Diazepam Nasal Spray and Amitriptyline: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Amitriptyline
Diazepam Nasal Spray
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.
What happens
Psychomotor deficits (decreased reaction time, decreased vigilance)
Interaction Deep Dive
A controlled study observed that coadministration of diazepam with amitriptyline resulted in additive deficits in several psychomotor tests1. The potential interaction between diazepam and amitriptyline was studied in four depressed patients receiving 75 to 150 mg daily of amitriptyline and 10 to 15 mg daily of diazepam 2. Researchers were unable to demonstrate any change in blood levels of amitriptyline or nortriptyline. Additional controlled studies or case reports are necessary to determine the degree of impairment resulting from coadministration of these two agents.
Why it happens (mechanism)
Additive psychomotor deficits
Literature reports
1 report — tap to read
a) In a controlled study of performance of 90 healthy volunteers, the effects of fluoxetine, amitriptyline, or placebo on diazepam were studied. Volunteers received one of six treatment combinations, and were given performance tests including a critical tracking test, divided attention test, visual search task, memory test, and vigilance test. Fluoxetine alone did not affect performance, but when fluoxetine was added to diazepam, there was a significant increase in the divided attention tracking error and significant impairment on the vigilance test. For amitriptyline alone and during coadministration with diazepam significant impairment was observed. On most tests, the combination of amitriptyline and diazepam resulted in additive effects. The authors concluded that the combination of diazepam and an antidepressant may increase an individual's risk during driving and while performing other complex tasks 1.
Common questions
Can I take Diazepam Nasal Spray and Amitriptyline together?
Psychomotor deficits (decreased reaction time, decreased vigilance) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Diazepam Nasal Spray and Amitriptyline interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
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 Diazepam Nasal Spray 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 anything you'd monitor while I'm on both?
References (2)
- Moskowitz H & Burns M: The effects on performance of two antidepressants, alone and in combination with diazepam. Prog Neuropsychopharmacol Biol Psychiatry 1988; 12:783-792. DOI
- Otani K, Norton C, & Bertilsson L: No interaction of diazepam on amitriptyline disposition in depressed patients. Ther Drug Monit 1987; 9:120-122. PubMed
Keep reading about Amitriptyline
Keep reading about Diazepam Nasal Spray
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