Drug & supplement interaction

Yohimbe + Fluoxetine

Fluoxetine brand names: Prozac, Sarafem.

Moderate Interaction
The bottom line Moderate

Fluoxetine falls into 3 drug categories that Yohimbe can interact with; the most serious is rated moderate. Theoretically, yohimbe might increase the levels and adverse effects of CYP2D6 substrates.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Yohimbe and Fluoxetine

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Yohimbe interacts with whole categories of medication. Fluoxetine falls into 3 of those categories, so it can interact with Yohimbe in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

1 of 3

Why this applies to Fluoxetine

Fluoxetine falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Yohimbe interacts with.

Theoretically, yohimbe might increase the levels and adverse effects of CYP2D6 substrates.
In vitro research suggests that yohimbine, a constituent of yohimbe bark, inhibits CYP2D6 enzyme 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 fluoxetine (Prozac) and yohimbe. Your liver uses an enzyme called CYP2D6 to help clear fluoxetine out of your system. Lab studies suggest yohimbine, the active piece of yohimbe, can slow that enzyme down. In theory, that could let fluoxetine build up a bit higher than usual, which may mean more of its typical side effects like jitteriness, trouble sleeping, headache, nausea, or feeling wired.

I want to be honest though: this is based only on test-tube research, not real patients, so it's more of a caution than a proven problem. What concerns me more is that yohimbe itself can raise blood pressure and heart rate, and fluoxetine can too. Please check with your pharmacist or doctor before pairing them.

References
  1. VandenBrink, B. M., Foti, R. S., Rock, D. A., Wienkers, L. C., and Wahlstrom, J. L. Prediction of CYP2D6 drug interactions from in vitro data: evidence for substrate-dependent inhibition. Drug Metab Dispos. 2012;40(1):47-53. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS

2 of 3

Fluoxetine also falls under CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS.

Theoretically, CYP3A4 inhibitors might increase the levels and adverse effects of yohimbine, a constituent of yohimbe bark.
In vitro and clinical research shows that the yohimbe bark constituent, yohimbine, is metabolized by CYP3A4 enzymes. Theoretically, drugs that inhibit CYP3A4 might increase the levels and adverse effects of yohimbine.
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 thing to know if you take Prozac (fluoxetine) and are thinking about a yohimbe supplement. Your body uses an enzyme called CYP3A4 to break down yohimbine, the active part of yohimbe. Fluoxetine can slow that enzyme down. So in theory, the yohimbine could clear out more slowly and build up to higher levels in your body.

Why that matters: yohimbine on its own can cause a fast heart rate, jumpy or anxious feelings, high blood pressure, and trouble sleeping, and fluoxetine can add to that anxious, wired feeling. So you might get more of those effects than expected. To be fair, this concern is mostly theoretical and based on how the drugs work, not strong patient studies. Still, please check with your pharmacist or doctor before combining them.

References
  1. Le Corre P, Parmer RJ, Kailasam MT, et al. Human sympathetic activation by alpha2-adrenergic blockade with yohimbine: Bimodal, epistatic influence of cytochrome P450-mediated drug metabolism. Clin Pharmacol Ther. 2004;76(2):139-53.
  2. Bharucha AE, Skaar T, Andrews CN, et al Relationship of cytochrome P450 pharmacogenetics to the effects of yohimbine on gastrointestinal transit and catecholamines in healthy subjects. Neurogastroenterol Motil. 2008;20(8):891-9. PubMed
Moderate

CYTOCHROME P450 2D6 (CYP2D6) INHIBITORS

3 of 3

Fluoxetine also falls under CYTOCHROME P450 2D6 (CYP2D6) INHIBITORS.

CYP2D6 inhibitors may increase the levels and adverse effects of yohimbine, a constituent of yohimbe.
In vitro and clinical research shows that the yohimbe bark constituent, yohimbine, is metabolized by CYP2D6 isoenzymes. Paroxetine, a cytochrome P450 (CYP) 2D6 inhibitor, increases the maximum serum concentration of yohimbine and reduces the clearance of yohimbine compared to yohimbine alone in patients who are extensive CYP2D6 metabolizers..
Severity Moderate Likelihood Probable Evidence B

Interaction 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..

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

Here's the thing to know if you take fluoxetine (Prozac) and you're thinking about a yohimbe supplement. Fluoxetine is a strong blocker of a liver enzyme called CYP2D6, and that same enzyme is what your body uses to clear yohimbine, the active compound in yohimbe. So when the two are combined, the yohimbine isn't broken down as quickly and can build up to higher levels than expected.

Why does that matter? Yohimbine on its own can already cause a racing heartbeat, spikes in blood pressure, anxiety, jitteriness, and trouble sleeping, and higher levels make those more likely. Since fluoxetine can also bump up anxiety and restlessness for some people, the combination may stack those effects. This is rated a probable, moderate interaction, so please check with your pharmacist or doctor before mixing them rather than starting or stopping anything on your own.

References
  1. Le Corre P, Parmer RJ, Kailasam MT, et al. Human sympathetic activation by alpha2-adrenergic blockade with yohimbine: Bimodal, epistatic influence of cytochrome P450-mediated drug metabolism. Clin Pharmacol Ther. 2004;76(2):139-53.
  2. Mueller-Schoell A, Michelet R, Weinelt F, Kloft C, Mikus G. CYP2D6 phenotype explains reported yohimbine concentrations in four severe acute intoxications. Arch Toxicol. 2021. PubMed
  3. Bharucha AE, Skaar T, Andrews CN, et al Relationship of cytochrome P450 pharmacogenetics to the effects of yohimbine on gastrointestinal transit and catecholamines in healthy subjects. Neurogastroenterol Motil. 2008;20(8):891-9. PubMed
  4. Vay M, Meyer MJ, Blank A, et al. Oral yohimbine as a new probe drug to predict CYP2D6 activity: results of a fixed-sequence phase I trial. Clin Pharmacokinet. 2020;59(7):927-939. 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

Yohimbe Also Interacts With Other Medications

Yohimbe has 9 major, 679 moderate, 436 minor known drug interactions in our database — the Fluoxetine one above is among them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Yohimbe

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

From our Q&A

Questions About Yohimbe or Fluoxetine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Yohimbe or Fluoxetine, 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 Fluoxetine

This page covers Yohimbe only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Fluoxetine page lists 163 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: 8 major · 127 moderate · 28 minor.

From our pharmacist’s overview on the Fluoxetine page

“Grapefruit is the surprise at the top of fluoxetine's (Prozac) supplement list. In large amounts it can stretch the QT interval, the electrical pause between heartbeats, and fluoxetine, a widely prescribed antidepressant, can do the same, raising the odds of a dangerous rhythm.”

Reviewed by 2 · Jul 18, 2026

Open the Fluoxetine interaction page

One more smart check

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

We hold 1,054 real supplement products containing Yohimbe, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Yohimbe. Your product may carry other ingredients that interact with Fluoxetine too, on top of Yohimbe — 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 Yohimbe and Fluoxetine 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 Yohimbe
Top 25%

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

29 days ago today
Medication Fluoxetine
Top 1%

#26 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 Yohimbe

What is Yohimbe?

Yohimbe
  • Erectile dysfunction
  • Low sex drive
  • Sexual performance
  • Weight loss
  • Athletic performance

Yohimbe is a West African tree bark that contains yohimbine, a compound mainly promoted for erectile dysfunction and as an aphrodisiac. A prescription form of yohimbine has some evidence for erectile dysfunction, but over-the-counter yohimbe supplements vary widely in content and can cause serious side effects like high blood pressure and fast heart rate. Because of these safety concerns, talk to your pharmacist or doctor before using it.

Read the full Yohimbe monograph & all interactions
Medication

About Fluoxetine

What Is Fluoxetine Used For?

Brand names: Prozac, Sarafem

Fluoxetine is approved to treat four conditions: major depressive disorder (MDD), obsessive-compulsive disorder (OCD), bulimia nervosa (a binge-eating and purging disorder), and panic disorder — with or without agoraphobia (fear of situations that feel hard to escape).

It works for adults across all four conditions, and for children and teens with depression (ages 8–18) and OCD (ages 7–17).

See full Fluoxetine drug information
Keep checking

Other Drugs & Yohimbe

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

9Major
679Moderate
436Minor
1,705No known interaction
Major

9 interactions

Moderate

679 interactions

Showing 60 of 679 moderate interactions — see all 679 on the Yohimbe page.

Minor

436 interactions

Showing 60 of 436 minor interactions — see all 436 on the Yohimbe page.

No interaction 1,705 drugs checked — show the list
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

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Pharmacist Counseling Corner

Taking Yohimbe and Fluoxetine Together: Common Questions

Can you take Yohimbe with Fluoxetine?
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 3 interactions listed for Yohimbe and Fluoxetine?
Fluoxetine belongs to more than one drug category, and Yohimbe 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 Yohimbe and Fluoxetine 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 Fluoxetine and Yohimbe?

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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.