Ketamine effectively treats depression. Do the benefits outweigh the risks?

BY MERYL DAVIDS LANDAU

PUBLISHED NOVEMBER 16, 2023 • 7 MIN READ

A polarized microscopic view of crystallized ketamine.

A polarized microscopic view of crystallized ketamine.
MICROGRAPH BY M. I. WALKER, SCIENCE PHOTO LIBRARY

Ketamine therapy has been shown to change lives by treating severe depression and anxiety. But experts say it must be taken with supervision in places equipped to handle medical and psychological emergencies.

Patient testimonials and hundreds of small studies point to the prescription anesthetic ketamine as a potentially useful treatment for mental health conditions such as severe depression and suicidal thinking. But health experts are alarmed by its growing and widespread use under lax safety conditions.

Last month the U.S. Food and Drug Administration published a notice to patients and providers outlining potentially serious physical and psychological dangers from ketamine, which is frequently administered in clinics or practitioners’ offices by intravenous infusion or injection and induces a quasi-psychedelic state filled with fantastical thoughts and imagery.

The FDA also asserted that because it had only approved the use of this drug during surgery, robust clinical trials for the wide range of pain and mental health conditions it is used for are lacking.

“The overall benefit-risk profile of ketamine for treatment of psychiatric disorders is unknown,” the agency asserted. (The statement does not cover Spravato, a nasal spray delivery of a specific form of ketamine, esketamine, which the FDA approved in 2019 for adults with treatment-resistant depression when taken with antidepressants. But some research shows the spray is not as effective as the intravenous version.)

It’s not that nobody should try the drug. “Ketamine does work in a lot of people. I’ve seen it change lives,” says Sophie Holmes, a psychiatry and neurology researcher at the Yale School of Medicine who has documented positive changes in brain imaging while under the drug’s influence. But it’s definitely a case of patient beware, she says.

“Ketamine is unique in how rapid a response it provides,” says Emily Whinkin, a naturopathic physician in Seattle, who recently described significant improvements in anxiety and depression after one to six ketamine-assisted psychotherapy sessions in 18 patients at her clinic with substance use disorder.

Conditions like suicidal depression, anxiety, or post-traumatic stress disorder “are really impactful in people’s functioning and quality of life and are difficult to treat even with good psychotherapy and expert medication management,” Whinkin says.

Significant side effects

Ketamine should only be administered in settings equipped to handle medical emergencies, Holmes says, which is not generally the case for the many wellness clinics and telehealth providers adopting the drug for a wide range of mental health applications and fueling a $3 billion industry that is projected to grow 10 percent annually through the end of the decade.

Holmes says that more research is needed to better understand who might benefit from ketamine therapy, what the proper protocol should be, and, importantly, how it works. Current thinking is the drug increases the connections between synapses in the brain, allowing for new thought pathways to develop.

While some people experience only mild and fleeting nausea, headaches, or upset stomach while on the drug, others may have slowed breathing or increased blood pressure.

“If someone has a preexisting cardiac issue, this could be dangerous,” says Holmes, who notes that all prospective ketamine patients at Yale undergo an electrocardiogram heart test beforehand and their vitals are monitored during each session.

Equally crucial, some clinics also don’t provide sufficient psychological support. Patients may be frightened during the hallucinations, Whinkin says. These generally last under an hour, much shorter than for true psychedelics like psilocybin or lysergic acid diethylamide, or LSD. (To capitalize on the growing interest in psychedelic medicine, many clinics advertise ketamine as psychedelic-assisted therapy even though it is not an actual psychedelic.)

Post-treatment “integration” sessions are a vital part of the experience. “It is an opportunity to explore psychological material that came up during the journey, and if there’s any confusion or confrontation of preexisting beliefs about the self or the world, that deserves skilled support,” Whinkin says.

As its name implies, integration therapy, when properly done, also incorporates the altered experience into practical actions. “What’s the way forward to harness the experience to make a notable change to how you live day to day?,” she says.

Perhaps the biggest concern is the growing use of ketamine at home—via oral capsules or pills held under the tongue, which are two delivery systems that are poorly understood. Thanks to regulations that began in 2020 after the start of the pandemic, only a brief telehealth appointment rather than an in-person visit is needed before ketamine arrives at the home.

“Prescribing it for at-home use is irresponsible, because it needs to be taken under supervision by trained professionals,” Holmes insists. Using these products without concurrent monitoring by a healthcare provider “may put patients at risk for serious adverse events,” the FDA notice states.

At-home usage also increases the potential for abuse, since ketamine is illegally sold recreationally under the name Special K. This is especially troubling since some clinics use it to treat substance abuse, says Michael Schatman, a pain medicine and medical ethics expert at New York University’s School of Medicine, who outlined his concerns in a medical journal this year. “I’ve seen my pain patients, opioid dependent, given nasal ketamine and they’ve gone home and abused it” by stocking up and then binging, he says.

For some, lasting relief

Others worry that a medicine they consider a lifeline is being misused. Shira Renee Thomas, the 45-year-old artistic director of a Southern California performing arts company, believes she might not be here were it not for ketamine.

For 25 years, Thomas experienced bouts of such extreme depression she regularly pondered suicide. Unable to leave her bed for months at a time, the disease severely impacted her quality of life and derailed an opera singing career.

Over the years she was hospitalized multiple times, prescribed some 20 different medications—individually and in combination—and even had electroconvulsive therapy, which she had to stop after losing so much memory she couldn’t remember how to drive a car or sign her name on a check.

Four years ago, Thomas found a clinic offering ketamine.

“My very first infusion was like magic,” she recalls. While under its spell, she watched an earth goddess effortlessly flick away the demeaning words she would yell at herself while depressed, such as that she was stupid or useless. That behavior subsequently ceased.

It took several years for other symptoms to be extinguished, but after close to 100 ketamine sessions, with maintenance sessions ongoing, she has not had a depressive episode in almost a year. (This cost her family some $30,000, because ketamine treatment is often not covered by insurance, although her insurer recently agreed to start paying.)

Given its potential and its risks, Schatman wants people to be clearly informed of the pros and cons of ketamine therapy before they receive a treatment.

“I have patients go into infusion clinics being told this will help them, who are not even aware they might hallucinate,” he says. People should also know there is no scientifically proven protocol, he says, so each provider can invent their own rules about how much and how often to give it.

“People need to understand they are experimenting,” Schatman says. Some are in so much pain they are willing to roll the dice.

If they do so they should boost their odds by seeing a practitioner with deep knowledge of the drug who takes safety seriously, he says, “as opposed to some local clinic or telehealth provider.”

https://www.nationalgeographic.com/science/article/ketamine-depression-anxiety-treatment

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