Club Drug Ketamine Nears FDA Approval for Depression Treatment

By Kelly Burch 02/14/19

Ketamine can relieve the symptoms of depression, but it's especially effective at reducing suicidal thoughts quickly, sometimes within 40 minutes.

Depressed woman with head down, comforted by therapist and considering ketamine
“It took a conceptual leap for people to really wrap their heads around that this anesthetic somehow was acting as a mood elevator." - Dr. Steven Mandel ID 49321966 © Katarzyna Bialasiewicz |

Within an hour of Matthew Ayo’s first ketamine infusion treatment, his mother looked at him and said “I have my son back.”

Ayo, who is now 23, had been treated for depression, anxiety, and other mental disorders throughout his teens and early twenties. A little more than a year ago his psychiatrist recommended that he try ketamine infusion therapy. For Ayo, the results were immediate and life-changing. He shows off a graph charting his depressive symptoms: “That first sky-rocket up was my first infusion,” he said. “I went from severe depression to no depression symptoms.”

A year later, Ayo has remained depression-free and has gone from needing 24 pills each day to just 6. He’s moved out of his family’s home, secured a job, and is social. Although he still gets panic attacks, he says he’s better able to handle them.

“It helped with every aspect: anxiety, depression, psychosis,” Ayo said. “I know that’s not what it’s for, but in my case it changed everything.”

Stories like Ayo’s are awe-inspiring. Anyone who has experienced depression or watched helplessly as a loved one tries medication after medication hoping to find relief knows that too often the current treatments for depression and other mental illnesses just don’t work. Against this backdrop, ketamine infusion therapy can seem like a miracle treatment. When it works, it works quickly and effectively, often causing a dramatic reduction in symptoms of depression. However, medical providers caution that while ketamine shows a lot of promise, there’s still a long way to go toward understanding how the drug should be used to treat mental health conditions.

A Conceptual Leap

Ketamine — also known as the club drug “Special K” or “K”— is a well-established anesthetic, used since the 1970s to sedate people for medical procedures. Because it is safe and effective, ketamine is used widely by the military. During the wars in Iraq and Afghanistan, doctors began noticing that soldiers who were given ketamine for anesthesia often had fewer symptoms of post-traumatic stress disorder (PTSD), according to Dr. Steven Mandel, president of The American Society of Ketamine Physicians.

“It took a conceptual leap for people to really wrap their heads around that this anesthetic somehow was acting as a mood elevator,” Mandel said.

Mandel has practiced as an anesthesiologist for decades, but also has a master’s degree in psychology. As he looked into the research on ketamine, he became convinced that it could benefit people with depression, anxiety, and trauma. In 2014, he opened the Ketamine Clinics of Los Angeles and began offering treatments directly to patients, including Ayo. Mandel says that in his patients, ketamine treatments relieve the symptoms of depression 83 percent of the time and stop suicidal ideation more than 90 percent of the time.

“It almost sounds too good to be true,” he said.

Like Mandel, the wider medical community has been impressed by ketamine’s potential for treating psychiatric disorders. Although the Food and Drug Administration had only approved ketamine for anesthesia, providers began to use it off-label in ketamine infusion therapy — an intravenous administration of the drug — to provide swift relief of depression symptoms. At the same time, pharmaceutical companies hurried to develop a ketamine formulation specifically for treating mental health conditions.

The result is Esketamine, developed by Johnson & Johnson, a nasal spray based on ketamine that can be used to treat depression. On Tuesday, February 12th, an FDA expert panel recommended that Esketamine receive federal approval. If approved, the medication will be covered by many insurance plans. Currently, almost all patients must pay out-of-pocket for ketamine infusions, which cost thousands of dollars. Doctors are hopeful that this will change as insurance companies realize that even off-label ketamine treatments can reduce the medical costs for people with mental illness.

Risk-Benefit Analysis

Speaking to Mandel and his patients, it’s impossible not to feel excited about ketamine. However, other providers are more cautious in their optimism.

“There are certain scenarios where ketamine makes a whole lot of sense, and there are certain scenarios where it’s very unclear what the role of ketamine should be,” said Dr. Nolan Williams, assistant professor of Psychiatry and Behavioral Sciences at the Stanford University Medical Center. “I think that the idea that ketamine is going to be a treatment for everyone chronically for their depression forever is not realistic.”

Most providers still reserve ketamine treatments for people who have already tried more traditional treatments. While the side effects of older medications like SSRIs (such as Prozac and Zoloft) are well understood, there still isn’t a firm medical understanding of ketamine for psychiatric use, said Dr. Robert C. Meisner, the medical director of the Ketamine Service in the Psychiatric Neurotherapeutics Program at McLean Hospital, which is affiliated with Harvard Medical School.

“One must balance clinical necessity with clinical uncertainty, as well as availability of other treatments,” he said. “We know more about [first-line treatments like SSRIs], so the risk-benefit is easier to access.”

Meisner oversees ketamine treatments daily for his patients, but says he would like to see further research into the long-term effects of ketamine, what an optimal dose is, and what markers might indicate that a person will respond positively to ketamine.

The early indications are reassuring, he said. Ketamine appears to be very safe and have a low risk for addiction or dependency. However, studies of recreational users have shown that people who use high levels of ketamine for long periods can have complications in the bladder, liver, biliary tract and suffer cognitive deficits. In order to be more comfortable with ketamine, scientists need to better understand at what point the drug goes from relatively harmless to potentially dangerous.

“As the risks and benefits become better defined, especially over the long run, it is possible that there may come a point where ketamine isn’t a second- or third-line option, but is used earlier,” Meisner said. “As the research comes in, people will become more or less comfortable recommending ketamine sooner.”

A Life-Saving Medication

One area where people have been more apt to use ketamine is among patients who are highly suicidal. Ketamine is especially effective at reducing suicidal ideation, in as little as 40 minutes, making it a potentially powerful medication for people who are acutely suicidal in the emergency room.

Even outside of emergency situations, ketamine can be lifesaving for people at risk for suicide. SSRIs and other antidepressant medications start working slowly, sometimes not reaching their peak effectiveness until six to eight weeks have passed. This period of time between starting the medication and the onset of full therapeutic effects is considered high-risk for suicide, because someone who is acutely depressed might still be suicidal, but now have enough energy to follow through on a plan that they previously couldn’t execute. Ketamine can be used as a bridging agent in these situations, giving quick, short-term relief of symptoms.

“Relatively speaking, this is a fast way to rescue some percentage of people with depression from the horrific depths of it, and sustain them until the medication to which we’re bridging becomes therapeutic and can take over,” Meisner said.

What the Future Holds

Today, experts and the public hold diverging views about ketamine. Some, like Mandel and Ayo, see ketamine infusion therapy as a life-changing treatment. Much of the medical community, however, is waiting to see more research and to follow the results from these early uses of ketamine.

“Some argue there is an ethical imperative to move quickly to ketamine,” Meisner said, but he also points out that it’s only been used to treat psychiatric illness in the last ten years, which is not long at all in terms of medicine.

“Many doctors who work in neurotherapeutics see IV ketamine not as the end of the story, or the treatment that has at last arrived, but as a treatment modality that is evolving and will change as the mechanism is better understood and drugs that leverage that novel mechanism are developed,” he said. “I have high hopes for where the early work on ketamine leads us as we better understand its complex mechanisms.”

Please read our comment policy. - The Fix
Kelly Burch Contrib.jpg

Kelly Burch writes about addiction and mental health issues, particularly as they affect families. Follow her on TwitterFacebook, and LinkedIn.