Ketamine Clinics Diverge From APA Recommendations

The proliferation of ketamine clinics in the U.S. has veered far off course from the recommendations of the nation's premier psychiatric association when it comes to using the anesthetic to treat mood disorders, experts say.

In 2017, the American Psychiatric Association (APA) issued a consensus statement on the use of ketamine in treating mood disorders, published in JAMA Psychiatry.

But the ketamine clinics cropping up across the U.S. don't appear to follow that guidance, Smita Das, MD, PhD, MPH, of Stanford University and a spokesperson for the APA, told MedPage Today.

"[Intravenous] ketamine is being offered in smaller clinics off-label and there isn't a practice guideline from the American Psychiatric Association that's recommending ketamine for use in the way that it's being used," Das said, noting that these clinics -- which tend not to involve psychiatric or mental health professionals -- often tout ketamine as a "miracle treatment."

She said the surge of ketamine clinics is something of a "wild west" where vulnerable patients are being offered treatment without being informed of the downsides.

Only one ketamine product -- the nasal spray esketamine (Spravato), made by Johnson & Johnson -- has been approved for treating a mood disorder by the FDA. It's specifically indicated for use in conjunction with an oral antidepressant for adults with treatment-resistant depression. In addition, it's only available through a Risk Evaluation and Mitigation Strategy (REMS) program.

Yet those restrictions and cautions seem to have little impact on the public demand for ketamine in mood disorders.

APA members have raised concerns about patients taking ketamine outside of their prescribed treatment regimens, Das said.

There's also been an increasing number of psychiatrists who have said that perhaps they should be more involved with these clinics, at the very least to help guide best practices and treatment decisions, as these clinics don't always employ mental health professionals, she noted.

Other members have expressed an interest in learning more about when ketamine may be appropriate for their patients, she added.

The organization has developed some continuing medical education (CME) courses about ketamine, including one titled, "Ketamine for Depression: Is the Hype Holding Up?"

For now, the best guidance for practice is the 2017 consensus statement, Das said. It was drafted by the APA's Council of Research Task Force on Novel Biomarkers and Treatments, and that group continues to monitor trends in ketamine use as well as the body of evidence behind it. Das said she expects the council will update the guidance when there's sufficient additional evidence.

The 2017 statement focused on data from seven published placebo-controlled, double-blind randomized clinical studies on ketamine infusions for depression, totaling 147 patients -- an exceedingly small number.

It details expectations for appropriate clinical training, dosing, and treatment setting, and notes important key components of using ketamine for mood disorders, including a comprehensive diagnostic evaluation; a thorough review of depression severity, past responses to medications, and medical status; and informed consent including review of alternative treatments and discussion of IV ketamine as an off-label treatment.

Clinicians delivering the treatment should be licensed to administer Schedule III medication and obtain an Advanced Cardiac Life Support certification, it states. Ketamine should also be administered in facilities equipped to monitor basic cardiovascular and respiratory function, including access to electrocardiograms and end-tidal CO2 monitors. And facilities should be able to stabilize patients in the event of a respiratory event.

Since the 2017 guidance, additional studies have been published, including one in the New England Journal of Medicine that found ketamine equivalent to electroconvulsive therapy in treatment-resistant major depression. However, the APA has not confirmed a timeline for an updated literature review and, thus, updated guidance.

The organization currently stands by the 2017 guidance, which it says remains sound. Nonetheless, Das warned that it's not frequently followed by ketamine infusion clinics.

Robert Freedman, MD, of the University of Colorado School of Medicine and a former editor of the APA's American Journal of Psychiatry, cautioned that the booming use of the drug, without enough guardrails to ensure patient safety, could ultimately spell its end in psychiatric indications.

"We just have to be careful that it doesn't become a drug that has its usefulness curtailed because there are people who are having so many bad reactions," Freedman told MedPage Today.

He noted that the FDA has limited regulatory authority when it comes to using ketamine in mood disorders. The agency released a compounding risk alert for ketamine in October, in response to the rise of compounding pharmacies producing unregulated versions of the drug. That alert emphasized that ketamine is not approved for treatment of any psychiatric condition. The agency also published a similar alert 2 years ago.

In a statement to MedPage Today, the FDA reiterated that ketamine "is not FDA-approved for the treatment of any psychiatric disorder. However, we are aware that some healthcare providers may be prescribing ketamine for psychiatric disorders when they judge that it is medically appropriate for their patient."

"We are not aware of sufficient evidence to suggest that ketamine is safer, more effective, or works faster than medications that are FDA-approved for the treatment of certain psychiatric disorders, including depression," the statement continued. "We continue to monitor data and evidence, which we will use to identify additional regulatory actions and non-regulatory activities as appropriate."

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