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NYTimes
New York Times
16 Dec 2023
Andrew Jacobs


NextImg:What to Know About Ketamine

An autopsy report released by the Los Angeles County medical examiner on Friday said the death of “Friends” actor Matthew Perry, who was found face down and unresponsive in a hot tub at his home on Oct. 28, resulted from the “acute effects” of ketamine, an anesthetic with psychedelic properties.

Ketamine has become increasingly popular as a therapy for treatment-resistant depression and other mental health issues. It is also used recreationally.

Mr. Perry had publicly acknowledged his long struggle with alcohol and drug use, but the report said he had been sober for 19 months and little was known about his relationship to ketamine.

What is ketamine, and is it legal?

Ketamine is an injectable, short-acting dissociative anesthetic that can have hallucinogenic effects at certain doses. It distorts perceptions of sight and sound and makes users feel detached from pain and their surroundings.

Developed as a battlefield anesthetic in the 1960s, ketamine has been legal since 1970 for use in both people and animals. It is frequently used as an anesthetic for children, especially in the developing world.

But the psychiatric use of ketamine is still unapproved and unregulated, although it is increasingly used off label for treating depression, suicidal ideation and chronic pain.

In 2019, the Food and Drug Administration approved a nasal spray version of ketamine for treatment-resistant depression that is marketed as esketamine.

Ketamine has the potential for abuse, which may lead to moderate or low physical dependence or high psychological dependence, but experts consider it a safe medication.

Those who use it recreationally often snort the drug in powder form or administer it intranasally by spray.

“People shouldn’t be afraid to use ketamine if it’s prescribed by their physician and it’s delivered correctly in a health care setting,” said Dr. Gerard Sanacora, director of the Yale Depression Research Program and co-director of the Yale New Haven Hospital Interventional Psychiatry Service.

Can ketamine be lethal?

Ketamine is rarely lethal, but an overdose can cause unconsciousness and dangerously slowed breathing, according to the Drug Enforcement Administration. The amount of ketamine found in Mr. Perry’s system was extremely high, comparable to an anesthetic dose, the medical examiner’s office wrote.

Side effects like increased blood pressure and paranoia are rare and typically occur at very high doses. Frequent users of the drug can develop bladder problems.

The F.D.A. in October issued a warning about the dangers of using compounded versions of ketamine. Compounded drugs are those that have been modified or tailored in a lab for the specific needs of an individual patient.

The agency, citing adverse incident reports, warned that the unsupervised use of compounded ketamine heightened the risk of dangerous psychiatric reactions and health problems like increased blood pressure, respiratory depression and urinary tract issues that can lead to incontinence.

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Matthew Perry had more ketamine in his system than the amount used for a typical infusion, the autopsy report showed.Credit...Carlo Allegri/Reuters

Dr. Steven Radowitz, chief medical officer at Nushama, a ketamine clinic in New York, said patients must pass a full medical and psychiatric screening “to ensure they are a fit for treatment.”

At Nushama and other clinics, doses are administered at “sub-anesthetic” levels so that patients remain conscious during their therapy sessions, Dr. Radowitz said.

What is known about Mr. Perry’s ketamine use?

Mr. Perry had been undergoing medically supervised ketamine infusion therapy for depression and anxiety, and he had received an infusion a week and a half before he died, according to the autopsy report. The medical examiner’s office determined that treatment was unrelated to his death because the drug remains in the system for just a few hours.

Although the report did not say so, that suggests Mr. Perry was using ketamine at home at the time of his death.

Law enforcement authorities did not find any ketamine at his home, the medical examiner said.

The report did not detail the exact sequence of events that led to Mr. Perry’s death, but it cited three contributing factors: drowning, coronary artery disease and buprenorphine, a prescribed medication that he was taking to treat opioid addiction.

“At the high levels of ketamine found in his postmortem blood specimens, the main lethal effects would be from both cardiovascular overstimulation and respiratory depression,” the report read.

At high doses, ketamine can cause dangerous changes in blood pressure that may be particularly harmful for people with cardiovascular disease.

The sedating effects of ketamine could have been compounded by the buprenorphine Mr. Perry was taking.

Dr. Sanacora of Yale University said the plethora of risk factors made it hard to pinpoint what caused Mr. Perry’s death.

“I’m not a coroner or a forensic pathologist, but he had a lot of risk factors and there are a lot of potential things that could have happened,” he said. “The most important takeaway is that ketamine is not a drug to be taken at home.”