Asenapine (Saphris) and Ketamine Therapy | Tovani Health
Saphris (Asenapine) (also: Secuado) — Atypical antipsychotic (sublingual / transdermal)
Verdict at Tovani Health
Compatible; same D2-attenuation framework as other atypicals.
Asenapine and ketamine are compatible. The D2 antagonism may modestly attenuate ketamine's antidepressant response, as with other atypicals. Asenapine is unusual in two ways: sublingual administration (Saphris) requires no food or drink for 10 minutes after dosing for full absorption, which is independent of KAP planning, and the transdermal patch (Secuado) gives steady-state coverage. Modest sedation and orthostasis are typical side effects.
If you take Saphris 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 Saphris interacts with ketamine
Asenapine antagonizes D2, 5-HT2A, and several other monoamine receptors. Hepatic metabolism via UGT1A4 and CYP1A2 (minimal CYP3A4); no meaningful effect on ketamine PK.
What we do at intake
Disclose dose and formulation (sublingual vs patch). Continue as prescribed.
Bottom line
Asenapine and ketamine are compatible. The D2 antagonism may modestly attenuate ketamine's antidepressant response, as with other atypicals. Asenapine is unusual in two ways: sublingual administration (Saphris) requires no food or drink for 10 minutes after dosing for full absorption, which is independent of KAP planning, and the transdermal patch (Secuado) gives steady-state coverage. Modest sedation and orthostasis are typical side effects.
Ready to find out if at-home ketamine fits your situation?
We’ll note that you’re on Saphris (Asenapine) 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.
- Pharmacodynamic Interactions Between Ketamine and Psychiatric Medications Used in the Treatment of Depression. Veraart JKE, Smith-Apeldoorn SY, et al.. International Journal of Neuropsychopharmacology. 2021. PMID: 34170315
Clinically reviewed
Reviewed by Benjamin Soffer, DO on May 19, 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.