How Safe Is Ketamine to Treat Depression?

The once-taboo drug has been repurposed to treat depression and is even available for delivery. But how safe is it?,

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Chris Gathman, 40, has lived with chronic depression, a condition that runs in his family, for most of his life. He’s used a combination of antidepressants and cognitive behavioral therapy to treat his symptoms, with limited success. In 2018, he sunk into an even deeper depression that began impacting his ability to socialize and complete daily tasks.

“I knew I needed to do something,” said Mr. Gathman, who lives in Miami. So when his primary care physician suggested ketamine — an anesthetic that has improved symptoms of depression in early studies — he reached out to a clinic nearby.

“I woke up the next day and felt completely normal,” he said about his first IV infusion, administered at Ketamine Health Centers. “I didn’t feel depressed at all.” Mr. Gathman then persuaded his parents to seek out the therapy at the same clinic for their depression, and they both reported immediate relief as well.

Ketamine — an anesthetic first popular with the 1970s counterculture movement and then as a club drug known as “Special K” — has recently emerged as a promising mental health treatment. Unlike conventional antidepressants, which work by increasing serotonin levels, ketamine appears to impact a neurotransmitter called glutamate, which is thought to play a role in regulating mood.

In early trials, patients suffering from a wide range of drug-resistant mood disorders — including major depressive disorder, bipolar disorder, obsessive compulsive disorder and social anxiety disorder — have seen symptoms improve, often immediately.

Thanks to these success stories, hundreds of new ketamine providers have popped up across the country. Typically patients take ketamine through an IV, nasal spray or tablet once or twice a week for six to eight weeks (though some may need to take it longer). Sessions last between one and two hours and can cause feelings of dissociation, or feeling disconnected from reality, and euphoria.

Mr. Gathman, for instance, said the treatment made him “sleepy” and provoked an “out of body” experience. He described these sensations as “pleasant” — though he struggled with his balance and a sense of being “dazed” for several hours following each session. The ketamine boom has increased access to thousands who may benefit, but some scientists and doctors worry the drug is not yet ready for widespread use.

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Chris Gatham struggled with chronic depression for decades before finding relief through intravenous ketamine treatments. “I woke up the next day and felt completely normal,” he said.Credit…Gesi Schilling for The New York Times

“I understand the rush for ketamine, in both private and public clinics,” said Dr. Carolyn Rodriguez, director of the Translational Therapeutics Lab at Stanford University, who conducted an early small trial of ketamine to treat obsessive compulsive disorder and saw an impressive and immediate decrease in symptoms. But given the lack of long-term data, potential for troubling side effects and possibility for abuse, “I believe that ketamine is not yet ready for safe general use,” she said.

Ketamine on Demand

Ketamine’s success in early trials has surprised and excited researchers who study mood disorders, a field where drugs like Prozac and Zoloft, paired with talk therapy, have been the main treatment options for decades. But, as with Mr. Gathman, interventions don’t work for up to 30 percent of those suffering from major depression.

Moreover, it can take up to two months to determine whether these interventions have any effect at all — a dangerously long time for those suffering from suicidal thoughts and other mood disorders, said Dr. Joshua Berman, the medical director for interventional psychiatry at Columbia University, who helps lead the development of the department’s ketamine program. Ketamine’s effects, on the other hand, are often immediate.

Though relatively new in the field of mental health, ketamine has been used in hospitals and on battlefields as an anesthetic since 1970. While the drug’s clearance by the Food and Drug Administration does not yet extend most ketamine treatments to mood disorders, any physician can prescribe it off-label to patients whom they believe might benefit — allowing the commercial ketamine business to flourish.

Chris Walden, the co-founder of Ketamine Media, a public relations firm that works with ketamine providers, said that ketamine clinics have grown from a few dozen to “many hundreds” in the United States but couldn’t give exact numbers.

Some of these providers are associated with academic institutions conducting clinical trials. Others operate out of private boutique-like clinics such as Nushama, which was recently opened on Park Avenue in New York City by designer Jay Godfrey.

And some patients skip the clinic entirely. Mindbloom, which launched in late 2018, is an at-home delivery service that sends ketamine lozenges directly to the homes of patients. The company — among the fastest growing of several at-home ketamine delivery services, like My Ketamine Home and TrippSitter — pairs its clients with psychiatric clinicians certified to prescribe drugs, who determine if the drug is appropriate for them. Then other employees, called “psychedelic guides,” meet with patients virtually before and after sessions to process the experience. There are no formal requirements to becoming a psychedelic guide, but most have completed training in fields such as mental health, life coaching or crisis management.

Dylan Beynon, Mindbloom’s chief executive and founder, said over 80 percent of his clients suffering from depression or anxiety experience significant improvement after four sessions — and that just 5 percent of patients experience side effects, which were mostly mild.

By shipping directly to clients, the company has lowered the cost of ketamine therapy — which averages $400 to $800 per session at many in-person clinics — to $120 to $190 per session, said Mr. Beynon. Given that ketamine is rarely covered by insurance, this is still prohibitively expensive for many.

Still, many experts do not believe patients should be self-administering ketamine — which can produce powerful dissociative sensations and even a seemingly catatonic state — outside of a clinical setting. Other side effects — like increased blood pressure, paranoia and suicidal thoughts — are rare and typically only appear at very high doses.

Dr. Leonardo Vando, Mindbloom’s medical director, claimed that out of tens of thousands of doses administered, the company has only observed mild side effects, like nausea.

Dr. Gerard Sanacora, director of the Yale Depression Research Program and the Yale-New Haven Hospital Interventional Psychiatry Service, agreed that serious side effects are rare but has seen patients experience chest pains and worried about exacerbating heart conditions. “If you treat enough people, something is going to go wrong,” he said.

“With a drug like ketamine that can affect heart rate and blood pressure, it’s especially important to get a well-documented cardiac history, laboratory screening assessments, and to be monitored during the infusions,” said Dr. Rodriguez. Screening candidates in this way led her to discover an undiagnosed heart condition in one patient. “It would not have been a good idea to give ketamine to that person.”

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Mindbloom’s at-home kit, nicknamed the Bloombox, contains ketamine tablets you can take at home, along with sleeping mask and journal.Credit…Erica Gannett for The New York Times

A Promising Yet Unregulated Industry

Many ketamine providers, including Mindbloom, require clients to meet with a psychiatric clinician to ensure they are a good fit for the therapy. Mr. Beynon said his company, which conducts these screenings remotely, turns away roughly 35 percent of those that apply — including people whose symptoms aren’t severe enough to warrant it or are too severe for at-home treatment. He declined to provide documentation to support this claim.

However, this level of screening is not required by law and some patients just find a prescribing doctor online who will issue the drug through a private pharmacy with no other oversight.

The potential for abuse is reason to be cautious about ketamine’s use outside of a carefully controlled clinical setting, said Dr. Rodriguez — particularly in clinics that may be providing higher doses than what has been studied. “There is potentially this opioid effect, this rush, that taps into brain regions that may be susceptible to addiction,” she said.

Ketamine’s impacts can also be transient, Dr. Berman said, meaning some patients may need to keep taking it — but most research has not looked at the long-term effects of ketamine therapy.

There is one exception. In 2019 the Food and Drug Administration approved esketamine, a ketamine nasal spray, for the treatment of drug-resistant depression and suicidality. This approval was given only after large, randomized, placebo-controlled trials, said Dr. Sanacora. This research also led to the creation of strict guidelines for use of the product — like conducting the therapy in a certified doctor’s office or clinic and monitoring a patient for two hours after treatment.

“I am not sure why the same evaluation and management guidance isn’t being used for other forms of the treatment,” Dr. Sanacora said.

Dr. Rodriguez said she believed ketamine providers should be relying on a 2017 Consensus Statement issued by an American Psychiatric Association task force, of which both she and Dr. Sanacora are members. The statement includes best practices for screening potential patients and for administering the drug — some of which would be difficult outside of a well-equipped clinical setting.

Waiting For Data

Most experts agree much more research about ketamine’s effectiveness in mental health is needed, and dozens of trials are currently underway globally.

However, there are real barriers to new large-scale trials like those conducted with esketamine, said Dr. Berman, since pharmaceutical companies are unlikely to pay for research into a drug that can already be prescribed off label. “The nasal spray was new technology so there was a greater incentive for the private sector to invest in large trials,” he said.

In the absence of this research, Dr. Sanacora and others have suggested the creation of a registry — similar to the Risk Evaluation and Mitigation Strategy program, which the F.D.A. requires for certain medications with serious safety concerns — to help gather data on side effects and how the drug is being administered.

Some researchers believe this type of data, once gathered, could be used to develop better standards in the industry — and could even expand ketamine’s use, rather than restrict it.

For instance, though ketamine has mostly been studied in drug-resistant patients, some believe it could prove to be an effective first-line treatment option for severe depression, said Dr. Berman, since its impacts are often felt immediately.

While more data is collected, Dr. Rodriguez said that plenty of patients are truly suffering. “They’re in such deep, deep pain,” she said. “As long as patients understand the limits of current research and are able to make an informed decision with their clinical care team, shouldn’t they be allowed to weigh potential side effects against the deep pain that they’re in?”

David Dodge is a freelance writer focusing on health, wellness, parenting, travel and the L.G.B.T.Q. community.

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