Amitriptyline and Thiopental: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Amitriptyline
Thiopental
No brand names on record
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.
Here's what's going on. Thiopental is a barbiturate, and barbiturates can speed up how your body breaks down amitriptyline. That means your amitriptyline levels can drop, so it may not work as well for your mood or other symptoms.
At the same time, both drugs can make you very sleepy and can slow your breathing when combined, and amitriptyline can make seizures a little easier to trigger. The good news is that this is manageable. Your care team can watch you closely and adjust your doses if needed, so please don't change anything on your own. Just talk with your doctor or pharmacist.
Mechanism: Thiopental (barbiturate) induces hepatic metabolism of amitriptyline, reducing TCA serum concentrations and potentially efficacy. Neither agent is affected via prodrug activation, so induction lowers active drug exposure.
- Direction: reduced amitriptyline exposure; possible additive CNS/respiratory depression.
- Onset: delayed (enzyme induction).
- Evidence: probable; scattered case reports of decreased TCA levels.
- Additional risk: TCAs lower seizure threshold, potentially worsening seizure control.
Management: Monitor for reduced antidepressant response and for excessive sedation/respiratory depression. TCA dose may need individualization based on clinical response (and levels where available). Watch seizure control.
What happens
Reduced tricyclic antidepressant exposure and possible additive adverse effects
Interaction Deep Dive
When a barbiturate is taken together with a tricyclic antidepressant (TCA), the metabolism of the TCA may be enhanced. Isolated cases have described patients who showed reduced serum TCA concentrations while receiving a barbiturate123. TCAs may also compromise seizure control by lowering the seizure threshold. Furthermore, these agents produce additive depressant effects on the CNS and respiratory function4.
Why it happens (mechanism)
Increased tricyclic antidepressant metabolism
How to manage this interaction
How your care team can handle this:
- They may check whether your amitriptyline is still working well, since a barbiturate can lower its levels, and adjust the dose to fit you if needed.
- They may monitor you more closely for heavy drowsiness or slowed breathing, since both drugs can add to those effects.
- If you have a seizure history, they may keep a closer eye on your seizure control.
What you should do: Keep taking both exactly as prescribed unless told otherwise. Tell your pharmacist or prescriber if your mood symptoms return, or if you feel unusually sleepy or short of breath.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) The pharmacokinetics of a single oral 100 mg dose of desipramine were evaluated in eight patients with epilepsy receiving long-term PHENobarbital therapy and in eight healthy controls who were not taking any drugs. Every participant was an extensive metabolizer with regard to the genetically determined CYP2D6 metabolic polymorphism. Relative to the controls, the epilepsy patients showed reduced peak plasma desipramine levels (74 nmol/L vs. 107 nmol/L), lower desipramine area under the concentration-time curve figures (1943 nmol/L/h vs. 3234 nmol/L/h), and briefer desipramine elimination half-lives (15.1 h vs. 20.6 h). It is thought that all barbiturates produce comparable effects that induce hepatic enzymes, and the 2D6 isozyme is considered important in the metabolism of most or all TCAs. Consequently, comparable effects should be anticipated with any pairing of a TCA and a barbiturate 5.
Common questions
Can I take Amitriptyline and Thiopental together?
Thiopental can speed up the breakdown of amitriptyline, lowering its effect, while both drugs together can add to drowsiness and slowed breathing. Keep taking both as prescribed and let your care team monitor and adjust your dose. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Thiopental interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How is the Amitriptyline and Thiopental interaction managed?
How your care team can handle this: They may check whether your amitriptyline is still working well, since a barbiturate can lower its levels, and adjust the dose to fit you if needed. They may monitor you more closely for heavy drowsiness or slowed breathing, since both drugs can add to those effects. If you have a seizure history, they may keep a closer eye on your seizure control. What you shou… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Amitriptyline or Thiopental 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 a safer alternative to one of these medications for me?
References (5)
- Moody JP, Whyte SF, MacDonald AJ, et al: Pharmacokinetic aspects of protriptyline plasma levels. Eur J Clin Pharmacol 1977; 11:51-56. PubMed
- Silverman G & Braithwaite R: Interaction of benzodiazepines with tricyclic antidepressants (letter). Br Med J 1972; 4:111. PubMed
- Burrows GD & Davies B: Antidepressants and barbiturates. Br Med J 1971; 4:113. PubMed
- Brodie MJ: Drug interactions in epilepsy. Epilepsia 1992; 33(suppl 1):S13-S22. PubMed
- Spina E, Avenoso A, Campo GM, et al: Phenobarbital induces the 2-hydroxylation of desipramine. Ther Drug Monit 1996; 18:60-64. DOI
Keep reading about Amitriptyline
Keep reading about Thiopental
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