FDA Alert: Ketamine Is Not Approved For the Treatment of Any Psychiatric Disorder

Ketamine is not FDA-approved as a treatment for any psychiatric disorders, the Food and Drug Administration (FDA) clarified in an alert last week.

The drug has received previous FDA approval in some forms and is often used as an injectable anesthetic in hospitals and clinics. Some of the drug’s effects, like its hallucinogenic quality, have been explored for potential as a therapy for mental health disorders, mainly depression. 

However, the FDA has not approved ketamine for the treatment of any psychiatric condition.

In its new alert, the organization said it’s aware that people are increasingly seeking out compounded ketamine—an altered version from its FDA-approved state. 

Not only is ketamine not approved for treating any mental health condition, but it could be dangerous.

“Compounded drugs pose a higher risk to patients than FDA-approved drugs because compounded drugs do not undergo FDA premarket review for safety, effectiveness or quality,” FDA spokesperson Jeremy Khan told Health. 

Here are the risks associated with compound drugs like ketamine, why some healthcare providers may prescribe ketamine off-label, and how experts predict the drug will impact future mental health care.

Compound Drugs Are Not Regulated By the FDA

Compounded drugs, like compounded ketamine, are legal in the United States, but they exist with a lot of stipulations.

For example, someone who cannot take an FDA-approved version of a drug may be eligible to take a slightly altered compounded version that doesn’t include a particular non-active ingredient that the person is allergic to, such as a dye.

The FDA also maintains a drug shortage list. When drugs appear on this list, it’s legal for the roughly 7,500 licensed compounding pharmacies in the U.S. to mix, alter, or combine FDA-approved drugs with different ingredients to make up some of the supply. 

Compounded drugs are not regulated by the FDA, so there is no assurance that drugs purchased from a compounding pharmacy are what companies claim they are.

With ketamine, the risks are even greater. 

“The concern is that because it’s being compounded, more and more people are going to take it at home,” said Amit Anand, MD, director of psychiatry translational clinical trials at Brigham and Women’s Hospital in Boston and professor of psychiatry at Harvard Medical School.

Since ketamine is FDA-approved as an anesthesia, drug companies readily make it. Compounding pharmacies use this supply to make unapproved ketamine tablets and nasal sprays that people can take at home without any oversight from a medical professional.

This lack of healthcare supervision makes potential side effects more dangerous.

According to the recent FDA alert, ketamine can cause increased blood pressure, urinary tract infections (UTIs), and too-slow breathing.

An alert from February 2022 noted that the drug also carries the risk of abuse, sedation, and dissociation.

Ketamine May Be Prescribed Off-Label, But It’s Not FDA-Approved

Ketamine is not FDA-approved for the treatment of depression, but some psychiatrists use it off-label. Off-label simply means administering a drug for something it isn’t approved to treat. 

“If a patient and their healthcare provider decide to use an approved drug for an unapproved use to treat a disease or medical condition, the FDA has not determined that the drug is safe and effective for the unapproved use,” Khan said. 

Because it is not FDA-approved, off-label ketamine treatment is not covered by insurance companies, making it expensive, and not every psychiatrist is willing to try it. 

But, just because off-label use of ketamine for psychiatric disorders is not illegal doesn’t mean it’s a good idea. Khan explained there needs to be more clinical trials to solidify that the potential benefits outweigh the risks before the FDA can support ketamine use for psychiatric disorders.

“People are trying to take a shortcut to get ketamine through compounding, and because ketamine is not approved by the FDA for psychiatric conditions, compounded drugs are in some ways easier to get,” Anand said.

There is another option other than a compounded ketamine, but it comes with its own set of access hurdles.

In 2019, the FDA approved a version of ketamine, called Spravato (esketamine), as a nasal spray used to treat treatment-resistant depression in adults as well as depressive symptoms in adults with major depressive disorder (MDD) who are experiencing suicidal ideation or behavior. Spravato is only approved for use at certified health care providers, and only in conjunction with antidepressant medication. 

Patients have to stay in the health care facility for two hours after they receive a dose of Spravato so providers can monitor them for potentially dangerous side effects. 

So while that is an FDA-approved psychiatric disorder treatment, it isn’t readily available. Patients have to have access to a facility that can administer it and the money to pay for it—the drug often costs more than $1,000 out of pocket.

“Most people cannot get the nasal spray,” said Anand. “It is very expensive, even for hospitals that are giving it.”

And, even Spravato has not escaped compounded dupes.

The drug is the only FDA-approved ketamine-based nasal spray, but compounding pharmacies are creating their own, unregulated versions of ketamine nasal spray and selling them to people who can use them without the requirement of going to an approved healthcare provider. 

“With these obstacles in place, people are understandably finding shortcuts to getting it, and that is what is raising the alarm,” Anand told Health.

Ketamine As Depression Treatment Is an Ongoing Conversation

While ketamine for psychiatric disorders hasn’t received FDA approval, research on the drug for mental health is still in motion.

Studies have shown that, in small doses, ketamine can be an effective treatment-resistant depression. 

A clinical trial published in June of this year included more than 400 patients who had MDD. Half received a therapy called electroconvulsive therapy (ECT) three times per week for three weeks; the other half received ketamine.

At the six-month follow-up, 55% of those who received ketamine treatment reported at least a 50% improvement in depressive symptoms and no major side effects, compared to 41% of those who received ECT.

Anand explained that depression is the only psychiatric condition that has shown consistently solid evidence in favor of ketamine therapy being a treatment option for some people.

Despite this, ketamine is often touted as a treatment for other psychiatric conditions, including post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD). 

“It’s not established that ketamine is effective for OCD or PTSD,” Anand said. “The evidence really isn’t there.”

If someone is interested in trying ketamine as a treatment for depression, Anand said the safest way to do so is to work with a doctor or psychiatrist who can administer a very small dose through an IV. This can cost more than $1,000 for a single session.

“The second best thing would be to get Sprovato,” he said, noting that ketamine should only be taken in the short-term, as an acute therapy used only when depressive symptoms are particularly bad and resisting other treatments.

“We’re not really sure about the safety of long-term ketamine use,” he clarified, “as it is being advocated for with Sprovatto.”