Experts are cautiously optimistic a drug related to ketamine, recently approved by the US Food and Drug Administration, could be a “watershed” moment in the treatment of depression, and one of the first drugs to be a “rapid acting” medicine to treat the chronic disease.
The new drug, called esketamine, will be sold under the brand name Spravato, and was approved to treat people with depression who don’t respond to traditional psychiatric drugs.
“For a long time, all our standard antidepressants have been ‘me too’ drugs,” said Dr Walter S Dunn, a professor of psychiatry at the University of California Los Angeles, and a member of the FDA advisory committee which recommended the drug be approved.
“As much as the companies like to say our drug is better than the next, they were pretty much all the same,” said Dunn, referring to brand name drugs which work on similar pathways in the brain, such as selective serotonin re-uptake inhibitors like Prozac.
The newly-approved drug builds on years of research into ketamine as a treatment for major depression. Ketamine has long been seen as a safe drug for anesthesia, and has recently developed as a treatment for depression.
“All the medicines have been operating under the same mechanisms so it was time to explore some of these other compounds that, yes, have been associated with recreation and abuse as potential pathways or compounds to treat depression,” said Dunn.
The drug’s approval, while greeted favorably within the psychiatry community, has raised a host of new questions about accessibility for US patients.
How would the new treatment work?
Psychiatrists such as Dunn believe the drug could be the first in a class of so-called rapid acting depression treatments, because their effects would be felt within hours or days, not weeks like traditional depression treatments.
Although the mechanism at work in the brain is not clearly understood, ketamine, which is typically used as an anesthetic, has been used in clinics intravenously to treat depression since the early 2000s. However, it still has the potential for abuse, once known as a party drug nicknamed Special K, since it can cause what psychiatrists call a “dissociative” or out-of-body experience.
For that reason, patients will not be able to take the drug home. Esketamine will have to be administered in an approved clinic, and patients will be required to stay there for at least two hours, and not allowed to drive until after a night of rest. The FDA advisory committee hopes this will also prevent the drug from entering the black market.
Will it be widely available?
There are a number of possible barriers to widespread use of the drug, including the need for it to be administered in a clinical setting. Patients will need to stay at a clinic for two hours, twice a week, with possible boosters of the drug.
The time commitment could be a logistical challenge for doctors and patients alike, who would need to set aside a significant amount of time to be treated. As well, it’s unclear how widely insurance companies will cover the drug, which is expensive at between $4,720 and $6,785 in the first month.
While studies for esketamine included patients who did not respond to two traditional antidepressant treatments, it’s possible insurance companies could further restrict the group of people who have payment approved for the drug. For example, they could require patients fail to respond to four traditional antidepressants.
If ketamine is generic, why not use that?
Economics thwarted ketamine’s widespread use. Without an FDA-approved use for ketamine as a depression treatment, insurance companies did not cover the drug. And because it had long been generic, drug companies did not see it as a way to make money, and did not fund the clinical trials necessary to have it approved specifically to treat depression.
Therefore, without any drug companies applying to sell the drug, it was relegated to a relatively small number of clinics running cash operations, and delivering ketamine intravenously.
However, Dunn said it is possible ketamine could become a more broadly accepted treatment for depression because of the approval of esketamine. Doctors may see data about esketamine, and work with compounding pharmacies to make a ketamine nasal spray much like the delivery system for esketamine developed by Janssen Pharmaceuticals, an arm of Johnson & Johnson, Dunn said.
What does this mean for the treatment of depression?
With other new rapid-acting drugs to treat depression in development, Dunn believes esketamine could be seen as paving the way for a new class of drugs for depression treatment.
“This is really the first, and there are several in various phases of development, and over the next couple years you will see more coming out on the market,” said Dunn.
The biggest challenge psychiatrists will face, Dunn said, is much the same as the one they face now: keeping patients in treatment.
“The challenge we’ve all faced in psychiatry is keeping people on their medications,” he said. “Patients have gotten better, they don’t have symptoms anymore, so why take the medication?”
“The more barriers, or difficult it is to take a medication in the maintenance period, the less likely they’re going to take it,” he said. “The barrier is going to be coming in, taking two hours out of your day. That we might see as more of a problem.”