Amantadine (Symmetrel, Gocovri) and Ketamine Therapy | Tovani Health
Symmetrel (Amantadine) (also: Gocovri, Osmolex ER) — NMDA antagonist / dopaminergic (Parkinson's, dyskinesia, off-label depression)
Verdict at Tovani Health
Direct NMDA mechanism overlap with ketamine, weaker than ketamine itself but worth flagging.
Amantadine alongside ketamine requires individual evaluation because of direct mechanism overlap. Amantadine is a weak NMDA receptor antagonist (also has dopaminergic effects), and there's growing off-label interest in it as a depression adjunct via the same NMDA mechanism ketamine targets. The combination is unstudied. For Parkinson's-disease patients on amantadine for dyskinesia, the question is whether KAP adds meaningful additional benefit or just compounds the NMDA blockade. For off-label antidepressant use, we typically recommend choosing one NMDA-pathway intervention rather than stacking.
If you take Symmetrel regularly and are considering at-home ketamine therapy, the combination is depends on your specific situation. This page covers the brief pharmacologic context and what we do at intake.
How Symmetrel interacts with ketamine
Amantadine is a non-competitive NMDA antagonist with affinity considerably lower than ketamine's. Also enhances dopamine release. Used for Parkinson's disease (motor symptoms, dyskinesia) and historically as an antiviral for influenza A. Renally cleared, no CYP interactions with ketamine.
What we do at intake
Disclose dose, indication, and prescriber. We discuss whether KAP adds value on top of amantadine's NMDA effect, or whether one or the other is the better choice.
Bottom line
Amantadine alongside ketamine requires individual evaluation because of direct mechanism overlap. Amantadine is a weak NMDA receptor antagonist (also has dopaminergic effects), and there's growing off-label interest in it as a depression adjunct via the same NMDA mechanism ketamine targets. The combination is unstudied. For Parkinson's-disease patients on amantadine for dyskinesia, the question is whether KAP adds meaningful additional benefit or just compounds the NMDA blockade. For off-label antidepressant use, we typically recommend choosing one NMDA-pathway intervention rather than stacking.
Ready to find out if at-home ketamine fits your situation?
We’ll note that you’re on Symmetrel (Amantadine) 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.
- Ketamine: A Review of Clinical Pharmacokinetics and Pharmacodynamics in Anesthetic and Pain Therapy. Peltoniemi MA, Hagelberg NM, Olkkola KT, Saari TI. Clinical Pharmacokinetics. 2016. PMID: 27028535
Reviews ketamine NMDA pharmacology including comparisons to other NMDA-affecting agents.
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.