Drug & supplement interaction

Phosphatidylserine + Amitriptyline

Amitriptyline brand name: Elavil.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Phosphatidylserine has a moderate interaction with Amitriptyline. Theoretically, phosphatidylserine might decrease the effectiveness anticholinergic drugs.

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

Phosphatidylserine and Amitriptyline

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

Moderate

ANTICHOLINERGIC DRUGS

Why this applies to Amitriptyline

Amitriptyline falls under ANTICHOLINERGIC DRUGS — the group Phosphatidylserine interacts with.

Theoretically, phosphatidylserine might decrease the effectiveness anticholinergic drugs.
Phosphatidylserine is thought to increase acetylcholine levels, which could theoretically interfere with the activity of anticholinergic agents.
Severity Moderate Likelihood Possible Evidence B

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 idea behind this pairing. Amitriptyline has anticholinergic activity, meaning part of how it works (and where its side effects come from) involves blocking a brain chemical called acetylcholine. Phosphatidylserine is thought to do the opposite and nudge acetylcholine levels up. So in theory, the supplement could slightly push against amitriptyline's anticholinergic side, possibly making it work a touch less the way you expect.

I want to be honest about the evidence here: this is mostly theoretical and based on weak data, so for most people it's unlikely to cause a real problem. Still, if you notice changes in your mood, sleep, or how the medicine is helping, mention it to your pharmacist or doctor before changing anything.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Crook T, Petrie W, Wells C, Massari DC. Effects of phosphatidylserine in Alzheimer's disease. Psychopharmacol Bull 1992;28:61-6.
  2. 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
  3. 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

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

Phosphatidylserine Also Interacts With Other Medications

Phosphatidylserine has 218 moderate known drug interactions in our database — the Amitriptyline one above is one of them. If you take anything else, check it against the full list below.

Moderate 218 No known interaction 2,612 (incl. Amitriptyline)
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.

From our Q&A

Questions About Phosphatidylserine or Amitriptyline

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 Amitriptyline, 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 Amitriptyline

This page covers Phosphatidylserine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Amitriptyline page lists 296 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), American Hellebore (major), Arsenic (major) and Beer (major).

By severity: 17 major · 228 moderate · 51 minor.

From our pharmacist’s overview on the Amitriptyline page

“Amitriptyline (Elavil), an older antidepressant now often prescribed for nerve pain, migraines, and sleep, is one of the drugs I genuinely want patients to be careful with, and 17 of the 296 supplement and herbal ingredients on this list carry a major rating. Most of the serious ones deepen the drowsiness amitriptyline already causes,…”

Reviewed by 2 · Jul 18, 2026

Open the Amitriptyline 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. Your product may carry other ingredients that interact with Amitriptyline too, on top of Phosphatidylserine — 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 Phosphatidylserine and Amitriptyline 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 Amitriptyline
Top 5%

#52 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 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.

Read the full Phosphatidylserine monograph & all interactions
Medication

About Amitriptyline

What Is Amitriptyline Used For?

Brand name: Elavil

Amitriptyline HCL and Amitriptyline Hydrochloride tablets are used to relieve symptoms of depression. Depression that originates from within the body (called endogenous depression) tends to respond better than other types of depression.

See full Amitriptyline 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
218Moderate
0Minor
2,611No known interaction
218 Moderate 2,611 No interaction
Moderate

218 interactions

Showing 60 of 218 moderate interactions — see all 218 on the Phosphatidylserine page.

No interaction 2,611 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 2,611 medications checked with no known interaction — see the full Phosphatidylserine list.

See the full Phosphatidylserine interactions page
See every supplement checked against Amitriptyline, ranked by severity
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

Keep exploring
Phosphatidylserine monograph › Uses, safety, and every drug interaction in one place Amitriptyline supplement interactions › Every supplement checked against Amitriptyline, ranked by severity Amitriptyline drug information › The full plain-English guide to this medication Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Phosphatidylserine and Amitriptyline Together: Common Questions

Can you take Phosphatidylserine with Amitriptyline?
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.
How serious is the Phosphatidylserine and Amitriptyline 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 Amitriptyline and Phosphatidylserine?

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.