SUICIDALITY | +40 articles

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Dr J. John Mann

Single infusion of ketamine rapidly reduces suicidal thoughts

by Megan Brooks | Medscape | 11 Nov 2021

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

"Previously it was shown that ketamine rapidly improved depression and that explained part of the rapid improvement in suicidal ideation," senior author J. John Mann, MD, with Columbia University in New York City, told Medscape Medical News.

"What was unclear was what else changed that could decrease suicidal ideation and the risk for suicidal behavior. This study identifies a second new domain of improvement — namely rapid improvement in several cognitive functions that can potentially reduce suicide risk," said Mann.

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

Boosts cognitive function

A total of 78 adults with major depressive disorder and clinically significant suicidal ideation underwent neuropsychological testing before, and 1 day after, double-blind treatment with a single intravenous infusion of ketamine or midazolam.

"Ketamine produced rapid improvement in suicidal ideation and mood" compared with midazolam, the authors report.

Ketamine was linked to specific improvement in reaction time and cognitive control/interference processing — a measure that has been associated with previous suicide attempt in depression.

A subgroup of patients whose suicidal ideation did not remit on midazolam were later treated with unblinded ketamine and retested. In these individuals, reaction time and cognitive control/interference processing also improved relative to pre-ketamine assessments.

Neurocognitive improvement, however, was not correlated with changes in depression, suicidal thinking, or general mood, the researchers note.

Nonetheless, they say "ketamine had a positive therapeutic effect on neurocognition 1 day after treatment on at least one measure associated with suicidal behavior in the context of depression."

"The results suggest additional independent therapeutic effects for ketamine in the treatment of depressed patients at risk for suicidal behavior," they write.

"Ketamine modulates many neurotransmitter systems including glutamate transmission which is crucial for learning and memory. It increases the number of synapses or connections between neurons. These effects are fundamental to cognition and are logical explanations of the beneficial effects observed in this study," Mann told Medscape Medical News.

"Our study helped us gain a better understanding of how ketamine works in the brain and how quickly it can improve distorted thinking. Being able to think more clearly can make someone feel less suicidal," study investigator Ravi. N. Shah, MD, chief innovation officer, Columbia Psychiatry, said in a news release.

Important research with caveats

Reached for comment, James Murrough, MD, PhD, director, Depression and Anxiety Center for Discovery and Treatment at Mount Sinai in New York City, said "the study is important and adds to a growing understanding of how ketamine affects brain systems and thinking in the context of depression and suicide risk."

"One reason this study is significant is that prior studies have shown that ketamine can have harmful effects on cognitive functioning in the context of ketamine misuse and exposures to high doses for long periods of time," Murrough, who wasn't involved in the study, told Medscape Medical News.

"In contrast in this study, a single low-dose treatment of ketamine can have the opposite effects, actually boosting some markers of cognitive functioning, at least in the short-term," he noted.

Murrough said one caveat to the study is that it only examined the effect of ketamine on cognition once, 1 day after a single treatment.

"While this is an important initial observation, we don't yet have any understanding of how persistent this effect on cognition is, or how this observed change may be related to any benefit ketamine may have on depression or suicide risk," Murrough said.

"In fact, the researchers found that there was no association between change in cognitive functioning following ketamine and change in depression or suicidal thinking. The patients who showed improved cognitive function following ketamine did not differ in terms of mood or suicide risk compared to patients who did not show an improvement in cognition," Murrough noted.

"This raises the important question of what is the relevance of change in cognition to the potential benefits of ketamine. This is an important area and should be the focus of future research in order to improve outcomes for patients with depression and who are at risk for suicide," he added.

Also weighing in, Roger McIntyre, MD, professor of psychiatry and pharmacology and head of the Mood Disorders Psychopharmacology Unit, University of Toronto, Canada, said "the study is very interesting and in keeping with some previous work that he and his colleagues have done showing that ketamine seems to benefit aspects of cognition which is a core element in depression."

"It's a testable hypothesis that the improvement in cognition now being reported and replicated could play some role in the improved quality of life and functioning with this treatment and as well reduce reducing suicide," said McIntyre.

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

Single Infusion of Ketamine Rapidly Reduces Suicidal Thoughts

Ketamine rapidly improves distorted thinking and reasoning to diminish suicidal thoughts, independent of improvement in depressive symptoms, new research shows.

www.medscape.com

 

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Imperial College London
​

Psychedelics associated with decreases in depression severity and suicidal ideation

Richard J. Zeifman1, Anne C. Wagner, Ros Watts, Hannes Kettner, Lea J. Mertens1, and Robin L. Carhart-Harris

Imperial College London | Frontiers In Psychiatry | 7 Aug 2020

Psychedelic therapy shows promise as a novel intervention for a wide range of mental health concerns but its therapeutic action is incompletely understood. In line with acceptance and commitment therapy’s (ACT’s) transdiagnostic model, qualitative research has suggested that reductions in experiential avoidance are an important component of therapeutic outcomes associated with psychedelics. However, limited research has quantitatively explored the association between decreases in experiential avoidance and therapeutic outcomes associated with psychedelics. Therefore, in two prospective studies, using convenience samples of individuals with plans to use a psychedelic, we explored the impact of psychedelic use on experiential avoidance, depression severity, and suicidal ideation, as well as relationships between changes in these outcomes.

Participants completed self-report questionnaires of depression severity, suicidal ideation, and experiential avoidance: 1) before using a psychedelic (in ceremonial and non-ceremonial contexts), as well as 2) 2-weeks and 3) 4-weeks after psychedelic use. Across both studies, repeated measures ANOVAs indicated significant decreases in experiential avoidance, depression severity, and suicidal ideation after psychedelic use. Furthermore, decreases in experiential avoidance were significantly associated with decreases in depression severity and suicidal ideation. These results suggest that psychedelics may lead to significant decreases in experiential avoidance, depression severity, and suicidal ideation. Additionally, these findings imply that reduced experiential avoidance may be a transdiagnostic mechanism mediating treatment success within psychedelic therapy. We conclude that integrating psychedelics with psychotherapeutic interventions that target experiential avoidance (e.g. ACT) may enhance therapeutic outcomes.

Serotonergic psychedelics, a class of pharmacological agents that act as serotonin 2A receptor (5-HT2AR) agonists, including psilocybin, LSD, and DMT; are currently receiving attention within psychiatry and mental health as novel interventions for a wide range of mental health concerns . Randomized controlled trials and open-label trials have found promising results for psychedelic therapy in the treatment of distress associated with a life-threatening illness, substance use disorders, obsessive-compulsive disorder, depression [e.g., and suicidal ideation.

Given the wide range of mental health concerns for which psychedelic therapy has shown promise, it has been suggested that this treatment approach may target underlying transdiagnostic mechanisms. Recent research has indicated that the intensity of “mystical-type” or “peak” experiences engendered by psychedelics is predictive of positive therapeutic outcomes; however, it remains unclear how (i.e., via what fundamental psychological and neurobiological mechanisms) psychedelic therapy brings about lasting therapeutic changes. Identifying such underlying mechanisms is important for a number of reasons, including that it might improve our overall understanding of psychopathology, optimize therapeutic outcomes, and choice of treatment for clients, as well as guide treatment development, refinement and delivery.

Discussion

Previous research has indicated that psychedelics hold promise for the treatment of a wide range of psychiatric concerns; however, little research has been done to assess the impact of psychedelics on depression severity or suicidal ideation among non-clinical samples. Across two separate studies, we found significant decreases in depression severity and suicidal ideation 4-weeks after psychedelic use. Importantly, we did not find significant increases in depression severity or suicidal ideation from 2-weeks to 4-weeks, suggesting that the positive effects of psychedelics were reliably sustained for at least 1-month post-psychedelic use. These results are in line with clinical studies indicating that psychedelics can lead to decreases in depression severity and suicidal ideation and that these effects are sustained over time. Importantly, in both studies, the majority of the participants exhibited subclinical levels of baseline depression severity. Therefore, our results provide additional support for the possibility that the effects of psychedelics extend along the full spectrum of depression severity, from the severe to the mild end of the spectrum. Furthermore, in light of previous research showing that first-line interventions for depression lead to minimal to no decreases in suicidal ideation, it is promising and highly relevant to observe reductions in suicidal ideation here, in relation to psychedelic use.

*From the article (including references) here :

Post-Psychedelic Reductions in Experiential Avoidance Are Associated With Decreases in Depression Severity and Suicidal Ideation

Psychedelic therapy shows promise as a novel intervention for a wide range of mental health concerns but its therapeutic action is incompletely understood. In line with acceptance and commitment therapy’s (ACT’s) transdiagnostic model, qualitative research has suggested that reductions in...

www.frontiersin.org

 

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Ketamine an emergency deterrent for people at risk of suicide*

by Amy Norton | 7 Jun 2022

A new clinical trial strengthens the case that ketamine -- once famous as a club drug -- can rapidly ease suicidal thoughts.

Researchers found that among 156 adults hospitalized for severe suicidal thoughts, those given two doses of ketamine often saw those disturbing ideas go away within a few days.

By day three, 63% were in full remission, compared to just under 32% of patients given a placebo in addition to standard care.

The study -- published Feb. 2 in the British Medical Journal -- is the latest to look at the mental health effects of ketamine. The drug was approved in the United States decades ago as an anesthetic, and then became popular as a party drug -- known by names like "special K" -- because of its mind-altering effects.

But researchers have long been aware of ketamine's potential, at low doses under well-controlled conditions, to treat psychiatric symptoms.

In recent years, it has emerged as something of a wonder drug for patients with severe depression that does not improve with standard treatment.

For those people, ketamine can sometimes bring rapid relief, even within a day. Experts say that is especially critical for people at high risk of harming themselves.

The new findings add to evidence that ketamine can help get those patients through the crisis, said Dr. Paul Kim, an assistant professor of psychiatry and behavioral sciences at Johns Hopkins University School of Medicine in Baltimore.

Of course, that is not the end of the story, and people need follow-up care. Kim said that might involve changing any antidepressant therapy a patient has been taking, including the dosage.

"Sometimes it's found that they're not on an effective therapeutic dose," noted Kim, who was not involved in the study.

While ketamine can work quickly, it is not simple to take. It has to be given by infusion, under careful medical supervision, largely due to its "dissociative" effects -- or what lay people call a trip.

Ketamine typically triggers altered perceptions of reality, such as hallucinations, soon after it's given. It can also cause a short-term spike in blood pressure.

Exactly how ketamine brings relief to people in deep distress is not fully clear. But researchers know the drug has brain targets that are different from standard antidepressants, and that includes boosting activity in a chemical called glutamate, which helps brain cells communicate with each other. Studies also suggest ketamine fosters the regrowth of synapses -- connections among brain cells that can be depleted in people with long-standing depression.

In the new study, researchers in France recruited patients who were voluntarily admitted to the hospital for severe suicidal thoughts. All received standard care, including antidepressants, talk therapy and meetings with family.

In addition, 73 were randomly assigned to receive two infusions of ketamine, 24 hours apart. The rest of the patients were given placebo infusions for comparison.

By day three, ketamine patients had double the rate of remission, meaning their suicidal thoughts had resolved. The difference was no longer statistically significant after six weeks, as patients in both groups were faring better: 69.5% of ketamine patients were in remission, as were 56% of placebo patients.

The trial did turn up an unexpected result: The early benefit of ketamine was seen mostly in patients with bipolar disorder, rather than major depression.

That's surprising because ketamine is generally given to people with severe depression, and not bipolar disorder, said Dr. Riccardo De Giorgi of the University of Oxford in England, who wrote an editorial published with the study.

"It may suggest that the biological and psychological mechanisms behind suicidal ideation perhaps differ between these two disorders -- an important avenue for further research," he said.

But given past evidence that ketamine can benefit people with depression and suicidal thoughts, the picture is unclear. The bottom line is that ongoing research is needed, according to De Giorgi.

Ketamine is not approved by the U.S. Food and Drug Administration for treating depression. But doctors can and do prescribe it "off label" for that reason.

In addition, there is an FDA-approved version of ketamine called esketamine (Spravato). It was first approved in 2019 for treatment-resistant depression, and later for people with depression and acute suicidal thoughts and behaviors.

Because esketamine is FDA-approved and more likely to be covered by insurance, it may be the choice over ketamine in the real world, according to Kim.

Another difference is that esketamine is given by nasal spray.

However, Kim said, esketamine is still given under medical supervision -- not at home -- because it can have the same side effects as ketamine.

He agreed that ongoing research is necessary. Ketamine and esketamine are still new in the field of managing depression and suicidal thoughts, Kim said, and providers are trying to figure out how to best integrate them into care.

But people should know help is out there, Kim and De Giorgi said.

"Even when life seems at its darkest, help is available," De Giorgi said. "If suicidal thoughts are the issue, please do call for help."

Whether ketamine is an option, he said, will depend on the individual's circumstances, as well as the availability of the medication. There is no one-size-fits-all, and De Giorgi said people need to speak with their provider about the best treatment plan for them.

*From the article here :

Ketamine May Be Emergency Deterrent for People at Risk of Suicide

MONDAY, Feb. 7, 2022 (HealthDay News) -- A new clinical trial strengthens the case that ketamine -- once famous as a club drug -- can rapidly ease suicidal thoughts.Researchers found that among 156 adults hospitalized for severe suicidal thoughts, those given two doses of ketamine often saw...

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