Was ketamine therapy approved too quickly?

The FDA keeps making the same mistakes

In March 2019, the FDA approved ketamine, under the trade name Spravato (esketamine), for clinical use in treatment-resistant depression therapy. Alongside racemic ketamine, which is commonly used in ketamine infusion therapy, ketamine is the first hallucinogen approved for therapeutic usage in the United States.

While anecdotal reports of success matter, the industry has been plagued with problems.

• First, as we’ll see below, the FDA trials appear to have been rushed—with troubling results in the public record.

• Secondly, when 13 clinics were quickly shuttered earlier this year, hundreds of patients were left with nowhere to turn, highlighting the challenges of adding new therapies, with tons of investment dollars, into a for-profit healthcare system.

While ketamine falls under the umbrella of “psychedelic therapy,” it’s not a psychedelic but rather a hallucinogen and dissociative. (While ketamine has psychedelic effects, traditional psychedelics bind to the 5-HT2B receptor.) Still, advocates for psychedelic therapy recognize ketamine as a gateway for traditional psychedelics, such as psilocybin and LSD, to be considered for therapeutic usage.

To understand the proliferation of ketamine clinics across North America, the origins of this peculiar substance—one that went from battlefields to veterinary clinics to dance clubs in the span of two decades—must be discussed.

Then we’ll look at the problems with the approval process.

History of ketamine

In 1962, chemistry professor Calvin Stevens synthesized ketamine while researching alpha-hydroxyimine rearrangements. The first human tests were conducted on prisoners in 1964. Ketamine soon replaced phencyclidine (PCP) as the go-to anesthetic in hospitals. It was initially used on soldiers during the Vietnam War following FDA approval in 1970. Thanks to its success on the battlefield, ketamine was placed on the World Health Organization’s List of Essential Medicines.

Ketamine has been used broadly as a sedative and anesthetic; to aid in emergency surgeries in war zones; as a bronchodilator for severe asthmatics; to treat certain types of seizures; and in postoperative pain management. Now, ketamine infusions and nasal sprays are being used for depression. Ketamine is also showing potential efficacy in treating chronic pain and suicidal ideation, though more research needs to be done.

Of all of those uses, ketamine has predominantly been used as an anesthetic in humans and animals. While it restricts breathing less than other similar medications, ketamine also produces hallucinations (thus, it’s labeled as a dissociative anesthetic). The list of potential side effects from using ketamine is long, including nausea, double vision, breathing problems, impaired memory, liver enzyme abnormalities, urinary tract problems, and even increased depression — an alarming possibility given its growing use as an antidepressant replacement.

Small-scale studies on using ketamine to treat depression were conducted in 2000 and 2006. Further research confirmed its role in alleviating depressive symptoms, including the possibility that the antidepressant effects of a single dose can persist for weeks. In 2016, the FDA fast-tracked ketamine trials for depression.

Fast-tracking drugs is important, especially when current protocols are not efficacious. Yet this process also opens the doors for unintended consequences.