Does Berberine Interact With Prozac?

In our latest question and answer, our pharmacist discusses the potential interaction between Prozac and berberine.


Does Berberine interact with Prozac?

Asked by KJM74 On May 23, 2023

Answered by
Medical Content Reviewed By HelloPharmacist Staff

Published May 23, 2023
Last updated Jun 13, 2024

Key points

  • Berberine may interact with Prozac (fluoxetine) based on preliminary clinical studies indicating that berberine can inhibit the activity of the CYP2D6 enzyme responsible for metabolizing Prozac.
  • Specific reports documenting problems when combining berberine and Prozac are currently lacking, but it is recommended to consult with a doctor before combining any medications or supplements to ensure personalized monitoring and appropriate management of potential interactions.


Thanks so much for reaching out! As our herbal interaction tool shows, there is a theoretical interaction between berberine and Prozac (fluoxetine).

Specifically, preliminary clinical studies suggest that berberine may partially inhibit an enzyme (CYP2D6) that is responsible for metabolizing Prozac. This, in turn, could slow how quickly Prozac is metabolized and eliminated from the body, increasing the risk of side effects.

Additional Interaction Details

While there have not been any studies to my knowledge that have specifically evaluated the effects that berberine has on Prozac, we can infer a potential interaction based on other published studies that have shown berberine can inhibit the metabolizing enzyme CYP2D6.

One such study, published in the European Journal of Clinical Pharmacology, aimed to evaluate the effects of berberine administration on the major pharmacokinetic parameters of other known drugs metabolized by several different cytochrome P450 (CYP) enzymes.

The study involved healthy male volunteers who received berberine (300 mg, three times a day, orally) for a period of two weeks. The researchers measured the pharmacokinetic parameters of probe drugs metabolized by CYP3A4, CYP1A2, CYP2C19, CYP2D6, and CYP2C9, and compared them between the placebo and berberine administration phases. The results revealed significant alterations in the activity of certain CYP enzymes following berberine treatment.

The activity of CYP2D6, responsible for metabolizing dextromethorphan, was found to be inhibited, as indicated by a ninefold increase in the 0-8 hour urinary dextromethorphan/dextrorphan ratio (CYP2D6 metabolizes dextromethorphan into a substance called dextrorphan, which is then eliminated from the body. An increase in the ratio, as noted by the study, means that more dextromethorphan was present compared to dextrorphan. It is this change in the ratio that suggests that the activity of CYP2D6 was reduced).

Other studies have noted similar findings.

Can They Be Taken Together?

Although there may be an interaction between berberine and Prozac (fluoxetine), as described above, it is important to note that specific reports documenting problems when the two are combined are currently lacking in human studies.

The interaction between berberine and Prozac is, therefore, more theoretical at this point.

If an interaction does occur and Prozac metabolism is decreased, we may expect some dose-related side effects, such as nausea, dizziness, insomnia, gastrointestinal disturbances, and so on.

As a general rule of thumb, it is always advisable to consult with your doctor before combining any medications or supplements, including berberine and Prozac.

There certainly could be situations where your doctor clears you for taking both together, but bringing your doctor in the loop can ensure that you are monitored appropriately and that any potential interactions or concerns are properly addressed.

Final Words

Thanks so much for reaching out and please feel free to do so again anytime.


  • Repeated administration of berberine inhibits cytochromes P450 in humans, PubMed
  • Human cytochrome p450 inhibition and metabolic-intermediate complex formation by goldenseal extract and its methylenedioxyphenyl components, PubMed

About the Pharmacist

Dr. Brian Staiger, PharmD

Dr. Brian has been practicing pharmacy for over 13 years and has wide-ranging experiences in many different areas of the profession. From retail, clinical, program development, and administrative responsibilities, he's your knowledgeable and go-to source for all your pharmacy and medication-related questions! Dr. Brian Staiger also has herbalist training and educational certificates in the field of medical ethnobotany. Feel free to send him an email at [email protected]! You can also connect with Dr. Brian Staiger on LinkedIn.

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