How Matthew Perry’s Death Sheds a Harsh Light on Ketamine Treatment

Actor Matthew Perry, who has long struggled with addiction, became intrigued by ketamine a few years ago during a stay at a rehab clinic in Switzerland, where he received daily infusions of the powerful anesthetic “to ease pain and help with depression.”

“It has my name written all over it — they might as well have called it ‘Matty,’” he later wrote of ketamine, known for its dissociative properties, in his 2022 memoir, “Friends, Lovers and the Great Terrible Thing.” It felt, he said, “like a big sigh.”

“As the music played, it became all about ego and ego death,” he wrote. “And I often thought I was dying during that hour. Oh, I thought, this is what happens when you die.” As much as he was drawn to it, he wrote, he found the hangover unpleasant and ultimately decided that “ketamine was not for me.”

But he eventually returned to the drug, receiving ketamine treatments from doctors at clinics and then, as he became addicted to it, buying it from illicit sources and giving himself multiple injections a day at his Los Angeles home, authorities said. On Oct. 28, after receiving multiple injections from his personal assistant, he died — face down in his hot tub. An autopsy determined that Perry died from the “acute effects of ketamine,” with drowning being one of several contributing factors.

“Matthew Perry sought treatment for depression and anxiety and went to a local clinic where he became addicted to intravenous ketamine,” Anne Milgram, head of the Drug Enforcement Administration, said at a news conference last week. “When doctors at the clinic refused to increase his dosage, he turned to unscrupulous doctors who saw Perry as a way to make a quick buck.”

The death of Perry, a beloved figure who starred in the sitcom “Friends,” has put a harsh spotlight on the illegal ketamine trade. Five people, including two doctors, have been arrested and charged with providing him with the ketamine that led to his death. Three of them have pleaded guilty, including a doctor who was accused of filing a fraudulent ketamine prescription in the name of a former patient.

But it also raised questions about the growing reliance on ketamine by doctors who see it as a promising alternative therapy for depression and other mental health disorders, even though it remains largely untested for that purpose. Was someone like Perry, whose struggles with substance abuse were widely known, a good candidate for treatment with ketamine, which itself has been abused as a party drug? How careful is the medical industry about ketamine?

Several doctors who treat patients with ketamine or are researching the drug — which has been used safely as a sedative during surgery for decades — said in interviews that patients with a history of substance abuse present complicated issues. In the absence of widely accepted guidelines, they said, providers are left to weigh the risks and benefits of initiating ketamine treatment.

“I wouldn’t say it’s absolutely a no-go because there are some patients who can really benefit from the antidepressant effects, but you would have to really think about the negative aspects and whether it could trigger a relapse,” said Dr. Sanjay Mathew, a psychiatrist at Baylor College of Medicine. “We have very little data in the scientific literature on this issue.”

Important considerations, the doctors said, included how long the patient had been sober and the level of support — family, friends, treatment groups — that would be available. All said they would monitor these patients more closely, and some said they would require periodic drug testing to ensure that their patients had not returned to using other substances.

Studies have found that ketamine can dramatically ease symptoms of depression, but even those who support the drug’s use for psychiatric disorders generally acknowledge that evidence of long-term safety and effectiveness is scant. While ketamine carries a lower risk of dependence than opioids, it can produce an out-of-body experience that some people enjoy, and abuse has been linked to serious health problems, including bladder damage.

“This is a drug that could potentially be life-saving for many people, but it really is a drug that carries serious risks and needs to be handled with care,” said Dr. Gerard Sanacora, a psychiatrist at Yale School of Medicine who studies ketamine.

Some companies and medical providers, seeing a business opportunity in the hype surrounding ketamine and psychedelic-like treatments, have downplayed the risks and taken advantage of the lack of oversight.

Clinics offering infusions and telehealth providers selling tablets or lozenges for home use have been rushing into a regulatory vacuum. Because the Food and Drug Administration approved ketamine for one purpose — sedating patients during surgery — more than 50 years ago, doctors can prescribe it for other uses.

In September, about a month before Perry’s death, the actor asked his personal assistant to illegally obtain ketamine, according to court documents.

One of the two doctors who were criminally charged told authorities that he was told Perry had requested ketamine to help him quit smoking, which the doctor knew was not a legitimate medical use for the drug.

Law enforcement officials described how, in his final days, Perry appeared to become increasingly dependent on ketamine.

A patient’s requests for higher doses could be a warning sign, said Dr. Sandhya Prashad, a Houston psychiatrist who is president of the American Society of Physicians, Psychotherapists and Ketamine Practitioners. And a rapidly increasing tolerance — in which more and more ketamine is needed to achieve the same effect — could indicate that a patient was receiving additional ketamine outside of a clinic.

“That would raise concerns that something is going on,” Prashad said. In Perry’s case, indeed, something was going on.

In the last month of Perry’s life, prosecutors say the two doctors who have been criminally charged sold Perry tens of thousands of dollars’ worth of ketamine. Court documents say his personal assistant, Kenneth Iwamasa, injected him with at least 27 doses of ketamine in the five days leading up to his death, including at least three on the day he died.

“Give me a big dose,” Perry told Iwamasa, according to a plea agreement that described their interactions on the day of Perry’s death. Iwamasa complied and then left Perry’s home to run some errands, according to court documents. When Iwamasa returned, he found Perry dead.

Efforts to contact Iwamasa and the other defendants were unsuccessful.

Sanacora and other doctors have long advocated for the creation of a registry to track the long-term risks and benefits of ketamine treatment, but such an initiative does not easily fall under the jurisdiction of any federal agency.

Without such a registry, evidence of ketamine’s potential for addiction and abuse among medical users comes mostly from individual case reports. The New York Times previously spoke to dozens of patients receiving ketamine treatment, and while most said they used the drug as directed, some admitted to using it inappropriately and trying to get more outside their provider’s supervision.

In his 2022 memoir, Perry described a period after he suffered a collapsed colon when he wanted more opiates than a hospital was willing to provide, so he pretended to be experiencing severe stomach pains. While recovering in his home on the 40th floor of a Century City building, he said he would call a drug dealer and sneak downstairs to hand over cash in an empty cigarette pack.

At various points, Perry wrote that he wondered why he had been spared from death even when others suffering from addiction had not been.

During the most intense period of his addiction, he wrote, he could have two distinct thoughts running through his mind at the same time: “I don’t want to die, but if that’s what it takes to get enough drugs, then amen to oblivion,” he wrote. “I can distinctly remember holding pills in my hand and thinking, This could kill me, and yet taking them.”