FDA Warns Against Using Compounded Ketamine Products

The U.S. Food and Drug Administration (U.S.) issued a warning of the potential risks of using compounded ketamine products for the treatment of psychiatric disorders.

The agency says it has not approved ketamine and compounded ketamine products, including oral formulations, for treating any psychiatric disorder despite them being marketed for depression, anxiety, obsessive-compulsive disorder (OCD), and other conditions.

Moreover, the FDA has not evaluated the safety and effectiveness of compounded ketamine products, and they don’t have any FDA-approved indications or routes of administration.

Ketamine hydrochloride, or ketamine, is a Schedule III controlled substance approved by the FDA for inducing and maintaining general anesthesia.

The use of ketamine products is associated with multiple adverse events, such as:

• Sedation (sleepiness)
• Dissociation (disconnection between a person’s thoughts, feelings, and sense of space, time, and self)
• Psychiatric events or worsening of psychiatric disorders
• Abuse and misuse
• Increases in blood pressure
• Respiratory depression (slowed breathing)
• Lower urinary tract and bladder symptoms

The FDA warning describes a case of a patient who experienced respiratory depression after taking compounded oral ketamine outside of a healthcare setting for treating PTSD. Additionally, the patient’s ketamine blood level appeared to be twice the blood level typically obtained for anesthesia.

Last year, the agency issued a risk alert about using compounded ketamine nasal spray. The warning included FDA-authorized Spravato (esketamine), which has a Risk Evaluation and Mitigation Strategy (REMS) in its approval. This drug safety program requires Spravato, intended for treatment-resistant depression (TRD), to be dispensed and administered in healthcare settings that are certified in the REMS.

"Spravato (esketamine) cannot be dispensed for use outside the certified healthcare setting. Patients must be monitored inside the healthcare setting after administration for a minimum of two hours until patients are safe to leave," the FDA then said.

According to a 2020 systematic review, ketamine appears promising in the short-term treatment of TRD, as a strong effect was observed within four hours following a single infusion and peaked at 24 hours. However, the authors concluded that more clinical and experimental data is needed on its efficacy, tolerance, and safety of long-term administration.

Despite increasing popularity, ketamine products should be used only under the supervision of health care professionals, as they can cause severe adverse events.