Amitriptyline and Secobarbital: 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
Secobarbital
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 secobarbital (a barbiturate). There are two things worth knowing here. First, the barbiturate can speed up how fast your body breaks down the amitriptyline, so your antidepressant may end up at a lower level and might not work as well over time.
Second, both medicines can make you very sleepy and can slow your breathing, and those effects can add up. Amitriptyline can also make seizures a bit more likely. The good news is your care team can manage all of this by watching how you're doing and adjusting your doses if needed. Please don't change either medicine on your own, just talk with your doctor or pharmacist.
Effect: Barbiturate-induced enzyme induction increases hepatic metabolism of the TCA, lowering amitriptyline serum concentrations and potentially reducing antidepressant efficacy (delayed onset as induction develops).
Additional concerns:
- Additive CNS and respiratory depression (sedation, hypoventilation).
- TCAs lower seizure threshold, potentially worsening seizure control.
Evidence: Probable; scattered case reports of reduced TCA levels. Severity: major.
Management: Monitor for reduced antidepressant response and for excessive sedation/respiratory depression. Amitriptyline dose may need to be individualized and adjusted by the care team; monitor mood, clinical response, and CNS/respiratory status. Consider TCA plasma levels where available.
What happens
Reduced tricyclic antidepressant exposure and possible additive adverse effects
Interaction Deep Dive
When barbiturates are taken alongside tricyclic antidepressants (TCAs), the metabolism of the TCA may be enhanced. Isolated case reports have described patients whose serum TCA concentrations fell when a barbiturate was also present123. Beyond this, TCAs may impair seizure control because they lower the seizure threshold. The two drug classes further produce additive depression of both 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 care team tells you otherwise. Here is what your team typically does with this combination:
- Watch whether your amitriptyline is still working, since the barbiturate can lower its level. Your amitriptyline dose may need to be adjusted and individualized by your care team.
- Monitor you more closely for heavy drowsiness or slowed breathing, since both drugs are sedating.
- Be alert for any change in seizure activity if you have a seizure history.
Call your pharmacist or prescriber if your mood symptoms return, or if you notice unusual sleepiness, confusion, or trouble breathing.
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 epilepsy patients receiving long-term PHENobarbital therapy and in eight drug-free healthy control subjects. Every participant was an extensive metabolizer with regard to the genetically determined CYP2D6-related metabolic polymorphism. Relative to the controls, the epilepsy patients showed lower peak plasma desipramine levels (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). 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 would be anticipated with any pairing of a TCA and a barbiturate 5.
Common questions
Can I take Amitriptyline and Secobarbital together?
Secobarbital can lower amitriptyline levels and reduce its effect over time, and both drugs add to sedation and slowed breathing. Take both as prescribed and let your care team monitor you and adjust the dose as needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Secobarbital 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 Secobarbital interaction managed?
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. Here is what your team typically does with this combination: Watch whether your amitriptyline is still working, since the barbiturate can lower its level. Your amitriptyline dose may need to be adjusted and individualized by your care team. Monitor you more closely for heavy drowsiness or slowed breathing,… 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 Secobarbital 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 Secobarbital
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