Perphenazine (Trilafon) and Ketamine Therapy | Tovani Health
Trilafon (Perphenazine) — Phenothiazine antipsychotic (typical)
Verdict at Tovani Health
Compatible; older phenothiazine with EPS and anticholinergic considerations.
Perphenazine and ketamine are compatible. As an older phenothiazine, perphenazine has more EPS, more anticholinergic load, and more sedation than newer atypicals. The D2-attenuation concern that applies to all D2 antagonists applies here as well. Continue as prescribed; we plan session timing around sedation.
If you take Trilafon 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 Trilafon interacts with ketamine
Perphenazine is a piperazine phenothiazine with potent D2 antagonism and modest sedative, anticholinergic, and alpha-1 blocking activity. No meaningful CYP3A4 interaction with ketamine.
What we do at intake
Disclose dose, indication, and any EPS or anticholinergic side effects (dry mouth, urinary retention).
Bottom line
Perphenazine and ketamine are compatible. As an older phenothiazine, perphenazine has more EPS, more anticholinergic load, and more sedation than newer atypicals. The D2-attenuation concern that applies to all D2 antagonists applies here as well. Continue as prescribed; we plan session timing around sedation.
Ready to find out if at-home ketamine fits your situation?
We’ll note that you’re on Trilafon (Perphenazine) 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.