Ketamine shows promise against treatment-resistant depression in trial

By Sarah D. Collins Health Day Reporter

TUESDAY, July 18, 2023 (HealthDay News) — Dr. And IosifescuThe patient had a history of depression and had been doing well for several years. But the disease returned with a vengeance.

“They really tried to get better with a series of different drugs, and none of them did anything. On the contrary, they were experiencing a lot of side effects,” Iosifescu said, rendering them “unable to participate in their normal life routines, becoming more estranged from their families, unable even to do their daily routines”.

Then the patient was given ketamine and everything changed.

“The ketamine treatment over a period of just a few weeks was dramatic, basically a 180 degree resolution of all these symptoms where the person miraculously returned to their previous level of functioning and their previous level of relatively good mood,” said Iosifescu, professor of psychiatry at NYU School of Medicine in New York.

Ketamine has been studied for several years as a way to treat depression, a leading cause of disability worldwide. The drug is a “dissociative” anesthetic.

A new study from Australia and New Zealand has found that an inexpensive version of ketamine helped 20% of participants with severe depression achieve complete remission of their symptoms, while a third saw their symptoms improve by at least 50%. In comparison, only 2% of the control group achieved complete remission of their symptoms. The trial is the largest in the world to date to compare generic ketamine to a placebo for severe depression, the researchers said.

For the study, the researchers recruited 179 people with treatment-resistant depression, including those who had received electroconvulsive therapy – generally considered a last resort – with unsuccessful results. All participants were injected with ketamine or a placebo twice a week for one month. Neither the patients nor the researchers administering the drug knew what the patients were receiving. Participants also received a flexible dosage.

“The study showed that individualized dose adjustment, based on clinical response, was very important to optimize the benefits of ketamine,” said Dr. Colleen Looprincipal investigator of the study and professor of psychiatry at the University of New South Wales in Australia.

“In my opinion, ketamine is the most effective treatment for depression in the past 80 years,” she said. “Interestingly, effective treatments for depression [ECT, ketamine, medications, and also psychedelics] have similar effects on the brain at a microscopic level, improving brain cell health [neurons] and their ability to communicate with each other, and at a macro brain level, changing the way the brain works at the circuit level.

Iosifescu, who was not part of the study but was quoted in it, said the speed of ketamine also brings out the method of treatment.

“One of the problems with treating depression is that even when traditional antidepressants work, they take weeks or even months before they actually offer clinical benefit,” he said. “And you can’t even tell if something is going to help or not until you’ve waited six or eight weeks to see if there’s a difference. And with ketamine, you can actually see the effects a lot more faster than that.”

But while ketamine’s benefits for depression are largely undisputed at this point in the medical field, several hurdles remain for the drug.

For one thing, not everyone can benefit from ketamine, and some people aren’t suited to the drug, especially those with psychotic disorders. The effects also wear off relatively quickly, requiring indefinite continued treatment. And ongoing treatment may be inaccessible at this stage, as each administration takes a long time and most ketamine treatments are very expensive. In Australia, where the study took place, the patented S-ketamine nasal spray costs about $800 per dose and about $300 for medical care to ensure the experience is safe.

For this study, scientists used generic ketamine which costs as little as $5, but with the added cost of medical care, a session can cost around $350 in Australia.

In the United States, insurance is unlikely to cover the cost of treatment because ketamine is prescribed “off-label”, so costs can vary, but average several hundred dollars per infusion .

“The main hope is that there would be a similar compound that could be taken orally and that people could take themselves at home,” Iosifescu said. “And even if it’s not as 100% effective, it would be helpful to kind of continue those initial positive benefits that ketamine got.”

In his mind, this is the most important next step. “Several companies are working on ketamine-like molecules that would be administered orally. Some of them are quite advanced in their development,” Iosifescu said, but their effectiveness has yet to be proven.

SOURCES: Dan Iosifescu, MD, professor, department of psychiatry, NYU Grossman School of Medicine, New York; Colleen Loo, MBBS (Hons), FRANZCP, MD (Research Doctorate), Professor, Psychiatry, University of New South Wales and Black Dog Institute, Sydney, Australia; British Journal of Psychiatry, July 13, 2023

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