Amobarbital and Amitriptyline: 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
Amobarbital
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.
You've been prescribed amitriptyline (an antidepressant) and amobarbital (a barbiturate). Here's what to know. The barbiturate can speed up how fast your body breaks down amitriptyline, so the antidepressant may not work as well over time. On top of that, both drugs can make you very drowsy and can slow your breathing, so combining them can add up and make you feel more sleepy or foggy than usual.
Please don't stop or change either medicine on your own. This is very manageable. Your care team can watch how you're doing, adjust your doses to fit you, and check that your depression is still well controlled. Let them know if you feel unusually sleepy or short of breath.
Effect: Barbiturate (amobarbital) induction of hepatic microsomal enzymes accelerates amitriptyline metabolism, lowering TCA serum concentrations and potentially reducing efficacy. Onset is delayed (enzyme induction), evidence is probable, severity major.
Additional concerns:
- Additive CNS and respiratory depression (both sedating agents).
- TCAs lower seizure threshold, potentially undermining barbiturate seizure control.
Management:
- Monitor for loss of antidepressant response; dose may need individualization by the care team, with TCA levels where available.
- Monitor for excess sedation and respiratory depression.
- Assess seizure control if amobarbital is used for that indication.
What happens
Reduced tricyclic antidepressant exposure and possible additive adverse effects
Interaction Deep Dive
Taking barbiturates together with tricyclic antidepressants (TCAs) can lead to enhanced metabolism of the TCA. Isolated cases have described patients whose TCA serum concentrations dropped when a barbiturate was present123. TCAs may also lower the seizure threshold, thereby worsening seizure control. Furthermore, both 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 exactly as prescribed unless your prescriber tells you otherwise. Here's how a care team usually handles this:
- Watching your response: because the barbiturate can lower amitriptyline levels, your team may check that your mood symptoms stay controlled and may adjust and individualize your antidepressant dose.
- Monitoring for sedation: both drugs cause drowsiness and can slow breathing, so your team may monitor you more closely, especially early on.
Tell your pharmacist or prescriber if you feel very sleepy, confused, short of breath, or if your depression symptoms return.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) Investigators examined the pharmacokinetics of a single oral 100 mg dose of desipramine in eight epilepsy patients receiving long-term PHENobarbital therapy and in eight healthy controls not taking any drugs. 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 lower peak plasma desipramine concentrations (74 nmol/L vs. 107 nmol/L), reduced 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). 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 Amobarbital and Amitriptyline together?
Amobarbital can lower amitriptyline levels (reducing its effect) while both add to drowsiness and slowed breathing. Keep taking both as prescribed and let your care team monitor and adjust your doses. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amobarbital and Amitriptyline 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 Amobarbital and Amitriptyline interaction managed?
Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Here's how a care team usually handles this: Watching your response: because the barbiturate can lower amitriptyline levels, your team may check that your mood symptoms stay controlled and may adjust and individualize your antidepressant dose. Monitoring for sedation: both drugs cause drowsiness and can sl… 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 Amobarbital 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 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 Amobarbital
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