Ketamine, once known on the street as “Special K,” was abused in the past as a “recreational drug” because of its hallucinogenic and tranquilizing effects. But over the last decade, it has shown promise as a treatment for individuals with depression who are seriously considering suicide.

First used in the US as a surgical anesthetic (American soldiers in Vietnam were treated with it in the 1970s), ketamine was approved (in March 2019) for a different application — to treat treatment-resistant depression.1

More recently (August 2020), a type of ketamine called esketamine, was approved as a nasal spray to give relief to adults with major depressive disorder who are experiencing acute suicidal ideation or behavior.2 For many patients who are in the ER for suicidal thoughts, this drug (the brand name for the nasal spray is Spravato) can help quickly, experts say.

“It’s an important treatment in our field and the evidence supports the view that ketamine improved suicidal thoughts in people not just by reducing their depression but also by improving the thought processes that are involved when someone is considering suicide,” says Sudhakar Selvaraj, MD, PhD, associate professor of psychiatry at the McGovern Medical School at UTHealth in Houston. “Ketamine immediately enables an effective way people can problem-solve their situation while at the same time lifting their depression and improving their mood. It can work within two hours.”

Ketamine seems to help people more quickly than traditional antidepressants (SSRI medication like Lexapro or Zoloft take seven to 14 days to reduce symptoms) , says Daniel Wasserman, co-author of an article titled, The Influence of Ketamine on Drug Discovery in Depression published in Drug Discovery Today. “While some antidepressants can take weeks or months to achieve full effectiveness, ketamine can produce significant reductions in depression within hours to days of a single dose,” he explains. “This is particularly significant for patients who are acutely suicidal and need immediate help.”

Ketamine can be administered via nasal spray or intravenously in the emergency room under medical supervision, Dr. Selvaraj adds. It’s effective in around 60% of people, but it is only part of a long-term solution, he explains.

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“A person who has experienced suicidal ideation also needs professional help to address the multiple problems facing anyone who is considering suicide,” he says. “Whatever the cause for their suicidal ideation, they need to learn coping skills for the long-term benefit.”

How Does Ketamine Work?

People consider suicide not because they want to die but because they want their pain to stop, says John Huber, PsyD, a clinical forensic psychologist based in Austin, Texas. “Ketamine can lift a person’s defense mechanisms and helps them reframe their perspective,” he explains. “It can make them realize that things will get better if they stay alive. It lets a person let go of their false narrative long enough to see that there is a different way to look at the world.”

Studies on the effectiveness of ketamine are now ongoing, Dr. Selvaraj says. One article describing the study of ketamine both for depression and suicidal ideation noted the “robust antidepressant effects and anti-suicidal effects of ketamine.”

“The discovery…is regarded as the greatest advancement in mood disorder research in the past 60 years,” noted the author.3

National Institute of Mental Health-supported researchers are involved in suicide prevention research, such as treatments like ketamine infusions for individuals with treatment-resistant depression and active suicidal ideation.4

Two types of ketamine are now in use. Racemic ketamine, typically given as an infusion, was approved decades ago by the FDA as an anesthetic and is used off-label as an anti-depression medication.

It’s actually a mixture of two mirror-image molecules, “R” and “S” ketamine. The second, the nasal spray called esketamine (Spravato), uses just the “S” molecule, and was given FDA approval in March 2020.5

[Click to Read Ketamine for Depression: Two Patients Share Their Story]

Timothy Sullivan, MD, chair of psychiatry and behavioral sciences at Northwell Health, Staten Island University Hospital in Staten Island, says he hopes the FDA approval of ketamine will help facilitate insurance approval of the drug for individuals who could benefit from it.

“If someone has severe suicidality and there are concerns about their safety, with the new approval now the patient does not have to try several antidepressants and have them not be effective before trying ketamine,” he says. “The FDA approval means that worrisome suicidality can be addressed quickly. The high cost has been one barrier to using ketamine.”

While his hospital so far has not used ketamine because of the pandemic, he says plans are underway for it to be used. “In the COVID environment, this can be difficult because administering the nasal spray is inherently an aerosolizing procedure,” Dr. Sullivan says. “But we are working on plans now to begin using it.”

Ketamine Side Effects

It’s important to note that like most other medications, ketamine doesn’t work for everyone and there are side effects, too. Ketamine is not indicated for patients with psychotic symptoms, and it can have disadvantages, says Dr. Selvaraj.

“In patients with psychotic symptoms, ketamine could even make things worse,” he says.
And there are some concerns, he says, such as the possibility of long-term cognitive difficulties and the risk of substance abuse. “Based on the evidence, researchers have not seen this so far,” he says.

Ketamine treatment should be limited to adults who have treatment-resistant depression and who do not have a history of substance abuse or alcohol abuse or other significant medical conditions, studies suggest.6

Asked if ketamine could be effective with children and teenagers, Dr. Selvaraj says, “It’s possible, but there is limited evidence so far. Studies are ongoing.”

He’s not sure how prevalent the use of ketamine is for suicidal ideation. “Ketamine has been widely used for depression but I don’t have any specific data for ketamine use in suicidal ideations,” he says.

In the ER, it is a one-time dose, but more repeated infusions are required for depression treatment, along with other antidepressant medications, Dr. Selvaraj explains.

A physician may opt for the nasal spray over the IV ketamine due to the ease of administration. “The nasal spray is not quicker or longer-lasting,” he says. “IV ketamine due to its bioavailability is more effective than the intranasal form.”

One drawback, says Wasserman, is that ketamine does have abuse and addiction potential. “This makes it more challenging to administer,” he says. “And the acute effects can be disorienting for patients.”

The side effects of ketamine, in addition to addiction, include bladder problems and out of body experiences. And, of course, it’s not a cure. The effects wear off within a few weeks to months.7

But for many other individuals, ketamine just may be lifesaving.

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Last Updated: Sep 23, 2020