Drug & supplement interaction

Lithium + Perphenazine

Perphenazine brand name: Trilafon.

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

Perphenazine falls into 2 drug categories that Lithium can interact with; the most serious is rated moderate. Theoretically, taking lithium supplements with antipsychotic drugs might increase the risk of encephalopathic syndrome.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Lithium and Perphenazine

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Lithium interacts with whole categories of medication. Perphenazine falls into 2 of those categories, so it can interact with Lithium in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

ANTIPSYCHOTIC DRUGS

1 of 2

Why this applies to Perphenazine

Perphenazine falls under ANTIPSYCHOTIC DRUGS — the group Lithium interacts with.

Theoretically, taking lithium supplements with antipsychotic drugs might increase the risk of encephalopathic syndrome.
Encephalopathic syndrome has been reported in multiple patients taking prescription lithium and antipsychotics concomitantly. Symptoms have included weakness and lethargy, fever, confusion, and extrapyramidal symptoms. In some patients, resulting brain damage was irreversible. Although there is no established causal relationship between these symptoms and the combination of lithium and antipsychotic medications, there is a theoretical relationship. It is unclear if this interaction would occur with the smaller doses found in lithium supplements.
Severity Moderate 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 situation with combining lithium supplements and perphenazine (Trilafon). Over the years, a handful of case reports have described people taking prescription lithium alongside antipsychotics who developed something called encephalopathic syndrome. The reported symptoms included weakness, sluggishness, fever, confusion, and worsened movement problems like stiffness, tremor, or restlessness (what we call extrapyramidal symptoms). In rare cases the brain effects didn't fully reverse.

I want to be honest about how shaky this evidence is. Nobody has proven that the combination itself causes this, and it's based on scattered anecdotes, not solid studies. It's also unclear whether the small amounts in supplements like lithium orotate would ever matter. Still, perphenazine on its own can cause drowsiness and movement side effects, so I'd rather you not stack an unproven lithium product on top. Please run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/017812s028,018421s027lbl.pdf. Accessed Nov. 21, 2018
Moderate

PHENOTHIAZINES

2 of 2

Perphenazine also falls under PHENOTHIAZINES.

Theoretically, taking lithium supplements with phenothiazines might decrease the levels and clinical effects of phenothiazines.
Concomitant use of lithium with phenothiazines might reduce lithium concentrations. Lithium might also reduce phenothiazine concentrations, making the pharmacokinetic effect unpredictable. It is unclear if these interactions would occur with the smaller doses found in lithium supplements.
Severity Moderate Likelihood Probable Evidence D

Interaction 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..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist if you're thinking about pairing a lithium supplement with perphenazine (Trilafon). On paper, these two may lower each other's blood levels. For perphenazine, that could mean it doesn't quiet the brain as well as it should, so symptoms it usually keeps in check (like disordered thinking or severe nausea) might not stay controlled. Lithium levels can drop too, making the whole combo a bit unpredictable.

I want to be honest, though: this is a theoretical concern based on how these drugs behave, not strong real-world proof, and it's unclear whether the tiny doses in lithium supplements matter at all. Perphenazine isn't a prodrug, so the worry is mainly weaker effect, not toxicity. Still, please run any lithium product past your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Martindale W. Martindale the Extra Pharmacopoeia. Pharmaceutical Press, 1999.
  2. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.

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

Lithium Also Interacts With Other Medications

Lithium has 259 major, 255 moderate known drug interactions in our database — the Perphenazine one above is among them. If you take anything else, check it against the full list below.

Major 259 Moderate 255 No known interaction 2,316 (incl. Perphenazine)
Taking anything else?

Check Another of Your Medications Against Lithium

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

From our Q&A

Questions About Lithium or Perphenazine

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

This page covers Lithium only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Perphenazine page lists 147 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Henbane (major), Indian Snakeroot (major), Rauvolfia Vomitoria (major) and Scopolia (major).

By severity: 5 major · 108 moderate · 34 minor.

From our pharmacist’s overview on the Perphenazine page

“Perphenazine (Trilafon) treats schizophrenia and severe nausea, and this list deserves real care. Five of the 147 ingredients on file rate major, and those five are the ones to understand first.”

Reviewed by 2 · Jul 18, 2026

Open the Perphenazine interaction page

One more smart check

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

We hold 330 real supplement products containing Lithium, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Lithium. Your product may carry other ingredients that interact with Perphenazine too, on top of Lithium — 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 Lithium and Perphenazine 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 Lithium
Top 25%

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

29 days ago today
Medication Perphenazine
Top 25%

#673 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 Lithium

What is Lithium?

Lithium
  • Mood support
  • Bipolar disorder (prescription)
  • Healthy mental function
  • Irritability or stress
  • Sleep support

Lithium is a naturally occurring metal that, in prescription form (lithium carbonate or citrate), is an FDA-approved, well-proven treatment for bipolar disorder. Low-dose supplement forms like lithium orotate are sold for mood support, but there is very little reliable evidence that they work, and even small amounts of lithium can be risky for some people. Always talk to a pharmacist or doctor before taking any lithium product.

Read the full Lithium monograph & all interactions
Medication

About Perphenazine

What Is Perphenazine Used For?

Brand name: Trilafon

Perphenazine tablets are approved to treat schizophrenia in adults. They are also used to control severe nausea and vomiting in adults when other measures are not enough.

Perphenazine has not been shown effective for managing behavioral problems in patients with intellectual disabilities, and it is not approved for dementia-related psychosis in elderly patients.

See full Perphenazine drug information
Keep checking

Other Drugs & Lithium

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

259Major
255Moderate
0Minor
2,315No known interaction
259 Major 255 Moderate 2,315 No interaction
Major

259 interactions

Showing 60 of 259 major interactions — see all 259 on the Lithium page.

Moderate

255 interactions

Showing 60 of 255 moderate interactions — see all 255 on the Lithium page.

No interaction 2,315 drugs checked — show the list

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

Showing the 60 most looked-up of 2,315 medications checked with no known interaction — see the full Lithium list.

See the full Lithium interactions page
See every supplement checked against Perphenazine, 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
Lithium monograph › Uses, safety, and every drug interaction in one place Perphenazine supplement interactions › Every supplement checked against Perphenazine, ranked by severity Perphenazine 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 Lithium and Perphenazine Together: Common Questions

Can you take Lithium with Perphenazine?
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.
Why are there 2 interactions listed for Lithium and Perphenazine?
Perphenazine belongs to more than one drug category, and Lithium interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Lithium and Perphenazine 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 Perphenazine and Lithium?

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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.