Drug & supplement interaction

Phosphatidylserine + Esketamine

Esketamine brand name: Spravato.

No Known Interaction
Medically reviewed by · Updated July 2026 · Pair last verified Sep 20, 2026
The bottom line No known interaction

We found no known interaction between Phosphatidylserine and Esketamine 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

Phosphatidylserine and Esketamine

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 Esketamine and Phosphatidylserine 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.

Phosphatidylserine safety at a glance

Phosphatidylserine overall Use caution Generally well tolerated in studies, but long-term safety is not fully established.
Pregnancy Avoid There is not enough safety information, so it is best to avoid use during pregnancy.
Breastfeeding Avoid Safety while breastfeeding is unknown, so avoidance is recommended.

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

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

Why No Interaction Is Listed for Esketamine

Interactions in our licensed database are recorded against drug classes, not just single drug names. Esketamine is filed under 2 classifications — tricyclic antidepressants (tcas), antidepressant drugs. Phosphatidylserine has documented interactions with 2 drug classes — the most serious being anticholinergic drugs (moderate) and cholinergic drugs (moderate) — and none of Esketamine’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

Phosphatidylserine Does Interact With Other Medications

Phosphatidylserine has 219 moderate known drug interactions in our database — Esketamine isn’t one of them. If you take anything else, check it against the full list below.

Moderate 219 No known interaction 2,611 (incl. Esketamine)
Taking anything else?

Check Another of Your Medications Against Phosphatidylserine

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

What to actually watch for

No Interaction Found — But Data Suggests Phosphatidylserine and Esketamine 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.

  • Nausea reported in 5.4% of FDA reports for Esketamine Additional detail

    Phosphatidylserine

    “Orally, phosphatidylserine can cause gastrointestinal upset such as flatulence or nausea. Gastrointestinal upset can occur at doses of 200-300 mg/day.”

    Phosphatidylserine · Natural Medicines adverse-effect record, reported in flatulence.

    5 sources cited
    1. 7116. Pepping J. Phosphatidylserine. Am J Health-Syst Pharm 1999;56:2038,2043-4.
    2. 7121. Kidd PM. Phosphatidylserine; Membrane nutrient for memory. A clinical and mechanistic assessment. Altern Med Rev 1996;1:70-84.
    3. 15539. Schreiber S, Kampf-Sherf O, Gorfine M, et al. An open trial of plant-source derived phosphatydilserine for treatment of age-related cognitive decline. Isr J Psychiatry Relat Sci 2000;37:302-7.
    4. 68862. Monteverde, A., Gnemmi, P., Rossi, F., Monteverde, A., and Finali, G. C. Selegiline in the treatment of mild to moderate Alzheimer-type dementia. Clin.Ther 1990;12(4):315-322.
    5. 90711. Vakhapova V, Cohen T, Richter Y, Herzog Y, Kam Y, Korczyn AD. Phosphatidylserine containing omega-3 Fatty acids may improve memory abilities in nondemented elderly individuals with memory complaints: results from an open-label extension study. Dement Geri PubMed

    Esketamine

    Listed in the ADVERSE REACTIONS section of the FDA label for Esketamine, and in voluntary FDA adverse-event reports. Read the label on DailyMed ›

  • Headache Additional detail

    Phosphatidylserine

    “Orally, phosphatidylserine can cause insomnia. Insomnia is more likely to occur with a higher dose of 600 mg. Headache has also been reported.”

    Phosphatidylserine · Natural Medicines adverse-effect record, reported in cluster headache.

    3 sources cited
    1. 7121. Kidd PM. Phosphatidylserine; Membrane nutrient for memory. A clinical and mechanistic assessment. Altern Med Rev 1996;1:70-84.
    2. 68844. Pepping, J. Phosphatidylserine. Am J Health Syst.Pharm. 10-15-1999;56(20):2038, 2043-2038, 2044.
    3. 90711. Vakhapova V, Cohen T, Richter Y, Herzog Y, Kam Y, Korczyn AD. Phosphatidylserine containing omega-3 Fatty acids may improve memory abilities in nondemented elderly individuals with memory complaints: results from an open-label extension study. Dement Geri PubMed

    Esketamine

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

Reported for Phosphatidylserine but not commonly for Esketamine: stomach upset, bloating or gas and trouble sleeping.

Effects for Esketamine come from the ADVERSE REACTIONS section of its FDA label; effects for Phosphatidylserine come from the Natural Medicines adverse-effect record, quoted above. Where a percentage is shown, it is the share of 17,728 voluntary FDA FAERS reports for Esketamine that mention that effect — a reporting proportion, not an incidence rate and not evidence the drug caused it. 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 Esketamine Is Prescribed For, and What Phosphatidylserine Has Been Studied For

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

Esketamine is prescribed for: Spravato nasal spray is approved for two uses in adults. First, it treats treatment-resistant depression (TRD) — depression that has not responded to other antidepressants — either on its own or alongside an oral antidepressant. Second, it treats depressive symptoms in adults with major depressive disorder (MDD) who have acute suicidal ideation or behavior, always used together with an oral antidepressant in this case. Important limits: Spravato has not been shown to prevent suicide or reduce suicidal thoughts or behavior on its own.

Read the rest of what Esketamine is prescribed for

It is not a replacement for hospitalization if that is clinically needed, and it is not approved as an anesthetic.

Phosphatidylserine has been studied for:

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

    Phosphatidylserine for depression

    It is unclear if oral phosphatidylserine is beneficial for depression.

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 Esketamine on your own; if you are taking Phosphatidylserine for the same health topic, tell your prescriber, especially if the medicine is being adjusted to a target.

From our Q&A

Questions About Phosphatidylserine or Esketamine

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

This page covers Phosphatidylserine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Esketamine page lists 11 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Scopolia (major), Cowhage (moderate), Dhea (moderate), Griffonia Simplicifolia (moderate) and Indian Snakeroot (moderate).

By severity: 1 major · 6 moderate · 4 minor.

From our pharmacist’s overview on the Esketamine page

“Esketamine (Spravato) is the nasal spray for depression that hasn't responded to standard treatment, and its supplement list deserves genuine respect. Scopolia carries the only major rating and is the entry to understand before any other; pairing it with the medication can raise the risk of anticholinergic effects, meaning dry mouth, b…”

Reviewed by 2 · Jul 18, 2026

Open the Esketamine interaction page

One more smart check

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

We hold 1,754 real supplement products containing Phosphatidylserine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Phosphatidylserine. Even though Phosphatidylserine itself has no known interaction with Esketamine, 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 Phosphatidylserine and Esketamine 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 Phosphatidylserine
Top 10%

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

29 days ago today
Medication Esketamine
Steady interest

#2,708 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 Phosphatidylserine reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 20, 2026. The Phosphatidylserine and Esketamine 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 Phosphatidylserine

What is Phosphatidylserine?

Phosphatidylserine
  • Memory and cognitive support
  • Age-related cognitive decline
  • Attention and focus (ADHD)
  • Mental performance under stress
  • Exercise recovery

Phosphatidylserine is a natural fat-like compound found in cell membranes, especially in the brain, and it is sold mainly to support memory and thinking. Some research suggests possible benefits for age-related memory problems, but the evidence is limited and far from conclusive. It is generally well tolerated, but check with your pharmacist or doctor before using it, especially during pregnancy or breastfeeding.

Phospholipid derived from soy lecithin, sunflower lecithin, or (historically) bovine brain · Capsules, softgels, tablets, powders

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

Phosphatidylserine: dosing

There is no official standardized dose for phosphatidylserine. Amounts used in studies have varied, and the right amount for any individual is not well established.The safest approach is to follow the dose printed on the product label and not exceed it. Taking it earlier in the day may help reduce the chance of sleep problems.

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

Read the full Phosphatidylserine monograph & all interactions
Medication

About Esketamine Nasal Spray

What Is Esketamine Nasal Spray Used For?

Brand name: Spravato

Spravato nasal spray is approved for two uses in adults. First, it treats treatment-resistant depression (TRD) — depression that has not responded to other antidepressants — either on its own or alongside an oral antidepressant. Second, it treats depressive symptoms in adults with major depressive disorder (MDD) who have acute suicidal ideation or behavior, always used together with an oral antidepressant in this case.

Important limits: Spravato has not been shown to prevent suicide or reduce suicidal thoughts or behavior on its own. It is not a replacement for hospitalization if that is clinically needed, and it is not approved as an anesthetic.

Most-Reported Side Effects for Esketamine

From FAERS, the FDA’s public side-effect reporting system (17,728 reports, all brands). Reports are voluntary and are not proof the drug caused the effect.

Dissociation 3,733 reports
Sedation 2,706 reports
Suicidal ideation 1,351 reports
Nausea 957 reports
Depression 873 reports
See full Esketamine Nasal Spray drug information
Keep checking

Other Drugs & Phosphatidylserine

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

0Major
219Moderate
0Minor
2,610No known interaction
219 Moderate 2,610 No interaction
Moderate

219 interactions

Showing 60 of 219 moderate interactions — see all 219 on the Phosphatidylserine page.

No interaction 2,610 drugs checked — show the list

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

Showing the 60 most looked-up of 2,610 medications checked with no known interaction — see the full Phosphatidylserine list.

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

Phosphatidylserine References

The 9 references that drive our Phosphatidylserine 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. Crook T, Petrie W, Wells C, Massari DC. Effects of phosphatidylserine in Alzheimer's disease. Psychopharmacol Bull 1992;28:61-6.
  2. Pepping J. Phosphatidylserine. Am J Health-Syst Pharm 1999;56:2038,2043-4.
  3. Kidd PM. Phosphatidylserine; Membrane nutrient for memory. A clinical and mechanistic assessment. Altern Med Rev 1996;1:70-84.
  4. Kim HY, Akbar M, Lau A, et al. Inhibition of neuronal apoptosis by docosahexaenoic acid (22:6n-3). Role of phosphatidylserine in antiapoptotic effect. J Biol Chem 2000;275:35215-23.. PubMed
  5. Zanotti A, Valzelli L, Toffano G. Chronic phosphatidylserine treatment improves spatial memory and passive avoidance in aged rats. Psychopharmacology (Berl) 1989;99:316-21.. PubMed
  6. Schreiber S, Kampf-Sherf O, Gorfine M, et al. An open trial of plant-source derived phosphatydilserine for treatment of age-related cognitive decline. Isr J Psychiatry Relat Sci 2000;37:302-7.
  7. Pepping, J. Phosphatidylserine. Am J Health Syst.Pharm. 10-15-1999;56(20):2038, 2043-2038, 2044.
  8. Monteverde, A., Gnemmi, P., Rossi, F., Monteverde, A., and Finali, G. C. Selegiline in the treatment of mild to moderate Alzheimer-type dementia. Clin.Ther 1990;12(4):315-322.
  9. Vakhapova V, Cohen T, Richter Y, Herzog Y, Kam Y, Korczyn AD. Phosphatidylserine containing omega-3 Fatty acids may improve memory abilities in nondemented elderly individuals with memory complaints: results from an open-label extension study. Dement Geri 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 Phosphatidylserine and Esketamine Together: Common Questions

Is it safe to take Phosphatidylserine with Esketamine?
We do not list a known interaction between Phosphatidylserine and Esketamine. 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 Phosphatidylserine and Esketamine have any of the same side effects?
Yes — our sources link each of them separately to 2 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 Phosphatidylserine and Esketamine 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 Phosphatidylserine in each. That is a conversation for your prescriber, especially if Esketamine is being adjusted to a target.
How was the Phosphatidylserine and Esketamine combination checked?
Interactions in our licensed database are recorded against drug classes. Esketamine is filed under 2 classifications, and Phosphatidylserine has documented interactions with 2 drug classes — none of Esketamine'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 Phosphatidylserine interact with any other medications?
Yes. Phosphatidylserine has 219 documented drug interactions in our database — Esketamine 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 Esketamine interact with any supplements?
Yes. Esketamine has documented interactions with 11 supplements in our database — Phosphatidylserine is not one of them. The Esketamine 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

Phosphatidylserine monograph Uses, safety profile, and every drug interaction in one place Esketamine Nasal Spray drug information The full plain-English guide to this medication Esketamine supplement interactions Every supplement checked against Esketamine, 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 9 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Esketamine and Phosphatidylserine?

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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.