The Anesthetic Ketamine May Lift Depression

The first new treatment in decades may come soon.

For decades now, doctors have used the drug ketamine to minimize pain during surgery. Many people noticed that patients who received ketamine felt much better the day after the operation than patients who had been given a different kind of anesthesia. About 15 years ago, the first research appeared showing that a slow intravenous infusion of ketamine could rapidly lift the mood of extremely depressed patients. 

Now the Food and Drug Administration has put a variation called esketamine in the form of a nasal spray on the fast track to official approval for treating severe depression. If it is approved, it will be the first completely new kind of treatment for major depression in almost 50 years. It may be a godsend for preventing suicides, which have soared to 30-year highs in the United States. 

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But be clear: You can’t get the same benefits with the party drug “Special K,” a form of ketamine. For starters, people typically inject or snort Special K — which doesn’t have the good effect of the slow, low-dose infusion. Neither does smoking it or taking a pill. 

In very high doses, Special K induces a “K-hole,” with vivid hallucinations. If you’re depressed, those hallucinations will reflect your state of mind — and could very well be ugly and sad. You may also become nauseated and, if you’re lying down, choke on your vomit. Yes, that’s how people often die from heroin. If you do see people lying down on ketamine, roll them on their side and call 911.

Because ketamine is approved for use as a painkiller, some doctors have already been prescribing it off-label for depressed people who haven’t found relief with other approaches, and clinics providing an IV drip have popped up around the country. There is concern that ketamine could be addictive, and all agree that more research on its long-term effects is needed — but some patients are desperate for help.  Current antidepressants usually take up to two months to help, and, for each drug, only 30 percent of patients will respond. So many people go from one drug to the next, and can lose hope that any will help. In tough cases, they try every drug and nothing works. 

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Ketamine changes mood in minutes. “It blew the doors off what we thought we knew about depression treatment,” psychiatrist James Murrough, MD, at Mount Sinai Hospital in New York City told Scientific American. Murrough’s research team has reported that ketamine reduced depression 24 hours after treatment in 64 percent of a group of patients who received an IV infusion and had already tried at least three drugs without success. 

A day of relief may feel like a miracle, but it’s still unclear how long the benefits last for most patients. According to a 2015 overview, by the well-regarded Cochrane group, the evidence meeting its standards demonstrated gains for up to a week.   

Even if it doesn’t permanently change mood, ketamine seems to shift people away from thoughts about suicide, some researchers have found. The U.S. suicide rate has risen mainly because so many people don’t get treatment, but also because people intent on suicide can fool psychiatrists: People often die in the first week after discharge from a psychiatric unit. Ketamine could become a valuable tool for psychiatrists making those tricky discharge decisions. 

The drug works in a completely different way than medications for depression, bipolar disorder, post-traumatic stress disorder, or anxiety. Most of these work by changing the availability of certain brain chemicals continuously. Ketamine is more like a “reboot,” when you turn your computer off and back on to banish a problem. While you are connected to the IV, the drug blocks a type of receptor in the brain from receiving signals. Once you are no longer receiving the drug, the blockade ends within minutes. 

However, the slow drip seems to trigger a rapid growth of brain connections, which persist in some patients. Ketamine is also a powerful anti-inflammatory, and, because depression is associated with chronic inflammation, fighting inflammation may be part of the mood boost. 

The blocked pathway is associated with memory and thinking; before ketamine, no one had linked it to depression, Murrough explains. Psychotherapists, of course, know that memory and thought patterns are central to the depression puzzle. 

The trouble is that severely depressed patients may be too exhausted and overwhelmed to explore memories or change their thinking. After a ketamine drip, the hope is that they can do that work, though they may need more infusions. Research on ketamine also could lead to other effective solutions, since it works in a novel way, and will help us better understand depression. If you or someone you know who has been suffering with untreatable depression, let ketamine give you hope.  

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