Depression: 4-week ketamine injections prove effective

Evan Walker
Evan Walker TheMediTary.Com |
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Inexpensive ketamine injections are effective against treatment-resistant depression, study finds. Image credit: Pansfun Images/Stocksy.
  • Clinical trial participants who had treatment-resistant depression received injections of racemic ketamine or a placebo twice a week over a month.
  • Approximately one in five participants achieved total remission of their symptoms with ketamine, while almost a third saw their symptoms improve by at least 50%.
  • The study was a collaboration between six clinical mood disorder centers in Australia and one in New Zealand.

A growing number of researchers are looking at psychedelics, a range of substances that can alter consciousness, as a possible treatment for depression.

Many are interested, specifically, in ketamine, a drug that has been used as an anesthetic for decades.

The British Journal of Psychiatry recently published a paper on a double-blind trial out of Australia that compared the ability of racemic ketamine to a placebo in reducing the symptoms of treatment-resistant depression.

Treatment-resistant depression is defined as depression that does not respond to two or more lines of treatment.

Participants were randomly assigned to receive injections of racemic ketamine or midazolam, which is often used to help patients relax prior to surgery.

Health practitioners gave injections into the participants’ abdominal walls twice a week for 4 weeks, with at least 3 days off between each treatment.

Participants did not seem disturbed to receive injections in the abdomen, according to Dr. Loo.

“The injection used a very small needle to inject ketamine under the skin,” she said. “It can be done anywhere — arm, leg, abdomen — but we did it in the abdomen because there is usually more fat there under the skin [so] it is more comfortable.”

Neither participants nor researchers administering the drug knew which participants received racemic ketamine. Midazolam was chosen as the placebo because like ketamine, it causes sedation, which helped to keep participants from knowing which drug the would receive.

Initially, 73 participants were randomized to receive a fixed dose of either 0.5 milligrams per kilogram of racemic ketamine or 0.025 milligrams per kilogram of midazlolam.

At a routine Data Safety Monitoring Board meeting “a revisiting of drug dosage was recommended as no participants in the entire masked sample had remitted and the safety profile was good,” write the authors of the study,

As a result, dosing was revised and in a second group, 108 participants were randomized to receive flexible dosing of ketamine or midazolam. A response-guided dosing was implemented. If patients had not improved by 50% from baseline scores in sessions two, four, or six, racemic ketamine doses were escalated to 0.6 milligrams per kilogram, 0.75 milligrams per kilogram, and 0.9 milligrams per kilogram. Participants receiving midazolam also received escalated doses.

Participants were included in the trial if they received at least one injection. The study authors note that “most” received all eight doses.

Dr. David Mahjoubi, the medical director at the Ketamine Healing Clinic of Los Angeles and Orange County, not involved in this study, stressed to MNT that the trial looked at delivering racemic ketamine through injections.

“So that’s different than the IV [intravenous] form because you don’t enter that dissociative experience, which we believe contributes at least something to the therapeutic mechanism.”
— Dr. David Mahjoubi

Additionally, Dr. Mahjoubi noted that not all participants in the trial received the same number of racemic ketamine injections, “[s]o that’s one huge variable.”

“People with the same number of [injections] should have been compared,” advised Dr. Mahjoubi.

The physician, who opened his first clinic eight years ago, has found patients often do not benefit from ketamine after the first or second infusion. “It takes three or four infusions,” he said.

He suggested more participants might have seen their symptoms improve if they had all received all eight injections.

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