Actor Matthew Perry. Photo / Frederick M. Brown, Getty Images
Actor’s death heightens concerns among experts about inadequate oversight of the growing use of ketamine to treat depression.
Matthew Perry’s relationship with ketamine ended in addiction and death, allegedly fed by illicit purchases from doctors and a dealer dubbed the “ketamine queen”.
But it began with a therapy session at a clinic — one of the paths making it easier than ever to legally obtain the powerful anesthetic.
Ketamine clinics and telehealth providers in the United States have proliferated in recent years with relatively little regulatory oversight, seizing on the drug’s potential to deliver rapid relief for people suffering from depression.
Patients can see a provider virtually and, if they have a qualifying diagnosis, have ketamine shipped directly to their homes. That convenience has made the drug accessible to tens of thousands of people.
Social media posts promoting ketamine therapy feature images of smiling people dappled by sunlight, promises of rapid, “transformative” experiences, and accounts of emotional trauma brought under control.
Yet, as Perry’s death in October showed, ketamine is a powerful and potentially dangerous drug. As the US Food and Drug Administration has warned, it has not been approved for mental health treatment. Experts are increasingly concerned that it’s being marketed to people who may overlook the risks.
Because there is so little government oversight, authorities and researchers can’t answer basic questions, including how many patients are getting ketamine and whether physicians and mental health providers are following crucial guidelines to protect patients from abuse, addiction, and accidental deaths.
“A lot of us have been saying it’s the Wild West because it’s largely unregulated and we don’t truly know what’s going on,” said Joseph Palamar, associate professor of population health at New York University.
Anne Milgram, administrator of the Drug Enforcement Administration, said last week that Perry “sought treatment for depression and anxiety and went to a local clinic where he became addicted to intravenous ketamine”.
When the clinic doctors refused to increase his dosage, she said, two other doctors not connected to the clinic saw a way to make money from Perry and supplied him with ketamine illicitly.
Federal indictments unveiled in Los Angeles this month told the harrowing story of how Perry, the Friends star, spiralled into a steady habit that ended with him dying in his hot tub after an assistant allegedly gave him a dose of the powerful anaesthetic that rendered him unconscious.
Ketamine can be hazardous even when not being abused. In January, emergency physicians at UMass Memorial Medical Centre reported that a 35-year-old woman overdosed while taking oral ketamine tablets at home and was revived at a hospital, saying the amount she ingested was equivalent to a dose reserved for anaesthesia.
While acknowledging that expanded ketamine access can benefit people with severe depression, the physicians wrote, “the current lack of regulation poses significant safety risks”.
There are signs recreational ketamine use is on the rise in the US. One 2023 study reported that the number of ketamine seizures by law enforcement increased from 55 in 2017 to 247 in 2022. America’s poison centres logged 529 reports of ketamine exposures last year, a 40% increase from 2022.
As with many medications, doctors can prescribe ketamine to treat conditions not approved by the FDA in what is known as “off-label” use, most commonly for depression and other mood disorders. In these cases, ketamine is generally not covered by insurance.
Despite the promise it has shown as an antidepressant in studies, there’s little incentive for a pharmaceutical company to run the expensive trials needed to win the FDA’s endorsement for psychiatric treatment because ketamine isn’t protected by patents. This has given ketamine providers broad latitude in how they can prescribe it.
“This drug appears safe and effective when used as directed,” said Gerard Sanacora, director of the Yale Depression Research Programme. But if research-based guidance isn’t followed, “I think there’s good evidence that it could really exacerbate substance use issues, unfortunately as was the case with Mr Perry”. Ketamine used in high doses and frequencies can also cause damage to the brain and bladder.
The most rigorous studies come from a Johnson & Johnson subsidiary, which patented a derivative form of ketamine, esketamine, and developed it into a nasal spray that won FDA approval for treating depression in 2019.
Sanacora is an unpaid consultant and has received fees in the past from the company. US sales of the spray, Spravato, have steadily grown to $226 million in the second quarter of this year. Still, the FDA has a strict risk protocol for Spravato, requiring it to be dispensed in healthcare settings with monitoring for at least two hours.
Experts say many patients prefer the relative convenience of paying out of pocket to have generic ketamine delivered to their homes.
Cost is another reason why many patients turn to sources of ketamine other than Spravato. One nasal treatment of Spravato can cost $800 to $1200 before insurance, not including the costs for the visit.
It needs to be given twice weekly at the beginning of treatment, and the regimen may continue indefinitely for some at-risk patients. Ketamine ordered online for at-home use, often as tablets or lozenges, doesn’t require medical supervision and can cost a couple of hundred dollars for a month’s supply.
“This is like the weight-loss clinic,” Jenni Wai, Ohio’s chief pharmacist, said of ketamine providers at a June workshop held by the Reagan-Udall Foundation, a congressionally created nonprofit that advises the FDA. “This is like the med spas and the Botox that is popping up everywhere.”
With the increase in home use, she said, “we have concerns when we’re starting to see a shift in standard of care, a shift in supervision”.
Telehealth companies are drawing on their own patient data to make the case that at-home ketamine is safe and effective — and not in need of rigorous regulation.
A recent study backed by Mindbloom, one of the largest telehealth ketamine providers, of more than 11,000 clients found patients with depression benefitted and had a low rate of bad reactions. But the research has significant limitations, such as the lack of a control group.
Mindbloom promotes ketamine for “burnout” and “getting unstuck.” It is also piloting a programme that sends injectable ketamine to patients who haven’t benefitted from its typical tablet that dissolves under the tongue.
Leonardo Vando, Mindbloom’s medical director, said the company’s clinicians can only prescribe ketamine if a patient is diagnosed with anxiety, depression, or post-traumatic stress disorder.
The company is trying out injectable ketamine, he said, for patients who may not be absorbing the medicine under the tongue, adding that the risk of reselling it is lower than with tablets.
Perry’s death, Vando said, was not the result of ketamine therapy but because the Hollywood star “acquired ketamine illegally from people who wanted to exploit his struggles with addiction”.
Getting ketamine at home took off during the pandemic, with the temporary suspension of a US federal law requiring doctors to meet patients in person before prescribing medications that are tightly controlled by the Drug Enforcement Administration because of their potential for abuse.
The DEA has proposed a rule that would restore a requirement for in-person visits, but the waiver of that requirement remains in place until the end of 2024.
Barely two weeks before Perry’s death, the FDA put out a warning on pharmacy-made ketamine often used by telehealth services, noting “increasing public interest” in this formulation and cautioning that it is not approved by the agency. An FDA spokesperson said this week that promoting prescription drugs “must be truthful, non-misleading and accurate”.
In a 2023 review of ketamine providers in Maryland, researchers identified numerous false or misleading claims.
Maryland-based Medpsych Health Services incorrectly described ketamine on its website as approved by the FDA to treat depression. Medpsych’s founder didn’t respond to a request for comment, but the language on its website was corrected hours after being contacted by the Washington Post.
Now is the time to consider how to thoughtfully regulate ketamine in a way “that allows patient access while also providing some measure of safety”, said Boris Heifets, an associate professor of anaesthesiology at the Stanford School of Medicine.
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