Dr. Dan Iosifescu’s patient had a history of depression and had done well for a number of years. But the illness returned with a vengeance.

“They truly tried to get better with a series of different medications, and none of them did anything. If anything, they were experiencing a lot of side effects,” Iosifescu said, rendering them “unable to take part in their normal life routines, becoming more estranged from their family, unable to do even their daily routines.”

Then the patient was given ketamine, and everything changed.

“The treatment with ketamine over a span of just a few weeks was dramatic, essentially 180-degree resolution of all these symptoms where the person, as if by miracle, essentially returned to their previous level of functioning and previous level of relatively good mood,” said Iosifescu, a psychiatry professor at NYU School of Medicine in New York City.

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

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

For the study, researchers recruited 179 people with treatment-resistant depression, notably including those who had received electroconvulsive therapy — usually considered a last resort — with unsuccessful results. All participants received an injection of either ketamine or a placebo twice a week for a month. Neither the patients nor the researchers administering the drug knew what patients were receiving. The participants were also given flexible dosing.

“The study showed that individualized dose adjustment, based on clinical response, was very important in optimizing the benefit of ketamine,” said Dr. Colleen Loo, lead researcher of the study and a professor of psychiatry at University of New South Wales in Australia.

“In my opinion, ketamine is the most effective treatment to emerge for depression in the last 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, enhancing the health of brain cells [neurons] and their ability to communicate with each other, and at a macro brain-level, changing the way the brain functions at a circuit level.”

Iosifescu, who was not part of the study but was cited in it, said ketamine’s speed also makes the treatment method stand out.

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

But while the benefits of ketamine on depression are largely unquestioned at this point in the medical field, several obstacles for the drug remain.

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

For this study, the scientists used generic ketamine that costs as little as $5, but with the added cost of medical care a session can be 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 they average several hundred dollars per infusion.

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

In his mind, that’s the most important next step. “There are several companies working on ketamine-like molecules that would be administered orally. Some of them are fairly advanced in development,” Iosifescu said, but they still have to be proven effective.

The study was published July 13 in the British Journal of Psychiatry.

More information:

Harvard Health has more on ketamine.

SOURCES: Dan Iosifescu, MD, professor, department of psychiatry, NYU Grossman School of Medicine, New York City; 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