Cyclobenzaprine (Flexeril) and Ketamine Therapy | Tovani Health
Flexeril (Cyclobenzaprine) (also: Amrix) — Skeletal muscle relaxant (tricyclic-structure)
Verdict at Tovani Health
Compatible; sedation and QT are what we plan around, not serotonin syndrome.
Cyclobenzaprine and ketamine are compatible. Cyclobenzaprine is structurally a TCA and was historically flagged for serotonergic monitoring with ketamine; the actual ketamine-specific evidence does not support that framing (ketamine is not meaningfully serotonergic). We plan around sedation and modest QT, the same TCA-class considerations we apply to amitriptyline.
If you take Flexeril 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 Flexeril interacts with ketamine
Cyclobenzaprine is structurally related to amitriptyline and shares sedating and anticholinergic properties. It is strongly sedating and modestly QT-prolonging. Ketamine adds sedation and brief sympathomimetic activity; the historical serotonin syndrome framing has been retired here for the same reason as the TCAs.
What we do at intake
Disclose dose and frequency. We schedule sessions in the morning if you take it at bedtime. Avoid same-day use before a session when possible.
Bottom line
Cyclobenzaprine and ketamine are compatible. Cyclobenzaprine is structurally a TCA and was historically flagged for serotonergic monitoring with ketamine; the actual ketamine-specific evidence does not support that framing (ketamine is not meaningfully serotonergic). We plan around sedation and modest QT, the same TCA-class considerations we apply to amitriptyline.
Frequently Asked Questions
I take Flexeril for back pain. Is that an issue for KAP?
Manageable. We plan timing around the sedation and brief you on serotonergic monitoring as we would with a TCA.
Ready to find out if at-home ketamine fits your situation?
We’ll note that you’re on Flexeril (Cyclobenzaprine) 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: 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.
- 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 16, 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.