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3 Things to Know About Ketamine Therapy

Use of the drug has become increasingly popular, but doctors warn it shouldn’t be taken without medical supervision

spinner image IV infusion for ketamine therapy set on light blue background
Olga Yastremska, New Africa, Africa Studio / Getty Images

The drug ketamine has been thrust into the spotlight after an autopsy report showed that Friends star Matthew Perry died from “acute effects” of the medication, raising questions about its use and its role in health care.

While sometimes thought of as a party drug that goes by the name Special K, ketamine has long been a staple in operating rooms as an anesthetic. More recently, doctors have been turning to ketamine as a treatment option for some patients with chronic pain, depression and other health conditions.

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Here are three things to know about ketamine therapy.

1. Ketamine’s use is increasing 

Ketamine was approved as an anesthetic for surgery by the Food and Drug Administration (FDA) in 1970, and in 2019, a form of the drug, called esketamine, was approved as a nasal spray to treat depression in adults who don’t respond to antidepressant medicines.

However, increasingly, the drug is being used off-label — often as an infusion — at outpatient clinics and in some major medical centers. Off-label use is when doctors prescribe an approved drug for an unapproved use; the Agency for Healthcare Research and Quality says the practice is both legal and common.

Wellness and telemedicine companies are even selling altered ketamine tablets and sprays for at-home use, though health experts caution that the drug should not be used without medical supervision, and that doing so can be dangerous.

spinner image close up of a bottle of therapeutic ketamine for ketamine infusions to treat depression and anxiety on a physician's desk
The Denver Post, MediaNews Group / Getty Images

One reason for ketamine’s recent rise in popularity has to do with the high burden of mental health issues we’re seeing in the U.S., says Smita Das, M.D., a clinical associate professor of psychiatry and behavioral sciences at the Stanford School of Medicine and chair of the American Psychiatric Association’s Council on Addiction Psychiatry. “With COVID especially, there was an increase in depression and anxiety symptoms among adults and children in the U.S.,” Das says. And now, people are looking for ways to treat it. 

There’s also been a swell of research supporting the drug’s effectiveness for treating depression, especially treatment-resistant depression. A large study, published in The American Journal of Psychiatry, found that patients with treatment-resistant depression saw their symptoms significantly improve when they started taking esketamine nasal spray along with their antidepressant. Another study, published in JAMA Psychiatry, found that patients who took esketamine with their antidepressant stayed in remission longer than people who took only their antidepressant.

What was especially exciting in the research, says Michael F. Grunebaum, M.D., an associate professor of psychiatry at Columbia University Medical Center, was that ketamine seemed to work quicker than standard antidepressants, which can take weeks to kick in. The effects of ketamine can be seen in a few hours, Grunebaum says, though, he adds, we still don’t have good data around its long-term use.

Another reason for the increased interest in ketamine: Sometimes the treatments that we have for various health conditions don’t work for everyone, says Pavan Tankha, D.O., an anesthesiologist at Cleveland Clinic and medical director of the Comprehensive Pain Recovery Program, which offers low-dose ketamine infusions to treat some patients with chronic pain. That’s where ketamine comes into play: It’s an option when patients have “exhausted other conventional treatments,” Tankha says. 

In addition to depression and chronic pain, ketamine is being studied as a novel treatment for post-traumatic stress disorder, eating disorders, alcohol use disorder and more.

“With all medications if they’re around long enough, people wonder, well what else can it do? And so ketamine has found other indications besides anesthesia and treatment-resistant depression,” Tankha says.  

Still, it’s important to note the FDA has not approved ketamine as a treatment for these conditions, and it could remain that way, given that the drug is generic, and it costs a lot of money to fund large trials needed for federal approval.  

2. You shouldn’t take ketamine without medical supervision

When a patient is thoroughly screened and ketamine is administered by a trained health care professional, Tankha says it’s “not only safe, but it can be effective for what we’re using it for.” (Perry, the Friends actor, was reportedly receiving ketamine therapy, according to the Associated Press, though the high levels of ketamine in his blood at the time of his death couldn’t be attributed to his most recent treatment session a week and a half prior.)

That’s not to say there aren’t any side effects with the drug — and these effects are one reason health experts say people should be under the care of a health care provider during treatment. Some people can experience nausea, vomiting, agitation, hallucinations and a disassociation from reality. “The experience can be a little unusual,” Tankha says — some have even described it as “unnerving” or anxiety-producing.

Tankha says these side effects are dose-dependent, meaning you’re more likely to experience symptoms at higher doses. Older adults may be more vulnerable to side effects, he says, since “over time, as our [metabolism slows], medication side effects are more likely to occur.”

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Ketamine can also exacerbate underlying heart and blood pressure conditions, Grunebaum says, “and so there needs to be adequate medical monitoring and supervision available for safety.” Even the FDA-approved esketamine nasal spray requires patients to use the medicine in a doctor’s office or clinic, under the supervision of a health care provider. 

What’s more, with ketamine, a controlled substance, there’s potential for addiction, Tankha says, “and so close monitoring must be done.”

In October, the FDA issued a warning about using ketamine products at home and without medical supervision. The agency said it “understands that the ability to obtain such products through telemedicine platforms and compounders for at-home use may be attractive to some patients. However, the lack of monitoring for adverse events, such as sedation and dissociation, by an onsite health care provider may put patients at risk.”

The FDA said it received an adverse event report for a person who experienced respiratory depression — breathing too slowly or shallowly — after taking an oral form of ketamine outside of a health care setting for the treatment of PTSD. “The patient’s ketamine blood level appeared to be twice the blood level typically obtained for anesthesia,” the agency said.

According to the U.S. Drug Enforcement Agency, an overdose of ketamine can cause unconsciousness and dangerously slowed breathing, which can lead to respiratory failure or heart attack.   

3. It’s not a first-option treatment

If you’re interested in learning more about ketamine therapy, skip the mail-order marketers and start by talking to your primary care physician, Tankha says. If they’re not familiar with ketamine, ask to be referred to a provider who is — and then, consider getting a second opinion. “When we’re talking about off-label uses, you want to be an informed consumer and get as much information as possible,” he says.

Grunebaum predicts ketamine therapy, which for some can be lifesaving, will stick around, especially for people with treatment-resistant depression. Research suggests that around 30 percent of people with depression don’t respond to traditional treatments. “But I wouldn’t expect to see it become a widespread, first-line treatment for someone early in their natural history of their illness,” he says. 

“We have strong evidence-based ways of treating depression and anxiety that should be considered before ketamine,” Das says. “And unfortunately, those options are underutilized, or they’re not fully utilized.” Studies show about half of people with a mental illness don’t receive treatment for it.

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