Drug & supplement interaction

Sage + Amitriptyline, Chlordiazepoxide

Amitriptyline, Chlordiazepoxide brand name: Limbitrol DS.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Amitriptyline, Chlordiazepoxide falls into 7 drug categories that Sage can interact with; the most serious is rated moderate. Theoretically, taking sage might increase the sedative and adverse effects of CNS depressants.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions7
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Sage and Amitriptyline, Chlordiazepoxide

These two interact in 7 distinct ways. Each one is explained separately below.

Why Are There 7 Interactions?

Sage interacts with whole categories of medication. Amitriptyline, Chlordiazepoxide falls into 7 of those categories, so it can interact with Sage in 7 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CNS DEPRESSANTS

1 of 7

Why this applies to Amitriptyline, Chlordiazepoxide

Amitriptyline, Chlordiazepoxide falls under CNS DEPRESSANTS — the group Sage interacts with.

Theoretically, taking sage might increase the sedative and adverse effects of CNS depressants.
Some constituents of sage have CNS depressant activity.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist with Limbitrol DS, which pairs amitriptyline (an antidepressant) with chlordiazepoxide (a benzodiazepine). Both of these already slow down your central nervous system, so they tend to cause drowsiness, dizziness, foggy thinking, and slowed reflexes. Some compounds in sage appear to have a mild calming, sedative-type effect of their own. In theory, adding concentrated sage on top of this combo could deepen that sleepy, sluggish feeling.

I want to be honest about the evidence here: this concern comes only from lab and animal studies, not real people, so it's more of a maybe than a proven problem. Cooking with sage almost certainly won't matter. If you're thinking about regular sage supplements or the essential oil, just run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Perry NS, Bollen C, Perry EK, Ballard C. Salvia for dementia therapy: review of pharmacological activity and pilot tolerability clinical trial. Pharmacol Biochem Behav 2003;75:651-9.. PubMed
Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

2 of 7

Amitriptyline, Chlordiazepoxide also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.

Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP2D6.
In vitro evidence suggests that aqueous extracts of sage can inhibit CYP2D6. So far, this interaction has not been reported in humans.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Limbitrol DS combines amitriptyline (an older antidepressant) with chlordiazepoxide (a sedative in the benzodiazepine family). The amitriptyline part is partly cleared by a liver enzyme called CYP2D6. In lab tests, water-based sage extracts seem to slow that enzyme down. If that happened in your body, amitriptyline could build up a bit, which might mean more drowsiness, dry mouth, constipation, blurred vision, dizziness, or a faster heartbeat.

Here's the honest part: this is only a theoretical, test-tube finding, and it has never actually been reported in people. Everyday cooking with sage is very unlikely to matter. Concentrated sage capsules or essential oil are a different story. If you use those regularly, just check with your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Foster BC, Vandenhoek S, Hana J, et al. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine 2003;10:334-42.. PubMed
  2. Hellum BH, Nilsen OG. The in vitro inhibitory potential of trade herbal products on human CYP2D6-mediated metabolism and the influence of ethanol. Basic Clin Pharmacol Toxicol. 2007 Nov;101:350-8.
Moderate

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES

3 of 7

Amitriptyline, Chlordiazepoxide also falls under CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES.

Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP2C19.
In vitro evidence suggests that aqueous extracts of sage can inhibit CYP2C19. So far, this interaction has not been reported in humans.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Limbitrol DS combines amitriptyline (an older antidepressant) with chlordiazepoxide (a benzodiazepine). Both can be processed in part by a liver enzyme called CYP2C19. In lab dish studies, concentrated sage extract slowed this enzyme down. If that happened in your body, these medicines could clear a little more slowly and build up, which might mean stronger drowsiness, dizziness, dry mouth, constipation, blurred vision, or grogginess the next morning.

Here is the reassuring part: this is only a theoretical concern based on test-tube work, and it has never been reported in real people. Everyday cooking with sage is not the issue. If you are thinking about regular sage capsules, tablets, or the essential oil, just run it past your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Foster BC, Vandenhoek S, Hana J, et al. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine 2003;10:334-42.. PubMed
Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

4 of 7

Amitriptyline, Chlordiazepoxide also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP2C9.
In vitro evidence suggests that aqueous extracts of sage can inhibit CYP2C9. So far, this interaction has not been reported in humans.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Limbitrol DS combines two active medicines: amitriptyline (an older antidepressant) and chlordiazepoxide (a benzodiazepine for anxiety). Neither one is a prodrug, so they don't need to be switched on by your liver to work. The concern here is that sage may slow down a liver enzyme called CYP2C9, which helps clear these kinds of medicines. If that enzyme works slower, more of the drug can hang around in your body.

In plain terms, you could feel more of the usual effects: extra drowsiness, dizziness, dry mouth, constipation, or a foggy, sluggish feeling. I'll be honest though, this is only a theoretical worry seen in lab studies, never reported in real people, and a sprinkle of sage in cooking is very unlikely to matter. Concentrated sage capsules or oil are a different story. Check with your pharmacist before starting them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Foster BC, Vandenhoek S, Hana J, et al. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine 2003;10:334-42.. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

5 of 7

Amitriptyline, Chlordiazepoxide also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP3A4.
In vitro evidence suggests that aqueous extracts of sage can inhibit CYP3A4. So far, this interaction has not been reported in humans.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Limbitrol DS combines amitriptyline (an older antidepressant) with chlordiazepoxide (a benzodiazepine for anxiety). Your liver uses an enzyme called CYP3A4 to help break both ingredients down. In lab studies, water-based sage extracts seem to slow that enzyme a bit. In theory, that could let these medicines build up slightly, which might mean more drowsiness, dizziness, dry mouth, constipation, blurred vision, or a foggy, oversedated feeling.

I want to be honest with you: this is only seen in test tubes, never reported in real people, so it's a weak, theoretical concern. The sage on your dinner plate is very unlikely to matter. Concentrated sage capsules or essential oil are a different story. Before adding a sage supplement, just run it past your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Foster BC, Vandenhoek S, Hana J, et al. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine 2003;10:334-42.. PubMed
  2. Hellum, B. H. and Nilsen, O. G. In vitro inhibition of CYP3A4 metabolism and P-glycoprotein-mediated transport by trade herbal products. Basic Clin Pharmacol Toxicol. 2008;102(5):466-475.
Moderate

BENZODIAZEPINES

6 of 7

Amitriptyline, Chlordiazepoxide also falls under BENZODIAZEPINES.

Theoretically, taking sage might increase the sedative and adverse effects of benzodiazepines.
In vitro evidence suggests that certain components of common sage (Salvia officinalis) can bind to benzodiazepine receptors. This effect has not been reported in humans.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Limbitrol combines amitriptyline (an older antidepressant) with chlordiazepoxide (a benzodiazepine), and both already tend to make people drowsy. The concern here is pretty mild: in lab dish studies, certain compounds in common sage attached to the same brain receptors that benzodiazepines work on. In theory, that could add a little to the calming effect. Importantly, this has never actually been shown to happen in real people, so the evidence is thin.

If anything did stack up, you might feel extra sleepy, foggy, dizzy, or unsteady on your feet. Cooking with sage is very unlikely to matter. Concentrated sage extracts or the essential oil are a different story, so check with your pharmacist or doctor before adding those.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Kavvadias, D., Monschein, V., Sand, P., Riederer, P., and Schreier, P. Constituents of sage (Salvia officinalis) with in vitro affinity to human brain benzodiazepine receptor. Planta Med. 2003;69(2):113-117.
Moderate

ANTICHOLINERGIC DRUGS

7 of 7

Amitriptyline, Chlordiazepoxide also falls under ANTICHOLINERGIC DRUGS.

Theoretically, sage might decrease the clinical effects of anticholinergic drugs.
In vitro evidence suggests that common sage (Salvia officinalis) and Spanish sage (Salvia lavandulaefolia) can inhibit acetylcholinesterase and might increase acetylcholine levels.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist with Limbitrol DS (which combines amitriptyline, an older antidepressant, and chlordiazepoxide, a benzodiazepine). The amitriptyline part works partly by blocking acetylcholine, which is why it can cause dry mouth, blurry vision, constipation, and grogginess. Sage may do the opposite by nudging acetylcholine levels up. In theory, that could slightly blunt amitriptyline's anticholinergic action.

I want to be honest with you: this is based only on lab (test tube) studies, not real people, so it's a very weak, mostly theoretical concern. A pinch of sage in cooking is no worry at all. Concentrated sage extracts taken daily are where I'd pause. Before adding any sage supplement, just run it by your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Orhan, I., Kartal, M., Kan, Y., and Sener, B. Activity of essential oils and individual components against acetyl- and butyrylcholinesterase. Z.Naturforsch.C. 2008;63(7-8):547-553.
  2. Perry, N. S., Houghton, P. J., Theobald, A., Jenner, P., and Perry, E. K. In-vitro inhibition of human erythrocyte acetylcholinesterase by salvia lavandulaefolia essential oil and constituent terpenes. J Pharm Pharmacol 2000;52(7):895-902.
  3. Savelev, S. U., Okello, E. J., and Perry, E. K. Butyryl- and acetyl-cholinesterase inhibitory activities in essential oils of Salvia species and their constituents. Phytother Res 2004;18(4):315-324.
  4. Kennedy, D. O., Pace, S., Haskell, C., Okello, E. J., Milne, A., and Scholey, A. B. Effects of cholinesterase inhibiting sage (Salvia officinalis) on mood, anxiety and performance on a psychological stressor battery. Neuropsychopharmacology 2006;31(4):84 PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Sage Also Interacts With Other Medications

Sage has 1,295 moderate known drug interactions in our database — the Amitriptyline, Chlordiazepoxide one above is among them. If you take anything else, check it against the full list below.

Moderate 1,295 No known interaction 1,535 (incl. Amitriptyline, Chlordiazepoxide)
Taking anything else?

Check Another of Your Medications Against Sage

Covers the 2,830 medications we’ve checked against Sage. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Amitriptyline, Chlordiazepoxide

This page covers Sage only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Amitriptyline, Chlordiazepoxide page lists 298 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), American Hellebore (major), Arsenic (major) and Beer (major).

By severity: 17 major · 231 moderate · 50 minor.

From our pharmacist’s overview on the Amitriptyline, Chlordiazepoxide page

“Alcohol is the first thing to know about here. Beer and wine both carry major, well-documented interactions with Amitriptyline and Chlordiazepoxide (Limbitrol DS), because both drugs already slow the central nervous system, and anything sedating layered on top can deepen ordinary drowsiness into something dangerous.”

Reviewed by 2 · Jul 18, 2026

Open the Amitriptyline, Chlordiazepoxide interaction page

One more smart check

Taking Sage as Part of a Dietary Supplement Product? Check It for Interactions

We hold 718 real supplement products containing Sage, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Sage. Your product may carry other ingredients that interact with Amitriptyline, Chlordiazepoxide too, on top of Sage — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Sage and Amitriptyline, Chlordiazepoxide Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Sage
Top 25%

#263 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Amitriptyline, Chlordiazepoxide
Steady interest

#1,739 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Sage

What is Sage?

Sage
  • Sore throat and mouth irritation
  • Digestive upset
  • Excessive sweating
  • Memory and thinking
  • Menopause symptoms (hot flashes)
  • General antioxidant support

Sage is a common kitchen herb that is generally safe in food amounts and is traditionally used for sore throats, digestion, sweating, and memory. Some early research is encouraging for sore throat and menopausal hot flashes, but most uses are not well proven. Concentrated extracts and the essential oil should be used carefully because high doses contain a compound called thujone, which can be harmful.

Read the full Sage monograph & all interactions
Keep checking

Other Drugs & Sage

Browse every other medication we’ve checked against Sage — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
1,295Moderate
0Minor
1,534No known interaction
1,295 Moderate 1,534 No interaction
Moderate

1,295 interactions

Showing 60 of 1,295 moderate interactions — see all 1,295 on the Sage page.

No interaction 1,534 drugs checked — show the list

We also checked Sage against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,534 medications checked with no known interaction — see the full Sage list.

See the full Sage interactions page
See every supplement checked against Amitriptyline, Chlordiazepoxide, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Sage monograph › Uses, safety, and every drug interaction in one place Amitriptyline, Chlordiazepoxide supplement interactions › Every supplement checked against Amitriptyline, Chlordiazepoxide, ranked by severity Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Sage and Amitriptyline, Chlordiazepoxide Together: Common Questions

Can you take Sage with Amitriptyline, Chlordiazepoxide?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 7 interactions listed for Sage and Amitriptyline, Chlordiazepoxide?
Amitriptyline, Chlordiazepoxide belongs to more than one drug category, and Sage interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Sage and Amitriptyline, Chlordiazepoxide interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Amitriptyline, Chlordiazepoxide and Sage?

Our pharmacists answer your medication & supplement questions — free.

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.