Disulfiram and Amitriptyline: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Amitriptyline
Disulfiram
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
An increased risk of a psychotic and confusional mental state
Interaction Deep Dive
Concomitant amitriptyline and disulfiram therapy has been reported to result in the development of a confusional and psychotic mental state1. Another researcher reported that amitriptyline may potentiate the disulfiram reaction to ethanol 2. However,this finding was disputed by 3, 4, and 5.
Why it happens (mechanism)
Elevated levels of various monoamines and potentially increased dopamine levels
Literature reports
1 report — tap to read
a) Two cases of organic brain syndrome (OBS) occurred in a 33-year-old male receiving 200 mg amitriptyline nightly and disulfiram, and another in a 57-year-old male receiving amitriptyline 100 mg daily disulfiram 250 mg daily. In the first case, the onset of OBS was four weeks after starting amitriptyline and seven weeks after starting disulfiram. In the 57-year-old, onset of OBS occurred one week after starting amitriptyline and five weeks after starting disulfiram. The first patient recovered five days after discontinuing both medications and the second patient recovered three days after stopping disulfiram and reducing the dose of amitriptyline to 50 mg daily. The mechanism appeared to be an elevation in various monoamines, potentially leading to increased dopamine levels, which is a pharmacologic effect of both drugs 1.
Common questions
Can I take Disulfiram and Amitriptyline together?
An increased risk of a psychotic and confusional mental state Always confirm with your pharmacist or prescriber before making any change.
How serious is the Disulfiram and Amitriptyline interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Disulfiram or Amitriptyline need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there anything you'd monitor while I'm on both?
References (5)
- Maany I, Hayashida M, Pfeffer SL, et al: Possible toxic interaction between disulfiram and amitriptyline (letter). Arch Gen Psychiatry 1982; 39:743-744. DOI
- MacCallum WAG: Drug interactions in alcoholism treatment (letter). Lancet 1969; 1:313. DOI
- Pullar-Strecker H: Drug interactions in alcoholism treatment (letter). Lancet 1969; 1:735. DOI
- Burnett GB & Reading HW: Drug interactions in alcoholism treatment (letter). Lancet 1969; 1:415. PubMed
- Ciraulo DA, Barnhill JG, & Boxenbaum HG: Disulfiram and antidepressants (letter). Am J Psychiatry 1986; 143:10-11.
Keep reading about Amitriptyline
Keep reading about Disulfiram
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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