Ketamine, a drug long approved by the FDA for anesthesia, has shown significant promise in treating severe mental health conditions such as treatment-resistant depression and suicidality. However, its use in psychiatry remains off-label, meaning the FDA does not officially sanction it for these purposes despite compelling evidence from multiple studies demonstrating its potential benefits. While offering hope to many, this off-label usage also opens the door to unregulated practices and safety concerns, as starkly illustrated by Matthew Perry’s case.

The recent scrutiny surrounding the actor’s death, which involved illegal injections of ketamine, underscores the urgent need for a standardized, FDA-approved protocol for the use of ketamine in treating mental illnesses such as depression and PTSD. Without such a framework, clinicians have no choice but to make judgments in emergent situations that can increase the risk of unsafe practices.

The FDA’s cautious stance on approving ketamine for psychiatric use is understandable, given the known safety concerns associated with the drug, including its potential for abuse, psychiatric events, respiratory depression, and other adverse effects. However, this caution has left many patients suffering from severe mental illnesses waiting for more accessible and officially sanctioned treatment options.

Currently, the only FDA-approved form of ketamine for mental health treatment is intranasal esketamine, which is available under strict conditions. Patients must have failed trials with other antidepressants and must use esketamine in conjunction with another antidepressant. This narrow approval criterion has created a bottleneck, driving some patients to seek off-label Ketamine Infusion Therapy at significant personal cost and risk. The high cost of Ketamine Infusion Therapy, which can run into thousands of dollars, further exacerbates the issue, making these treatments inaccessible to many who need them. Lacking FDA approval specifically for the use in PTSD treatment prevents insurance from covering the cost of these treatments for individuals with PTSD. These factors contribute considerably to inequities in the accessibility and affordability of these “off-label” treatments.

For over 50 years, ketamine has been FDA-approved for intravenous or intramuscular injection as a solution for the induction and maintenance of general anesthesia. However, despite multiple studies demonstrating significant advantages in using ketamine to manage life-threatening mental health symptoms, the FDA has not yet approved it specifically for psychiatric conditions. These factors have restricted the use of ketamine for mental health to research clinics or off-label settings, where the lack of stringent safety protocols can pose serious risks.

The tragic outcome of Perry’s off-label ketamine use highlights the need for greater oversight and regulation of this practice. It will take several steps to address the issues:

First, there needs to be a concerted effort to accelerate the research and regulatory approval process for ketamine and other psychedelic treatments. This process would involve rigorous studies to establish clear guidelines for safe and effective use and expand access to these treatments for those in need.

Second, greater oversight and regulation of off-label ketamine use will be essential to ensure that patients receive this treatment in a safe and controlled environment. Ensuring patient safety would include implementing standardized protocols and certification requirements for ketamine therapy clinics.

Finally, there needs to be a broader discussion about the affordability and accessibility of these treatments. Ensuring that insurance coverage is available for FDA-approved ketamine therapies could help bridge the gap and make these treatments more accessible to a broader population.

Matthew Perry’s tragic death serves as a sobering reminder of the challenges and risks associated with the current state of psychedelic treatments for mental health. While these therapies hold great promise, we must prioritize effectiveness and safety to prevent further tragedies and ensure that those who need help can access them safely and affordably. The path forward involves caution but a commitment to advancing these treatments in a way that protects and benefits patients.

Kay T. Jewels is Chief of Research and Technological Development at Advanced Pain Management Center

Matthew Perry’s cause of death was revealed to be an accidental overdose of ketamine. (Photo by Phillip Faraone/Getty Images for GQ)