Amitriptyline and Fluoxetine: Drug Interaction Guide
Quick answer: This is a major interaction — avoid combining Amitriptyline and Fluoxetine unless specifically directed by your doctor.
How Amitriptyline interacts with Fluoxetine
Fluoxetine inhibits CYP2D6 metabolism of amitriptyline, raising tricyclic levels and adding to risks of QT prolongation, anticholinergic toxicity, and serotonin syndrome.
What you should do
Avoid combination where possible; if essential, use low-dose amitriptyline, obtain ECG, and monitor for sedation and arrhythmia.
Key facts
Severity
Major — avoid combination
Mechanism
Fluoxetine inhibits CYP2D6 metabolism of amitriptyline, raising tricyclic levels and adding to risks of QT prolongation,...
Action
Avoid combination where possible; if essential, use low-dose amitriptyline, obtain ECG, and monitor for sedation and arr...
Frequently asked questions
Can I take Amitriptyline and Fluoxetine together?
No — this combination should generally be avoided. Avoid combination where possible; if essential, use low-dose amitriptyline, obtain ECG, and monitor for sedation and arrhythmia.
What is the severity of this interaction?
The interaction between Amitriptyline and Fluoxetine is classified as Major — avoid combination. Fluoxetine inhibits CYP2D6 metabolism of amitriptyline, raising tricyclic levels and adding to risks of QT prolongation, anticholinergic toxicity, and serotonin syndrome.
What should I do if I'm prescribed both?
Avoid combination where possible; if essential, use low-dose amitriptyline, obtain ECG, and monitor for sedation and arrhythmia. Always consult your prescribing clinician — do not stop or change medications without medical guidance.
Last reviewed: by iMedic Medical Editorial Team. Our editorial process.