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Ketamine, or "Special K" as its known, is a psychedelic party drug that brings on hallucinations. It's also the next great hope for people with treatment resistant depression.

Catherine DiBenedetto
November 04, 2015

Ketamine, or "Special K" as its known, is a psychedelic party drug that brings on hallucinations. You're more likely to hear about it in the context of drug abuse these days, so you might be surprised to hear that some doctors around the country are now offering ketamine off-label to help patients with severe, treatment-resistant depression.

But in fact, ketamine already has a medicinal history: it was originally FDA-approved back in the 1970s as a fast-acting general anesthetic (although it is not approved for treating depression). Here’s everything you should know about the drug's possible new use.

Study results are promising

In 2006 scientists at the National Institute of Mental Health (NIMH) found that a single dose of intravenous ketamine led to “robust” antidepressant effects within hours. The study was encouraging given that current antidepressants (like Lexapro or Prozac) can take weeks to kick in.

What’s more, the participants in the study had what’s called treatment-resistant depression, which suggests ketamine could help people who don’t respond to the traditional medications and therapy, including electroconvulsive therapy (which is used for severe depression). Another study done in 2013 reported similar rapid results. And last year, the director of the NIMH, Tom Insel, MD, wrote on his blog that recent data suggest intravenous ketamine may be “the most important breakthrough in antidepressant treatment in decades.”

The problem? There are a ton of unanswered questions about who it might work for, and whether or not it's safe. (Keep reading.)

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Ketamine clinics are popping up around the country

The Ketamine Advocacy Network lists 18 clinics and providers across the U.S. During a typical IV session, a patient might experience some hallucinations and perceptual distortions—but those side effects go away. The fee per treatment ranges. A clinic in Manhattan lists a cost of $525, for example, while a doctor in Watsonville, Calif., charges $1000.

In a New York Times story published last year, Dominic A. Sisti, an assistant professor of medical ethics at the University of Pennsylvania, expressed concern about clinics that are run by anesthesiologists who don’t provide psychiatric treatment; and clinics opened by psychiatrists who may not have adequate experience with ketamine.

David Feifel, MD, a psychiatry professor at the University of California, San Diego, echoed that concern to NPR: “We’ve seen ketamine clinics open up as pure business models.” Dr. Feifel, who has been administering ketamine off-label since 2010, says his fear is that a mishap at one of these clinics could delay efforts to make the drug available to more people.

How it actually works is still unclear...but there are theories

In high doses, ketamine can cause a dissociative effect that makes a person feel detached from reality, which is why it became so popular as a club drug. But researchers have yet to figure out why it's seems to be such a potent antidepressant.

Current evidence suggests that it might have something to do with the neurotransmitter glutamate, which is important for strengthening connections between neurons (aka brain cells). A 2012 review of the research in the journal Science posited that ketamine might work by spurring a release of glutamate that re-builds the connections in the brain that have been damaged by depression.

It’s not a miracle cure

Despite the initial relief, ketamine’s effects on depressive symptoms don’t last long. Studies show the drug can work for up to two weeks. Dr. Feifel told NPR that for one of his patients, relief fades after just one day. But as he pointed out in another interview with Medscape, even a brief respite is “a big deal to someone whose entire waking existence is unrelenting misery.”

The long-term safety is TBD

“While the science is promising, ketamine is not ready for broad use in the clinic,” NIMH director Dr. Insel concluded in his blog post about the drug. He also pointed out basic questions that still need to be answered—including the best dose and the risk of repeated injections.

For now, though, the FDA has designated ketamine a "breakthrough therapy,” which means the agency will expedite its development and review. Dr. Insel is encouraged by the move: “This speaks not only to the scientific opportunity but the public health need for having a rapid antidepressant.”

But some doctors don’t want to wait until all the results are in. Dr. Feifel told the New York Times that if he didn’t administer the drug, “I’m consigning you to lose another decade until ketamine might be ready. I just don’t feel that presumptuous.”

Pharma hopes to develop a safer alternative

A number of drug companies are testing medications similar to ketamine, sans the trippy side effects. Naurex, for example, is aiming for FDA approval of an IV drug called GLYX-13, by 2019. Johnson & Johnson is working on a nasal spray that contains a derivative of ketamine. And a small Baltimore company called Cerecor has invested $33 million in a daily pill. Earlier this year, Al Jazeera America reported that Cerecor "might be the odds-on favorite to hit the market first."

In the meantime, some people are using it despite the lack of information about the risks and benefits. Dennis Hartman, 48, a businessman from Seattle, told the New York Times that off-label ketamine saved his life: "I look at the cost of not using ketamine—for me it was certain death."

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