Drug & supplement interaction

Cascara Sagrada + nefazodone

nefazodone brand name: Serzone.

Minor Interaction
The bottom line Minor

Cascara Sagrada has a minor interaction with nefazodone. Theoretically, cascara sagrada might decrease the effects of CYP3A4 substrates.

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

Cascara Sagrada and nefazodone

Here is the interaction we found between these two, with the evidence behind it.

Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Why this applies to nefazodone

nefazodone falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Cascara Sagrada interacts with.

Theoretically, cascara sagrada might decrease the effects of CYP3A4 substrates.
In vitro research suggests that cascara sagrada can induce CYP3A4 enzymes, albeit to a much lower degree than rifampin, a known CYP3A4 inducer.
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

Here's the gist for nefazodone (Serzone). Your liver clears this antidepressant using an enzyme called CYP3A4. Lab studies hint that cascara sagrada may gently speed up that same enzyme. If that happened in real life, your body could break nefazodone down a little faster, which in theory might make it work slightly less well. That could show up as your depression symptoms not being controlled as well as usual.

I want to be honest about how thin this evidence is. It comes only from test-tube research, the effect was much weaker than known strong inducers, and it's rated a minor, possible interaction. Occasional short-term laxative use likely won't upset your treatment. Still, check with your pharmacist or doctor before pairing them, and never adjust your nefazodone on your own.

References
  1. Mazzari ALDA, Lacerda MG, Milton FA, et al. In vitro effects of European and Latin-American medicinal plants in CYP3A4 gene expression, glutathione levels, and P-glycoprotein activity. Front Pharmacol 2022;13:826395. 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

Cascara Sagrada Also Interacts With Other Medications

Cascara Sagrada has 122 moderate, 622 minor known drug interactions in our database — the nefazodone one above is one of them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Cascara Sagrada

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

Everything else you take

See Every Supplement That Interacts With nefazodone

This page covers Cascara Sagrada only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the nefazodone page lists 159 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Grapefruit (major), Lithium (major), St. John's Wort (major) and 5-htp (moderate).

By severity: 4 major · 114 moderate · 41 minor.

From our pharmacist’s overview on the nefazodone page

“Nefazodone (Serzone) treats depression by working on serotonin, and it also strongly blocks a liver enzyme called CYP3A4, which is exactly why this list deserves your close attention. The largest group, 121 ingredients, are ones nefazodone can push to higher levels because it slows their breakdown.”

Reviewed by 2 · Jul 18, 2026

Open the nefazodone interaction page

One more smart check

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

We hold 849 real supplement products containing Cascara Sagrada, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Cascara Sagrada. Your product may carry other ingredients that interact with nefazodone too, on top of Cascara Sagrada — 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 Cascara Sagrada and nefazodone 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 Cascara Sagrada
Top 25%

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

29 days ago today
Medication nefazodone
Steady interest

#2,532 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 Cascara Sagrada

What is Cascara Sagrada?

Cascara Sagrada
  • Constipation
  • Bowel cleansing before procedures
  • Hemorrhoids
  • Traditional liver and gallbladder remedy

Cascara sagrada is a stimulant laxative made from the aged bark of a Pacific Northwest tree, used mainly for short-term relief of constipation. Because it can cause cramping, dehydration, and electrolyte problems—and was removed from over-the-counter laxative products in the U.S. due to safety concerns—it should only be used briefly, if at all, and with guidance from a pharmacist or doctor.

Read the full Cascara Sagrada monograph & all interactions
Medication

About Nefazodone

What Is Nefazodone Used For?

Brand name: Serzone

Nefazodone Hydrochloride tablets are approved to treat depression, specifically major depressive disorder (MDD). Clinical trials established its effectiveness over 6 to 8 weeks in outpatients and 6 weeks in hospitalized patients with depression.

Nefazodone has also been shown to help prevent depression from coming back in patients who responded well to initial treatment. Because of a serious risk of liver failure, prescribers are advised to consider other antidepressants before turning to nefazodone.

See full Nefazodone drug information
Keep checking

Other Drugs & Cascara Sagrada

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

0Major
122Moderate
622Minor
2,085No known interaction
Moderate

122 interactions

Showing 60 of 122 moderate interactions — see all 122 on the Cascara Sagrada page.

Minor

622 interactions

Showing 60 of 622 minor interactions — see all 622 on the Cascara Sagrada page.

No interaction 2,085 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 Cascara Sagrada and nefazodone Together: Common Questions

Can you take Cascara Sagrada with nefazodone?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Cascara Sagrada and nefazodone interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

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

Still Have a Question About nefazodone and Cascara Sagrada?

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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.