CTInsider article:
Jayesh Kamath said the use of ketamine therapies for treatment of depression could be “groundbreaking.”

“We’ve been stuck with antidepressants for decades,” he said.

Kamath is a professor of psychiatry at the University of Connecticut Health Center. He said traditional antidepressants can take weeks or even months to take effect.

“When we give people antidepressants we say, ‘I’m sorry, it’s not going to work for four to six weeks, and it may not work at all. So you have to wait,” he said. “They come back after four weeks and say, ‘I’m not better.’ Then we try another one. And then try another.”

Ketamine, particularly the form of it that can be administered as a nasal spray called esketamine, works almost immediately. Kamath said it makes a “huge difference.”

“When esketamine works, it works in hours and days,” he said. “That and that’s why the suicidality studies work because people came in they were suicidal and in the suicidality resolved.”

The value of ketamine as a treatment for mental health is well known. It is traditionally used as a sedative, but as Kamath noted, it’s been used off-label, administered intravenously, to treat depression.

There are already clinics that treat patients suffering from depression with intravenous ketamine, even though it technically is off-label use.

After drug-maker Janssen developed esketamine years ago, supported by studies that included Kamath’s group at UConn, federal regulators approved it in 2019 for clinical use to treat depression.

“Intranasal esketamine is an on-label, approved, FDA-approved use for treatment of depression,” Kamath said.

Known also as a street drug, the U.S. Department of Justice describes ketamine as “a dissociative anesthetic that has some hallucinogenic effects.”

“It distorts perceptions of sight and sound and makes the user feel disconnected and not in control,” the DOJ says on its website.

Kamath and his group at UConn are part of studies examining the use of esketamine formulations that do not have any hallucinative properties. Those euphoric effects make the drug addictive.

“There are compounds by other companies, and we are involved in those studies, which separate the dissociative or euphoric effects from the antidepressant,” Kamath said. “That’s where the real promise is.”

There are two problems with the hallucinatory effects of ketamine. First, there are side effects. For some people, the hallucinations are too much to handle.

“They can’t tolerate the dissociation,” Kamath said. “It’s a completely terrifying experience for them.”

Those side effects may be worth it, Kamath said, for patients with severe depression: “If they have struggled all of their life and they’re on multiple medications, and still sometimes end up in the hospital, if a person like that gets better with the medication, even with the with some dissociative effects, and stays better, can come off of their medications, no hospitalizations and a good level of functioning? Why not?”

But the risk of addiction is real. So significant that Kamath won’t allow a patient to take part in a study if they have any recent history of drug use.

“When we enroll patients in our studies, there are very strict criteria, especially in terms of vulnerability to substance use,” he said. “If they’re using any kind of drugs, including marijuana, if they meet a certain threshold, they can’t even participate in the studies.”

That’s not a concern for every patient. Kamath said he tells students that “there is a patient, there is a medication. There is a medication for a patient and there is a patient for a medication. Not every medication works for every patient.”

But he’s excited about what esketamine without the dissociative effects could mean. Studies are ongoing, and he said he expects a conclusion within five years.

“Just that step, that things can work in hours and days, is revolutionary for our field,” he said.