SUICIDALITY | +40 articles

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Joe Wright in New York City

Is Ketamine the key to reversing America’s rising suicide rate?

by Cynthia Koons and Robert Langreth | Bloomberg Businessweek | 5 Feb 2019

Joe Wright has no doubt that Ketamine saved his life. A 34-year-old high school teacher who writes poetry every day on a typewriter, Wright was plagued by suicidal impulses for years. The thoughts started coming on when he was a high schooler himself, on Staten Island, N.Y., and intensified during his first year of college. “It was an internal monologue, emphatic on how pointless it is to exist,” he says. “It’s like being ambushed by your own brain.”

He first tried to kill himself by swallowing a bottle of sleeping pills the summer after his sophomore year. Years of treatment with Prozac, Zoloft, Wellbutrin, and other antidepressants followed, but the desire for an end was never fully resolved. He started cutting himself on his arms and legs with a pencil-sharpener blade. Sometimes he’d burn himself with cigarettes. He remembers few details about his second and third suicide attempts. They were halfhearted; he drank himself into a stupor and once added Xanax into the mix.

Wright decided to try again in 2016, this time using a cocktail of drugs he’d ground into a powder. As he tells the story now, he was preparing to mix the powder into water and drink it when his dog jumped onto his lap. Suddenly he had a moment of clarity that shocked him into action. He started doing research and came upon a Columbia University study of a pharmaceutical treatment for severe depression and suicidality. It involved an infusion of Ketamine, a decades-old anesthetic that’s also an infamous party drug. He immediately volunteered.

His first—and only—Ketamine infusion made him feel dreamlike, goofy, and euphoric. He almost immediately started feeling more hopeful about life. He was more receptive to therapy. Less than a year later, he married. Today he says his dark moods are remote and manageable. Suicidal thoughts are largely gone. “If they had told me how much it would affect me, I wouldn’t have believed it,” Wright says. “It is unconscionable that it is not already approved for suicidal patients.”

The reasons it isn’t aren’t strictly medical. Over the past three decades, pharmaceutical companies have conducted hundreds of trials for at least 10 antidepressants to treat severe PMS, social anxiety disorder, and any number of conditions. What they’ve almost never done is test their drugs on the sickest people, those on the verge of suicide. There are ethical considerations: Doctors don’t want to give a placebo to a person who’s about to kill himself. And reputational concerns: A suicide in a drug trial could hurt a medication’s sales prospects.

The risk-benefit calculation has changed amid the suicide epidemic in the U.S. From 1999 to 2016, the rate of suicides increased by 30 percent. It’s now the second-leading cause of death for 10- to 34-year-olds, behind accidents. (Globally the opposite is true: Suicide is decreasing.) Growing economic disparity, returning veterans traumatized by war, the opioid crisis, easy access to guns—these have all been cited as reasons for the rise in America. There’s been no breakthrough in easing any of these circumstances.

But there is, finally, a serious quest for a suicide cure. Ketamine is at the center, and crucially the pharmaceutical industry now sees a path. The first ketamine-based drug, from Johnson & Johnson, could be approved for treatment-resistant depression by March and suicidal thinking within two years. Allergan Plc is not far behind in developing its own fast-acting antidepressant that could help suicidal patients. How this happened is one of the most hopeful tales of scientific research in recent memory.

Dennis Charney

Dennis Charney, dean of the Icahn School of Medicine at Mount Sinai in New York, works from an office filled with family pictures, diplomas, and awards from a long career in research. One thing on the wall is different from the rest: a patent for the use of a nasal-spray form of ketamine as a treatment for suicidal patients. The story of the drug is in some ways the story of Charney’s career.

In the 1990s he was a psychiatry professor, mentoring then associate professor John Krystal at Yale and trying to figure out how a deficit of serotonin played into depression. Back then, depression research was all about serotonin. The 1987 approval of Prozac, the first selective serotonin reuptake inhibitor, or SSRI, ushered in an era of what people in the industry call me-too drug development, research that seeks to improve on existing medicines rather than exploring new approaches. Within this narrow range, pharmaceutical companies churned out blockbuster after blockbuster. One in eight Americans age 12 and older reported using antidepressants within the past month, according to a survey conducted from 2011 to 2014 by the U.S. Centers for Disease Control and Prevention.

Charney was a depression guy; Krystal was interested in schizophrenia. Their curiosity led them to the same place: the glutamate system, what Krystal calls the “main information highway of the higher brain.” (Glutamate is an excitatory neurotransmitter, which helps brain cells communicate. It’s considered crucial in learning and memory formation.) They had already used ketamine to temporarily produce schizophrenia-like symptoms, to better understand glutamate’s role in that condition. In the mid-1990s they decided to conduct a single-dose study of ketamine on nine patients (two ultimately dropped out) at the Yale-affiliated VA Connecticut Healthcare System in West Haven to see how depressed people would react to the drug.

“If we had done the typical thing … we would have completely missed the antidepressant effect.”

Outside the field of anesthesiology, ketamine is known, if it’s known at all, for its abuse potential. Street users sometimes take doses large enough to enter what’s known as a “K hole,” a state in which they’re unable to interact with the world around them. Over the course of a day, those recreational doses can be as much as 100 times greater than the tiny amount Charney and Krystal were planning to give to patients. Nonetheless, they decided to monitor patients for 72 hours—well beyond the two hours that ketamine produces obvious behavioral effects—just to be careful not to miss any negative effects that might crop up. “If we had done the typical thing that we do with these drug tests,” Krystal says, “we would have completely missed the antidepressant effect of Ketamine.”

Checking on patients four hours after the drug had been administered, the researchers saw something unexpected. “To our surprise,” Charney says, “the patients started saying they were better, they were better in a few hours.” This was unheard of. Antidepressants are known for taking weeks or months to work, and about a third of patients aren’t sufficiently helped by the drugs. “We were shocked,” says Krystal, who now chairs the Yale psychiatry department. “We didn’t submit the results for publication for several years.”

When Charney and Krystal did publish their findings, in 2000, they attracted almost no notice. Perhaps that was because the trial was so small and the results were almost too good to be true. Or maybe it was ketamine’s reputation as an illicit drug. Or the side effects, which have always been problematic: Ketamine can cause patients to disassociate, meaning they enter a state in which they feel as if their mind and body aren’t connected.

But probably none of these factors mattered as much as the bald economic reality. The pharmaceutical industry is not in the business of spending hundreds of millions of dollars to do large-scale studies of an old, cheap drug like Ketamine. Originally developed as a safer alternative to the anesthetic phencyclidine, better known as PCP or angel dust, ketamine has been approved since 1970. There’s rarely profit in developing a medication that’s been off patent a long time, even if scientists find an entirely new use for it.

Somehow, even with all of this baggage, research into Ketamine inched forward. The small study that almost wasn’t published has now been cited more than 2,00
Suicide is described in medicine as resulting from a range of mental disorders and hardships—a tragedy with many possible roots. Conditions such as severe depression, bipolar disorder, and schizophrenia are known risk factors. Childhood trauma or abuse may also be a contributor, and there may be genetic risk factors as well.

From these facts, John Mann, an Australian-born psychiatrist with a doctorate in neurochemistry, made a leap. If suicide has many causes, he hypothesized, then all suicidal brains might have certain characteristics in common. He’s since done some of the most high-profile work to illuminate what researchers call the biology of suicide. The phrase itself represents a bold idea—that there’s an underlying physiological susceptibility to suicide, apart from depression or another psychiatric disorder.

Mann moved to New York in 1978, and in 1982, at Cornell University, he started collecting the brains of people who’d killed themselves. He recruited Victoria Arango, now a leading expert in the field of suicide biology. The practice of studying postmortem brain tissue had largely fallen out of favor, and Mann wanted to reboot it. “He was very proud to take me to the freezer,” Arango says of the day Mann introduced her to the brain collection, which then numbered about 15. “I said, ‘What am I supposed to do with this?’ ”

Some of Mann's brain collection.

They took the work, and the brains, first to the University of Pittsburgh, and then, in 1994, to Columbia. They’ve now amassed a collection of some 1,000 human brains—some from suicide victims, the others, control brains—filed neatly in freezers kept at –112F. The small Balkan country of Macedonia contributes the newest brains, thanks to a Columbia faculty member from there who helped arrange it. The Macedonian brains are frozen immediately after being removed and flown in trunks, chaperoned, some 4,700 miles to end up in shoe-box-size, QR-coded black boxes. Inside are dissected sections of pink tissue in plastic bags notated with markers: right side, left side, date of collection.

In the early 1990s, Mann and Arango discovered that depressed patients who killed themselves have subtle alterations in serotonin in certain regions of the brain. Mann remembers sitting with Arango and neurophysiologist Mark Underwood, her husband and longtime research partner, and analyzing the parts of the brain affected by the deficit. They struggled to make sense of it, until it dawned on them that these were the same brain regions described in a famous psychiatric case study.

In 1848, Phineas Gage, an American railroad worker, was impaled through the skull by a 43-inch-long tamping iron when the explosives he was working with went off prematurely. He survived, but his personality was permanently altered. In a paper titled “Recovery From the Passage of an Iron Bar Through the Head,” his doctor wrote that Gage’s “animal propensities” had emerged and described him as using the “grossest profanity.” Modern research has shown that the tamping iron destroyed key areas of the brain involved in inhibition—the same areas that were altered in the depressed patients who’d committed suicide. For the group, this was a clue that the differences in the brain of suicidal patients were anatomically important.

Victoria Arango

"Most people inhibit suicide. They find a reason not to do it,” Underwood says. Thanks to subtle changes in the part of the brain that might normally control inhibition and top-down control, people who kill themselves “don’t find a reason not to do it,” he says.

About eight years ago, Mann saw Ketamine research taking off in other corners of the scientific world and added the drug to his own work. In one trial, his group found that ketamine treatment could ease suicidal thoughts in 24 hours more effectively than a control drug. Crucially, they found that the antisuicidal effects of ketamine were to some extent independent of the antidepressant effect of the drug, which helped support their thesis that suicidal impulses aren’t necessarily just a byproduct of depression. It was this study, led by Michael Grunebaum, a colleague of Mann’s, that made a believer of Joe Wright.

“It’s like you have 50 pounds on your shoulders, and the ketamine takes 40 pounds off.”

In 2000, the National Institutes of Health hired Charney to run both mood disorder and experimental drug research. It was the perfect place for him to forge ahead with ketamine. There he did the work to replicate what he and his colleagues at Yale had discovered. In a study published in 2006, led by researcher Carlos Zarate Jr., who now oversees NIH studies of ketamine and suicidality, an NIH team found that patients had “robust and rapid antidepressant effects” from a single dose of the drug within two hours. “We could not believe it. In the first few subjects we were like, ‘Oh, you can always find one patient or two who gets better,’ ” Zarate recalls.

In a 2009 study done at Mount Sinai, patients suffering from treatment-resistant depression showed rapid improvement in suicidal thinking within 24 hours. The next year, Zarate’s group demonstrated antisuicidal effects within 40 minutes. “That you could replicate the findings, the rapid findings, was quite eerie,” Zarate says.

Finally, Ketamine crossed back into commercial drug development. In 2009, Johnson & Johnson lured away Husseini Manji, a prominent NIH researcher who’d worked on the drug, to run its neuroscience division. J&J didn’t hire him explicitly to develop ketamine into a new pharmaceutical, but a few years into his tenure, Manji decided to look into it. This time it would come in a nasal-spray form of esketamine, a close chemical cousin. That would allow for patent protection. Further, the nasal spray removes some of the challenges that an IV form of the drug would present. Psychiatrists, for one thing, aren’t typically equipped to administer IV drugs in their offices.

While these wheels were slowly turning, some doctors—mostly psychiatrists and anesthesiologists—took action. Around 2012 they started opening ketamine clinics. Dozens have now popped up in major metropolitan areas. Insurance typically won’t touch it, but at these centers people can pay about $500 for an infusion of the drug. It was at one time a cultural phenomenon—a 2015 Bloomberg Businessweek story called it “the club drug cure.” Since then, the sense of novelty has dissipated. In September the American Society of Ketamine Physicians convened its first medical meeting about the unconventional use of the drug.

“You are literally saving lives,” Steven Mandel, an anesthesiologist-turned-Ketamine provider, told a room of about 100 people, mostly doctors and nurse practitioners, who gathered in Austin to hear him and other early adopters talk about how they use the drug. Sporadic cheers interrupted the speakers as they presented anecdotes about its effectiveness.

There were also issues to address. A consensus statement in JAMA Psychiatry published in 2017 said there was an “urgent need for some guidance” on Ketamine use. The authors were particularly concerned with the lack of data about the safety of prolonged use of the drug in people with mood disorders, citing “major gaps” in the medical community’s knowledge about its long-term impact.

The context for the off-label use of Ketamine is a shrinking landscape for psychiatry treatment. An effort to deinstitutionalize the U.S. mental health system, which took hold in the 1960s, has almost resulted in the disappearance of psychiatric hospitals and even psychiatric beds within general hospitals. There were 37,679 psychiatric beds in state hospitals in 2016, down from 558,922 in 1955, according to the Treatment Advocacy Center. Today a person is often discharged from a hospital within days of a suicide attempt, setting up a risky situation in which someone who may not have fully recovered ends up at home with a bunch of antidepressants that could take weeks to lift his mood, if they work at all.

A Ketamine clinic can be the way out of this scenario—for people with access and means. For Dana Manning, a 53-year-old Maine resident who suffers from bipolar disorder, $500 is out of reach. “I want to die every day,” she says.

After trying to end her life in 2003 by overdosing on a cocktail of drugs including Xanax and Percocet, Manning tried virtually every drug approved for bipolar disorder. None stopped the mood swings. In 2010 the depression came back so intensely that she could barely get out of bed and had to quit her job as a medical records specialist. Electroconvulsive therapy, the last-ditch treatment for depressed patients who don’t respond to drugs, didn’t help.

Her psychiatrist went deep into the medical literature to find options and finally suggested Ketamine. He was even able to get the state Medicaid program to cover it, she says. She received a total of four weekly infusions before she moved to Pennsylvania, where there were more family members nearby to care for her.

The first several weeks following her Ketamine regimen were "the only time I can say I have felt normal in 15 years," she says. “It’s like you have 50 pounds on your shoulders, and the ketamine takes 40 pounds off.”

She’s now back in Maine, and the depression has returned. Her current Medicare insurance won’t cover Ketamine. She lives on $1,300 a month in disability income. “Knowing it is there and I can’t have it is beyond frustrating,” she says.

Mark Underwood

Ketamine is considered a “dirty” drug by scientists—it affects so many pathways and systems in the brain at the same time that it’s hard to single out the exact reason it works in the patients it does help. That’s one reason researchers continue to look for better versions of the drug. Another, of course, is that new versions are patentable. Should Johnson & Johnson’s esketamine hit the market, the Ketamine pioneers and their research institutions stand to benefit. Yale’s Krystal, NIH’s Zarate, and Sinai’s Charney, all of whom are on the patent on Charney’s wall, will collect royalties based on the drug’s sales. J&J hasn’t said anything about potential pricing, but there’s every reason to believe the biggest breakthrough in depression treatment since Prozac will be expensive.

The company’s initial Esketamine study in suicidal patients involved 68 people at high risk. To avoid concerns about using placebos on actively suicidal subjects, everyone received antidepressants and other standard treatments. About 40 percent of those who received esketamine were deemed no longer at risk of killing themselves within 24 hours. Two much larger trials are under way.

When Johnson & Johnson unveiled data from its Esketamine study in treatment-resistant depression at the American Psychiatric Association meeting in May, the presentation was jammed. Esketamine could become the first-ever rapid-acting antidepressant, and physicians and investors are clamoring for any information about how it works. The results in suicidal patients should come later this year and could pave the way for a Food and Drug Administration filing for use in suicidal depressed patients in 2020. Allergan expects to have results from its suicide study next year, too.

“The truth is, what everybody cares about is, do they decrease suicide attempts?” says Gregory Simon, a psychiatrist and mental health researcher at Kaiser Permanente Washington Health Research Institute. “That is an incredibly important question that we hope to be able to answer, and we are planning for when these treatments become available.”

Exactly how Ketamine and its cousin Esketamine work is still the subject of intense debate. In essence, the drugs appear to provide a quick molecular reset button for brains impaired by stress or depression. Both Ketamine and Esketamine release a burst of glutamate. This, in turn, may trigger the growth of synapses, or neural connections, in brain areas that may play a role in mood and the ability to feel pleasure. It’s possible the drug works to prevent suicide by boosting those circuits while also reestablishing some of the inhibition needed to prevent a person from killing himself.

“We certainly think that Esketamine is working exactly on the circuitry of depression,” Manji says. “Are we homing in exactly on where suicidal ideation resides?” His former colleagues at NIH are trying to find that spot in the brain as well. Using polysomnography—sleep tests in which patients have nodes connected to various parts of their head to monitor brain activity—as well as MRIs and positron emission tomography, or PET scans, researchers can see how a patient’s brain responds to ketamine, to better understand exactly what it’s doing to quash suicidal thinking.

Concerns about the side effects of Ketamine-style drugs linger. Some patients taking esketamine have reported experiencing disassociation symptoms. Johnson & Johnson calls the effects manageable and says they cropped up within an hour of the treatment, a period in which a person on the drug would likely be kept in the doctor’s office for monitoring. Some patients also experienced modest spikes in blood pressure within the same timeframe.

University of New South Wales

Nasal-spray dosing brings other issues. The Black Dog Institute in Australia and the University of New South Wales in Sydney, which teamed up to study a nasal-spray form of Ketamine, published their findings last March in the Journal of Psychopharmacology. The researchers found that absorption rates were variable among patients. J&J says its own studies with Esketamine contradict these findings.

But in the wake of the opioid crisis, perhaps the biggest worry is that loosening the reins too much on the use of Ketamine and similar drugs could lead to a new abuse crisis. That’s why Wall Street analysts are particularly excited by Allergan’s rapid-acting antidepressant, rapastinel, which is about a year behind esketamine in testing. Researchers say it likely acts on the same target in the brain as Ketamine, the NMDA receptor, but in a more subtle way that may avoid the disassociation side effects and abuse potential. Studies in lab animals show the drug doesn’t lead creatures to seek more of it, as they sometimes do with Ketamine, says Allergan Vice President Armin Szegedi. Allergan’s medicine is an IV drug, but the company is developing an oral drug.

For its suicide study, Allergan is working hard to enroll veterans, one of the populations most affected by the recent spike in suicides, and has included several U.S. Department of Veterans Affairs medical centers as sites in the trial. More than 6,000 veterans died by suicide each year from 2008 to 2016, a rate that’s 50 percent higher than in the general population even after adjusting for demographics, according to VA data.

“How the brain mediates what makes us who we are is still a mystery, and maybe we will never fully understand it,” Szegedi says. “What really changed the landscape here is you had clinical data showing ‘This really does the trick.’ Once you find something in the darkness, you really have to figure out: Can you do something better, faster, safer?”

If you or someone you know is having suicidal thoughts, the National Suicide Prevention hotline is 1 (800) 273 8255.

https://www.bloomberg.com/news/feat...could-soon-be-used-to-treat-suicidal-ideation​

 

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​

Can Psychedelics Help Prevent Suicide?

by Derek Beres | BIG THINK | 13 Jun 2018

New research in psychedelics is showing them to be a powerful antidote to depression. We need to implement them into therapy.

In his new book on psychedelics, How to Change Your Mind, Michael Pollen writes about Patrick Mettes, who, while suffering from bile duct cancer decided to end his grueling chemotherapy regimen. Death was imminent. Mettes had heard about an NYU study in which researchers were distributing a synthetic form of psilocybin for terminally ill patients undergoing “existential distress.” Against the wishes of his wife, he decided to enroll.

During the last days of his life, Patrick’s wife, Lisa, was the one being consoled. Mettes, who had never taken a psychedelic before, underwent a transformative experience. His life was suddenly filled with meaning, while the mindset switch—the deactivation of the parts of his brain related to ego, which is, in large part, how psychedelics work—made death a less harrowing prospect. Mettes died content, filled with gratitude.

While I’ve used (and continue to use, on occasion) psychedelics, the bulk was done in college. The risk of being caught loomed every time I ingested (or “dropped”) LSD, psilocybin, or mescaline, resulting in a frustrating undertone to the experience. Once a college security guard approached a friend and I “painting” a blank wall in Voorhees Mall; we ended up chatting for hours about art and life, though the whole time we were waiting for reinforcements to arrive. (They never did; he was a grad student and likely knew what was going on.) When you’re undergoing a transformative experience under duress it’s challenging to let go and enjoy the moment.

Which is important, because psychedelics are being therapeutically reevaluated, not a moment too soon. As Pollan highlights, much of the research being conducted is not new, but a return to what the studies of the forties and fifties, when the Swiss-based Sandoz Laboratories would ship LSD-25 to any researcher who wanted to find a potential application. They knew their chemist, Albert Hoffman, had isolated something important. They just didn’t know what.

Much of modern medicine is predicated on the idea that a substance has to have biological specificity in order to be effective. This is ironic, considering our current “best” treatment for depression (outside of talk therapy), SSRIs, targets serotonin in the brain, even though 95 percent of our body’s serotonin is produced in the gut. An entire holistic market rightfully, if somewhat unsoundly, exists for treating depression and anxiety through diet. Big Pharma would never admit that such an approach is feasible. They have too much invested in their means, even if their means are proving more and more ineffective.

One commonality among those contemplating suicide is a lack of meaning in life. Someone doesn’t care about them, the world doesn’t care, they’ve been hurt and no bright future is ahead. Clinically, depression is tied with a lack of hope. Since there is no “hope neurotransmitter," pinpointing one brain region or chemical is unlikely to work. We need a holistic approach to healing, one that psychedelics offer.

Creating meaning in life is dependent upon hope, and it begins with the story we tell ourselves about ourselves. Consciousness, in part, is a continual narrative we both invent and listen to inside of our heads. And there are brain regions involved in that process, which is why Pollan sees psychedelics as a potentially potent therapy for when those interior voices go awry:​

Getting overly attached to these narratives, taking them as fixed truths about ourselves rather than as stories subject to revision, contributes mightily to addiction, depression, and anxiety. Psychedelic therapy seems to weaken the grip of these narratives, perhaps by temporarily disintegrating the parts of the default mode network where they operate.​

My psychedelic immersion forever changed how I view the world. Even today, my biannual retreats are a reboot, a recharge, a reminder—Pollan and others note that you don’t have to be depressed to receive benefits.

Many of the assumptions we’ve held as firm truths are being put into question in America. What we thought of as reality and the reality on our screens are not matching up. Yet what is frightening can also be liberating. Over the last half-century, the medical establishment, taking a cue from Nixonian politics, has viewed mental health through a narrow lens. To ignore emotions and narrative is to miss fundamental aspects of health—aspects we can no longer afford to overlook. For many suffering from depression, psychedelics might be the medicine they need.

If you or someone you know needs to talk to someone, call (800)273-8255, the National Suicide Prevention Lifeline, 24 hours a day. For international readers, a list of crisis centers can be found here.

*From the article here :

Can psychedelics help prevent suicide?

New research in psychedelics is showing them to be a powerful antidote to depression. We need to implement them into therapy.

bigthink.com

 

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First nasal spray approved for treating suicidal people*

by Cynthia Koons | Medical Xpress | 3 Aug 2020

Johnson & Johnson's Spravato has been approved as the first antidepressant for actively suicidal people, as doctors are becoming increasingly concerned about COVID-19's effect on the mental health of Americans.

The Food and Drug Administration approval means the quick-acting nasal spray will be available to people with suicidal thoughts and a plan to put them into action, said Michelle Kramer, vice president of J&J's U.S. neuroscience medical affairs unit. That constitutes 11% to 12% of as many as 17 million Americans who have major depressive disorder.

"Spravato has been used by about 6,000 people for treatment-resistant depression since its approval in March 2019," Kramer said. J&J's decision to study it in depressed people actively contemplating suicide bucks a trend among drugmakers who routinely exclude such patients from trials.

"Part of the thinking behind the decision was that Spravato's ability to act quickly could mean it works differently than older antidepressants that can take weeks to kick in," Kramer said. In its studies, J&J found those who got the drug had a rapid reduction in the severity of their thinking, although the results didn't differ in a statistically significant way from patients given a placebo.

"The data from studies of the drug show it may offer clinicians a new way to provide support to patients quickly in the midst of an urgent depressive episode and help set them on the path to remission," said Gerard Sanacora, director of Yale's Depression Research Program and a trial investigator.

America had been in the throes of a suicide crisis even before the pandemic, with the rate rising 30% from 1999 to 2016. COVID-19 closures limited the number of people given the spray as a depression treatment in-person at specified centers.

Ultimately, though, the numbers improved as patients and centers adapted and concerns grew within the mental health community that physical distancing and social isolation of quarantine may exacerbate people's existing problems or introduce new ones.

"Relatively rapidly within a few weeks we saw the numbers stabilize, which was pretty interesting for us and validating in the sense that clinic and patients alike were continuing to make this available," Kramer said. "We certainly see more and more sites sign on and more and more patients are treated."

Spravato is a close chemical cousin of the anesthetic ketamine, which differs from existing antidepressants because it acts on the glutamate system in the brain rather than on serotonin or norepinepherine. Scientists have been working to better understand how the drug helps patients and why it works so quickly.

The drug's approval last year marked the first major breakthrough for depression since 1987. President Donald Trump has since trumpeted the drug as having the potential to curb veteran suicides, but a Veterans Affairs medical panel only approved the drug's use on a limited basis.

*From the article here:

Nasal spray approved for treating suicidal people

Johnson & Johnson's Spravato has been approved as the first antidepressant for actively suicidal people, as doctors are becoming increasingly concerned about COVID-19's effect on the mental health of Americans.

medicalxpress.com

Explore further :
Ketamine-based nasal spray to treat depression​

 

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Ketamine offers lifeline for people with severe depression, suicidal thoughts

by Ben Tinker abd Dr. Sanjay Gupta | CNN

A few months ago, Alan Ferguson decided he was ready to die – for the third time. In 2014, he attempted suicide twice, and the persistent thoughts of “I need to be dead” were echoing in his brain once again.

Now 54 years old, Ferguson was diagnosed with clinical depression when he was 18. Since then, he estimates, he’s been prescribed more than a dozen medications – SSRIs, SNRIs, tricyclic antidepressants – all to little or no avail.

“I never got to the point that I thought, ‘OK, I’m feeling good,’ ” he said. “It was always, ‘OK, this is tolerable.’ But yet those thoughts of wanting to die were still there.”

Dr. Kevin Kane, a practicing anesthesiologist, is Ketamine Milwaukee’s medical director. Referring to the fact that there haven’t been any new classes of drugs developed to treat depression in decades, Kane said that using ketamine to successfully treat the disorder’s most stubborn cases might just be “the biggest breakthrough in mental health in the last 50 years.” He estimates that it is effective for 70% of patients with treatment-resistant depression.

“It’s indicated right now for … somebody who has tried and failed at least two medications, but that’s really not who we’re seeing,” Kane said. Instead, the patients who seek his care have tried more medications than they can count. Some of them have been depressed for as long as they can remember.

“The people we’re seeing aren’t walking off the street because [they’re] feeling a little down,” he said. “They’ve been struggling without relief for a long time.”

The ketamine is administered intravenously, and relief can come quickly – in just a matter of hours.

Ferguson said he woke up the next morning anxiously anticipating his pervasive “I need to be dead” thoughts. But there were none. Mid-morning: still none. Afternoon: none. Evening: none.

“No negative thoughts!” he recalled. “My problems still existed … but things were different. My most faithful, lifelong companion was gone!”

Ferguson doesn’t like to use what he calls the “m-word”: miracle. But he will refer to the way in which ketamine worked for him a medical marvel.

Whatever you call it, the treatment doesn’t come cheap. Infusions at Ketamine Milwaukee cost $495 each, and Kane typically recommends an initial series of five to six infusions, after which patients generally return every four to six weeks for booster infusions.

Because treating depression with ketamine is an “off-label” use of the drug, it is not covered by health insurance, even when it is recommended by a doctor. Ferguson was able to scrape together enough cash for his first infusion. A good friend gave him the money for his second. And his church rallied around him and paid for his third treatment. But the results, he will tell you, are priceless.

The efficacy of Ferguson’s treatment is evident in the mood chart above provided to CNN by Kane. The black lines indicate Ferguson’s ketamine infusion dates, and the red dots are his scores on the PHQ-9 (a standardized depression questionnaire). On May 25, the day of his first infusion, Ferguson’s depression was rated “severe.” By his second infusion on June 1, it had improved to “moderate.” And by his third infusion on June 8, for the first time in his adult life, Ferguson’s depression rating measured “none.”

No more suicidal thoughts

Because of how quickly and how well ketamine works in some patients, some doctors have referred to it as a “save shot” for people who are suicidal.

“The ketamine may be a way to improve their mood and stop their suicidal thinking until the other antidepressants – the more standard antidepressants – have the six-week time window to work,” Kane said. “Ketamine may be just the thing that gets someone through that window until other medications get the chance to kick in."

“Sometimes, when you get so depressed that you can barely get out of bed, it’s hard to do the things that your therapist tells you to do to try and help yourself,” he said. “My hope is … that it gives people that lift in mood that allows them to start doing the other things that they know they can do to help themselves.”

A rat neuron before, top, and after ketamine treatment. The increased number of orange nodes are restored connections in the rat's brain.

Kane explained that ketamine works in depressed patients by growing synapses in areas of the brain that have atrophied, namely the hippocampus and prefrontal cortex. “If you think of it like a tree that loses its leaves in wintertime, ketamine helps grow those leaves back,” he said. “It doesn’t necessarily have to grow an entire new branch or an entire new tree. It just has to sprout new leaves.”

Moreover, the same dissociative properties that made ketamine a popular party drug are what makes the medication so effective in treating severe depression.

“Sometimes, that can be a very powerful thing, that dissociation,” Kane said. “While you’re dissociating from your body, you may be dissociating [from] your mind as well. And, you may be able to see your problems and your issues that have really been consuming you as, ‘Yes, they’re still here, but now they’re over there. They’re in a little ball in the corner, and they don’t have the power over me anymore.’ "

“Sometimes, people can have very profound thoughts along those lines and realizations that they can take back to their therapy session, and it can be a really wonderful stepping stone for them to help maintain their relief.”

Dr. Gerard Sanacora, a psychiatry professor at the Yale School of Medicine, said little to no doubt remains about the rapid, robust anti-suicidal effect of ketamine. “I think the bigger question is: How do you maintain this? And how do you decide who is the best patient to receive this?”

Clinical studies have established that immediate side effects of ketamine can include increased heart rate and blood pressure. But Sanacora said further research is needed to determine the long-term cognitive impacts of ketamine treatment, as well as to develop standard dosing guidelines.

Sanacora, who is a co-author of “A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders,” published in the medical journal JAMA Psychiatry, said that “for the majority of people – not everybody – symptoms do tend to return after some period of time.”

At least as of now, more than two months since beginning ketamine therapy, Ferguson said he hasn’t had a single thought of taking his own life.

“It really is remarkable for me to be able to wake up and not be sorry I woke up in the morning,” he said. Still, Ferguson is keenly aware that the drug is not a miracle cure, and he will require ongoing care for the rest of his life.

After receiving a ketamine infusion in June, Ferguson thanked Kane not just for saving his life but for giving him a life he never knew was possible.
​

If you suspect someone may be suicidal:

1. Do not leave the person alone.
2. Remove any firearms, alcohol, drugs or sharp objects that could be used in a suicide attempt.
3. Call the U.S. National Suicide Prevention Lifeline at 1-800-273-TALK (8255).
4. Take the person to an emergency room or seek help from a medical or mental health professional.

Source: American Foundation for Suicide Prevention. For more tips and warning signs, click here.

Ketamine offers lifeline for people with suicidal thoughts

Ketamine has been shown to reduce or eliminate suicidal thoughts in people with severe clinical depression.

www.cnn.com

 

[mr peabody]

Psilocybin and the Will to Live​

by Abigail Calder, MSc | Psychedelic Science Review | 6 May 2021

Psilocybin may help suicidal patients renew their sense of meaning.

A cancer diagnosis is one of the worst bombshells life can drop on someone. It’s depressing, and it’s scary. Up to 40% of cancer patients develop clinical symptoms of depression or anxiety after diagnosis, and the worse the cancer, the more likely that is.

But one could doubt whether “clinically depressed” is the best way to describe someone’s mental state after finding out they have cancer. Clinical depression can have ambiguous causes or no obvious ongoing cause at all. But these patients have learned that they may be dying of cancer. According to the tests, yes, they’re depressed. But more accurately: they have a massive problem that might never go away again, and they are having a reasonable emotional reaction to it. An imminent and unexpectedly early death can be an intense ontological shock, leading people to question the meaning of their lives and feel demoralized, hopeless, or spiritually empty. Often patients are in considerable physical and emotional pain, and unsurprisingly, a cancer diagnosis increases someone’s risk of suicide four-fold. Although antidepressants may take the edge off, no pill can truly fix that.

But perhaps a mushroom can.

An antidote to despair

Back in 2016 – and several times since – psilocybin therapy made headlines for drastically and enduringly reducing symptoms of anxiety and depression in patients with life-threatening cancer. Stephen Ross and colleagues, who conducted a 2016 trial with cancer patients at NYU, have recently returned to their data to examine how exactly psilocybin therapy influenced these patients. What could possibly make a cancer patient less depressed about having cancer?

To find out, they focused specifically on 11 out of the original 20 patients who reported suicidal ideation prior to psilocybin therapy. These patients were suffering so badly from their cancer that they were considering ending their lives. But after a single session of psilocybin therapy, that had changed. Patients’ ratings of suicidal ideation were cut in half immediately after psilocybin treatment, and they stayed just as low for at least 6 months. This corresponded to the changes in depressive symptoms, which also declined immediately and stayed down.

How did psilocbyin make this happen?

It may have something to do with psychedelics’ ability to create meaning. During a psychedelic experience, people often have important and highly emotional insights into their lives, their problems, and what they feel to be their true values. In the words of one patient: “The psilocybin experience brought my beliefs to life, made them real, something tangible and true – it made my beliefs more than something to think about, really something to lean on and look forward to.”

Patients from psilocybin trials show that this can happen in almost infinitely many ways, with more common experiences being a diminished fear of death, re-experiencing important memories, or feelings of deep connectedness with the world. Although the details differ, people who take psychedelics – whether in a trial or otherwise – often count their experiences as some of the most meaningful of their entire lives.

In the words of Friedrich Nietzsche, “He who has a why to live can bear almost any how.”

For people who are suffering, meaning and purpose can be powerful antidotes to despair. The details will vary as much as people do, but in general, someone’s sense of meaning is made of their own experiences, beliefs, values, and goals, and it is something each person must find for themselves. A strong sense of one’s personal purpose in life can make people resilient even when their circumstances become difficult. When people lose this, psychological well-being can die out with it. At the beginning of the trial, many of these patients reported that they had lost their sense of meaning. But after the psilocybin sessions, it somehow came back – and stayed, too, even at the 5-year follow-up. This change correlated with reductions in suicidal ideation, and patients also reported that they felt less hopeless and demoralized. Perhaps the psilocybin experience helped them find their Why.

Behind the neural curtain

“Take this and discover the meaning of life” sure sounds like a con. But one’s sense of meaning, like any other sensation, is assumed to be generated by the brain. (Don’t think that takes the deep mystery out of life – it’s not like we understand brains.) Psilocybin and other psychedelics may specifically activate those neural circuits which are involved in attributing meaning and significance to events in one’s life. A study that used LSD to enhance the meaning of music implicated areas of the pre-frontal cortex, as well as the supplementary motor area, which is involved in self-relevant processing. We still have a very incomplete picture of exactly how the brain generates meaning, but however it does, psychedelics seem to send that process into overdrive in a way that is therapeutically helpful.

A drug that can help people find meaning and reduce suicidality has obvious clinical uses. Doctors and researchers have been wary about giving psychedelics to suicidal patients thus far, with good reason but mainly out of an abundance of caution. Promising data on suicidality from trials like Ross et al. may allow a careful relaxation of that caution for certain patients. If psilocybin proves to be more broadly effective against suicidality, it would be the only drug apart from ketamine known to immediately and enduringly boost someone’s will to live with a single dose.

And there is probably nothing special about cancer, as horrible life events go. People can lose their sense of meaning and will to live in the face of many serious health problems, traumas, and tragedies. If psychedelic therapy helps cancer patients, it may very well help others. In fact, there is already evidence that psychedelics increase the sense of meaning in diverse patient groups, as well as in healthy participants. By drawing people closer to what they find meaningful in life, psychedelics may help people find their way through their worst seasons, to come out stronger and more resilient on the other side.

Psilocybin and the Will to Live

Psilocybin may help suicidal patients renew their sense of meaning.

psychedelicreview.com

 

[mr peabody]

Psilocybin may reduce suicidal thoughts in terminally ill patients, study

by Jasmine Virdi | LUCID | 1 Jun 2021

Suicide is among of the leading causes of death within the US, and cancer patients are considered to be at greater risk of suicide than the general population due to factors like psychiatric and existential distress. However, a recent study conducted by researchers at NYU Langone Health Center for Psychedelic Medicine found psilocybin-assisted psychotherapy to be potentially effective in reducing suicidal ideation in advanced cancer patients, presenting itself as an effective alternative to existing antidepressant medications.

Currently SSRIs are the first-line of treatment for depression, and have limited success for treating suicidality – even worsening suicidal ideation in some cases. Compared with other treatments for suicidality, psilocybin was shown to be effective at reducing suicidal ideation as early as 8 hours after the experience. The positive effects persisted for 6.5 months after dosing.

Stephen Ross, the study’s lead author and associate professor in psychiatry at NYU Grossman School of Medicine, says that in both the pilot trial and long-term follow-up study, “The findings suggest that psilocybin-assisted psychotherapy produced rapid, substantial and sustained (weeks to years) improvements in anxiety, depression, existential distress and quality of life.”

The data was taken from a double-blind randomized trial in which psilocybin-assisted psychotherapy was used to treat anxiety and depression in terminally-ill patients with cancer. The study was funded by grants from the Heffter Research Institute, the RiverStyx Foundation, the National Institutes of Health, and private donors.

The parent trial included 29 participants in a crossover design, in which they either received a single moderate-to-high dose of psilocybin or a dose of the active control, which was in this case 250 mg of niacin. Both psilocybin and the control drug were paired with psychotherapy to treat anxiety, depression, and existential distress. From the 29 participants of the original study, only 11 were included in the secondary analysis examining the antisuicidal effects of psilocybin due to threshold levels of suicidal ideation.

In order to measure suicidal ideation in the follow-up study, researchers created a combined score based on two items from the the Beck Depression Inventory-II (BDI) and the Brief Symptom Inventory (BSI).

Patients with terminal diagnoses often experience what is referred to as “loss of meaning,” a facet of demoralization or existential distress characterized by the feeling that life lacks purpose, which can be a predictor of suicidal ideation. In order to assess loss of meaning, researchers used the Demoralization Scale (DS), a 24 item questionnaire created to measure existential distress in advanced cancer patients. Beyond this, researchers also looked at hopelessness, spiritual well-being and other depressive symptoms more generally.

Suicidal ideation in the subjects was measured at several milestones: before dosing; 8 hours and 2 weeks after the initial dose; 7 weeks after the initial dose; 1 day prior to the second dose; and 6.5 months after the second dose. Loss of meaning was evaluated at similar times. When compared with the control group, the psilocybin-first group experienced significant reductions in suicidal ideation and loss of meaning after the psychedelic session, which were measured at a 6.5 month follow-up. Decreases in loss of meaning for some subjects remained significant at follow-ups years later.

Previous studies have shown similar findings. In the 1970s, a series of trials indicated that N,N-Dipropyltryptamine (DPT), a shorter acting drug with similar effects to LSD, in conjunction with therapy decreased levels of depression, anxiety, hysteria, paranoia, hypomania, and schizophrenic qualities in cancer patients.

Another study from 2020 found psilocybin-assisted psychotherapy was able to produce clinically meaningful changes in demoralization for HIV/AIDS survivors, a population with elevated rates of desire for hastened death and past histories of suicide attempts.

In addition, three randomized controlled trials in the past decade (UCLA-Harbor, NYULH/Bellevue Hospital, and Johns Hopkins) have examined the effectiveness of a single-dose psilocybin- assisted psychotherapy in patients with advanced-cancer-related psychiatric and existential distress. Findings across all three studies suggest that a single moderate to high dose of psilocybin may facilitate significant, sustained decreases in anxiety, depressive symptoms, and existential distress.

Typically, psychedelic trials have not included subjects with more progressive forms of suicidality. However, Ross says "the research suggests that we do not have to absolutely exclude participants with cancer diagnoses who have depression and associated suicidal ideation.”

“Future trials need to occur that specifically target suicidality in cancer patients and that are adequately designed and powered to address the research questions of whether psilocybin assisted psychotherapy reduces suicidality in this patient cohort,” says Ross. “The findings suggest the psilocybin assisted-psychotherapy could be helpful for cancer patients at any stage of illness including: terminal, early diagnosis, chronic illness.”

Studies like Ross’s could potentially help to pave the way to making psilocybin-assisted therapy available for terminally ill patients countrywide. Beyond this, individuals suffering from suicidal ideation more generally could be put on the radar of those eligible for psilocybin-assisted therapy.

Psilocybin May Reduce Suicidal Thoughts in Terminally Ill Patients, Suggests New Study - Lucid News

Researchers found that psilocybin-assisted psychotherapy for advanced cancer patients may be an effective alternative to existing antidepressant medications to prevent suicide.

www.lucid.news

 

[mr peabody]

Cambridge

Use of Ketamine in Adolescent Mood Disorders and Suicidality

David S. Mathai, Alexis G. McCathern, Andrew G. Guzick, Sophie C. Schneider, Saira A. Weinzimmer, Sandra L. Cepeda, Albert Garcia-Romeu, Eric A. Storch

Published Online: 14 Oct 2021

The decision to use psychotropic treatments in children and adolescents is complex and challenged by noteworthy social and ethical criticisms of modern practice. Professional psychiatric associations have responded with emphasis on an integrated “developmental perspective," namely approaching the decision for pharmacological intervention by considering the unique context of each child, their family, and the dynamic environment. Notably, international guidelines differ in weight assigned to nonpharmacological alternatives to treatment, with implications on how interventions are relatively available, recommended, and implemented. However, the risks of medicating adolescents must be considered pragmatically and alongside the consequences of untreated psychiatric illness.

Pediatric mood disorders are associated with interpersonal difficulties, poor academic performance, occupational instability, and other mood or substance use disorders later in life. Earlier onset of illness and prolonged periods of depression in children have also been linked to worse long-term prognosis.

Troublingly, the prevalence of mood disorders in adolescents appears to be increasing, for whom suicide remains a leading, and rising, cause of death. Although a sense of clinical urgency is apparent, pharmacological interventions in these populations are few in number and variably efficacious. Treatment is further thwarted by the slow onset, low tolerability, paradoxical suicide risk, and long-term adverse effects of current pharmacotherapies.

Ketamine has gained popularity as a mechanistically novel, rapid-acting, and ultimately hopeful intervention for treatment-resistant depression and suicidality in adults. The use of ketamine in children has been historically limited to anesthetic and analgesic applications, although a growing number of studies suggest broader value of the drug in the treatment of psychiatric mood disorders.

For instance, a recent randomized controlled trial of intravenous ketamine in 17 adolescents (age 13–17) with major depression found rapid significant reductions in depressive symptoms lasting as long as 2 weeks post-treatment and no serious adverse effects associated with ketamine. While caution is needed in interpreting early findings and assessing both safety and efficacy of ketamine in minors, this research agenda merits keen attention considering the rates of illness and treatment resistance in this population. Examination of parental attitudes toward ketamine is also vital as interest in ketamine treatment for minors continues to develop.

As parents maintain decision-making capacity over their child's medical care, parental consent is a key factor in the adoption of new treatments for adolescents. To our knowledge, no existing studies have examined parental attitudes toward using ketamine to treat childhood psychiatric disorders. There are limited empirical data on what use of ketamine in children is deemed acceptable by parents at all. In one study examining parental attitudes to using ketamine for procedural sedation and analgesia in children with hematologic malignancy, parents generally favored using ketamine for pain control if it was found to be effective. Parents also reported dissatisfaction when children had adverse, including hallucinogenic-type, effects.

Other broad concerns about the psychiatric use of ketamine in adults may be represented in parents of minors who may benefit from treatment. For example, several groups advocate for careful selection of patients who are offered ketamine as treatment due to abuse risk. Preclinical data suggesting that ketamine may be neurotoxic in certain contexts are especially consequential for the vulnerable developing brain. Investigation into parental decision-making processes involving ketamine is of high priority, given the necessary role of parents in consenting to a treatment that may offer unique benefits in youth but is not without risks.

In this study, we examined parental perceptions of ketamine for the treatment of adolescent mood disorders and suicidality. Parents were asked questions to determine their concerns related to psychiatric use of ketamine, acceptability of this treatment, and their attitudes toward treatment. As a chiral compound, ketamine exists as a mixture of (S)-ketamine (esketamine) and (R)-ketamine (arketamine) enantiomers, which have been studied independent of racemic ketamine and with esketamine distinctly carrying United States Food and Drug Administration (FDA) approval for psychiatric use in adults. While initial preclinical evidence suggests pharmacological and behavioral divergence between these forms, the clinical significance of these findings is not yet known.

As such, ketamine and esketamine were generally assessed together in our survey and without discrimination. Congruent with our instrument wording and for the purpose of simplicity: “ketamine” will be used hereafter to capture data for both esketamine and ketamine. Overall, we had three exploratory aims as follows: (1) to characterize perceptions, acceptability, preferences, and concerns surrounding ketamine, (2) to compare acceptability of ketamine between different clinical/diagnostic presentations, and (3) to identify demographic variables associated with ketamine acceptability.

Discussion

The current study is the first to our knowledge to examine parental perceptions of ketamine as a treatment for pediatric mood disorders and suicidality. Parents recruited through MTurk completed an online survey that assessed concerns related to psychiatric use of ketamine, ratings of treatment acceptability, and factors related to treatment acceptability—including familial experiences with mental health conditions and treatments. Despite the experimental nature of ketamine treatment in minors, most parents reported positive attitudes toward use of ketamine in response to clinical vignettes involving MDD, bipolar disorder, and suicidality in adolescents.

Ketamine acceptability for suicidality was greater than that for bipolar disorder and MDD, while acceptability for bipolar disorder and MDD did not significantly differ, indicating greater openness to novel treatments for adolescent suicidality. This finding is consistent with the known burden of suicide in adolescents and supports the argument that clinical acuity should be factored into decisions involving interventional treatments. Moreover, when considered alongside evidence that ketamine may confer antisuicidal properties independent of its antidepressant effects, there is emerging rationale for short-term applications of ketamine in acute psychiatric settings.

However, these data must be reconciled with other uncertainties. For instance, there have been indicators of increased risk for suicidal ideation and completed suicide in certain adults receiving or following discontinuation (McIntyre et al. 2021) of treatment with esketamine. There is also insufficient research into ketamine's “rebound effects,” which have been demonstrated for other central nervous system drugs and imply that the transient benefits of symptomatic relief are tempered by risks of subsequent relapse and iatrogenic drug-seeking behavior.

Responses here point to preference for short-term applications of ketamine, such as limited drug sessions or less than 1 month of treatment for psychiatric stabilization, although a slight majority of parents conveyed openness to a longer course of treatment until symptoms improved. Importantly, there is still considerable hesitancy among clinical experts about what maintenance treatment with ketamine should look like, with no straightforward answers and perhaps varying widely on an individual basis.

A conservative approach to treatment, then, might best serve existing concerns. For instance, it has been proposed that use of ketamine in a psychotherapeutic context improves outcomes and decreases long-term need for medications in adults. This approach contrasts markedly with other strategies to sustain the efficacy of ketamine by increasing frequency of dosing. Parents reasonably may be interested in drug- or time-limited clinical paradigms such as ketamine-assisted psychotherapy in children.

For all indications assessed in our study, the primary concerns around ketamine involved its potential side effects and lack of FDA approval and, to a lesser extent, concerns about abuse potential, age of the child, or the child's capacity to make their own decision regarding treatment.

Parents were largely agreeable to treatment in children over 6 years of age, although more so for children older than 12. Parents were more comfortable with nasal and oral ketamine over more invasive, intravenous or intramuscular, routes of administration. Parental factors such as higher degree of education, personal history of psychiatric illness, familiarity with psychological treatments, and especially, comfort using other interventions in their children predicted greater acceptability toward ketamine. Prior knowledge of ketamine did not affect how parents rated acceptability.

Although there is accumulating evidence for the efficacy, safety, and tolerability of ketamine in younger populations, these remain open inquiries and are reflected in concerns reported here. In children, treatment-emergent dissociation, nausea, and hemodynamic changes are most commonly attributed to ketamine and generally mild and transient in nature. These safety data converge with adult reports, which have further characterized the possibility of rare but more severe adverse events involving cardiovascular, genitourinary, neurocognitive, and psychiatric systems and including abuse liability. An increased neurodevelopment sensitivity to ketamine in adolescents is theoretically plausible and certainly requires further investigation, although may depend on the dose and chronicity of administration.

Consistent with an ongoing understanding of the risks and benefits of treatment, the American Academy of Child and Adolescent Psychiatry (AACAP) does not yet recommend use of ketamine outside of research protocols. Candidate adolescents and their families are likely served best, then, by ongoing longitudinal and rigorous study of ketamine, which might be used toward FDA evaluation and approval.

As the case with approval of esketamine in adults, the way forward will presumably involve patentable and comparable ketamine derivatives, for which trials are already underway. Studies in adults establishing the benefits of intravenous, intranasal, oral, and intramuscular formulations of ketamine will require replication in children. Ultimately, provider sensitivity to parent knowledge, apprehension, and preferences as explored here could meaningfully guide conversations around psychoeducation, treatment readiness, and drug consent.

Other central questions remain to be answered. In adults, there is still no consensus on the appropriate position of ketamine in treatment algorithms, its optimal delivery, and the appropriate context for safe administration. These parameters may differ for minors. Although not addressed in this study, parental attitudes toward ketamine could be additionally shaped by knowledge of its dose-dependent psychedelic and dissociative effects, which have been shown to variably correlate with therapeutic outcome in adults.

Other psychedelic agents being explored in adults, such as psilocybin and 3,4-methylenedioxymethamphetamine, appear safe and effective when administered with adequate psychological support, consistent with best practices in hallucinogen research. However, the ethics of consent for and induction of altered states of consciousness in children requires careful examination.

An important limitation of this study was the use of crowdsourced convenience sampling as opposed to random sampling or clinical recruitment, bringing into question the ability to make larger, population-level inferences. Others have alternatively suggested that demographic characteristics of MTurk users are more representative of the general population than those of participants recruited from laboratory based samples. Given concerns about data quality associated with MTurk, we used stringent exclusion criteria and various mitigation strategies consistent with best practice to screen out automated, careless, or fraudulent reporting However, such strategies have also contributed to increasingly professionalized MTurk samples, with potential for bias due to “practice effects” and greater familiarity with social science research among qualified respondents.

Our findings further indicate disproportionate sampling of those with college or higher education, at a rate approximately double compared with the United States general adult population. It is possible, then, that familiarity and comfort with broad psychological treatments, knowledge of, and perhaps even acceptability toward ketamine are overrepresented in the current sample. As such, one valuable direction of study would be to replicate these findings in a clinical sample. Further work is needed to establish the reliability of this platform, although MTurk demonstrates promise as a tool for target sampling of special populations.

Conclusion

Although preliminary, our findings suggest that parents generally have positive attitudes toward the development and use of ketamine for treatment-resistant mood disorders and suicidality in youth. Our study provides orientation for further investigation and dissemination of knowledge around parental attitudes toward ketamine—an innovative and emerging treatment for adolescent mental health.

Clinical Significance

Ketamine has gained popularity as a mechanistically novel, rapid-acting, and promising psychiatric intervention in adults and is now being explored in adolescents. Investigation into parental decision-making processes involving ketamine is of high priority, given the necessary role of parents in consenting to treatment. We examined parental attitudes toward the emerging use of ketamine in adolescent mood disorders and suicidality and found high acceptability toward psychiatric applications of ketamine, with concerns primarily involving drug side effects and lack of FDA approval. Although ketamine is still an experimental treatment in children, these findings suggest that parents have interest in the application of ketamine as a treatment for pediatric mood disorders and point to future directions for research and clinical orientation.

*From the article (including references) here :

https://www.liebertpub.com/doi/10.1089/cap.2021.0078

 

[mr peabody]

Former Navy SEAL Marcus Capone and his wife Amber.

Approve Psychedelic Therapy to help prevent Veteran Suicides

by Marcus Capone | CAL MATTERS | May 3, 2021

After 13 years and multiple combat tours as a U.S. Navy SEAL, I was medically retired and ready to return to a normal life with my wife and children. But after being home, my family knew I was struggling to adapt to civilian life.

Every day I was struggling with a multitude of challenges including depression, anxiety, isolation, headaches, insomnia and impulsivity. Additionally, my wife began to notice my cognitive functions were starting to decline.

I was diagnosed with post-traumatic stress disorder, depression and anxiety. I visited therapists, was prescribed antidepressants and countless other pills, but nothing helped. While searching for treatments, we began learning more about traumatic brain injury. Thirteen years as an explosives expert, coupled with 15 years of tackle football had clearly taken a toll on me.

I had tried countless failed treatments and felt hopeless. But that’s when my wife found out about psychedelic therapy.

With no other options left, I felt I had nothing to lose by pursuing psychedelic treatment outside the U.S. Practically overnight, I felt a huge weight had been lifted and my cognitive functioning returned. After years of frustration and hopelessness, I got my life back.

The powerful and immediate relief I felt was too incredible not to pay forward. I knew we had to help my friends, former teammates and eventually all veterans access these lifesaving interventions. My wife, Amber, and I began a successful grassroots effort in 2017, which birthed our current organization, VETS Inc. Our goal is to change veteran health care and end the veteran suicide epidemic by providing resources, research and advocacy for military veterans seeking psychedelic therapies.

Now, California is taking groundbreaking steps to give all veterans access to psychedelic therapy through Senate Bill 519, introduced by Sen. Scott Wiener, a Democrat from San Francisco. It would be a vital line for life for so many in need.

Psychedelic therapy has become a promising approach for many veterans who have struggled with treatment-resistant trauma and life-altering injuries, including traumatic brain injury following their years of service. However, because treatment is only available legally in other countries, psychedelic therapy has been unavailable for many veterans, leading those who need it most to spend a great deal of money or risk arrest in order to receive the help that they need.

Addressing the current mental health crisis among our veterans requires immediate action. In recent years, veteran suicide rates have risen and the mental health crisis in this country has continued to grow. Many veterans have lost more of their fellow service members through suicide than they did while they were deployed. Past approaches to the mental health treatment of our veterans are simply not enough.

Treatments that may give veterans new hope and a chance to reclaim their lives should be made accessible and a priority. I applaud California for leading the way with SB 519, which will give veterans more access to these lifesaving treatments, and help end veteran suicide.

Marcus Capone is a former Navy SEAL and founder and chair of VETS Inc., [email protected].

Approve psychedelic therapy to help prevent veteran suicides | CalMatters

Our goal is to end the veteran suicide epidemic by providing research and advocacy for veterans seeking psychedelic therapies.

calmatters.org

 

[mr peabody]

Ketamine Monotherapy found to reduce suicidal ideation*

by Kalie VanDewater | Healio Psychiatry | 16 Sep 2021

In adults with treatment-resistant depression, ketamine monotherapy significantly reduced suicidal ideation compared with adjunctive ketamine, according to a retrospective study in Journal of Psychiatric Research.

“Ketamine has been almost exclusively studied as an antidepressant adjunct to other antidepressants, most commonly monoaminergic agents such as SSRIs,” Joshua D. Di Vincenzo, of University of Toronto’s University Health Network and Brain and Cognition Discovery Foundation and the Canadian Rapid Treatment Center of Excellence (CRTCE), and colleagues wrote. “Due to the dearth of high-quality clinical data on the safety and efficacy of ketamine as an antidepressant monotherapy, the majority of clinicians continue to prescribe ketamine to patients with the condition that they remain on a stable dose of one or more antidepressant drugs for the duration of treatment.”

Researchers analyzed data of 220 adults with treatment-resistant depression (TRD) who had four to six IV ketamine infusions for major depressive disorder at the CRTCE between August 2018 and May 2021.

They classified 39 participants (18 percent) not currently using other antidepressants, with the exception of psychostimulants and sedatives, as the monotherapy group and 181 participants (82 percent) using at least one other antidepressant drug as the adjunctive group.

“Importantly, baseline QIDS-SR16 SI subscores were significantly higher in the monotherapy group, so a greater decrease on the QIDS-SR16 SI in this group compared to the adjunctive group may be expected,” Di Vincenzo and colleagues noted.

In both groups, ketamine infusion had a significant large effect on overall depressive symptoms and anxiety, and a significant medium effect on suicidal ideation and functional impairment.

Limitations included retrospective design, absence of controls, use of a TRD population and incomplete data due to dropouts and participants not completing assessments. Di Vincenzo and colleagues indicated a need for larger study populations and suggested characterizing patients who will benefit from monotherapy.

“Future research should endeavor to determine which patients are most likely (or less likely) to benefit from combination treatment versus monotherapy in persons with MDD,” they wrote. “Moreover, whether a specific combination of ketamine and monoaminergic-based antidepressant is optimal also awaits empirical confirmation.”

*From the article here :

Ketamine monotherapy reduces suicidal ideation in adults with depression

In adults with treatment-resistant depression, ketamine monotherapy significantly reduced suicidal ideation compared with adjunctive ketamine, according to a retrospective study in Journal of Psychiatric Research.

www.healio.com

 

[mr peabody]

How psychedelics can help end the suicide epidemic

by Emily Jarvie | PSYCHEDELIC SPOTLIGHT | 21 Sep 2021

There is increasing scientific evidence that a variety of psychedelics can be used to treat a number of the risk factors linked to suicide, in addition to reducing suicidality.

Tragically, more than 700,000 people around the world die by suicide every year. This is equal to one person every 40 seconds. According to the World Health Organization, for every adult who has died by suicide, there may be more than 20 others attempting suicide. These figures are also likely to be underestimated due to the stigma around suicide and that some of these deaths are classified as unintentional injuries.

Even more tragically, suicide rates in the United States are increasing. According to the Centers for Disease Control and Prevention, they have increased 33% between 1999 and 2019, and suicide is the 10th leading cause of death for Americans.

But psychedelics provide new hope as a possible treatment for suicidal ideation and related mental health conditions such as depression, post-traumatic stress disorder (PTSD), trauma, and addiction.​

Understanding suicide’s risk factors​

What causes a person to commit suicide is incredibly complex. Risk factors include:

· Health factors such as depression, substance use problems, mental illness, and physical health conditions
· Environmental factors such as stressful life events, including divorce, unemployment, financial stress, or having been recently released from prison or jail
· And historical factors, including previous suicide attempts, a family history of suicide, or a history of childhood abuse or trauma

In the United States, men die by suicide 3.63 times more often than women, and veterans make up nearly a quarter of all suicide deaths in the country.

While there is no single cause for suicide, there is also no one, easy solution. In 2003, the World Health Organization recognized suicide as a public health crisis by creating World Suicide Prevention Day, held every year on September 10. In the United States, National Suicide Prevention Week is also held annually in September, this year from September 5 to 11.

“The goal of World Suicide Prevention Day is to shine a light on the problem in hopes of reaching people who are struggling,” Canadian Association for Suicide Prevention Executive Director Sean Krausert tells Psychedelic Spotlight. “It is a day dedicated to a very important message: suicides are preventable. It is observed in over 60 countries with hundreds of events around the world.”​

The potential of psychedelics in preventing suicide​

There is increasing scientific evidence that a variety of psychedelics can be used to treat a number of the risk factors linked to suicide, in addition to reducing suicidality—a term that refers to suicidal ideation, suicide plans, and suicide attempts—itself.

A 2021 systematic review published in ACS Pharmacology & Translational Science on the relationship between classic psychedelics and suicidality noted that while suicidality is a potential safety concern when it comes to classic psychedelics, it is concurrently a mental health concern that psychedelic therapy shows promise in targeting. “In recent psychedelic therapy clinical trials, we found no reports of increased suicidality and preliminary evidence for acute and sustained decreases in suicidality following treatment,” researchers said.

The results of two studies in 2017 also showed a decrease in suicidality due to psychedelics use. Participants in both studies completed self-report questionnaires on experiential avoidance, depression severity, and suicidal ideation before using a psychedelic in ceremonial and non-ceremonial settings, two weeks after psychedelic use, and again four weeks after psychedelic use. Researchers concluded: “These results suggest that psychedelics may lead to a significant decrease in experiential avoidance, depression severity, and suicidal ideation.”

The researchers also noted that given the limited efficacy of Selective Serotonin Reuptake Inhibitors (SSRIs) – which are widely used antidepressants – in treating mild to moderate depression and suicidal ideation, there is the scope to assess if psychedelics could improve and protect mental health in non-clinical populations. “Despite the burden associated with depression and suicide, there are significant limitations surrounding current first line interventions,” the researchers said. “We conclude that integrating psychedelics with psychotherapeutic interventions that target experiential avoidance, such as acceptance and commitment therapy, may enhance therapeutic outcomes.”

A third study from 2015 evaluated if psychedelic drug use could reduce the risk of suicidality in a community-based cohort of marginalized Canadian women in the Metro Vancouver area. Its multivariable analysis found reported lifetime use of naturalistic psychedelics was associated with a 60% reduced hazard for suicidality. “Our findings demonstrate that naturalistic psychedelic drug use is independently associated with reduced suicidality, while other illicit drug use (specifically crystal methamphetamine) and childhood trauma predispose women to suicidality,” researchers concluded.

Further, research published in 2015 by Johns Hopkins University and the University of Alabama based on a survey of more than 190,000 American adults found that certain non-addictive psychedelic drugs were associated with fewer suicidal thoughts, planning, and attempts. It found psychedelic use resulted in a 14% reduced likelihood of suicidal thinking within the past year, a 29% reduced likelihood of suicide planning within the past year, and a 36% reduced likelihood of attempting suicide within the past year. Study author Dr. Matthew Johnson said at the time: “These could be breakthrough medical treatments that we’ve been ignoring for the past 30 years. We need to carefully examine these cautiously and thoroughly.” ​

What's next for psychedelics and suicide prevention? ​

Fortunately, psychedelics are beginning to be recognized as a viable treatment option for suicidal ideation. In a bid to reduce the number of suicides occurring in the United States, the National Institute of Mental Health (NIMH) in May announced that it would be supporting eight projects that are investigating the feasibility and safety of rapid-acting suicide prevention interventions, involving ketamine, esketamine, or transcranial magnetic stimulation (TMS).

In addition, many leaders in the psychedelics space advocate the use of psychedelics in preventing suicide, with several companies carrying out their own research and drug development work to address suicidal ideation and associated conditions. One of these advocates is former professional hockey player and founder of life sciences company Wesana Health Daniel Carcillo, who has spoken openly about his own experience with suicidal ideation after suffering a traumatic brain injury. Carcillo had plans to take his own life when he found healing through psilocybin.

“Psychedelics really did save my life,” he told the Psychedelic Spotlight Podcast last year. “You are in a situation where you have a beautiful, healthy family, you have a car in the driveway, you have a roof over your head, you have money to buy food – and yet you are thinking about killing yourself. That is a really scary situation to be in. I was in the darkest place I’ve ever been, and it was a hero dose of psilocybin that brought me out of it.”

To mark World Suicide Prevention Day, Psychable, which connects those interested in legally exploring psychedelic-assisted therapy with practitioners, highlighted how the company is doing its part to advance the conversation surrounding the use of psychedelics as medicine to treat mental health issues such as depression.

“Suicide is a unique cause of death in the sense that it is fully preventable,” said Psychable CEO and Co-Founder Jemie Sae Koo. “With overdue conversations happening surrounding access to mental health resources, the increase of approved psychedelic-assisted therapy and depression treatment options, and enhanced understanding surrounding the use of psychedelics as medicine, our mission to connect those who struggle with depression to practitioners in the psychedelic-assisted therapy space is more imperative than ever.”

If you or someone you know is in crisis, you can seek help from:
· The National Suicide Prevention Lifeline: speak with a certified listener by calling 1-800-273-8255
· The Veterans Crisis Line and Military Crisis Line: speak to a US Department of Veterans Affairs responders by calling 1-800-273-8255 and pressing 1· The Crisis Text Line: connect with a trained listener by texting HELLO to 741741

How Psychedelics Can Help End the Suicide Epidemic | Psychedelic Spotlight

More than 700,000 people die by suicide every year, and there is increasing scientific evidence that psychedelics treat related risk factors.

psychedelicspotlight.com

 

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Ketamine rapidly improves cognitive function, making those in suicidal crisis less likely to harm themselves

by Columbia University Irving Medical Center | Medical Xpress | 3 Nov 2021

Ketamine, a drug used to treat mood disorders and severe depression, improved the thinking and reasoning of those who expressed thoughts of killing themselves within 24 hours, according to a Columbia University study.

Published today in the Journal of Clinical Psychiatry, the study found that one dose of ketamine not only reduced the severity of depression in people with suicide ideation, many of whom had not responded to other antidepressants, but also made them feel safer and less likely to harm themselves because it rapidly diminished their suicidal ideation.

"We found that suicidal ideation is not just related simply to severity of depression," said J. John Mann, MD, senior author and the Paul Janssen Professor of Translational Neuroscience (in Psychiatry and in Radiology) at Columbia University. "There are other reasons, including cognitive improvements that are related to a decline in suicidal ideation and thereby make those who are suicidal safer."

When they began the five-year trials, Columbia researchers knew that anesthetic ketamine, in much lower doses where it has no anesthetic effect, rapidly reduced depressive symptoms and suicidal ideation in some patients. But they wanted to obtain a better understanding of the mechanisms behind this effect and decided to examine the drug's impact on neurocognitive performance.

Study found improved cognition appeared quickly

Researchers followed 78 participants suffering with major depressive disorder and clinically significant suicidal ideation and found that a standard dose of ketamine given intravenously produced a rapid improvement of suicidal thoughts in some individuals, and part of this improvement was correlated with and improvement in problem-solving and thinking more clearly. This improvement in neurocognition—and suicidal ideation—occurred even when some of these individuals did not show comparable improvement in depressive symptoms.

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

The study compared the effects of intravenously administered ketamine—not yet approved by the FDA but provided off-label at treatment centers throughout the country—to midazolam, a sedative prescribed for anxiety and depression. It found greater cognitive improvements in thinking and reasoning in those who were given the ketamine.

Suicidal thinking diminished for six weeks with one ketamine treatment

Participants in the study who responded positively to the ketamine treatment continued to do well for up to six weeks after they were given an initial infusion in conjunction with other antidepressants that were tailored to the needs of each specific patient.

Suicide is the third leading cause of death for those ages 10-34 and the 10th leading cause of death overall in the United States. Dr. Mann said since 90 percent of those who die by suicide in the U.S. have a psychiatric illness and 60 percent of those people suffer a major depressive episode before a suicide attempt, it would be a major benefit if ketamine could be used to lessen suicidal risk.

Approved by the Food and Drug Administration for medical use in 1970, ketamine was first used as an anesthetic to treat injured soldiers during in the Vietnam War, but it soon became notorious as a party drug, nicknamed Special K, used illicitly in clubs for its hallucinogenic and dissociative effects.

But research into the drug's potential as a treatment for depression and antidote to suicidal thoughts continued, and in 2019 the FDA approved intra-nasal spray esketamine, derived from ketamine, to be used in conjunction with an oral depressant in adults with treatment-resistant depression.

Ketamine is clearly changing functioning of important neurotransmitter systems in many key areas of the brain, and further study of ketamine and other drugs like it could lead to new mental health treatments, the researchers said. However, more research is needed to determine why some people respond to ketamine—which alters the release of glutamate that regulates much of the nervous system and helps the brain rewire itself by creating new connections and pathways—and other patients do not.

Since neuropsychological risks of long-term repeated ketamine treatments are unknown, researchers said further study is needed. Designing rapid-acting antidepressants like ketamine without the side effects of "tripping" or out-of-body experiences that could be taken in pill form at home instead of in a clinical setting, is also important, Mann said.

Ketamine rapidly improves cognitive function, making those in suicidal crisis less likely to harm themselves

Ketamine, a drug used to treat mood disorders and severe depression, improved the thinking and reasoning of those who expressed thoughts of killing themselves within 24 hours, according to a Columbia University study.

medicalxpress.com

 

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​

Ketamine found to benefit neurocognition in depression, suicidal ideation*

by Joe Gramigna, MA | HEALIO | 23 Nov 2021

Ketamine improved neurocognitive outcomes at 24 hours among patients with depression and suicidal ideation, according to study results published in Journal of Clinical Psychiatry.

“Intravenous ketamine, an N-methyl-d-aspartate receptor antagonist, has robust therapeutic effects on both depression and suicidal ideation within hours to days in some depressed patients,” John G. Keilp, PhD, of the department of molecular imaging and neuropathology at New York State Psychiatric Institute, and colleagues wrote. “However, its impact on neurocognition, particularly aspects of neurocognition associated with suicidal behavior, is not well understood.”

The investigators reported neurocognitive results from a randomized trial that compared ketamine with midazolam among 78 patients with depression who had clinically significant suicidal ideation. Their primary goal was to examine neurocognitive changes between baseline and 24 hours after treatment and to assess correlations between these changes in neurocognitive performance and changes in depressive symptoms and suicidal thinking. Patients completed neuropsychological testing before and 1 day after double blind treatment with IV ketamine (n = 39) or midazolam (n = 39). A subgroup randomly assigned to midazolam who did not experience ideation remittance after initial infusion received open ketamine and other neurocognitive testing 1 day after treatment. Change in performance on this neurocognitive battery served as the primary outcome.

Results showed rapid improvement in suicidal ideation and mood associated with blinded ketamine vs. midazolam. Compared with midazolam, ketamine correlated with specific improvement in reaction time and interference processing/cognitive control, the latter measure having previously been shown to be linked to past suicide attempt in depression. Those who received midazolam but did not remit who later received open ketamine and retested exhibited improved reaction time and interference processing/cognitive control compared with both of their prior assessments. The researchers did not observe an association between neurocognitive improvement and changes in depression, suicidal thinking or general mood.

“Overall, in this sample of depressed adults with suicidal ideation, neurocognitive improvement at 24 hours after a single, subanesthetic ketamine infusion appeared specific to response time and interference processing/attention control tasks,” Keilp and colleagues wrote. “These improvements were independent of reductions in depression severity or suicidal ideation, suggesting that ketamine-related therapeutic effects on neurocognition may be orthogonal to ketamine’s effects on mood symptoms."

“Neuropsychological risks of long-term, repeated therapeutic ketamine treatment are unknown but warrant further study given that heavy, chronic use, as in addiction, is associated with neurocognitive impairment, with some impairment persisting even when use is discontinued,” they added.

*From the article here :

Ketamine benefits neurocognition in depression with suicidal ideation

Ketamine improved neurocognitive outcomes at 24 hours among patients with depression and suicidal ideation, according to study results published in Journal of Clinical Psychiatry. “Intravenous ketamine, an N-methyl-d-aspartate receptor antagonist, has robust therapeutic effects on both...

www.healio.com

 

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Depression and suicidal ideation reduced after psychedelic use

by Derek Beres | BIG THINK | 9 Sep 2020

Another study confirms the positive effects of psychedelics on mental health.​

• Two studies found reduced rates in depression severity, suicidal ideation, and experiential avoidance four weeks after taking psychedelics.​
• With hundreds of millions of dollars in investment flowing into psychedelics companies, a renaissance in the field is occurring.​
• Researchers hope these findings will lead to better therapeutic modalities for mental health disorders.​

From mysticism to mental health, the journey of psychedelics in American culture has been quite a trip. With hundreds of millions of dollars flowing into psychedelics startups—the "Rainbow Rush"—and a clinical study investigating the therapeutic effects of MDMA and LSD (besides many other single-substance trials), a renaissance is unfolding right before our eyes.



Dr Robin Carhart-Harris is the head of the Centre for Psychedelic Research at Imperial College London. He's published nearly a hundred studies on psychedelics. A recent research article, published in Frontiers in Psychiatry, found that the effects of psychedelics are associated with a decrease in the severity of depression and suicidal ideation.

The two studies in the article include 358 volunteers. Each participant filled out questionnaires about their levels of depression, suicidal ideation, and experiential avoidance—"openness to one's experiences and engagement in behaviors that are congruent with one's values." They then took part in either ceremonial psychedelic consumption (as in an ayahuasca ritual) or non-ceremonial usage. Carhart-Harris's team followed up two weeks and four weeks later.

The parameters of the first study were broad. The individuals had a variety of psychedelics to choose from: LSD, ayahuasca, DMT, salvia divinorum, mescaline, psilocybin mushrooms, or ibogaine. Interestingly, respondents that planned on using ketamine were excluded. While the sedative has recently been touted as a psychedelic, it's not classically considered in this regard.

The second study was slightly more structured, as the team accepted participants attending a psychedelic ceremony. This is especially important given the work by organizations like MAPS ( Multidisciplinary Association for Psychedelic Studies), which is training psychedelic therapists in the hopes of legalized MDMA by 2023.

"Such ceremonies usually involve the presence of one or more 'facilitators' — individuals who aim to provide a safe, conducive environment, emotional support, as well as certain contextual stimuli which are intended to enhance or structure the psychedelic experience."

This research differs from previous studies in that psychedelic usage was not conducted in a clinical setting. As the environment is an important component of the psychedelic ritual, researchers are more likely to receive real-world results from anecdotal experiences. Letting go in a clinic poses challenges.

The results, the team writes, were overwhelmingly positive.

"Across two separate studies, we found significant decreases in depression severity and suicidal ideation 4-weeks after psychedelic use… We found that use of psychedelics was associated with decreases in experiential avoidance 2-weeks later and was sustained for at least 4-weeks."

Psychedelic researchers will continue to face is the difficulty of implementing a control group, although at least one study found that the placebo effect is relevant. A larger barrier will be financial support from pharmaceutical companies with vested interests in current drug protocols.

That said, this renaissance shows no signs of slowing. During a time when rates of anxiety, depression, and suicide are rising, a return to psychedelic rituals can help chip away at the frustration and confusion of this moment. These substances have been used for millennia to keep societies intact. Such ceremonies are sorely needed right now.

How psychedelics can treat depression - Robin Carhart Harris

Dr Robin Carhart-Harris is the head of the Centre for Psychedelic Research at Imperial College London. He's published nearly a hundred studies on psychedelics. A recent research article, published in Frontiers in Psychiatry, found that the effects of psychedelics are associated with a decrease...

bigthink.com

 

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Psilocybin-assisted psychotherapy reduces suicidal ideation among cancer patients*

by Beth Ellwood | PsyPost | 15 Dec 2021

Recent findings published in the journal ACS Pharmacology & Translational Science suggest that psilocybin, in conjunction with psychotherapy, reduces suicidal ideation and loss of meaning among patients with life-threatening cancer. These mental health improvements were maintained months to years following treatment.

Cancer patients are at increased risk of suicidal ideation and completed suicide, particularly those with advanced illness. Such patients often experience existential distress and a loss of meaning in life, and little is known about pharmacological treatments that might alleviate these effects.

Researchers Stephen Ross and his colleagues say that there is evidence that the psychedelic drug psilocybin might alleviate suicidal ideation. The researchers were motivated to study whether psilocybin-assisted psychotherapy might produce sustained reductions in suicidal ideation among patients with life-threatening cancer.

Ross and his team analyzed data from a previous crossover study where they randomly assigned a sample of individuals with advanced cancer to one of two dosing sequences in conjunction with psychotherapy. Participants in one condition were given psilocybin on the first dosing session and niacin seven weeks later, while participants in a second condition were given niacin first and psilocybin seven weeks later. The niacin served as an active control.

For the current study, the researchers focused on participants who presented with suicidality at baseline, resulting in a sample of 11 participants with an average age of 60. At baseline, participants completed assessments of suicidal ideation, loss of meaning, hopelessness, and spiritual well-being. They then partook in various follow-up assessments throughout their psychotherapy treatment. Assessments for suicidal ideation were taken 8 hours after dose 1, 2 weeks after dose 1, 7 weeks after dose 1, and 6.5 months after dose 2. Assessments for loss of meaning, hopelessness, and spiritual well-being, were taken 2 weeks after dose 1, 6.5 months after dose 2, and 3.2 years and 4.5 years after baseline.

For the group who received psilocybin first, suicidal ideation and loss of meaning scores dropped significantly at every assessment point compared to baseline levels. This was not true for the group that received niacin first. Furthermore, when comparing the two groups, the psilocybin-first group had lower average loss of meaning scores compared to the niacin-first group at 2 weeks following dose 1.

According to the follow-up assessments, these changes were somewhat long-term. Within-subject decreases in suicidal ideation and loss of meaning (compared to baseline) were still apparent when assessed 6.5 months later. Moreover, reductions in loss of meaning were maintained at the 3.2-year and 4.5-year assessments.

Importantly, reductions in suicidal ideation were correlated with decreases in loss of meaning, hopelessness, and demoralization. While the study design does not allow causal inferences, the authors suggest that loss of meaning might mediate the link between suicidal ideation and a cancer diagnosis. They say that psilocybin-assisted psychotherapies that include existential components might lower suicidal thinking by “enhancing meaning-making” — a hypothesis that could be tested in future trials.

“These preliminary results suggest that psilocybin-assisted psychotherapy could be a novel pharmacological−psychosocial treatment modality for advanced-cancer-related suicidality,” Ross and colleagues say. “Further empirical research is needed to definitively establish its efficacy and potential mechanisms of action.” If such treatment proves effective, the implications are far-reaching. Similar therapies might be introduced to treat suicidality among patients with major depressive disorder (MDD) or patients with other life-threatening illnesses than cancer.

The study, “Acute and Sustained Reductions in Loss of Meaning and Suicidal Ideation Following Psilocybin-Assisted Psychotherapy for Psychiatric and Existential Distress in Life-Threatening Cancer,” was authored by Stephen Ross, Gabrielle Agin-Liebes, Sharon Lo, Richard J. Zeifman, Leila Ghazal, Julia Benville, Silvia Franco Corso, Christian Bjerre Real, Jeffrey Guss, Anthony Bossis, and Sarah E. Mennenga.

*From the article here :

Psilocybin-assisted psychotherapy reduces loss of meaning and suicidal ideation among cancer patients

Recent findings published in the journal ACS Pharmacology & Translational Science suggest that psilocybin, in conjunction with psychotherapy, reduces ...

www.psypost.org

 

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Regular oral doses of Ketamine significantly reduce suicidal thoughts

by Nick Lavars | NEW ATLAS | 7 Feb 2021

A new study has found that suicidal thoughts may be significantly reduced through regular oral doses of ketamine.

The notion of using ketamine as an anti-depressant is gathering steam on the back of enlightening research that has shown us how it can suppress the brain’s “anti-reward” center, mend broken neural circuits and interact with serotonin receptors to boost the release of dopamine. A new study has shown how this might work in practice, with chronic suicidality sufferers offered rapid relief through regular oral administration of the drug in clinical settings.

Among the many studies to probe the anti-depressant effects of ketamine was one published in 2017 which focused specifically on suicidal patients, the first to do so. The authors found that low-dose infusions of ketamine caused a major reduction in suicidal thoughts just 24 hours later, and had positive effects on mood, depression and fatigue that lasted for at least six weeks.

This new study, carried out at the University of the Sunshine Coast in Australia, again focuses on sufferers of acute suicidality, with the team hoping to build on earlier research, which has demonstrated ketamine’s anti-depressant potential when delivered via injection.

“Intravenous administration, however, is invasive, expensive and carries a higher chance of adverse reactions due to its injection straight into the blood stream,” says principal investigator Dr Adem Can. “So logistically it is a lot easier and faster to clinically administer an oral dose.”

The study involved 32 adults suffering from chronic suicidal thoughts, who were administered ketamine orally over a six-week period, The subjects were assessed using standard scales for suicidal thoughts and depressive symptoms, with 69 percent of them showing clinical improvement at the six-week point. Half of them, meanwhile, still reported significant improvements four weeks after the final dose.

“On average, patients experienced a significant reduction in suicide ideation, from a high level before the trial to below the clinical threshold by week six of the trial,” Dr Can says. “In medicine, this response rate is significant, particularly given it was experienced by patients with chronic suicidality, which can be difficult to treat.”

The study size is small but the team is enthused with the results, particularly because of the range of afflictions suffered by the subjects that led to their suicidal thoughts, including depression, anxiety and borderline personality disorder.

“Yet the treatment still worked across the group,” says study supervisor Professor Jim Lagopoulos. “This means the trial group was representative of the community we are serving, where suicidality is often accompanied by one or more other conditions. So results like these across the spectrum are very encouraging.”

The team does note, however, that more research is needed to further explore the efficacy of oral ketamine doses across randomized control groups.

The research was published in the journal Translational Psychiatry.

Regular oral doses of ketamine significantly reduce suicidal thoughts

The notion of using ketamine as an anti-depressant is gathering steam on the back of enlightening research that has shown us how it can suppress the brain’s “anti-reward” center, mend broken neural circuits and interact with serotonin receptors to boost the release of dopamine. A new study has…

newatlas.com

 

[mr peabody]

Ketamine found safe for acutely suicidal patients*

by Laurell Haapanen | Psychiatry Advisor

A single infusion of ketamine is a safe and feasible treatment option for suicidal patients presenting to the emergency department, according to study results published in Depression and Anxiety.

Enrollees at the University of Alabama at Birmingham’s emergency department were included if they met the criteria for major depression, bipolar depression, or depression not otherwise specified, according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, or dysthymia as confirmed by the Mini International Neuropsychiatric Interview. Clinically significant and active suicidal ideation was assessed using the Beck Scale for Suicidal Ideation and Columbia Scale for Suicide Severity Rating.

The trial enrolled 18 patients with acute suicidal ideation who required hospitalization. An equal number of patients were randomly assigned to receive either intravenous ketamine 0.2 mg/kg or a saline placebo. After 90 minutes of infusion, 88% of the ketamine group had achieved remission of suicidal ideation compared with 33% of the placebo group. No serious adverse events were noted. As a secondary objective, investigators looked at ketamine’s effect on depressive symptoms and suicide‐related constructs: hopelessness, pessimistic thoughts, anxiety, and impulsivity.

3 days post-infusion, there was a reduction of 91 percent in Beck Hopelessness Scale scores, and a decrease in pessimistic thoughts starting at 15 minutes after ketamine infusion and lasting to day 3. Anxiety was used to assess potential threats; 3 days after infusion, there was an 82 percent reduction of anxiety.

“A single infusion of ketamine, administered in the emergency department, is a safe and feasible treatment option for depressed, suicidal patients. We found it to alleviate suicidal ideation in the first hours after infusion,” the investigators concluded. “Future larger‐scale studies should consider using a higher dose of ketamine and addressing a transdiagnostic approach.”

*From the article here :

Ketamine Safe for Acutely Suicidal Patients in the Emergency Department Setting - Psychiatry Advisor

In patients with depression 88% of the ketamine group had achieved remission of suicidal ideation 90 minutes post-infusion, according to the investigators.

www.psychiatryadvisor.com

 

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69% of suicidal patients saw ‘significant’ improvement with ketamine therapy

by Jill Ettinger | Psychedelic Spotlight

New research out of Australia points to the benefits of ketamine therapy in reducing suicidal thoughts. The findings are published in the journal Translational Psychiatry.

According to the study, two-thirds of the patients who participated — more than 60 percent — experienced a significant reduction in suicidal thoughts after taking oral doses of ketamine for six weeks.

Participants were defined as suffering from chronic suicidality — ongoing thoughts of suicide.

“On average, patients experienced a significant reduction in suicide ideation, from a high level before the trial to below the clinical threshold by week six of the trial,” lead researcher Adem Can of the University of Sunshine Coast said in a statement. “In medicine, this response rate is significant, particularly given it was experienced by patients with chronic suicidality, which can be difficult to treat.”

But for the participants who experienced relief, the benefit was notable — dropping below the cut-off for “clinically significant” levels of suicidal ideation.

“Overall, oral ketamine led to significant short-term and prolonged improvements in suicidal ideation, affective symptoms, well-being and socio-occupational functioning in this sample of adults with a history of chronic suicidality and Major Depressive Disorder,” the authors wrote.

According to the researchers, this is first to explore the “feasibility, safety, and tolerability” of ketamine on chronic suicidality in patients with varying psychiatric conditions including mood, anxiety, and personality disorders.

Suicide rates in the U.S.

The U.S. is experiencing a suicide epidemic, according to the Centers for Disease Control and Prevention. Rates of suicide increased by more than 25 percent between 1999 and 2016.

According to the CDC, suicide was the tenth-leading cause of death in the U.S. in 2018.

The coronavirus pandemic has also taken a toll. According to the Brookings Institute, suicide calls were slightly higher in 2020 than in previous years. “But there are worrisome signs, such as sharp increases in gun sales (guns are responsible for most successful suicides),” Brookings noted.

Ketamine Therapy

Ketamine therapy is gaining traction around the world. With a growing number of legal treatment clinics now operational, it’s being used to treat a variety of issues from pain management to mental health.

Technically, not a psychedelic, ketamine is a hallucinogen and dissociative, but it works in some of the same ways as psychedelics. It can bring long-term relief after just a few doses, unlike pharmaceuticals for issues like depression that must be taken daily.

Ketamine’s pain management benefits have earned it an essential medicine designation by the World Health Organization; it’s especially effective in children. And it offers an opioid-free pain management system, helping to decrease the risk of drug abuse and addiction. Opioid addiction is a national crisis; 2018 data revealed 128 people in the U.S. die every day from opioid abuse.

Studies are finding mixed results on its benefits. Some studies, like this latest one on suicide, see extremely high success rates. But some studies, like those for people with treatment-resistant depression, have seen lower rates of success.

If you are having suicidal thoughts, please call the Suicide Prevention Lifeline at 1-800-273-8255 or visit the website.

Study: 69% of Suicidal Patients Saw 'Significant' Improvement With Ketamine Therapy

A new study links ketamine therapy to a significant reduction in thoughts of suicide for 69 percent of study participants.

psychedelicspotlight.com

 

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Ketamine hailed as a miracle for treating severe depression

by Sara Solovitch

It was November 2012 when Dennis Hartman, a Seattle business executive, managed to pull himself out of bed, force himself to shower for the first time in days and board a plane that would carry him across the country to a clinical trial at the National Institute of Mental Health (NIMH) in Bethesda.

After a lifetime of profound depression, 25 years of therapy and cycling through 18 antidepressants and mood stabilizers, Hartman, then 46, had settled on a date and a plan to end it all. The clinical trial would be his last attempt at salvation.

For 40 minutes, he sat in a hospital room as an IV drip delivered ketamine through his system. Several more hours passed before it occurred to him that all his thoughts of suicide had evaporated.

“My life will always be divided into the time before that first infusion and the time after,” Hartman says today. “That sense of suffering and pain draining away. I was bewildered by the absence of pain.”

Ketamine, popularly known as the psychedelic club drug Special K, has been around since the early 1960s. It is a staple anesthetic in emergency rooms, regularly used for children when they come in with broken bones and dislocated shoulders. It’s an important tool in burn centers and veterinary medicine, as well as a notorious date-rape drug, known for its power to quickly numb and render someone immobile.

Since 2006, dozens of studies have reported that it can also reverse the kind of severe depression that traditional antidepressants often don’t touch. The momentum behind the drug has now reached the American Psychiatric Association, which, according to members of a ketamine task force, seems headed toward a tacit endorsement of the drug for treatment-resistant depression.

Experts are calling it the most significant advance in mental health in more than half a century. They point to studies showing ketamine not only produces a rapid and robust antidepressant effect; it also puts a quick end to suicidal thinking.

Traditional antidepressants and mood stabilizers, by comparison, can take weeks or months to work. In 2010, a major study published in JAMA, the journal of the American Medical Association, reported that drugs in a leading class of antidepressants were no better than placebos for most depression.

A growing number of academic medical centers, including Yale University, the University of California at San Diego, the Mayo Clinic and the Cleveland Clinic, have begun offering ketamine treatments off-label for severe depression, as has Kaiser Permanente in Northern California.

The ‘next big thing’

“This is the next big thing in psychiatry,” says L. Alison McInnes, a San Francisco psychiatrist who over the past year has enrolled 58 severely depressed patients in Kaiser’s San Francisco clinic. She says her long-term success rate of 60 percent for people with treatment-resistant depression who try the drug has persuaded Kaiser to expand treatment to two other clinics in the Bay Area. The excitement stems from the fact that it’s working for patients who have spent years cycling through antidepressants, mood stabilizers and various therapies.

“Psychiatry has run out of gas in trying to help depressed patients for whom nothing has worked," she says. “There is a significant number of people who don’t respond to antidepressants, and we’ve had nothing to offer them other than cognitive behavior therapy, electroshock therapy and transcranial stimulation.”

McInnes is a member of the APA’s ketamine task force, assigned to codify the protocol for how and when the drug will be given. She says she expects the APA to support the use of ketamine treatment early this year.

The guidelines, which follow the protocol used in the NIMH clinical trial involving Hartman, call for six IV drips over a two-week period. The dosage is very low, about a tenth of the amount used in anesthesia. And when it works, it does so within minutes or hours.

“It’s not subtle,” says Enrique Abreu, a Portland, Ore., anesthesiologist who began treating depressed patients with it in 2012. “It’s really obvious if it’s going to be effective."

“And the response rate is unbelievable. This drug is 75 percent effective, which means that three-quarters of my patients do well. Nothing in medicine has those kind of numbers.”

So far, there is no evidence of addiction at the low dose in which infusions are delivered. Ketamine does, however, have one major limitation: Its relief is temporary. Clinical trials at NIMH have found that relapse usually occurs about a week after a single infusion.

Ketamine works differently from traditional antidepressants, which target the brain’s serotonin and noradrenalin systems. It blocks N-methyl-D-aspartate (NMDA), a receptor in the brain that is activated by glutamate, a neurotransmitter.

In excessive quantities, glutamate becomes an excitotoxin, meaning that it overstimulates brain cells.

“Ketamine almost certainly modifies the function of synapses and circuits, turning certain circuits on and off,” explains Carlos Zarate Jr., NIMH’s chief of neurobiology and treatment of mood disorders, who has led the research on ketamine. “The result is a rapid antidepressant effect.”

Rapid effect

A study published in the journal Science in 2010 suggested that ketamine restores brain function through a process called synaptogenesis. Scientists at Yale University found that ketamine not only improved depression-like behavior in rats but also promoted the growth of new synaptic connections between neurons in the brain.

Even a low-dose infusion can cause intense hallucinations. Patients often describe a kind of lucid dreaming or dissociative state in which they lose track of time and feel separated from their bodies. Many enjoy it; some don’t. But studies at NIMH and elsewhere suggest that the psychedelic experience may play a small but significant role in the drug’s efficacy.

“It’s one of the things that’s really striking,” says Steven Levine, a Princeton, N.J., psychiatrist who estimates that he has treated 500 patients with ketamine since 2011. “With depression, people often feel very isolated and disconnected. Ketamine seems to leave something indelible behind. People use remarkably similar language to describe their experience: ‘a sense of connection to other people,’ ‘a greater sense of connection to the world.’ ”

Although bladder problems and cognitive deficits have been reported among long-term ketamine abusers, none of these effects have been observed in low-dose clinical trials. In addition to depression, the drug is being studied for its effectiveness in treating obsessive-compulsive disorder, post-traumatic stress disorder, extreme anxiety and Rett syndrome, a rare developmental disorder on the autism spectrum.

Booster treatments

The drug’s fleeting remission effect has led many patients to seek booster infusions. Hartman, for one, began his search before he even left his hospital room in Bethesda.

Four years ago, he couldn’t find a doctor in the Pacific Northwest willing to administer ketamine. “At the time, psychiatrists hovered between willful ignorance and outright opposition to it,” says Hartman, whose depression began creeping back a few weeks after his return to Seattle.

It took nine months before he found an anesthesiologist in New York who was treating patients with ketamine. Soon, he was flying back and forth across the country for bimonthly infusions.

Upon his request, he received the same dosage and routine he’d received in Bethesda: six infusions over two weeks. And with each return to New York, his relief seemed to last a little longer. These days, he says that his periods of remission between infusions often stretch to six months. He says he no longer takes any medication for depression besides ketamine.

“I don’t consider myself permanently cured, but now it’s something I can manage,” Hartman says, “like diabetes or arthritis. Before, it was completely unmanageable. It dominated my life and prevented me from functioning.”

In 2012 he helped found the Ketamine Advocacy Network, a group that vets ketamine clinics, advocates for insurance coverage and spreads the word about the drug.

And word has indeed spread. Ketamine clinics, typically operated by psychiatrists or anesthesiologists, are popping up in major cities around the country.

Levine, for one, is about to expand from New Jersey to Denver and Baltimore. Portland’s Abreu recently opened a second clinic in Seattle.

Depression is big business. An estimated 15.7 million adults in the United States experienced at least one major depressive episode in 2014, according to the NIMH.

“There’s a great unmet need in depression,” says Gerard Sanacora, director of the Yale Depression Research Program. “We think this is an extremely important treatment. The concern comes if people start using ketamine before CBT [cognitive behavioral therapy] or Prozac. Maybe someday it will be a first-line treatment. But we’re not there yet.”

While a single dose of ketamine is cheaper than a $2 bottle of water, the cost to the consumer varies wildly, running anywhere between $500 and $1,500 per treatment. The drug itself is easily available in any pharmacy, and doctors are free to prescribe it — as with any medication approved by the Food and Drug Administration — for off-label use. Practitioners attribute the expense to medical monitoring of patients and IV equipment required during an infusion.

As a drug once known almost exclusively to anesthesiologists, ketamine now falls into a gray zone.

“Most anesthesiologists don’t do mental health, and there’s no way a psychiatrist feels comfortable putting an IV in someone’s arm,” Abreu says.

It’s a drug, in other words, that practically demands collaboration. Instead, it has set off a turf war. As the use of ketamine looks likely to grow, many psychiatrists say that use of ketamine for depression should be left to them.

“The bottom line is you’re treating depression,” says psychiatrist David Feifel, director of the Center for Advanced Treatment of Mood and Anxiety Disorders at the University of California at San Diego. “And this isn’t garden-variety depression. The people coming in for ketamine are people who have the toughest, potentially most dangerous depressions. I think it’s a disaster if anesthesiologists feel competent to monitor these patients. Many of them have bipolar disorder and are in danger of becoming manic. My question to anesthesiologists is: ‘Do you feel comfortable that you can pick up mania?’ ”

But ketamine has flourished from the ground up and with little or no advertising. The demand has come primarily from patients and their families; Zarate, for instance, says he receives “at least 100 emails a day” from patients.

"Nearly every one of them wants to know where they can get it."

*From the article here :

https://www.washingtonpost.com/national/health-science/a-one-time-party-drug-is-helping-people-with-deep-depression/2016/02/01/d3e73862-b490-11e5-a76a-0b5145e8679a_story.html?noredirect=on

 

[mr peabody]

​

Alcohol dependence significantly increases suicide risk, study

University of Otago | Neuroscience News | 9 March 2022

There are calls for changes to New Zealand’s national suicide prevention strategy in light of new research linking harmful drinking to a heightened risk of suicide.

The University of Otago, Christchurch study, published in the Australian and New Zealand Journal of Psychiatry, has found that alcohol use disorder (characterized as alcohol abuse or dependence) significantly increases the risk of suicidal thoughts in adults.

The study, led by Dr. Rose Crossin from the Department of Population Health, analyzed data from the renowned Christchurch Health and Development (CHDS) study, a birth cohort of 1,265 children born in 1977. The information from the study cohort was gathered in five data waves when participants were aged between 18 and 40.

“We found that before controlling the study data for common childhood and adult risk factor variables such as trauma, physical, mental health and substance abuse, alcohol dependence almost tripled the risk of suicidal ideation, and that after controlling for these variables suicidal ideation was still 50% higher in those with alcohol dependence.”

Dr. Crossin says such increased risk, observed in this study across ethnicities and in both males and females, backs up previous international studies linking harmful drinking to suicidal thoughts. She says alcohol use disorder is among the most consistently established risk factors for suicide and is the second-largest contributor to overall suicide rates after major depressive disorder.

She recommends these new findings be taken seriously in light of New Zealand’s alarming rates of hazardous drinking and suicide risk. Ministry of Health data from 2020 shows 21% of adults meet hazardous drinking criteria, while coronial data in the year to June 2021 confirms 607 New Zealanders tragically took their own lives.

“The World Health Organization highlights harmful drinking as a significant contributor to suicide, yet our national suicide prevention strategy does not specifically target this risk factor and has zero alcohol-related interventions. This study should be further cause for alarm at government level that strong action is now needed to reduce alcohol-related harm, notably suicidal risk, at both a population and individual level.”

Co-author and Director of the Christchurch Health and Development Study, Professor Joe Boden, says the use of the CHDS data strengthens the findings and efficacy of the study, by identifying and estimating the specific influence of problems with alcohol on suicidal behavior.

“Prior international studies have typically recruited patients already over the age of 16, limiting the ability to adjust for key childhood risk factors” Professor Boden says.

“Other studies have gathered data from cohort groups just once, for a limited time during adulthood or by examining males only. Comparatively, the participants in this study were interviewed five times before the age of forty, with their earlier documented childhood experiences also accounted for.”

The CHDS has, over the course of its history, measured a large variety of childhood factors which could potentially explain the relationship between alcohol and suicidal behavior.

For this study, factors were selected for analysis from the database due to their known association with alcohol use disorder and suicide; including family socioeconomic status, childhood punishment, abuse and neglect exposure, a family history of criminal offending and a history of alcohol abuse.

In addition, the study was also able to account for the potential influence of other indicators of adversity in adulthood, such as employment status, relationship instability and life satisfaction.

Dr. Crossin and Professor Boden are presently awaiting publication of a follow-up study using coronial data to determine the prevalence of acute alcohol use in suicide deaths in Aotearoa, as well as the characteristics of suicide involving acute alcohol use.

Alcohol Dependence Significantly Increases Suicide Risk - Neuroscience News

Alcohol use disorder is associated with a significant increase in suicidal thoughts in adults.

neurosciencenews.com

 

[mr peabody]

University of the Sunshine Coast, Queensland

Oral ketamine treatment reduced suicidal thoughts, study*

by B. David Zarley | Freethink | 13 Feb 2021

A small study out of University of the Sunshine Coast in Queensland, Australia, has found that oral ketamine treatment reduces chronic suicidal thoughts, results in line with the drug’s other antidepressant uses, New Atlas reports.

“On average, patients experienced a significant reduction in suicide ideation, from a high level before the trial to below the clinical threshold by week six of the trial,” principal investigator Adem Can told New Atlas.

While far from definitive, the study on oral ketamine may be an important step in making research easier and ketamine treatment more accessible. Most studies to date have administered ketamine via IV (although its sister compound, esketamine, uses nasal spray).

“Intravenous administration, however, is invasive, expensive and carries a higher chance of adverse reactions due to its injection straight into the blood stream,” Can said. “So logistically it is a lot easier and faster to clinically administer an oral dose.”

Both esketamine and ketamine treatment have been studied for reducing suicidal ideation before, Yale’s John Krsytal — who was not involved in the study — writes me by email.

Krystal’s lab discovered ketamine’s incredibly potent antidepressant capabilities in 2000. The drug, perhaps previously most famous as the sybaritic special k, works as a fast-acting antidepressant for people suffering from chronic, treatment-resistant depression.

Its efficacy was so startling, in fact, that it took the field years to come around on the results, Krystal previously told me.

Since then, studies and therapies revolving around ketamine for depression have been a key part of psychedelic drugs’ research renaissance. This past summer, researchers at Sweden’s Karolinska Institutet helped illuminate how ketamine uniquely impacts the brain’s serotonin receptors; the results may help lead to the development of new antidepressants.

Evidence of oral ketamine treatment efficacy

For their study, published in Translational Psychiatry, the Sunshine Coast team took 32 adults between the ages of 22 and 72 — over half women — suffering from chronic suicidal thoughts.

The subjects were given small, sub-anesthetic doses of ketamine for six weeks and then assessed using the Beck Scale for Suicidal Ideation, as well as secondary measures, including “scales for suicidality and depressive symptoms, and measures of functioning and well-being,” the authors wrote.

At the six-week mark, "69% of subjects had Beck scores significantly reduced from a high level of suicidal ideation,” with 50% still showing significant improvement by their follow-up assessment four weeks later.

“In medicine, this response rate is significant, particularly given it was experienced by patients with chronic suicidality, which can be difficult to treat,” Can told New Atlas.

Importantly, the patient’s suicidal thoughts stemmed from a range of psychiatric disorders, including anxiety, borderline personality disorder, and depression.

“Yet the treatment still worked across the group,” Jim Lagopoulos, the study supervisor, told New Atlas.

“This means the trial group was representative of the community we are serving, where suicidality is often accompanied by one or more other conditions. So results like these across the spectrum are very encouraging.”

Ketamine pioneer Krystal told me the study’s results are promising. However, there’s some caveats to consider.

The first is that the study is open label, meaning there was no control or inactive drug to compare against the effect of the oral ketamine treatment. “The risk is that we might overestimate the effectiveness of ketamine,” Krystal writes.

A crucial challenge in administering ketamine orally is ensuring you hit a high enough level of the drug and its metabolites to cause the clinical and neural effects you’re looking for.

“This study does not report the blood levels of ketamine or its metabolites norketamine or 2R-6R hydroxynorketamine,” Krystal points out. Combined with a lack of behavioral information, it’s difficult to tell if the proper blood levels were achieved.

Which ties into one final question. The subject’s suicidal thoughts were measured in the beginning and end of their ketamine treatment, and four weeks after. More incremental data could’ve shown whether ketamine’s uniquely speedy antidepressant abilities were reached.

“This would have helped us to understand whether the rapid (within 24 hours) antidepressant and anti-suicide effects of ketamine were observed,” Krystal writes.

“If not, it would again raise questions about the adequacy of the oral dosing.”
​

If you or someone you know has had thoughts of suicide, call the National Suicide Prevention Lifeline at 1-800-273-TALK (8255).

*From the article here :

Oral ketamine treatment reduced suicidal thoughts: Pilot study

A new, small study in Australia suggests that oral ketamine treatment may help treat suicidal thoughts.

www.freethink.com