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Ketamine Therapy Rapidly Reduces Suicidal Ideation, Study Finds

By Alexander Beadle

Published: Feb 11, 2022   
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Patients hospitalized for severe suicidal ideation could benefit from ketamine transfusions, according to new research led by scientists at the University of Montpellier.

Published in the BMJ, the research involved a double-blind, randomized placebo-controlled trial in which one group of participants received a placebo while another group received two ketamine infusion therapy sessions. By the end of the trial, more participants in the ketamine-group reached full remission from suicidal ideation compared to the placebo group.

This result, the researchers say, suggests that some patients struggling with suicidal thoughts may benefit from ketamine – especially those patients with bipolar disorder, who saw the largest benefit following ketamine therapy and have few other available treatment options.

Ketamine appears to relieve psychological pain

The trial took place in seven French teaching hospitals between April 2015 and March 2019 and involved a total of 156 adult patients who had voluntarily been admitted to hospital with current suicidal ideation. These patients were given either a 40-minute intravenous infusion of ketamine or a placebo, followed by the same treatment again 24 hours later.

The effect of the treatment was measured at day three by researchers using a 19-item clinician rated scale for suicidal ideation. Total scores of three or less (where individual items scored from zero to two) were interpreted as the patients being in full suicidal remission.

The researchers found that more participants receiving ketamine reached full remission at day three than those receiving placebo – approximately 63 percent of the ketamine group versus just 32 percent of the control group.

When the assessment was repeated at week six, remission in the ketamine group remained high but was not statistically significant as compared to the placebo group.

To try and better understand ketamine’s effect on mental health crises, the researchers also administered a patient-rated version of the suicidal ideation scale. Improvements in suicidal ideation appeared to be mediated by feelings of psychological pain, suggesting that ketamine’s effectiveness in combatting suicidal ideas may be explained by some analgesic action for psychological pain.

Study “challenges our current insights” on ketamine

The patients enrolled in the study were also subdivided based on whether they had been previously diagnosed with bipolar disorder, any depressive disorder, or other mental health disorders. When examining the study findings, the researchers saw that the effect of ketamine on suicidal ideation varied according to the patient’s diagnosis.

The patients with bipolar disorder benefited greatly from the ketamine infusions, however those with a depressive or other mental health disorder saw no statistically significant improvements.

“This unexpected outcome perhaps defies the prevailing notion that patients with major depression would benefit most from ketamine,” wrote Riccardo De Giorgi, a Wellcome Trust doctoral training fellow at the University of Oxford, in a BMJ Editorial accompanying the research article.

“In fact, both usual care and ketamine given with usual care led to low, comparable remission rates of 35.7% and 42.3% for suicidal ideation, respectively, in patients with depressive disorder.”

“While this study therefore confirms that many patients with depressive disorder and suicidal ideation remain poorly served by available treatments, it shows that another important group of patients with acute suicidal ideation, those with bipolar disorder, could benefit from ketamine,” De Giorgi concluded.

Will ketamine become a treatment for people in crisis?

This study is one of the first to measure the effect on suicidal ideation through studying the number of patients reaching remission, rather than those that showed response (a 50 percent reduction in symptoms). The study size was also relatively large and no significant side effects or safety risks were reported. However, the study authors do note some major limitations.

Firstly, although this is not the first study to examine ketamine’s usefulness in combatting suicidal ideation, it was conceived in 2013 and so there are some facets of the study that could be more modernized. For example, saline solution was used as the point of comparison for ketamine rather than midazolam, which has served as the comparator in more recent ketamine studies. Since 2013, esketamine, an s-enantiomer of ketamine, has also been approved by the European Medicines Agency for use in treatment-resistant depression; the fact the study worked with ketamine rather than esketamine (or both) reflects its long gestation.

As De Giorgi points out in the accompanying editorial, ketamine trials do still matter even though esketamine has been widely approved.

“[E]sketamine trials have not been able to fully replicate the positive findings on suicidality reported for ketamine,” he wrote. “Although this might change, it raises the possibility that these two compounds have distinct pharmacological activity profiles, and therefore underlying distinct clinical effects.”

Perhaps the more important question to be asked is whether ketamine will ever become the fast-acting anti-suicidal therapeutic that is suggested by these studies. There is a certain amount of societal pressure at play here – there are plausible concerns that widespread ketamine use could trigger another opioid crisis – and so more work is still needed to investigate the safety and actions of ketamine.

“Whether ketamine reduces suicidal ideation in some people is a matter of evidence — which this trial by Abbar and colleagues provides,” De Giorgi wrote. “But whether the emergency use of ketamine for suicidal crises will be recommended in practice depends on many other factors, including the values and preferences of patients, clinicians, researchers, and policymakers.”


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