Matthew Perry’s Death Raises Concerns Over Safety of At-Home Ketamine Therapy

Clinicians say that with proper supervision the risks are minimal.

The death of actor Matthew Perry has sparked concerns surrounding the safety of ketamine therapy, especially when administered in at-home settings.

The Los Angeles County medical examiner on Dec. 15 said that Perry died from the acute effects of ketamine. Contributing factors in Perry’s death include drowning, coronary artery disease and the effects of buprenorphine, a drug used to treat opioid-use disorder.

Perry had undergone intravenous ketamine therapy to treat depression, but his last treatment had occurred at least a week prior to his death, meaning he likely took additional doses outside the clinical setting, according to news reports.

The 54-year-old actor was found unresponsive in the pool at his home on Oct. 28. Several news outlets have reported that Perry’s blood contained 3,540 nanograms per milliliter of the substance. That amount is enough to induce general anesthesia, according to Dr. Philip Hansen, medical director and anesthesiologist at Albany Ketamine Infusions in Albany, New York.

“He acutely, likely used too much – whether it was a lozenge that was prescribed or something he got off the street, he basically induced general anesthesia in himself,” Hansen said. “In the hospital, blood levels of 1,000 nanograms per mill mean you’re under general anesthesia.”

Doctors often will prescribe maintenance doses of ketamine for at-home use in the form of lozenges, sometimes referred to as troches. In recent years, telemedicine companies such as Mindbloom have begun offering mail-order prescriptions of ketamine lozenges. A Wall Street Journal article published on Dec. 16 questioned whether Perry’s death could hurt the fast-growing startup.

The U.S. Food and Drug Administration also has warned against the use of at-home ketamine treatments. The FDA issued the advisory on Oct. 13, stating that the use of compounded ketamine products without medical supervision can lead to “serious adverse events.”

The FDA first published a ketamine compounding-risk alert on Feb. 16, 2022. Since publishing that alert, the agency received an adverse-event report of a patient who experienced respiratory depression after taking compounded oral ketamine outside of a health care setting for the treatment of post-traumatic stress disorder. The patient’s ketamine blood level appeared to be twice the blood level typically obtained for anesthesia.

The agency also noted that it has not established safe or effective dosing of ketamine for any psychiatric indication and that dosages marketed by compounders and telemedicine platforms may vary, making risks associated with those products unpredictable.

Safe with Proper Supervision

Despite the concerns, Hansen said ketamine is relatively safe with proper supervision. Cambridge Biotherapies, a clinic in Cambridge, Massachusetts, that provides ketamine treatments along with other therapies, issued a similar statement on LinkedIn.

“As experts in the medical use of Ketamine as a mental health treatment, we thought it’d be helpful to offer clarity based on what the evidence behind ketamine therapy tells us. When used under medical supervision, Ketamine is one of the safest and most effective treatments for certain mental health conditions,” Cambridge Biotherapies stated. “It’s essential to differentiate between medical and non-medical use. The doses used for mental health are considerably lower than anesthesia doses and are carefully controlled in a medical setting.”

In many cases, doctors will opt for ketamine over other drugs during surgery because it’s a safer option for patients who are critically ill, Hansen noted. It also can be safely prescribed for at-home use if doctors screen patients properly. Hansen says he only prescribes the lozenges to patients he has already treated with an infusion and won’t offer them to anyone with a history of drug abuse. He advises patients not to drive after taking the doses, which are usually on the lower end, around 100 mg.

“In addition to that, further surveillance is that every time I have a script refill, I have them come in and do a drug screen because I want to make sure that they’re taking the drugs that they’re supposed to be taking and that they’re not using any illicit meds that could interact with the ketamine and cause any issues,” Hansen said.

Warning signs of abuse include patients who come back for early refills or demonstrate a higher tolerance for the drug during their infusions, Hansen added.