadone (Opioid Agonist); Trazodone (Serotonin Antagonist and Reuptake Inhibitor (SARI)).
Methadone has 2 major-labeled pairs vs Trazodone's 1. This page itself is in the minor band, not the major band.
2 major · 2 moderate · 37 minor · 41 total
- Other minor peers for Methadone
- Gabapentin
- Sertraline
- Tramadol
- Cyclobenzaprine
1 major · 4 moderate · 35 minor · 40 total
- Other minor peers for Trazodone
- Tramadol
- Buspirone
- Clopidogrel
- Rivaroxaban
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.