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Atypical antipsychotic (D2 partial agonist)Reviewed May 15, 2026

Brexpiprazole (Rexulti) and Ketamine Therapy | Tovani Health

Rexulti (Brexpiprazole)Atypical antipsychotic (D2 partial agonist)

Verdict at Tovani Health

Less sedating partial-agonist antipsychotic; compatible with KAP.

Brexpiprazole and ketamine are compatible. As a D2 partial agonist (like aripiprazole), it has a lighter sedation and metabolic profile than olanzapine. The pharmacodynamic note about antipsychotic blunting of ketamine response is theoretically smaller for partial agonists but still warrants honest expectation-setting.

If you take Rexulti regularly and are considering at-home ketamine therapy, the combination is safe with monitoring or dose adjustment. This page covers the brief pharmacologic context and what we do at intake.

How Rexulti interacts with ketamine

Brexpiprazole is a partial agonist at D2 and 5-HT1A and an antagonist at 5-HT2A. It is metabolized by CYP3A4 and CYP2D6; strong inhibitors or inducers can substantially alter levels.

What we do at intake

Tell us your dose, what it is being used for (depression augmentation, schizophrenia), and any CYP-active medications you take.

Bottom line

Brexpiprazole and ketamine are compatible. As a D2 partial agonist (like aripiprazole), it has a lighter sedation and metabolic profile than olanzapine. The pharmacodynamic note about antipsychotic blunting of ketamine response is theoretically smaller for partial agonists but still warrants honest expectation-setting.

Frequently Asked Questions

Is brexpiprazole better than aripiprazole for KAP?

Functionally similar. Brexpiprazole is marginally less activating; aripiprazole is the better-studied of the two.

Ready to find out if at-home ketamine fits your situation?

We’ll note that you’re on Rexulti (Brexpiprazole) at intake. The eligibility check takes 5 minutes and gives you an honest answer about whether at-home ketamine fits your specific situation.

FL and NJ residents only. Benjamin Soffer, DO — Tovani Health.

Sources

The verdict and clinical guidance on this page are based on the following peer-reviewed literature and FDA prescribing information.

  1. Pharmacodynamic Interactions Between Ketamine and Psychiatric Medications Used in the Treatment of Depression: A Systematic Review. Veraart JKE, Smith-Apeldoorn SY, Bakker IM, et al.. International Journal of Neuropsychopharmacology. 2021. PMID: 34170315

    Systematic review of pharmacodynamic interactions between ketamine and psychiatric medications used in depression treatment.

  2. Real-world effectiveness of ketamine in treatment-resistant depression: A systematic review & meta-analysis. Alnefeesi Y, Chen-Li D, Krane E, et al.. Journal of Psychiatric Research. 2022. PMID: 35688035

    Meta-analysis of 2,665 patients across 79 studies — 45% response and 30% remission with ketamine in treatment-resistant depression.

Clinically reviewed

Reviewed by Benjamin Soffer, DO on May 15, 2026. Dr. Soffer is a board-certified physician (American Board of Internal Medicine) licensed in Florida and New Jersey, prescribing at-home ketamine therapy through Tovani Health.

This page is general information about how this medication interacts with at-home ketamine therapy at Tovani Health. It is not a substitute for medical advice from your prescribing physician about your specific situation. Always discuss medication changes with the doctor who prescribed them.