“I’ll Be There For You,” the iconic theme song of the TV show “Friends,” is fondly etched in our memories, along with the lively cast that became a household name, bringing laughter and joy into our lives. The show’s popularity makes the tragic and untimely loss of “Friends” star Matthew Perry on October 28, 2023, even tougher to swallow. The details that have since emerged are deeply concerning, particularly regarding the role of ketamine — a medication implicated in his death — and the complexity of his underlying medical conditions.
In light of the recent arrest of five people — three of whom have already pleaded guilty in the conspiracy — tied to the legal investigations into Perry’s death, the dangers of injectable ketamine administration by non-healthcare professionals and in non-traditional healthcare settings are evident. Approved as a general anesthetic in the 1970s, ketamine is used to provide sedation and pain relief, but it also has the potential to cause death. There is no safe, standardized dosing formula for injectable ketamine outside of a healthcare setting.
The Need for Standards and Protocols
The use of any anesthetic medications outside of clinical settings is unsafe and can be lethal. This is a critical point given the proliferation of for-profit ketamine clinics in recent years. These clinics are providing treatment with ketamine in off-label uses for mental health disorders and chronic pain. But the treatment providers at these clinics, as well as the patients, are in a gray area with regard to proper training and appropriate indications for use. It is time for the development of clear standards and best practices to ensure patient safety with this controlled substance.
The evidence supporting ketamine treatment regimens for anesthetic purposes and for pain relief is long-standing and robust. But when used in ketamine clinics, or at home, there are wide variations in treatment protocols. We need a multi-disciplinary effort to bring together psychiatrists and psychologists, who are experts in mental health, and anesthesiologists, who are experts in pain medicine, to identify and promote the right safety standards. This includes dosage, rate of infusion, frequency, duration of treatment, monitoring for adverse effects, and consideration of comorbidities.
In addition to clear concerns about the possibility of addiction, continuous use of ketamine also presents serious ethical and safety issues. Ketamine, a phencyclidine derivative, can cause hallucinations, vivid dreams, delirium, and dissociative anesthesia in which the patient feels detached from their body — an effect they might find distressing. As anesthesiologists, we are rigorously trained to administer anesthetic medications safely in monitored settings. Providers who are treating patients with ketamine through the increasingly popular ketamine clinics must have similar safety training and protocols.
Too Many Red Flags
According to news reports, ketamine was administered to Perry in large dosages by a non-medical individual in a non-clinical setting on the day he died. The ketamine was allegedly obtained illegally and administered at his home.
The case also underscores the numerous red flags that could be missed if someone were to obtain ketamine via telemedicine (this does not appear to be the case for Perry) without appropriate supervision during use. These include treatment regimens administered in subpar standard-of-care settings that place the patient at risk for serious adverse events, misuse, and abuse.
Finally, Perry’s death highlights the burden of depression and addiction. Depression is one of the most common forms of mental illness, and data show that the percentage of U.S. adults who report having been diagnosed with depression at some point in their lifetime has reached 29%. Meanwhile, ketamine has been known since the 1960s to cause addiction. Many of us likely know someone in our close circles who is struggling with depression, addiction, or both. A risk-benefit discussion is encouraged between patients and physicians when considering this as a treatment option administered by licensed providers and in monitored settings.
Where Do We Stand on “Do No Harm”?
In recent years, the rising demand for injectable ketamine treatment has led to a surge in the number of ketamine clinics across the country. As an experimental treatment, insurance coverage for this is limited to nonexistent, with most treatments currently offered on a cash-pay basis. The financial incentives associated with companies running these clinics raise critical ethical concerns, especially given the safety risks — widespread exposure to injectable ketamine may heighten the risk of addiction, overdose, and death.
As physicians who have led the fight against the opioid epidemic, anesthesiologists are at the forefront of recommending data-driven, evidence-based use of treatment regimens to prevent harm. We need to come together now — the anesthesia and pain medicine providers and the mental health providers — to study and standardize safe use of ketamine. There may be valuable benefits for ketamine treatment in off-label uses, but it’s complicated with many safety, ethical, and legal considerations. It’s time to chart a safer course with stronger guardrails so we avoid other tragedies like what occurred with the beloved Perry.
Rakhi Dayal, MD, is the program director of Pain Medicine and a professor in the Department of Anesthesiology & Perioperative Care at the University of California, Irvine.
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