Drug & supplement interaction

Rhodiola + Imipramine

Imipramine brand names: Tofranil, Tofranil PM.

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

Imipramine falls into 4 drug categories that Rhodiola can interact with; the most serious is rated moderate. Theoretically, rhodiola might increase levels of drugs metabolized by CYP2C9.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions4
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Rhodiola and Imipramine

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Rhodiola interacts with whole categories of medication. Imipramine falls into 4 of those categories, so it can interact with Rhodiola in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

1 of 4

Why this applies to Imipramine

Imipramine falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES — the group Rhodiola interacts with.

Theoretically, rhodiola might increase levels of drugs metabolized by CYP2C9.
In vitro research shows that rhodiola inhibits CYP2C9. This effect is highly variable and appears to be dependent on the rhodiola product studied. Also, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days reduces the metabolism of losartan, a CYP2C9 substrate, by 21% after 4 hours.
Severity Moderate Likelihood Possible Evidence B

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 basic idea: imipramine is partly cleared by a liver enzyme called CYP2C9, and rhodiola may slow that enzyme down a bit. If imipramine is broken down more slowly, a little more of it can hang around in your body. With a tricyclic like imipramine, that could mean stronger side effects such as drowsiness, dry mouth, constipation, blurry vision, dizziness when standing up, or a faster heartbeat.

I want to keep this in perspective, though. This concern is mostly theoretical and based on lab work plus one small study showing only a modest change. Imipramine actually leans more on other enzymes too, so the real-world effect may be minor. Still, it's worth a quick chat with your pharmacist or doctor before combining them, especially since they may want to watch how you feel.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Thu OK, Nilsen OG, Hellum B. In vitro inhibition of cytochrome P-450 activities and quantification of constituents in a selection of commercial Rhodiola rosea products. Pharm Bio. 2016 Dec;54(12):3249-3256.
  2. Thu OK, Spigset O, Nilsen OG, Hellum B. Effect of commercial Rhodiola rosea on CYP enzyme activity in humans. Eur J Clin Pharmacol. 2016 Mar;72(3):295-300. PubMed
  3. Woron J, Siwek M. Unwanted effects of psychotropic drug interactions with medicinal products and diet supplements containing plant extracts. Psychiatr Pol 2018;52(6):983-96. PubMed
Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 4

Imipramine also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Theoretically, rhodiola might increase levels of drugs metabolized by CYP1A2.
In vitro research shows that rhodiola inhibits CYP1A2. This effect is highly variable and appears to be dependent on the rhodiola product studied. However, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days does not inhibit the metabolism of caffeine, a CYP1A2 substrate.
Severity Minor Likelihood Possible Evidence B

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 basic idea with imipramine (Tofranil) and rhodiola. Your body partly clears imipramine using a liver enzyme called CYP1A2. In lab dish studies, rhodiola can slow that enzyme down a bit. If that happened in real life, imipramine could build up slightly, which might mean more of its usual side effects like drowsiness, dry mouth, constipation, blurred vision, or a faster heartbeat.

That said, I wouldn't lose sleep over this one. The concern is mostly theoretical, and a human study using rhodiola for two weeks showed no real change in how the body handled a similar CYP1A2 drug. The effect also varies a lot by product. Still, since imipramine is a strong medicine, run any new supplement past your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Thu OK, Nilsen OG, Hellum B. In vitro inhibition of cytochrome P-450 activities and quantification of constituents in a selection of commercial Rhodiola rosea products. Pharm Bio. 2016 Dec;54(12):3249-3256.
  2. Thu OK, Spigset O, Nilsen OG, Hellum B. Effect of commercial Rhodiola rosea on CYP enzyme activity in humans. Eur J Clin Pharmacol. 2016 Mar;72(3):295-300. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 4

Imipramine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, rhodiola might increase levels of drugs metabolized by CYP3A4.
In vitro research shows that rhodiola inhibits CYP3A4. This effect is highly variable and appears to be dependent on the rhodiola product studied. However, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days does not inhibit the metabolism of midazolam, a CYP3A4 substrate.
Severity Minor Likelihood Possible Evidence B

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 basic idea: your body uses a liver enzyme called CYP3A4 to help clear imipramine (Tofranil). In test tube studies, rhodiola can slow that enzyme down. If that happened in real life, imipramine could build up a bit, which might mean more of its usual side effects like dry mouth, drowsiness, constipation, blurry vision, or a faster heartbeat. Imipramine is an active drug, not a prodrug, so more of it means a stronger effect, not a weaker one.

That said, the evidence here is weak. A study in healthy men found that rhodiola did not actually change how the body cleared another CYP3A4 drug. So this is mostly theoretical. Still, since imipramine can be touchy, just let your pharmacist or doctor know before you combine them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Hellum BH, Tosse A, Hoybakk K, et al. Potent in vitro inhibition of CYP3A4 and P-glycoprotein by Rhodiola rosea. Planta Med 2010;76:331-8.
  2. Thu OK, Nilsen OG, Hellum B. In vitro inhibition of cytochrome P-450 activities and quantification of constituents in a selection of commercial Rhodiola rosea products. Pharm Bio. 2016 Dec;54(12):3249-3256.
  3. Thu OK, Spigset O, Nilsen OG, Hellum B. Effect of commercial Rhodiola rosea on CYP enzyme activity in humans. Eur J Clin Pharmacol. 2016 Mar;72(3):295-300. PubMed
Minor

ANTIDEPRESSANT DRUGS

4 of 4

Imipramine also falls under ANTIDEPRESSANT DRUGS.

Theoretically, rhodiola might increase the risk of adverse effects when taken with antidepressants.
A review of adverse event reports in Poland identified cases of tachyarrhythmias, myalgia, arthralgia, gum pain, restless leg syndrome, swallowing disorders, and changes in consciousness when rhodiola was taken in combination with paroxetine, escitalopram, fluoxetine, sertraline, trazodone, and/or duloxetine.
Severity Minor 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

If you're taking imipramine (Tofranil) for depression and thinking about adding rhodiola, here's the honest picture. The concern is mostly theoretical. Both rhodiola and imipramine can nudge brain chemicals like serotonin, so stacking them together could, in theory, raise the odds of side effects you'd already watch for with imipramine, things like a fast or irregular heartbeat, dizziness, dry mouth, or feeling foggy or off.

To be fair, the evidence here is weak. It comes from a handful of anecdotal case reports involving other antidepressants, not imipramine specifically, and the reactions ranged widely. Still, since imipramine already affects your heart rhythm, I'd play it safe and check with your pharmacist or doctor before starting rhodiola rather than combining them on your own.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Woron J, Siwek M. Unwanted effects of psychotropic drug interactions with medicinal products and diet supplements containing plant extracts. Psychiatr Pol 2018;52(6):983-96. 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

Rhodiola Also Interacts With Other Medications

Rhodiola has 623 moderate, 647 minor known drug interactions in our database — the Imipramine one above is among them. If you take anything else, check it against the full list below.

Moderate 623 Minor 647 No known interaction 1,560 (incl. Imipramine)
Taking anything else?

Check Another of Your Medications Against Rhodiola

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

From our Q&A

Questions About Rhodiola or Imipramine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Rhodiola or Imipramine, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Imipramine

This page covers Rhodiola only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Imipramine page lists 254 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), American Hellebore (major), Arsenic (major), Cesium (major) and Ephedra (major).

By severity: 11 major · 190 moderate · 53 minor.

From our pharmacist’s overview on the Imipramine page

“Imipramine (Tofranil) is an older tricyclic antidepressant, and the supplements on this page deserve real scrutiny before you add one. Most of the list acts on the liver enzymes that process the drug, so an ingredient can quietly raise or lower imipramine levels: grapefruit pushes them up, while St.”

Reviewed by 2 · Jul 18, 2026

Open the Imipramine interaction page

One more smart check

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

We hold 2,713 real supplement products containing Rhodiola, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Rhodiola. Your product may carry other ingredients that interact with Imipramine too, on top of Rhodiola — 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 Rhodiola and Imipramine 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 Rhodiola
Top 5%

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

29 days ago today
Medication Imipramine
Steady interest

#2,037 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 Rhodiola

What is Rhodiola?

Rhodiola
  • Fatigue and low energy
  • Stress and coping (adaptogen)
  • Mental performance and focus
  • Mild depression
  • Physical and exercise performance

Rhodiola is an herb traditionally used to fight fatigue and help the body cope with stress. Some small studies suggest it may modestly reduce fatigue and improve mood, but the evidence is limited and not strong. It is generally well tolerated for short-term use, but talk to your pharmacist or doctor before trying it, and avoid it during pregnancy and breastfeeding.

Read the full Rhodiola monograph & all interactions
Medication

About Imipramine

What Is Imipramine Used For?

Brand names: Tofranil, Tofranil PM

Imipramine is used to relieve symptoms of depression. Both Imipramine Hydrochloride tablets and Imipramine Pamoate capsules are approved for this use. Endogenous depression — the kind that seems to arise from within rather than a clear outside cause — tends to respond especially well. It may take one to three weeks before you notice the full benefit.

Imipramine Hydrochloride tablets are also approved as a short-term, add-on treatment to help reduce nighttime bedwetting (nocturnal enuresis) in children aged 6 and older, after a doctor has ruled out physical causes.

See full Imipramine drug information
Keep checking

Other Drugs & Rhodiola

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

0Major
623Moderate
647Minor
1,559No known interaction
623 Moderate 647 Minor 1,559 No interaction
Moderate

623 interactions

Showing 60 of 623 moderate interactions — see all 623 on the Rhodiola page.

Minor

647 interactions

Showing 60 of 647 minor interactions — see all 647 on the Rhodiola page.

No interaction 1,559 drugs checked — show the list

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

Showing the 60 most looked-up of 1,559 medications checked with no known interaction — see the full Rhodiola list.

See the full Rhodiola interactions page
See every supplement checked against Imipramine, 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
Rhodiola monograph › Uses, safety, and every drug interaction in one place Imipramine supplement interactions › Every supplement checked against Imipramine, ranked by severity Imipramine drug information › The full plain-English guide to this medication 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 Rhodiola and Imipramine Together: Common Questions

Can you take Rhodiola with Imipramine?
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 4 interactions listed for Rhodiola and Imipramine?
Imipramine belongs to more than one drug category, and Rhodiola 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 Rhodiola and Imipramine 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 Imipramine and Rhodiola?

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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.