Ketamine Can Treat Depression By Altering a Person’s Beliefs, Study Suggests

Ketamine can help people with treatment-resistant depression (TRD) by breaking their entrenched belief systems, according to a recent paper.

Researchers from the Pitié-Salpêtrière Hospital in France administered ketamine, on three separate occasions, to 26 people with TRD. After receiving their ketamine, the participants were asked to estimate the likelihood of certain “bad” life events, such as developing cancer.

The research team observed that the “depressed” participants given ketamine were more optimistic than the control group, who didn’t have TRD.

The researchers’ findings were published in JAMA Psychiatry.

A new way of thinking

To get their findings, the researchers recruited 56 patients, 26 with TRD and 30 without, from the Psychiatry Department of the Pitié-Salpêtrière Hospital, Paris.

All patients received three intravenous infusions of ketamine (0.5 milligrams per kilogram) over a week. “Belief updating” tasks were given 24 hours before the first injection, four hours after that, and then four hours after the third injections.

These tasks asked the patients to estimate the likelihood of experiencing an unfortunate life event, such as a cancer diagnosis, in the future. All participants were then informed of the actual likelihood of such an event happening.

The patients were also screened for depression using a standard depression rating scale.

When looking back through the results, the researchers found that, four hours after their first ketamine infusion, patients with TRD updated their beliefs more often after good news than after bad news relative to their baseline levels and testing in the controls who didn’t have TRD.

Patients who displayed stronger “optimism biases” in belief updating were also those who displayed fewer depressive symptoms.

Indeed, the researchers found that ketamine induced a rapid reduction in depression scores four hours after the first injection. Even one week on from the first infusion, depression scores stayed significantly lower than their baseline. One patient with TRD went into remission and five showed a treatment responsiveness at one week after treatment.

Ketamine therapy

The Pitié-Salpêtrière study is far from the first to investigate ketamine’s anti-depressive effects.

Published in the BMJ earlier this year, one study found that many patients hospitalized for severe suicidal ideation reached full remission when given ketamine infusions.

Another study, published in Journal of Psychiatric Research last year, found that individuals with TRD who received ketamine therapy went on to experience a greater reduction in suicidal ideation than those on antidepressants with adjunct ketamine.

How can ketamine produce such results? Recent research has identified dendritic spines in the brain as being a key site of action for ketamine’s effects. Dendritic spines are small membranous protrusions that extend off a neuron’s dendrite. In mouse experiments at Yale University, mice tended to have fewer dendritic spines in their frontal cortex when they were experiencing chronic stress. But after a single dose of ketamine, many of these spines were restored.

“[With] the ketamine, even though only a single dose was administered, you see a reversal of these dendritic spines,” Alex Kwan, an associate professor of psychiatry at Yale University, told Analytical Cannabis earlier this year.

“So there’s a loss with stress and then a restoration with ketamine, which is very exciting because it seems like the single dose of ketamine, at least structurally, was able to reverse the atrophy that we’re seeing out of chronic stress.”

“Perhaps psychedelics, through the increase in the formation of dendritic spines, could improve the integration of new experiences,” he added.