Drug interactions
Amitriptyline + Duloxetine
Severity: Major
Amitriptyline and Duloxetine: major interaction.
Last updated
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
Both drugs raise serotonergic and noradrenergic activity, which increases the risk of serotonin syndrome. Duloxetine also inhibits CYP2D6, which can raise amitriptyline concentrations and worsen anticholinergic and cardiac effects.
What this interaction means in plain words
Amitriptyline and Duloxetine 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; Duloxetine belongs to Central Nervous System.
Why it happens
Additive serotonin reuptake inhibition plus CYP2D6 inhibition by duloxetine increasing tricyclic exposure.
What to do
Avoid if possible; if used, start with a low amitriptyline dose and monitor for serotonin toxicity and tricyclic adverse effects. Consider plasma level monitoring and an ECG.
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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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 Duloxetine
- Duloxetine + Isocarboxazid Contraindicated
- Duloxetine + Linezolid Contraindicated
- Duloxetine + Methylene blue Contraindicated
- Duloxetine + Phenelzine Contraindicated
- Duloxetine + Procarbazine Contraindicated
- Duloxetine + Rasagiline Contraindicated
Frequently asked questions
Can I take Amitriptyline with Duloxetine?
MediHelp rates the interaction as major. Amitriptyline and Duloxetine 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. Both drugs raise serotonergic and noradrenergic activity, which increases the risk of serotonin syndrome. Duloxetine also inhibits CYP2D6, which can raise amitriptyline concentrations and worsen anticholinergic and cardiac effects.
How serious is the interaction between Amitriptyline and Duloxetine?
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 if possible; if used, start with a low amitriptyline dose and monitor for serotonin toxicity and tricyclic adverse effects. Consider plasma level monitoring and an ECG.
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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