Drug Interaction Report

Guanfacine and Amitriptyline: Interaction Details

A pharmacist-reviewed analysis of the Guanfacine and Amitriptyline interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Amitriptyline

Elavil
+

Guanfacine

Intuniv Intuniv® Tenex®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
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Interaction severity
Moderate
Can be significant — usually manageable with monitoring.
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.

Of 69 documented Guanfacine interactions, 55 are rated moderate — including this one.
Onset
delayed
Evidence
theoretical
Severity
Moderate

What happens

Decreased antihypertensive effectiveness

Interaction Deep Dive

Concomitant clonidine and tricyclic antidepressant therapy may impair the antihypertensive effects of clonidine. Since the mechanism of action of guanfacine is similar to clonidine, patients stabilized on guanfacine should be monitored for a hypertensive response when amitriptyline therapy is started23.

Why it happens (mechanism)

Unknown

Literature reports

1 report — tap to read

a) A case of a hypertensive female who was maintained on guanfacine 2 mg daily with mean blood pressure at 138/89 mm Hg was reported 1. After amitriptyline 75 mg daily was begun, her mean blood pressure was 150/100 mm Hg; upon discontinuation of the amitriptyline, the blood pressure returned to 136/91 mm Hg. A month later she was given imipramine 50 mg daily and experienced similar changes in loss of blood pressure control; upon discontinuation of imipramine, the blood pressure again returned to 137/90 mm Hg.

Common questions

Can I take Guanfacine and Amitriptyline together?

Decreased antihypertensive effectiveness Always confirm with your pharmacist or prescriber before making any change.

How serious is the Guanfacine and Amitriptyline interaction?

It is rated moderate. Can be significant — usually manageable with monitoring.

How quickly could this interaction happen?

The documented onset is "delayed". Effects tend to build up gradually over days to weeks.

How strong is the evidence for this interaction?

The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.

Questions for your pharmacist

  • Does my dose of Guanfacine 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 (3)

  1. Buckley M & Feely J: Antagonism of antihypertensive effect of guanfacine by tricyclic antidepreseants (letter). Lancet 1991; 337:1173-1174.
  2. Briant RH, Reid JL, & Dollery CT: Interaction between clonidine and desipramine in man. Br Med J 1973; 1:522-523. PubMed
  3. Hui KK: Hypertensive crisis induced by interaction of clonidine with imipramine. J Am Geriatr Soc 1983; 31:164-165. DOI
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Amitriptyline

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All Amitriptyline interactions (525)
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Guanfacine

Keep reading about Guanfacine

All Guanfacine interactions (69) Guanfacine drug information
Also serious with: Ensitrelvir Abametapir Apalutamide Avacopan
Beyond drug–drug

These medications also interact with supplements

Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:

Amitriptyline + 1,4-butanediol Activated Charcoal American Hellebore Arsenic Beer Cesium Ephedra Gamma-hydroxybutyrate (ghb) + 288 more
Guanfacine + Activated Charcoal American Hellebore American Mistletoe Tyramine Adrafinil Agmatine Algal Oil Andrographis + 128 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.