FDA Warning: Ketamine Not Authorized for the Treatment of Any Psychiatric Disorder

The Food and Drug Administration (FDA) issued an alert last week stating that ketamine is not approved as a treatment for any psychiatric disorders.

The drug, while previously approved by the FDA in some forms and commonly used as an injectable anesthetic in medical facilities, has not yet received approval for treating psychiatric conditions. Although some of ketamine's effects, such as its hallucinogenic property, have been examined for potential therapeutic use in mental health disorders like depression, the FDA does not endorse ketamine as a mental health treatment.

The FDA alert pointed out an increasing trend of people seeking compounded ketamine, which is an altered form of the FDA-approved drug. The use of ketamine for mental health treatment is not only unapproved but could also pose a danger.

According to FDA spokesperson Jeremy Khan, without FDA's premarket review to ascertain safety, efficacy, or quality, "compounded drugs pose a higher risk to patients than FDA-approved drugs".

The article goes on to explain the associated risks of compound drugs like ketamine, why they might be prescribed off-label, and opinions on how the drug could affect future mental health treatments.

Compounded drugs, which include ketamine, are legal in the U.S but operate within certain boundaries. For instance, individuals who can't tolerate FDA-approved versions of a drug may be allowed to take a compounded alternative that doesn't contain a specific non-active element they're allergic to, such as a dye.

Furthermore, the FDA has a drug shortage list, which compounding pharmacies are legally allowed to utilize in order to formulate different ingredients, if necessary, from FDA-approved drugs. Those compounded drugs, however, are not regulated by the FDA. Thus, there's no guarantee that these drugs, bought from a compounding pharmacy, are as advertised.

With ketamine, risks potentially escalate.

Dr. Amit Anand, director of psychiatry translational clinical trials at Brigham and Women's Hospital in Boston and professor of psychiatry at Harvard Medical School, articulated concerns about the rise in homemade usage of the drug due to its compounded production.

Compounding pharmacies often formulate ketamine tablets and nasal sprays that individuals can self-administer at home without medical supervision. Such lack of medical oversight escalates the potential danger associated with side effects.

The recent FDA alert has indicated that ketamine might lead to increased blood pressure, urinary tract infections, and exceptionally slow breath rate. An earlier alert in February 2022 also stated the potential for abuse, sedation, and dissociation as possible risks linked with the drug.

Although ketamine is not officially approved for the treatment of depression, some psychiatrists resort to off-label use. Off-label use involves the application of a drug to treat conditions it's not approved for.

Jeremy Khan from FDA explained that the administration hasn't established the safety and efficacy of an approved drug used for unapproved purposes.

Insurance companies do not cover off-label ketamine treatment due to its lack of FDA-approval, making it expensive and a less popular treatment option among psychiatrists.

Khan emphasized the need for more clinical trials to confirm the potential benefits outweigh the risks before the FDA can endorse ketamine use for psychiatric disorders.

Dr. Anand revealed that people are attempting shortcuts to obtain ketamine through compounding because the FDA has not yet approved it for psychiatric conditions.

Another option other than compounded ketamine is Spravato (esketamine), a version of ketamine that the FDA approved in 2019. It is a nasal spray used to treat treatment-resistant depression in adults as well as depressive symptoms in adults with major depressive disorder who harbor suicidal thoughts or display suicidal behaviors. Spravato can only be used at certified healthcare facilities and comes with its own set of accessibility challenges.

After Spravato administration, patients must remain at the healthcare facility for a two-hour monitoring period due to potential adverse 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.

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.”