Can I Take Ketamine With Lithium, Lamotrigine, or Valproate?

Can You Take Ketamine While on Mood Stabilizers?

Yes, if a licensed clinician determines it is medically appropriate. A mood stabilizer such as lithium, lamotrigine, or valproate is usually not an automatic barrier to ketamine therapy. Whether it is right for you depends on a clinical evaluation of your medicines and history.

Ketamine and mood stabilizers are generally used together, not swapped for each other. In research and in practice, ketamine is layered onto your existing treatment rather than used in its place. The term "mood stabilizer" here covers lithium, lamotrigine, valproate, and carbamazepine.

Never stop or lower a mood stabilizer on your own. Stopping suddenly can be risky, and it can bring back the symptoms the medicine controls. The specifics depend on which medicine you take, which the rest of this article covers.

Mindbloom treats depression, anxiety, and PTSD, not bipolar disorder, and its clinicians review your full medication list during screening. A licensed clinician will evaluate whether you are a good candidate for ketamine therapy. For a plain-language overview before your consult, Mindbloom publishes a guide to common ketamine drug interactions.

How Ketamine Works Differently From Mood Stabilizers

Ketamine is an NMDA receptor antagonist, which means it acts on the brain's glutamate system rather than the serotonin pathway many antidepressants target.¹ According to StatPearls, it temporarily increases glutamate signaling and helps the brain form new connections.

StatPearls describes ketamine as a medicine that can "elevate the levels of glutamate in the brain."¹ That process stimulates "synaptogenesis and elevated levels of brain-derived neurotrophic factor (BDNF)," the growth signals behind new brain connections.¹

Mood stabilizers work differently. They steady mood over time through other mechanisms, such as calming overactive electrical signaling. Because the two act on different pathways, ketamine is generally added to your current treatment rather than used in its place.

Ketamine has decades of medical use, and in published research it has been given alongside other psychiatric medicines rather than in place of them. For a plain-language explainer of how ketamine works, see Mindbloom's overview. That difference in mechanism is why the real question is usually not whether, but how each mood stabilizer interacts with ketamine.

Lithium, Lamotrigine, and Valproate With Ketamine: What the Evidence Shows

One note before the details: nearly all human evidence on these combinations comes from intravenous (IV) ketamine or intranasal esketamine studies. Mindbloom may use at-home sublingual tablets or subcutaneous injections, based on a clinician's assessment and individual fit. Those routes have not been tested directly with these medicines, so the findings below are extrapolated to them on mechanistic grounds.

IV ketamine is a well-established, in-clinic modality. Treatment setting alone does not determine effectiveness when care is supervised and protocol-driven. On Mindbloom's sublingual protocol, a peer-reviewed real-world study by Mathai and colleagues (2024, Journal of Affective Disorders) found symptom improvement comparable to in-clinic IV ketamine.² That IV comparator comes from McInnes and colleagues (2022, Journal of Affective Disorders).³ Individual results may vary.

Start with lithium, the most studied pairing.

Ketamine and Lithium

Lithium and ketamine are generally used together, not swapped. A 2010 randomized trial in Archives of General Psychiatry (Diazgranados and colleagues) gave intravenous ketamine as an add-on to therapeutic lithium or valproate.⁴ In that trial, 71% of patients responded to ketamine versus 6% to placebo.⁴

Lithium does not appear to strengthen or weaken ketamine's effect. In a pooled analysis of 36 bipolar-depression patients maintained on therapeutic lithium or valproate, Xu and colleagues (2015, Neural Plasticity) found both groups improved with ketamine, with no difference between the two stabilizers and no link between blood levels of either drug and how well ketamine worked.¹¹ And in a separate trial in unipolar treatment-resistant depression, Costi and colleagues (2019, Neuropsychopharmacology) found that adding lithium after ketamine gave no added benefit versus placebo.⁶

All of this evidence comes from IV ketamine, so it applies to at-home sublingual and subcutaneous ketamine only by extrapolation. Because lithium has a narrow safe range, your care team checks your lithium levels and kidney function during screening.

Lamotrigine is a different story, because it can change how the session itself feels.

Ketamine and Lamotrigine (Lamictal)

Lamotrigine is not a reason a clinician cannot offer you ketamine, but it may change how the session feels for some people. In supervised treatment, the dissociative state is often therapeutically meaningful, and lamotrigine may soften that acute experience for some people. Lamotrigine lowers glutamate release, and ketamine's effects involve glutamate, so the two overlap.

In a study of 16 healthy volunteers given IV ketamine, Anand and colleagues (2000, Archives of General Psychiatry) found that 300 mg of lamotrigine beforehand reduced ketamine's dissociative effects and, unexpectedly, slightly increased its short-term mood lift.⁶ Even so, no medication has been reliably shown to boost ketamine's antidepressant benefit, so this is a curiosity rather than a way to strengthen treatment. That was a healthy-volunteer, IV study. It does not directly describe patients on therapeutic lamotrigine receiving at-home sublingual or subcutaneous ketamine.

Whether lamotrigine changes ketamine's antidepressant benefit is not established. A 2017 review in the Journal of Clinical Psychiatry (Andrade) notes that lamotrigine's effect on ketamine's antidepressant action "is not known."⁷ The practical takeaway is simple: keep your lamotrigine dosing steady around sessions and tell your prescriber.

Valproate and carbamazepine round out the mood-stabilizer picture.

Ketamine and Valproate and Carbamazepine

Valproate (Depakote) and carbamazepine raise two different questions. In the same 2010 bipolar-depression trial (Diazgranados and colleagues, Archives of General Psychiatry), valproate was maintained alongside IV ketamine, much like lithium.⁴

As with lithium, this valproate evidence is from IV ketamine and is extrapolated to at-home sublingual and subcutaneous routes. Carbamazepine works differently, because the question is about drug metabolism, not mood.

According to the FDA prescribing information, carbamazepine is a potent inducer of CYP3A4 and CYP2B6.⁸ A 2017 review in the Journal of Clinical Psychiatry (Andrade) notes that inducers of these enzymes reduce exposure to ketamine.⁷ So carbamazepine could in theory lower ketamine levels.

That has not been directly measured in ketamine-therapy patients, so treat it as a mechanistic inference and tell your prescriber what you take. One reason your care team keeps you on these medicines is what they do for mania risk.

Bipolar Disorder and Why Staying on Your Mood Stabilizer Matters

Manic or hypomanic switching is a real but uncommon concern, and it is one reason mood stabilizers are continued through ketamine treatment. Hypomania is a period of unusually elevated, energized, or irritable mood. Ketamine is not appropriate during an active manic, mixed, or psychotic episode; those states are a contraindication, and confirming that your mood is stable is part of what screening is for.

Only 1.7% of patients developed manic or hypomanic symptoms across eight bipolar-depression studies where everyone stayed on a mood stabilizer. A 2023 systematic review in Therapeutic Advances in Psychopharmacology (Fancy and colleagues) found this rate was lower than the 3% to 10% seen with antidepressants.⁹

In the landmark 2010 trial (Diazgranados and colleagues), one subject receiving ketamine and one receiving placebo developed manic symptoms.⁴ The single ketamine case was matched by a placebo case.

These findings come from IV ketamine or intranasal esketamine, so they apply to sublingual and subcutaneous routes only by extrapolation. Ketamine can still trigger mania, which is why your care team keeps you on your stabilizer and watches for mood changes rather than stopping it. Monitoring is built into how ketamine and esketamine are delivered.

Esketamine, Monitoring, and Other Medications Your Clinician Reviews

Esketamine (Spravato) is an FDA-approved intranasal medication made from one half of the ketamine molecule (its S-enantiomer), so it is a closely related but distinct compound from the racemic ketamine used in most ketamine therapy, including Mindbloom's. Its label allows it to be used by itself or alongside an oral antidepressant, and it is cited here only as a regulatory reference point, not as a description of Mindbloom's medication. Its monitoring steps show the general safety mindset of layering ketamine onto other care.

According to the FDA prescribing information for esketamine (Spravato), providers should "assess blood pressure prior to dosing."¹⁰ The same label notes that "concomitant use with CNS depressants (e.g., benzodiazepines, opioids, alcohol) may increase sedation."¹⁰ These are requirements for the Spravato nasal spray, not a description of Mindbloom's protocol or a universal industry rule.

In the patients studied, short-term ketamine has not been shown to worsen psychosis, and antipsychotics are among the medicines your care team reviews. Your care team also reviews antidepressants, benzodiazepines, stimulants, and supplements, because timing and blood pressure can matter. As covered below, a thorough medication review is the shared safeguard, whatever you take.

How a Clinician Reviews Your Medications Before Ketamine Therapy

Your care team reviews your full list of prescriptions, over-the-counter drugs, and supplements, then coordinates with your prescribing psychiatrist. Share everything, and never stop a medicine on your own.

Supervised programs are designed to manage interactions like these. At Mindbloom, its medically supervised sessions include a required peer treatment monitor who stays present throughout each session. That monitor is a session-safety requirement, separate from the optional integration support Mindbloom also offers.

Building on decades of research on ketamine, Mindbloom has published one of the largest real-world safety studies to date. Mindbloom's real-world observational study of sublingual ketamine was published by Mathai and colleagues (2024, Journal of Affective Disorders).² In it, serious adverse events occurred in 6 of 11,441 patients, or 0.05%.² You can read a summary in its largest published study. Individual results may vary.

Talk to Your Care Team Before Combining Ketamine and Mood Stabilizers

A mood stabilizer is usually not a barrier to ketamine therapy. The specifics depend on which medicine you take, and the safe path is a review with your care team, not stopping anything yourself.

If you are exploring ketamine therapy for depression, anxiety, or PTSD, bring your full medication list to your consult. As covered above, your clinician reviews how ketamine and mood stabilizers fit together, and what to expect before, during, and after each session.