Drug interactions
Amitriptyline + Paroxetine
Severity: Major
Amitriptyline and Paroxetine: major interaction.
Last updated Sources: US FDA label
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Paroxetine strongly inhibits the metabolism of amitriptyline and can raise tricyclic concentrations substantially. Combined use increases the risk of anticholinergic effects, sedation, cardiac conduction abnormalities, seizures and serotonin syndrome.
What this interaction means in plain words
Amitriptyline and Paroxetine can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for.
Amitriptyline belongs to Central Nervous System; Paroxetine belongs to Central Nervous System.
Why it happens
Paroxetine is a potent CYP2D6 inhibitor that raises amitriptyline levels, and both drugs add serotonergic activity.
What to do
Avoid the combination where possible; if it is necessary, start amitriptyline at a low dose, titrate slowly and monitor ECG, tricyclic levels and for serotonin toxicity.
What to ask your pharmacist
- Does the benefit of taking both outweigh the risk in my case?
- Do I need any blood test, ECG or other check while on both?
- What early warning signs should I watch for, and what should I do if they appear?
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References
Other interactions of Amitriptyline
- Amitriptyline + Isocarboxazid Contraindicated
- Amitriptyline + Methylene blue Contraindicated
- Amitriptyline + Phenelzine Contraindicated
- Amitriptyline + Pimozide Contraindicated
- Amitriptyline + Procarbazine Contraindicated
- Amitriptyline + Safinamide Contraindicated
Other interactions of Paroxetine
- Isocarboxazid + Paroxetine Contraindicated
- Methylene blue + Paroxetine Contraindicated
- Paroxetine + Phenelzine Contraindicated
- Paroxetine + Pimozide Contraindicated
- Paroxetine + Procarbazine Contraindicated
- Paroxetine + Selegiline Contraindicated
Frequently asked questions
Can I take Amitriptyline with Paroxetine?
MediHelp rates the interaction as major. Amitriptyline and Paroxetine can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for. Paroxetine strongly inhibits the metabolism of amitriptyline and can raise tricyclic concentrations substantially. Combined use increases the risk of anticholinergic effects, sedation, cardiac conduction abnormalities, seizures and serotonin syndrome.
How serious is the interaction between Amitriptyline and Paroxetine?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Avoid the combination where possible; if it is necessary, start amitriptyline at a low dose, titrate slowly and monitor ECG, tricyclic levels and for serotonin toxicity.
What other medicines interact with Amitriptyline?
MediHelp also lists interactions of Amitriptyline with, for example, Isocarboxazid, Methylene blue, Phenelzine. The full list is on the Amitriptyline page.
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