Amitriptyline and Butabarbital: 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
Butabarbital
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.
Taking amitriptyline (Elavil) with butabarbital needs some care. Butabarbital is a barbiturate, and it can speed up how your body breaks down amitriptyline. That means there may be less of your antidepressant working, so it may not do its job as well over time.
At the same time, both of these medicines can make you sleepy, slow your breathing, and slow your thinking, so those effects can stack up together. Amitriptyline can also make seizures a little more likely in some people. The good news is your care team can manage this by checking how you are doing and adjusting doses if needed. Please don't stop either drug on your own, just talk with your doctor or pharmacist.
Effect: Barbiturate-induced enzyme activity (hepatic CYP induction) increases metabolism of the TCA, lowering amitriptyline serum concentrations and potentially reducing antidepressant efficacy. Neither drug is a prodrug, so the direction is straightforward: reduced TCA exposure.
- Direction: Reduced amitriptyline effect (PK); additive CNS/respiratory depression (PD).
- Onset: Delayed (induction develops over days to weeks).
- Evidence: Probable; scattered case reports of decreased TCA levels.
- Also note: TCAs lower seizure threshold, which may undermine barbiturate seizure control.
- Management: Monitor mood/therapeutic response and for excess sedation or respiratory depression; TCA dose may need to be individualized. Consider TCA level monitoring where available.
What happens
Reduced tricyclic antidepressant exposure and possible additive adverse effects
Interaction Deep Dive
Taking a barbiturate together with a tricyclic antidepressant (TCA) can lead to enhanced metabolism of the TCA. Isolated cases have described patients whose TCA serum concentrations fell when a barbiturate was also being administered123. TCAs may also compromise seizure control because they lower the seizure threshold. On top of this, the two agents produce additive depressant effects on the CNS and respiration4.
Why it happens (mechanism)
Increased tricyclic antidepressant metabolism
How to manage this interaction
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. Here is how a care team usually handles this pairing:
- They may watch your antidepressant response, since butabarbital can lower amitriptyline levels, and adjust the dose as needed. Your dose may be individualized by your care team.
- They may monitor you more closely for stacked sedation, such as heavy drowsiness, confusion, or slowed breathing.
- If you have a seizure disorder, mention it, since amitriptyline can affect seizure control.
Tell your pharmacist or doctor 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 investigated in eight epilepsy patients receiving long-term PHENobarbital therapy and in eight healthy controls not taking any medication. Every participant was classified as an extensive metabolizer according to the genetically determined CYP2D6-related 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 values (1943 nmol/L/h vs. 3234 nmol/L/h), and shorter desipramine elimination half-lives (15.1 h vs. 20.6 h). All barbiturates are thought to 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 Butabarbital together?
Butabarbital can lower amitriptyline levels and make it work less well, and both drugs together can pile on drowsiness and slowed breathing. Keep taking both as prescribed and let your care team monitor and adjust as needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Butabarbital 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 Butabarbital interaction managed?
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. Here is how a care team usually handles this pairing: They may watch your antidepressant response, since butabarbital can lower amitriptyline levels, and adjust the dose as needed. Your dose may be individualized by your care team. They may monitor you more closely for stacked sedation, such as heavy drowsiness, c… 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 Butabarbital 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 Butabarbital
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.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist