Drug interactions
Amitriptyline + Clomipramine
Severity: Major
Amitriptyline and Clomipramine: 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
Two tricyclic antidepressants given together produce additive QT prolongation, anticholinergic effects, sedation and serotonergic activity, and they compete for the same metabolic pathways. This increases the risk of arrhythmia, seizures and serotonin toxicity.
What this interaction means in plain words
Amitriptyline and Clomipramine 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; Clomipramine belongs to Central Nervous System.
Why it happens
Additive cardiac conduction effects and serotonin reuptake inhibition, plus competition for CYP2D6 and CYP2C19 metabolism.
What to do
Avoid combining two tricyclics; use a single agent at an optimised dose. If a cross-over is needed, do it gradually with ECG and plasma level monitoring.
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 Clomipramine
- Arsenic trioxide + Clomipramine Contraindicated
- Clomipramine + Dofetilide Contraindicated
- Clomipramine + Droperidol Contraindicated
- Clomipramine + Isocarboxazid Contraindicated
- Clomipramine + Methylene blue Contraindicated
- Clomipramine + Pentamidine Contraindicated
Frequently asked questions
Can I take Amitriptyline with Clomipramine?
MediHelp rates the interaction as major. Amitriptyline and Clomipramine 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. Two tricyclic antidepressants given together produce additive QT prolongation, anticholinergic effects, sedation and serotonergic activity, and they compete for the same metabolic pathways. This increases the risk of arrhythmia, seizures and serotonin toxicity.
How serious is the interaction between Amitriptyline and Clomipramine?
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 combining two tricyclics; use a single agent at an optimised dose. If a cross-over is needed, do it gradually with ECG and plasma level monitoring.
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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