Drug & supplement interaction

Lithium + Esketamine

Esketamine brand name: Spravato.

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 Lithium 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

Lithium 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 Lithium 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.

Lithium safety at a glance

Lithium overall Use caution Lithium has a narrow safety margin and prescription forms require blood monitoring; supplement forms are not well studied.
Pregnancy Possibly Unsafe When lithium carbonate and lithium citrate are used orally. Lithium can cause fetal toxicity and increases the risk for cardiac and other abnormalities, includi... Read the full pregnancy detail
Breastfeeding Likely Unsafe When used orally. Lithium is secreted into breast milk and may cause adverse effects in the nursing infant. Prescription lithium may be used in circumstances wh... Read the full breastfeeding detail

Pregnancy & breastfeeding ratings are from Natural Medicines (Therapeutic Research Center) — the full detail is in the Special populations card below. Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Esketamine and Lithium? 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. Lithium has documented interactions with 11 drug classes — the most serious being diuretic drugs (major), serotonergic drugs (major) and ace inhibitors (aceis) (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

Lithium Does Interact With Other Medications

Lithium has 259 major, 256 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.

Major 259 Moderate 256 No known interaction 2,315 (incl. Esketamine)
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.

What to actually watch for

No Interaction Found — But Data Suggests Lithium 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. One of them is worth acting on rather than waiting out — marked below.

  • Memory problems Worth acting on Additional detail

    Lithium

    “Orally, lithium can cause vertigo, muscle weakness, lethargy, fatigue, and a dazed feeling. These adverse effects often improve with continued use. Fine tremor can occur and may persist with continued use. Chronic use of lithium can cause mild cognitive and memory impairment, particularly in the presence of dehydration or hyponatremia (9,15,97745).”

    Lithium · Natural Medicines adverse-effect record, reported in bipolar disorder.

    6 sources cited
    1. 9. Martindale W. Martindale the Extra Pharmacopoeia. Pharmaceutical Press, 1999.
    2. 15. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
    3. 97745. Foulser P, Abbasi Y, Mathilakath A, Nilforooshan R. Do not treat the numbers: lithium toxicity. BMJ Case Rep. 2017;2017. pii: bcr-2017-220079. PubMed
    4. 105344. Benjelloun R, Motaib I, Otheman Y. Lithium-associated hypercalcemia presenting with neuropsychiatric manifestations in a patient with bipolar disorder. Case Rep Psychiatry. 2020;2020:6630838. PubMed
    5. 111316. Yang Q, Cheng X, Su Z, Sun L, Li M. Electroconvulsive therapy combined with lithium developed reversible pure anomic aphasia: a case report. BMC Psychiatry 2022;22(1):663. PubMed
    6. 111318. Ono R, Nishiguchi S, Kitagawa I. Lithium intoxication-associated mild encephalitis/encephalopathy with a reversible splenial lesion: A case report. Bipolar Disord 2022;24(5):551-552. PubMed

    Esketamine

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

  • Anxiety or restlessness Additional detail

    Lithium

    Recorded for Lithium in the same Natural Medicines adverse-effect record shown under Memory problems above.

    Esketamine

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

  • Tiredness / Dizziness Additional detail

    Lithium

    “Orally, prescription forms of lithium are generally well tolerated when used as prescribed. Plasma levels must be monitored to avoid toxicity. It is unclear how the lower doses of lithium found in supplements may alter the occurrence and likelihood of these adverse effects.

    Most Common Adverse Effects:

    Orally: Edema, fatigue, fine tremor, gastrointestinal symptoms, lethargy, muscle weakness, polydipsia, polyuria, ski…”

    Lithium · Natural Medicines adverse-effect record, reported in fatigue.

    Esketamine

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

Reported for Lithium but not commonly for Esketamine: a severe skin reaction, kidney problems, blood clots and a change in thyroid levels.

Effects for Esketamine come from the ADVERSE REACTIONS section of its FDA label; effects for Lithium 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.

Special populations

Lithium in Pregnancy & Breastfeeding

Pregnancy Possibly Unsafe

When lithium carbonate and lithium citrate are used orally. Lithium can cause fetal toxicity and increases the risk for cardiac and other abnormalities, including neural tube and urethral defects. However, it does not seem to increase the risk for preterm birth or low birth rate. Some research suggests lithium might increase the risk for spontaneous abortion. Based on a meta-analysis of 2 population studies, taking lithium during pregnancy may increase the risk for spontaneous abortion when compared with the general population, but not when compared with patients with affective disorders not taking lithium during pregnancy. This suggests that it may be the presence of affective disorder itself, or the possible associated use of other teratogenic drugs or substances during pregnancy, which may increase the risk for spontaneous abortion. When the potential benefits to the mother and child outweigh the possible risk to the fetus, prescription lithium may be used with close monitoring by a healthcare professional. The safety of lithium supplements during pregnancy is unknown.

Lactation Likely Unsafe

When used orally. Lithium is secreted into breast milk and may cause adverse effects in the nursing infant. Prescription lithium may be used in circumstances when the potential maternal benefits outweigh the possible risk to the infant. The infant should be closely monitored for signs of lithium toxicity.

DISCLAIMER: This tool is intended for informational purposes only, and should not be interpreted as specific medical advice. Patients should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.© 2026 Therapeutic Research Center

Overlapping uses

What Esketamine Is Prescribed For, and What Lithium 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. Lithium 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.

Lithium has been studied for:

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

    Lithium for depression

    Although there is interest in using oral lithium supplements for depression, there is insufficient reliable information about the clinical effects of lithium supplements for this condition.

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 Lithium for the same health topic, tell your prescriber, especially if the medicine is being adjusted to a target.

From our Q&A

Questions About Lithium 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 Lithium 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 Lithium 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 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. Even though Lithium 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 Lithium 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 Lithium
Top 25%

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

29 days ago today
Medication Esketamine
Steady interest

#2,428 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 Lithium reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 13, 2026. The Lithium and Esketamine records this page draws on were last updated July 11, 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 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.

Mineral element (not a plant); various lithium salts · Capsules, tablets (lithium orotate, lithium aspartate in supplements; lithium carbonate and citrate as prescription drugs)

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

Lithium: dosing

There is no established, well-tested dose for low-dose lithium supplements, and product strengths vary widely between brands.

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

Read the full Lithium 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 & 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
256Moderate
0Minor
2,314No known interaction
259 Major 256 Moderate 2,314 No interaction
Major

259 interactions

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

Moderate

256 interactions

Showing 60 of 256 moderate interactions — see all 256 on the Lithium page.

No interaction 2,314 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 2,314 medications checked with no known interaction — see the full Lithium list.

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

Lithium References

The 26 references that drive our Lithium 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. 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.
  3. Perlis RH, Sachs GS, Lafer B, et al. Effect of abrupt change from standard to low serum levels of lithium: a reanalysis of double-blind lithium maintenance data. Am J Psychiatry 2002;159:1155-9.. PubMed
  4. Pinelli JM, Symington AJ, Cunningham KA, Paes BA. Case report and review of the perinatal implications of maternal lithium use. Am J Obstet Gynecol 2002;187:245-9.. PubMed
  5. Sawagashira R, Sasagawa Y, Matsukura M, Takamaru Y. Case of myxedema coma induced by lithium carbonate in a patient with schizophrenia. Psychiatry Clin Neurosci. 2018;72(2):131. PubMed
  6. Foulser P, Abbasi Y, Mathilakath A, Nilforooshan R. Do not treat the numbers: lithium toxicity. BMJ Case Rep. 2017;2017. pii: bcr-2017-220079. PubMed
  7. https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/017812s028,018421s027lbl.pdf. Accessed Nov. 21, 2018
  8. Fornaro M, Maritan E, Ferranti R, et al. Lithium Exposure During Pregnancy and the Postpartum Period: A Systematic Review and Meta-Analysis of Safety and Efficacy Outcomes. Am J Psychiatry. 2020;177(1):76-92. DOI
  9. Rauf A, Gul S, Nasir M, Arif U, Oyenuga M. A Rare Case of Lithium-induced Partial Nephrogenic Diabetes Insipidus. Cureus. 2020;12(4):e7877. PubMed
  10. Hanna RM, Hasnain H, Sangalang MD, et al. Three Patients with Lithium-Associated Hyperparathyroidism: Literature Review Regarding Medical and Surgical Management. Case Rep Nephrol Dial. 2019;9(2):108-118. PubMed
  11. Rana P, Alba Aponte P, Babar G. An Adolescent Female with Bipolar Disorder Presenting with Lithium-Induced Hyperthyroidism. Case Rep Endocrinol. 2020;2020:1283464. PubMed
  12. Nwabufor PC, Omoniyi ON, Oyibo SO. A Case of Lithium-Associated Hypocalciuric Hypercalcemia. Cureus. 2020;12(9):e10606. PubMed
  13. Landa E, Wagner S, Makkar A, Liu A, Jung D. An atypical presentation of serotonin syndrome. Cureus. 2021;13(2):e13377. PubMed
  14. Benjelloun R, Motaib I, Otheman Y. Lithium-associated hypercalcemia presenting with neuropsychiatric manifestations in a patient with bipolar disorder. Case Rep Psychiatry. 2020;2020:6630838. PubMed
  15. Nombora O, Samico A, Venâncio Â. Lithium-Induced Dysgeusia and Hyposmia: A Case Report and a Literature Review. Clin Neuropharmacol 2023;46(1):31-33. 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 Lithium and Esketamine Together: Common Questions

Is it safe to take Lithium with Esketamine?
We do not list a known interaction between Lithium 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 Lithium and Esketamine have any of the same side effects?
Yes — our sources link each of them separately to 4 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 Lithium 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 Lithium in each. That is a conversation for your prescriber, especially if Esketamine is being adjusted to a target.
How was the Lithium and Esketamine combination checked?
Interactions in our licensed database are recorded against drug classes. Esketamine is filed under 2 classifications, and Lithium has documented interactions with 11 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 Lithium interact with any other medications?
Yes. Lithium has 515 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 — Lithium 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

Lithium 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 26 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Esketamine 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.