Amitriptyline and Aprobarbital: 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
Aprobarbital
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 (an antidepressant) and aprobarbital (a barbiturate). There are two things to know here. First, the barbiturate can speed up how fast your body breaks down amitriptyline, which can lower its levels and make it work less well over time. Second, both medicines can slow down your brain and breathing, so together they may make you extra drowsy or slow your breathing.
The good news is that your care team can manage this. They may check on how well your antidepressant is working, adjust your dose if needed, and watch for too much sleepiness. Please don't stop or change either medicine on your own. Just talk with your pharmacist or doctor.
Effect: Barbiturate (aprobarbital) induction of hepatic metabolism increases amitriptyline clearance, lowering TCA serum concentrations and risking reduced antidepressant efficacy. Direction: reduced TCA exposure (neither drug is a prodrug).
- Mechanism: enzyme induction accelerating TCA metabolism; onset delayed as induction develops.
- Additive PD risk: combined CNS and respiratory depression; TCAs also lower seizure threshold, potentially worsening seizure control.
- Evidence: probable; scattered case reports of decreased TCA levels.
- Management: monitor clinical response and sedation/respiratory status; individualize TCA dose; watch seizure control if applicable.
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 reports describe patients whose TCA serum concentrations fell when a barbiturate was also being used123. TCAs may also compromise seizure control because they lower the seizure threshold. Furthermore, the two drug classes produce additive depressant effects on the CNS and respiration4.
Why it happens (mechanism)
Increased tricyclic antidepressant metabolism
How to manage this interaction
This combination is manageable with attention from your care team. Typically they will:
- Watch how well your antidepressant is working, since the barbiturate can lower its levels over time.
- Adjust and individualize your amitriptyline dose as needed based on your response.
- Monitor you more closely for excessive drowsiness or slowed breathing, since both drugs are sedating.
- Keep an eye on seizure control if you have a seizure history.
Keep taking both exactly as prescribed. Tell your pharmacist or prescriber if you feel unusually sleepy, notice slowed breathing, or feel your depression is not being controlled.
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 patients with epilepsy who were receiving long-term PHENobarbital therapy and in eight drug-free healthy controls. Every participant was an extensive metabolizer according to the genetically determined CYP2D6-related metabolic polymorphism. Relative to the controls, the patients with epilepsy showed reduced peak plasma desipramine levels (74 nmol/L vs. 107 nmol/L), smaller 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 would be anticipated with any combination of a TCA and a barbiturate 5.
Common questions
Can I take Amitriptyline and Aprobarbital together?
The barbiturate can lower your amitriptyline levels and reduce its effect, and both drugs together increase 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 Aprobarbital 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 Aprobarbital interaction managed?
This combination is manageable with attention from your care team. Typically they will: Watch how well your antidepressant is working, since the barbiturate can lower its levels over time. Adjust and individualize your amitriptyline dose as needed based on your response. Monitor you more closely for excessive drowsiness or slowed breathing, since both drugs are sedating. Keep an eye on seizure con… 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 Aprobarbital 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 Aprobarbital
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