Hexobarbital 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
Hexobarbital
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.
You've been prescribed amitriptyline (a tricyclic antidepressant) along with hexobarbital (a barbiturate). Here's what that combination can do. The barbiturate can speed up how fast your body breaks down amitriptyline, so there may be less of the antidepressant in your blood, and it may not work as well.
At the same time, both drugs can make you very drowsy and can slow your breathing when taken together. Amitriptyline can also make seizures a little easier to trigger. The good news is your care team can manage this by watching how you respond, checking your symptoms, and adjusting your doses if needed. Don't stop either medicine on your own, but do talk with your pharmacist or doctor.
Effect: Barbiturate coadministration induces hepatic metabolism of the TCA, lowering amitriptyline serum concentrations and potentially reducing antidepressant efficacy (delayed onset as enzyme induction develops). Neither agent is a prodrug, so induction translates to reduced parent-drug exposure.
Additional concerns:
- Additive CNS and respiratory depression
- Amitriptyline lowers the seizure threshold, potentially worsening seizure control
Evidence: Probable; scattered reports of decreased TCA levels. Severity: major.
Management: Monitor mood/antidepressant response and for excessive sedation or respiratory depression. TCA dose may need to be individualized and titrated by the care team; consider therapeutic drug monitoring where available.
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 whose serum TCA concentrations fell while a barbiturate was present 123. TCAs may also compromise seizure control because they lower the seizure threshold. Furthermore, both agents produce additive depression of the CNS and respiratory function 4.
Why it happens (mechanism)
Increased tricyclic antidepressant metabolism
How to manage this interaction
This combination is manageable with attention from your care team. Because the barbiturate can lower how much amitriptyline stays in your body, and because both can add to drowsiness, your team may take a few steps:
- Watch whether your antidepressant is still working well
- Adjust and individualize your amitriptyline dose as needed
- Monitor you more closely for heavy sedation or slowed breathing
- Watch seizure control if that applies to you
What you should do: Keep taking both exactly as prescribed unless told otherwise. Tell your pharmacist or prescriber if you feel unusually sleepy, have trouble breathing, or notice your mood slipping.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) Researchers examined the pharmacokinetics of a single 100 mg oral dose of desipramine in eight epileptic patients receiving long-term PHENobarbital therapy and in eight healthy controls who were not taking any medications. Every participant was an extensive metabolizer with regard to the genetically determined CYP2D6-related metabolic polymorphism. In comparison with the controls, the epileptic 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). It is thought that all barbiturates produce comparable effects resulting in induction of hepatic enzymes, and the 2D6 isozyme is considered important in metabolizing most or all TCAs. Therefore, comparable effects should be anticipated with any pairing of a TCA and a barbiturate 5.
Common questions
Can I take Hexobarbital and Amitriptyline together?
Hexobarbital can lower amitriptyline levels (possibly weakening its effect) while both drugs add to sedation and breathing risks; 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 Hexobarbital 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 Hexobarbital and Amitriptyline interaction managed?
This combination is manageable with attention from your care team. Because the barbiturate can lower how much amitriptyline stays in your body, and because both can add to drowsiness, your team may take a few steps: Watch whether your antidepressant is still working well Adjust and individualize your amitriptyline dose as needed Monitor you more closely for heavy sedation or slowed breathing Watch… 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 Hexobarbital 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 Hexobarbital
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