Drug & supplement interaction

Pregnenolone + Fluoxetine

Fluoxetine brand names: Prozac, Sarafem.

No Known Interaction
Medically reviewed by · Updated July 2026 · Pair last verified Sep 13, 2026
The bottom line No known interaction

We found no known interaction between Pregnenolone and Fluoxetine in our sources. Absence of a documented interaction is not the same as proven safety, and does not guarantee one does not exist. Do not start, stop, or change a medication or supplement based on this page; confirm with your pharmacist or doctor first. Additionally, although there is no interaction, the two are separately associated with some of the same side effects, which would make a new symptom harder to attribute to one or the other.

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Interaction report

Pregnenolone and Fluoxetine

We checked these two against our interaction database. Here is what we found.

No Known Interaction Found

We did not find a documented interaction between Fluoxetine and Pregnenolone in our sources. This does not guarantee that the combination is completely free of risk — there is often limited research on supplements and herbal products, especially around drug interactions.

If you decide to take both, the practical routine is simple: add one new thing at a time and note the date you started it. If the combination is going to disagree with you, it usually shows in the first days to a couple of weeks — and a start date turns “I’ve been feeling off” into something a pharmacist can actually work with. Do not stop a prescribed medicine on your own.

Always talk with your pharmacist or doctor before making changes to your medications or supplements, particularly if you take several medications or have an ongoing health condition.

Pregnenolone safety at a glance

Pregnenolone overall Use caution It is a hormone with limited human safety data, so use only under guidance from a healthcare professional.
Pregnancy Avoid Hormone supplements should be avoided during pregnancy due to unknown risks.
Breastfeeding Avoid Not enough safety information exists, so avoid while breastfeeding.

Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Fluoxetine and Pregnenolone? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
How we checked

Why No Interaction Is Listed for Fluoxetine

Interactions in our licensed database are recorded against drug classes, not just single drug names. Fluoxetine is filed under 14 classifications — including antidepressant drugs, cytochrome p450 2c19 (cyp2c19) inhibitors, cytochrome p450 2c9 (cyp2c9) inhibitors. Pregnenolone has documented interactions with 5 drug classes — the most serious being benzodiazepines (moderate), estrogens (moderate) and progesterone (moderate) — and none of Fluoxetine’s classifications are among them.

Classification data comes from our licensed Natural Medicines dataset. A medication can belong to classes beyond those recorded there, so this describes how the check was run — it is not a safety guarantee.

Keep it in perspective

Pregnenolone Does Interact With Other Medications

Pregnenolone has 82 moderate known drug interactions in our database — Fluoxetine isn’t one of them. If you take anything else, check it against the full list below.

Moderate 82 No known interaction 2,748 (incl. Fluoxetine)
Taking anything else?

Check Another of Your Medications Against Pregnenolone

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

What to actually watch for

No Interaction Found — But Data Suggests Pregnenolone and Fluoxetine May Share Several of the Same Side Effects

This is not an interaction. Neither one changes how your body handles the other, and nothing here says they react together. What our sources do show is that each has separately been linked to the effects below — so taking both can make those effects more likely to turn up, and harder to pin on one or the other if they do.

  • Sun sensitivity Additional detail

    Pregnenolone

    “Orally, pregnenolone has been reported to cause skin abscesses, acne, and hair loss. A case of skin rash accompanied by a burning sensation on the back and sides of the hands has also been reported with oral pregnenolone use, possibly related to a photosensitivity reaction. The rash cleared on its own.”

    Pregnenolone · Natural Medicines adverse-effect record, reported in acne.

    2 sources cited
    1. 94027. Brown ES, Park J, Marx CE, et al. A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression. Neuropsychopharmacology 2014;39(12):2867-73. PubMed
    2. 94031. Meieran SE, Reus VI, Webster R, Shafton R, Wolkowitz OM. Chronic pregnenolone effects in normal humans: attenuation of benzodiazepine-induced sedation. Psychoneuroendocrinology 2004;29(4):486-500. PubMed

    Fluoxetine

    Listed in the ADVERSE REACTIONS section of the FDA label for Fluoxetine. Read the label on DailyMed ›

  • Tremor or shakiness / Sweating / Drowsiness Additional detail

    Pregnenolone

    “Orally, pregnenolone has been reported to cause restlessness, tiredness, sweating, and a case of cold extremities. Sleep problems, drowsiness, and tremor have also been reported; however, it not certain if these effects were due to pregnenolone.”

    Pregnenolone · Natural Medicines adverse-effect record, reported in common cold.

    3 sources cited
    1. 94026. Fung LK, Libove RA, Phillips J, Haddad F, Hardan AY.Brief report: an open-label study of the neurosteroid pregnenolone in adults with autism spectrum disorder. J Autism Dev Disord 2014;44(11):2971-7. PubMed
    2. 94032. Marx CE, Keefe RS, Buchanan RW, et al. Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia. Neuropsychopharmacology 2009;34(8):1885-903. PubMed
    3. 94031. Meieran SE, Reus VI, Webster R, Shafton R, Wolkowitz OM. Chronic pregnenolone effects in normal humans: attenuation of benzodiazepine-induced sedation. Psychoneuroendocrinology 2004;29(4):486-500. PubMed

    Fluoxetine

    Listed in the ADVERSE REACTIONS section of the FDA label for Fluoxetine. Read the label on DailyMed ›

  • Hair loss Additional detail

    Pregnenolone

    Recorded for Pregnenolone in the same Natural Medicines adverse-effect record shown under Tremor or shakiness / Sweating / Drowsiness above.

    Fluoxetine

    Listed in the ADVERSE REACTIONS section of the FDA label for Fluoxetine. Read the label on DailyMed ›

  • Anxiety or restlessness Additional detail

    Pregnenolone

    “Orally, pregnenolone has been reported to cause depressive affect and increased appetite. Increased excitement, agitation, increased motor activity, and anorexia have also been reported; however, it is not certain if these effects were due to pregnenolone.”

    Pregnenolone · Natural Medicines adverse-effect record, reported in anorexia.

    2 sources cited
    1. 94026. Fung LK, Libove RA, Phillips J, Haddad F, Hardan AY.Brief report: an open-label study of the neurosteroid pregnenolone in adults with autism spectrum disorder. J Autism Dev Disord 2014;44(11):2971-7. PubMed
    2. 94031. Meieran SE, Reus VI, Webster R, Shafton R, Wolkowitz OM. Chronic pregnenolone effects in normal humans: attenuation of benzodiazepine-induced sedation. Psychoneuroendocrinology 2004;29(4):486-500. PubMed

    Fluoxetine

    Listed in the ADVERSE REACTIONS section of the FDA label for Fluoxetine. Read the label on DailyMed ›

  • Reduced appetite Additional detail

    Pregnenolone

    Recorded for Pregnenolone in the same Natural Medicines adverse-effect record shown under Anxiety or restlessness above.

    Fluoxetine

    Listed in the ADVERSE REACTIONS section of the FDA label for Fluoxetine. Read the label on DailyMed ›

  • Constipation Additional detail

    Pregnenolone

    “Orally, pregnenolone may cause diarrhea. Constipation has also been reported after oral use; however, it is not certain if this effect was due to pregnenolone.”

    Pregnenolone · Natural Medicines adverse-effect record, reported in constipation.

    1 source cited
    1. 94026. Fung LK, Libove RA, Phillips J, Haddad F, Hardan AY.Brief report: an open-label study of the neurosteroid pregnenolone in adults with autism spectrum disorder. J Autism Dev Disord 2014;44(11):2971-7. PubMed

    Fluoxetine

    Listed in the ADVERSE REACTIONS section of the FDA label for Fluoxetine. Read the label on DailyMed ›

  • Tiredness Additional detail

    Pregnenolone

    Recorded for Pregnenolone in the same Natural Medicines adverse-effect record shown under Tremor or shakiness / Sweating / Drowsiness above.

    Fluoxetine

    Listed in the ADVERSE REACTIONS section of the FDA label for Fluoxetine. Read the label on DailyMed ›

  • Diarrhea Additional detail

    Pregnenolone

    Recorded for Pregnenolone in the same Natural Medicines adverse-effect record shown under Tremor or shakiness / Sweating / Drowsiness above.

    Fluoxetine

    Listed in the ADVERSE REACTIONS section of the FDA label for Fluoxetine. Read the label on DailyMed ›

Showing the 10 most notable of 11 shared effects — ranked by how unusual each one is, not just whether both lists mention it.

Reported for Pregnenolone but not commonly for Fluoxetine: increased appetite, muscle pain and acne.

Effects for Fluoxetine come from the ADVERSE REACTIONS section of its FDA label; effects for Pregnenolone come from the Natural Medicines adverse-effect record, quoted above. Wording is matched across sources by our own clinical vocabulary, so treat this as a prompt to pay attention, not a diagnosis.

Overlapping uses

What Fluoxetine Is Prescribed For, and What Pregnenolone Has Been Studied For

These two come up together because they touch the same health topic — not because they do the same job. Fluoxetine is a prescription medicine with approved uses on its FDA label. Pregnenolone is a supplement: what follows is what researchers have looked at it for, and how strong that evidence is.

Fluoxetine is prescribed for: 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).

Pregnenolone has been studied for:

  • Depression studied, not established Pregnenolone has been studied for this. Natural Medicines rates the evidence: Insufficient Reliable Evidence To Rate Read what the research shows

    Pregnenolone for depression

    Although there has been interest in using oral pregnenolone for depression, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.

Effectiveness ratings and the research summaries above are the verbatim record from the Natural Medicines database, which grades evidence from “Effective” down to “Insufficient Reliable Evidence To Rate”. A rating below the top of that scale means researchers have looked at it — not that it works, and never that it can stand in for a prescribed medicine. Do not stop or replace Fluoxetine on your own; if you are taking Pregnenolone for the same health topic, tell your prescriber, especially if the medicine is being adjusted to a target.

From our Q&A

Questions About Pregnenolone 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 Pregnenolone 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 Pregnenolone 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 Pregnenolone as Part of a Dietary Supplement Product? Check It for Interactions

We hold 303 real supplement products containing Pregnenolone, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Pregnenolone. Even though Pregnenolone itself has no known interaction with Fluoxetine, another ingredient on your label might. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Pregnenolone 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 Pregnenolone
Top 25%

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

29 days ago today
Medication Fluoxetine
Top 1%

#28 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.

Where does our data come from?
  • Source: the Natural Medicines (TRC Healthcare) clinical database — the evidence-graded professional reference for herb & supplement interactions.
  • Citation library: 103,510 references behind our interaction content, 65,311 of them resolved to verified PubMed/DOI sources. See every Pregnenolone reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 13, 2026. The Pregnenolone and Fluoxetine records this page draws on were last updated July 10, 2026.
  • What “no known interaction” means: no documented interaction in the sources above — not a guarantee of safety. Supplements are studied far less than prescription drugs, so we say exactly what the evidence supports, and nothing more.
Data structure & sourcing designed and verified by .
Supplement

About Pregnenolone

What is Pregnenolone?

Pregnenolone
  • Memory and cognitive support
  • Anxiety and stress
  • Anti-aging
  • Fatigue and low energy
  • Mood support

Pregnenolone is a hormone your body makes naturally and a building block for other hormones like cortisol, DHEA, estrogen, and testosterone. It is sold as a supplement for memory, mood, and anti-aging, but solid human evidence for these uses is very limited. Because it is a hormone, talk with your pharmacist or doctor before using it.

Naturally produced in the body; supplements are made synthetically (often from plant sterols like those in soy or wild yam) · Capsules, tablets, sublingual tablets, creams

An interaction check asks whether these two react with each other — it does not ask whether Pregnenolone is a good idea for someone in your situation. Here is what our Pregnenolone record says about it on its own.

Pregnenolone: dosing

There is no well-established or officially recommended dose for pregnenolone. Products vary widely in strength and form, and "more" is not safer with a hormone supplement.If your healthcare provider agrees you should try it, follow the directions on the product label and use the lowest amount that seems reasonable. Do not assume a higher dose works better.

From our Pregnenolone monograph — the full record covers uses, side effects and every documented interaction.

Read the full Pregnenolone 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 & Pregnenolone

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

0Major
82Moderate
0Minor
2,747No known interaction
82 Moderate 2,747 No interaction
Moderate

82 interactions

Showing 60 of 82 moderate interactions — see all 82 on the Pregnenolone page.

No interaction 2,747 drugs checked — show the list

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

Showing the 60 most looked-up of 2,747 medications checked with no known interaction — see the full Pregnenolone list.

See the full Pregnenolone interactions page
See every supplement checked against Fluoxetine, ranked by severity
Evidence & sources

Pregnenolone References

The 6 references that drive our Pregnenolone monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.

  1. Devlin TM, ed. Textbook of Biochemistry With Clinical Correlations. third ed. New York: Wiley-Liss Inc., 1992.
  2. Fung LK, Libove RA, Phillips J, Haddad F, Hardan AY.Brief report: an open-label study of the neurosteroid pregnenolone in adults with autism spectrum disorder. J Autism Dev Disord 2014;44(11):2971-7. PubMed
  3. Brown ES, Park J, Marx CE, et al. A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression. Neuropsychopharmacology 2014;39(12):2867-73. PubMed
  4. Ritsner MS, Gibel A, Shleifer T, et al. Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomized, controlled, 2-center, parallel-group trial. J Clin Psychiatry 20 PubMed
  5. Meieran SE, Reus VI, Webster R, Shafton R, Wolkowitz OM. Chronic pregnenolone effects in normal humans: attenuation of benzodiazepine-induced sedation. Psychoneuroendocrinology 2004;29(4):486-500. PubMed
  6. Marx CE, Keefe RS, Buchanan RW, et al. Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia. Neuropsychopharmacology 2009;34(8):1885-903. PubMed

Medication overviews come from MedlinePlus (NIH); supplement label data from the NIH Dietary Supplement Label Database. Content is written and reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

Pharmacist Counseling Corner

Taking Pregnenolone and Fluoxetine Together: Common Questions

Is it safe to take Pregnenolone with Fluoxetine?
We do not list a known interaction between Pregnenolone and Fluoxetine. That does not guarantee the combination is risk-free, so confirm with your pharmacist or doctor — especially if you take other medications or have a health condition.
Do Pregnenolone and Fluoxetine have any of the same side effects?
Yes — our sources link each of them separately to 10 of the same effects. That is not an interaction: neither changes how your body handles the other. It does mean that if one of those effects turns up, it can be harder to tell which one is behind it. They are listed on this page with the source behind each.
Are Pregnenolone and Fluoxetine used for the same thing?
They overlap in purpose, which usually means the real question is whether you need both rather than whether they are safe together. This page lists the shared uses and how strong the evidence is for Pregnenolone in each. That is a conversation for your prescriber, especially if Fluoxetine is being adjusted to a target.
How was the Pregnenolone and Fluoxetine combination checked?
Interactions in our licensed database are recorded against drug classes. Fluoxetine is filed under 14 classifications, and Pregnenolone has documented interactions with 5 drug classes — none of Fluoxetine's classifications are among them. A medication can belong to classes beyond those recorded in our dataset, so this describes how the check was run rather than guaranteeing safety.
Does Pregnenolone interact with any other medications?
Yes. Pregnenolone has 82 documented drug interactions in our database — Fluoxetine is simply not one of them. If you take anything else, it is worth checking each one; they are all listed on this page.
Does Fluoxetine interact with any supplements?
Yes. Fluoxetine has documented interactions with 163 supplements in our database — Pregnenolone is not one of them. The Fluoxetine interaction page linked on this page lists every one, ranked by severity.

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

Where next

Keep Exploring

Pregnenolone monograph Uses, safety profile, and every drug interaction in one place Fluoxetine drug information The full plain-English guide to this medication Fluoxetine supplement interactions Every supplement checked against Fluoxetine, 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 References The 6 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Fluoxetine and Pregnenolone?

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.