RACEMIC KETAMINE SIDE EFFECTS, ADVERSE REACTIONS, AND MONITORING

Racemic ketamine is not governed by a Risk Evaluation and Mitigation (REMS) program, giving practitioners broad latitude to prescribe varying doses, frequencies and formulations with few restrictions. This limited regulatory oversight posed few concerns in the early years of psychotropic ketamine use, when the route of administration was primarily intravenous and thus by necessity administered by a healthcare professional. The wide adoption of telehealth during the covid pandemic paired with compounding pharmacies capable of dispensing lozenges or nasal sprays directly to consumers has moved ketamine therapy into a higher-risk landscape. Ketamine clinics, telehealth practices and individual providers now offer ketamine in oral, intranasal and intramuscular routes along with varying levels of supervision including in-person, remote, or none at all. In 2022 and 2023, the FDA issued a series of warnings about compounded ketamine products. This guidance highlighted the lack of data to guide appropriate dosing of compounded ketamine products and three specific risks of ketamine in unmonitored settings: vital sign abnormalities, sedation, and dissociation. This lecture will review this guidance, the safety advantages of in-person monitoring for ketamine treatment, and highlight several strengths of intravenous infusion over 40 minutes. These include 100% bioavailability, precise weight-based dosing to achieve therapeutic sub-anesthetic blood levels, and the ability to pause or discontinue a partially-completed infusion if patients experience serious adverse reactions. Ketamine’s dissociative properties can cause a spectrum of affective responses, from euphoria to acute dysphoria complicated by suicidal ideation. Case examples and preliminary data from the Weill Cornell Medicine / Psychiatry ketamine infusion service will highlight these risks. A final risk of unmonitored, direct to consumer ketamine prescription is that there is no mechanism to prevent diversion, or self-escalation of a substance with known addiction potential. Rates of ketamine use disorder remain low but may be rising in western countries, and preliminary evidence supports a possible role for ketamine-assisted psychotherapy in substance use disorders. Nevertheless, patients with a history of substance use disorders and those requesting higher-than standard frequency or dosing may warrant additional counselling, or referral for alternate treatments to reduce the risks of development and sequela of ketamine use disorder such overdose, ketamine-induced cystitis, or neurotoxic effects, which will be focus of the second lecture.

References

Brody, B. D., Popeo, D. M., Smetana, R. W., and Kanellopoulos, D. (2025). How Do We Get Ketamine Safety Right? Three Questions From a Clinical Service. The Journal of clinical psychiatry, 86(3), 25com15946. Brody, B. D., Park, N., Christian, A., Shaffer, C. W., Smetana, R., Kotbi, N., … and Kanellopoulos, D. (2024). Ketamine for major depressive disorder during an inpatient psychiatric admission: Effectiveness, adverse events, and lessons learned. Journal of Affective Disorders, 351, 293-298.