Drinking Ketamine Effective Against Treatment-resistant Depression, Israeli Study Shows

Scientists have found that ketamine relieves the symptoms of depression immediately and keeps them at bay for up to a week

A syringe sits in a bottle of ketamine in an operating room.
Brent Lewin/Bloomberg

A new Israeli study shows that using ketamine to treat depression is effective when the drug is administered orally, not just intravenously, which would make the drug more accessible and less complicated to use.

The study also found that ketamine has an immediate effect on the symptoms of depression and its influence lasts for up to a week after treatment is administered.

Ketamine, which was first synthesized during the 1960s, has been in use for some 50 years as an anesthetic and sedative for both people and animals. One of its medical advantages over other anesthetics is that it has a less depressive effect on the respiratory system. Over the past several years, an increasing number of studies have shown that a dose of ketamine administered intravenously is effective in patients with persistent depression that do not respond to conventional therapies.

>> Down the K-hole: How ketamine became Tel Aviv's drug of choice

Both formal reports from clinical trials as well as anecdotal reports indicate that treatment with ketamine significantly improves patients’ quality of life. The fact that ketamine is already in use by the medical establishment alleviated some of the concerns about its safety, and made it accessible to doctors for therapeutic as well as research purposes; today there are Israelis being treated with it in hospitals and public clinics, and even in private clinics in the central region. Treatment until now has been by intravenous infusion.

Now a new study shows that ketamine is effective and safe when given to patients as a liquid in the appropriate dose. The study, published in the British Journal of Psychiatry, was conducted at Ichilov Hospital in Tel Aviv, led by Dr. Yoav Domany, Dr. Haggai Sharon, and Dr. Maya Bleich-Cohen of the psychiatric department and the hospital’s Institute of Brain Research.

The study involved 41 patients, men and women aged 18 to 75, who suffer from treatment-resistant depression. The subjects were divided randomly into a test group and a control group that was treated with a placebo. This was a double-blind study, meaning that neither the patients nor the researchers knew who was getting ketamine and who was getting the placebo.

The patients were treated for 21 days, three times a week, with the researchers monitoring the subjects’ conditions at different points in time – 40 minutes after taking the drug, four hours after, and then during the subsequent days. The outcome was measured using the Montgomery–Åsberg Depression Rating Scale, a commonly used scale for evaluating depression symptoms, including sadness, fear, apathy, suicidal feelings, lack of energy, sleep problems and lack of appetite.

After 21 days, the subjects treated with ketamine showed a 12.75 point drop in their MADRS score, compared to 2.49 points among those getting the placebo. For six of the 22 patients who received ketamine (27 percent), the symptoms of depression disappeared entirely. “One of the things that surprised us was that we saw a positive influence up to seven days after treatment, even though ketamine is a drug that exits the body very quickly,” Domany said.

Oral administration of ketamine is obviously more practical than intravenous treatment. Might this make ketamine doctors’ go-to drug for treating depression as opposed to conventional treatments?

“I doubt that ketamine will become the drug of choice for depression,” Domany said. “There are also risks. Ketamine is also a street drug and that’s a concern, particularly given the way use of opiate pills has become an epidemic in the United States. Ketamine helps patients but it isn’t totally innocent.

“What is true is that conventional drugs take at least three weeks until their effect is felt; ketamine could provide a bridge until that full effect [kicks in],” he said.