Medical Technology

Single Infusion of Ketamine Rapidly Reduces Suicidal Thoughts

A single dose of ketamine rapidly improves distorted thinking and reasoning to reduce suicidal thoughts, independent of the drug’s effects on severe depression, new research shows.

“It was previously demonstrated that ketamine quickly improved depression, and that explained part the rapid improvement in suicide thoughts,” J. John Mann is the senior author of the study at Columbia University in New York City said in Medscape Medical News.

“What else could be done to decrease suicidal thoughts, and reduce the risk of suicidal behavior was not clear. This study suggests a new area of improvementthe rapid improvement of several cognitive functions that could potentially lower suicide risk,” said Mann.

The study was published online in the Journal of Clinical Psychiatry on November 2.

Enhances Cognitive Function

A total of 78 people with major depression and clinically significant suicidal thoughts were tested prior to and after double-blind treatment that included an intravenous infusion of ketoamine and midazolam..

“Ketamine produced rapid improvement in suicidal ideation and mood” when compared to midazolam, the authors wrote.

The specific increase in reaction speed and cognitive control/interference processing was correlated with ketoamine, an indicator that has been linked to prior suicide attempts in depression.

A subset of patients suffering from suicidal thoughts that didn’t be resolved with midazolam treatment were treated with ketones that were not blinded and retested. The patients showed improvement in reaction time and cognitive control/interference handling when compared to pre-ketamine tests.

Neurocognitive improvement, however, was not correlated with changes in depression, suicidal thought, or general mood, as the researchers point out.

However, they claim that ketamine had the effect of having a “positive therapeutic effect” on the neurocognitive process after treatment of at least one measure related to suicidal behavior in depression.

The results suggest “additional therapeutic effects that are independent of Ketamine in the treatment of patients with depression at risk for suicidal behavior,” they write.

“Ketamine regulates many neurotransmitter systems, including glutamate transmission, which is crucial for memory and learning. It increases the number of connections between neurons. These effects are fundamental to cognition and are rational explanations for the positive results observed in this study,” Mann told Medscape Medical News.

“Our study has helped us gain an understanding of how ketamine operates in the brain and how quickly it can help improve distorted thinking. Being able to think more clearly can help someone feel less suicidal” study lead researcher Ravi. Columbia Psychiatry’s chief innovation officer, N. Shah, MD said in a news release.

Important Research With Caveats

Contacted for comment, James Murrough, MD Director, PhD Depression and Anxiety Center for Discovery and Treatment at Mount Sinai in New York City, said the research is important and “adds to the increasing understanding of the way ketamine affects brain systems and thinking in the context of depression and suicide risk.”

“One reason this study is significant is that previous studies have demonstrated that ketamine may have negative effects on cognitive functioning in the context of ketamine misuse and exposure to high doses for prolonged periods of time.” Murrough, who wasn’t involved in the study told Medscape Medical News.

“In contrast to this study the study found that a single treatment of ketamine can have the opposite effect, actually increasing some markers of cognitive functioning at least for a short time,” he noted.

Murrough said that one limitation to the study was that it only looked at the effects of ketamine cognition on one day after a single treatment.

Murrough stated that , although this is an important observation but we don’t know how long-lasting this effect on cognition might be, or how this observed change could be related to any benefit ketamine might have on depression or suicide risk.

“In fact, the researchers found that there was no link between change in cognitive functioning following ketamine treatment and the development of depression or suicidal thinking. Murrough declared that patients who had higher cognitive function following ketamine showed not differ in their suicide risk or mood as compared to those who did not.

“This raises the question of the relevance of altering cognition to the potential benefits of ketamine. This is an important area and should be the focus of future research to improve the outcomes of patients suffering from depression and who are at risk for suicide,” he added.

The study also has a voice, Roger McIntyre, MD who is a professor of psychiatry as well as psychopharmacology and the head of the Mood Disorders Psychopharmacology Unit, University of Toronto, Canada said the study is “very interesting and in keeping” with earlier work that he and his colleagues have done to prove that the ketamine “seems to improve aspects of cognition which is a core element in depression.”

McIntyre said, “It’s a testable hypothesis. It could play a role in the improvement of quality and efficiency of this treatment. And as well as reduce suicide.”

This study was funded by the National Institute of Mental Health. Mann is paid royalties for commercial use of Columbia-Suicide Severity Rating Scale. This scale was not used in this study. Murrough’s Mount Sinai institution was involved in research that involved esketamine (Spravato) for treatment-resistant depression. Mann also receives financial remuneration from the manufacturer of esketamine. McIntyre has been awarded research grants from the CIHR/GACD/Chinese NNR Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and Abbvie. McIntyre also serves as CEO of AltMed.

J Clin Psychiatry. Published online on November 2 2021. Abstract

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