- The Truth About Ketamine: Depression Cure, Health Fad, or Placebo? The Ringer
- How ketamine therapy can be used to treat depression The Telegraph
- A Boise clinic uses the drug ketamine to treat depression. Is it legal? How does it work? Idaho Statesman
- NRx Pharmaceuticals Announces Signing of a Data and Technical Information Agreement with Columbia University Accessing Key Data Demonstrating Efficacy and Safety of Intravenous Ketamine for the Treatment of Suicidal Depression Yahoo Finance
- Efficacy and safety of ketamine-assisted electroconvulsive therapy in major depressive episode: a systematic review and network meta-analysis | Molecular Psychiatry Nature.com
Tag Archives: Ketamine
Ketamine Found to Increase Brain Noise
Summary: By inhibiting NMDA receptors, ketamine increases noise to gamma frequencies in one layer of the thalamic nucleus and one lay of the somatosensory cortex. Findings suggest psychosis may be triggered by an increase in background noise impairing thalamocortical neurons which may be caused by a malfunction in NMDA receptors affecting the balance of inhibition and excitation in the brain.
Source: HSE
An international team of researchers including Sofya Kulikova, Senior Research Fellow at the HSE University-Perm, found that ketamine, being an NMDA receptor inhibitor, increases the brain’s background noise, causing higher entropy of incoming sensory signals and disrupting their transmission between the thalamus and the cortex.
This finding may contribute to a better understanding of the causes of psychosis in schizophrenia.
An article with the study’s findings has been published in the European Journal of Neuroscience.
Schizophrenic spectrum disorders affect approximately one in 300 people worldwide. The most common manifestations of these disorders are perceptual disturbances such as hallucinations, delusions and psychoses.
A drug called ketamine can induce a mental state similar to psychosis in healthy individuals. Ketamine inhibits NMDA receptors involved in the transmission of excitatory signals in the brain. An imbalance of excitation and inhibition in the central nervous system can affect the accuracy of sensory perception.
Similar changes in the functioning of NMDA receptors are currently believed to be one of the causes of perception disorders in schizophrenia. However, it is still unclear how exactly this process occurs in the brain regions involved.
To find out, neuroscientists from France, Austria and Russia studied how the brains of laboratory rats on ketamine process sensory signals. The researchers examined beta and gamma oscillations occurring in response to sensory stimuli in the rodent brain’s thalamo-cortical system , a neural network connecting the cerebral cortex with the thalamus responsible for the transmission of sensory information from the organs of perception to the brain.
Beta oscillations are brainwaves in the range of 15 to 30 Hz, and gamma waves are those in the range of 30 to 80 Hz. These frequencies are believed to be critical for encoding and integrating sensory information.
In the experiment, rats were implanted with microelectrodes to record the electrical activity in the thalamus and the somatosensory cortex , a region of the brain which is responsible for processing sensory information coming from the thalamus. The researchers stimulated the rats’ whiskers (vibrissae) and recorded the brain’s responses before and after ketamine administration.
A comparison of the two datasets revealed that ketamine increased the power of beta and gamma oscillations in the cortex and the thalamus even in the resting state before a stimulus was presented, while the amplitude of the beta/gamma oscillations in the 200–700 ms post-stimulus period was significantly lower at all recorded cortical and thalamic sites following ketamine administration.
The post-stimulation time lapse of 200–700 ms is long enough to encode, integrate and perceive the incoming sensory signal. The observed decrease in the power of sensory stimulus-induced oscillations can be associated with impaired perception.
Analysis also revealed that by inhibiting NMDA receptors, ketamine administration added noise to gamma frequencies in the post-stimulation 200–700 ms period in one thalamic nucleus and in one layer of the somatosensory cortex. It can be assumed that this observed increase in noise, ie a reduction in the signal-to-noise ratio, also indicates the neurons’ impaired ability to process incoming sensory signals.
These findings suggest that psychosis may be triggered by an increase in background noise impairing the function of thalamo-cortical neurons. This, in turn, could be caused by a malfunction of NMDA receptors affecting the balance of inhibition and excitation in the brain. The noise makes sensory signals less defined or pronounced. In addition, this may cause spontaneous outbursts of activity associated with a distorted perception of reality.
“The discovered alterations in thalamic and cortical electrical activity associated with ketamine-induced sensory information processing disorders could serve as biomarkers for testing antipsychotic drugs or predicting the course of disease in patients with psychotic spectrum disorders,” says Sofya Kulikova.
About this neuroscience research news
Author: Anastasia Lobanova
Source: HSE
Contact: Anastasia Lobanova – HSE
Image: The image is credited to Izhikevich, Edelman
Original Research: Open access.
“The psychotomimetic ketamine disrupts the transfer of late sensory information in the corticothalamic network” by Yi Qin et al. European Journal of Neuroscience
See also
Abstract
The psychotomimetic ketamine disrupts the transfer of late sensory information in the corticothalamic network
In prodromal and early schizophrenia, disorders of attention and perception are associated with structural and chemical brain abnormalities and with dysfunctional corticothalamic networks exhibiting disturbed brain rhythms. The underlying mechanisms are elusive.
The non-competitive NMDA receptor antagonist ketamine simulates the symptoms of prodromal and early schizophrenia, including disturbances in ongoing and task & sensory-related broadband beta−/gamma-frequency (17–29 Hz/30–80 Hz) oscillations in corticothalamic networks.
In normal healthy subjects and rodents, complex integration processes, like sensory perception, induce transient, large-scale synchronised beta/gamma oscillations in a time window of a few hundred ms (200–700 ms) after the presentation of the object of attention (e.g., sensory stimulation).
Our goal was to use an electrophysiological multisite network approach to investigate, in lightly anesthetised rats, the effects of a single psychotomimetic dose (2.5 mg/kg, subcutaneous) of ketamine on sensory stimulus-induced oscillations.
Ketamine transiently increased the power of baseline beta/gamma oscillations and decreased sensory-induced beta/gamma oscillations. In addition, it disrupted information transferability in both the somatosensory thalamus and the related cortex and decreased the sensory-induced thalamocortical connectivity in the broadband gamma range.
The present findings support the hypothesis that NMDA receptor antagonism disrupts the transfer of perceptual information in the somatosensory cortico-thalamo-cortical system.
Amygdala connectivity predicts ketamine treatment response among patients with anxious depression
A brain region known as the amygdala could play a key role in predicting symptom improvement following ketamine therapy in patients with treatment-resistant anxious depression, according to new research published in the Journal of Affective Disorders.
“Since the antidepressant effects of ketamine in patients with anxious depression remain unclear, it is necessary to investigate the potential biomarkers predicting the antidepressant efficacy of ketamine in patients with anxious depression,” said study author Bin Zhang of the Affiliated Brain Hospital of Guangzhou Medical University.
“Previous studies have pointed out that functional connectivity differences in the amygdala are linked to depression improvement after ketamine treatment in depressed patients, but their role in anxious depression patients is uncertain. Therefore, we investigated the correlation between depression improvement after ketamine treatment and amygdala functional connectivity in anxious depression patients.”
For their study, the researchers examined neuroimaging data from 31 patients with anxious depression and 18 patients with non-anxious depression.
The researchers only included participants who had a diagnosis of major depression without comorbid psychotic symptoms, had a score greater than 17 on the Hamilton Depression Rating Scale, had previously failed to improve after at least two antidepressant treatments, had completed fMRI brain scans, and had undergone six ketamine infusions.
Among the patients with anxious depression, about 60% (20 patients) exhibited clinically significant reductions in depression symptoms following their sixth ketamine infusion. The remaining 11 patients with anxious depression were classified as non-responders.
The researchers found that, prior to the ketamine infusions, those who responded to the treatment tended to have greater functional connectivity between the left laterobasal amygdala and the left precuneus compared to non-responders. Additionally, the connectivity between the two brain regions was significantly reduced post-treatment among responders.
Patients with anxious depression also tended to have reduced connectivity between the right centriomedial amgydala and the right middle temporal gyrus compared to patients with non-anxious depression, which predicted treatment response.
“Corresponding to the crucial role of the amygdala in emotion regulation, especially in negative emotion, our study shown that the amygdala functional connectivity is associated with depression improvement to ketamine infusions in patients with anxious depression,” Zhang told PsyPost.
“The most surprising finding of the current study was that the baseline hyperconnectivity of the amygdala-precuneus found in the responders relative to the non-responders was significantly reduced on day 13 compared to baseline after six ketamine infusions. It may point to a potential neural underpinning by which ketamine exerts its antidepressant effect in patients with anxious depression.”
The results provide new insights into the mechanisms underlying ketamine’s antidepressant effects. But as with any study, the new research includes limitations. The researchers noted that their sample size was relatively small. Future research with larger samples should be conducted to validate the findings.
“Though the findings in our study may suggest that amygdala functional connectivity is a significant predictor of treatment response to ketamine infusions in patients with anxious depression, further validation is required,” Zhang said. “Moreover, further studies exploring the potential antidepressant mechanisms of ketamine may aid in the treatment of anxious depression patients.”
The study, “Functional connectivity differences in the amygdala are related to the antidepressant efficacy of ketamine in patients with anxious depression“, was authored by Shiqi Yuan, Xin Luo, Xiaoyu Chen, Mingqia Wang, Yiru Hu, Yanling Zhou, Yuping Ning, and Bin Zhang.
for(var key in aepc_pixel_args) args[key] = aepc_pixel_args[key];
return args; };
// Extend args if ( 'yes' === aepc_pixel.enable_advanced_events ) { aepc_pixel_args.userAgent = navigator.userAgent; aepc_pixel_args.language = navigator.language;
if ( document.referrer.indexOf( document.domain ) < 0 ) {
aepc_pixel_args.referrer = document.referrer;
}
}
!function(f,b,e,v,n,t,s){if(f.fbq)return;n=f.fbq=function(){n.callMethod?
n.callMethod.apply(n,arguments):n.queue.push(arguments)};if(!f._fbq)f._fbq=n;
n.push=n;n.loaded=!0;n.version='2.0';n.agent="dvpixelcaffeinewordpress";n.queue=[];t=b.createElement(e);t.async=!0;
t.src=v;s=b.getElementsByTagName(e)[0];s.parentNode.insertBefore(t,s)}(window,
document,'script','https://connect.facebook.net/en_US/fbevents.js');
fbq('init', aepc_pixel.pixel_id, aepc_pixel.user);
setTimeout( function() {
fbq('track', "PageView", aepc_pixel_args);
}, aepc_pixel.fire_delay * 1000 );
Read original article here
More Successful Than Ketamine – A Shocking Depression Treatment
Electroconvulsive therapy is a psychiatric treatment that involves electrically inducing a generalized seizure to treat mental disorders.
Electroshock therapy, which is unfavorably depicted in movies and TV shows, consistently produces better outcomes for depression that is resistant to treatment.
According to an analysis of six studies that recently published their findings in JAMA Psychiatry, electroconvulsive therapy (ECT) is better than ketamine in quickly relieving major depression.
According to the World Health Organization, depression is a widespread condition that affects roughly 5% of individuals globally (WHO). Feeling sad, irritable, losing enjoyment in formerly delightful things, and even enduring inexplicable pain or fatigue for weeks at a time are all signs of depression. The most common first-line treatment for depression is the use of an oral antidepressant (in conjunction with psychotherapy). However, if oral antidepressants are ineffective or if the patient is in immediate danger of self-harm, there are other, quicker therapy options, including ECT and, more recently, ketamine or esketamine.
Ketamine is less often used in the US than esketamine, a nasal spray that has been given approval by the Food and Drug Administration to treat depression. However, there are no studies comparing the effectiveness of ECT with esketamine. Ketamine, a sister drug of esketamine, has been studied. Ketamine is typically used as an injectable anesthetic in medicine, but it has lately been investigated as a fast-acting intervention to help those suffering from serious depression.
T. Greg Rhee, a psychiatric epidemiologist at the University of Connecticut School of Medicine, and associates from Harvard University, Kyungnam University in Korea, McLean Hospital and Massachusetts General Hospital in Boston, University of Toronto, VA New England Mental Illness in West Haven, and Yale University examined six global clinical trial studies contrasting ketamine with ECT for major depression. The trials, which were carried out in hospitals in Sweden, Germany, Iran, and India, involved 340 patients in total.
All six of the studies independently found that ECT was more effective than ketamine at relieving severe depression symptoms.
“ECT is consistently more successful than ketamine” at helping patients with serious depression, says Rhee. “We found no differences by age, sex, or geographic location. So we could say anyone who is ECT eligible will benefit.”
Although ketamine did generally help patients, ECT had better results overall. Ketamine could be a viable treatment for people who cannot undergo ECT. The side effect profiles of the two treatments differed, with ECT more likely to cause headaches, muscle pain, and memory loss, while ketamine was more likely to cause dissociative symptoms, vertigo, and double vision.
There are two additional studies comparing ECT and ketamine ongoing, and Rhee hopes to add their data to the analysis when they are available.
“Every single study directly reports ECT works better than ketamine. But people are still skeptical of ECT, perhaps because of stigma,” Rhee says, or negative depictions in films such as “One Flew Over the Cuckoo’s Nest” and shows such as “Stranger Things.” “We need to improve public awareness of ECT for treatment-resistant depression.”
Reference: “Efficacy and Safety of Ketamine vs Electroconvulsive Therapy Among Patients With Major Depressive Episode: A Systematic Review and Meta-analysis” by Taeho Greg Rhee, Ph.D., Sung Ryul Shim, Ph.D., Brent P. Forester, MD, MSc, Andrew A. Nierenberg, MD, Roger S. McIntyre, MD, George I. Papakostas, MD, John H. Krystal, MD, Gerard Sanacora, MD, Ph.D. and Samuel T. Wilkinson, MD, 19 October 2022, JAMA Psychiatry.
DOI: 10.1001/jamapsychiatry.2022.3352
Americans Take Ketamine at Home for Depression With Little Oversight
Startups are prescribing ketamine online to treat serious mental-health conditions, raising concern among psychiatrists about the safety of taking the mind-altering anesthetic without medical supervision, sometimes at high doses that raise risks of side effects.
Ketamine is approved by the Food and Drug Administration to anesthetize people and animals and has been used safely in hospitals for decades. The out-of-body, hallucinogenic sensations it produces made it popular as a party drug known as Special K. Some doctors prescribe ketamine off-label to treat patients with conditions including severe depression, suicidal thoughts and post-traumatic stress disorder.
SHARE YOUR THOUGHTS
Is there enough support available for people taking ketamine at home because of mental-health concerns? Join the conversation below.
Generic ketamine isn’t approved for those conditions. Studies have shown it can rapidly alleviate symptoms of severe depression when other treatments have failed.
There is less data on ketamine’s effectiveness for other conditions including anxiety and PTSD, and little data on its long-term use.
The FDA has approved a chemically related version of the drug, called esketamine, from
Johnson & Johnson
for treatment-resistant depression with suicidal thoughts.
Clinics that are certified to administer J&J’s nasal spray must monitor patients for two hours afterward.
People taking generic ketamine at home aren’t subject to the same oversight.
Mindbloom Inc., Nue Life Health PBC and Wondermed LLC are among around a dozen companies now selling ketamine tablets or lozenges online, making use of relaxed restrictions on the prescription of controlled substances during the pandemic.
The companies work with clinicians who prescribe ketamine to patients based on a questionnaire and virtual evaluation. The generic ketamine pills or lozenges are mailed to patients’ homes. The companies say they instruct people to take the medication with someone nearby, among other safety measures.
Taking ketamine at home without medical supervision increases risks of patients falling and hurting themselves or taking more of the drug than prescribed, doctors said. Ketamine can be addictive, and patients might not get the help they need if they have a distressing experience while taking the drug, psychiatrists said.
“Places that are doing virtual ketamine are negotiating a compromise between accessibility and safety,” said Dr.
Benjamin Yudkoff,
medical director of the ketamine and esketamine program at Brigham and Women’s Faulkner Hospital in Boston.
Ketamine increases heart rate and blood pressure, raising the risk of rare complications including stroke or heart attack at the higher doses that some telehealth patients have been prescribed, medical experts said.
“Giving any drug like that has the potential to cause general anesthesia at home in a completely unmonitored environment,” said Dr.
Michael Champeau,
president of the American Society of Anesthesiologists.
The companies said prescribing ketamine-assisted therapy at home can help fill a need for people who don’t respond to existing medications or can’t reach or afford treatment in person. Ketamine blocks a receptor in brain cells important for brain adaptability, which researchers say might help facilitate changes in mood and mind-set.
Ketamine was prescribed for Leon New Valentine, who said it alleviated symptoms of treatment-resistant depression and PTSD.
Photo:
Tara Pixley for The Wall Street Journal
Mindbloom and Nue Life cited peer-reviewed research they published suggesting that many patients reported feeling better after taking ketamine and that few reported problems related to taking the drug.
Mindbloom, Nue Life and Wondermed said they decline to treat people who have symptoms that are too severe or histories of conditions such as substance-use disorder, psychosis or uncontrolled hypertension. Nue Life said it sometimes consults with a patient’s doctor before prescribing ketamine, and Mindbloom said it often asks for medical records. Wondermed said patients can choose to have their doctors work with the company during treatment.
“‘Places that are doing virtual ketamine are negotiating a compromise between accessibility and safety.’”
Nue Life said it starts patients at around 125 milligrams and prescribes at most 750 milligrams for a dose. Wondermed said it prescribes patients between 100 milligrams and 400 milligrams for a dose. Mindbloom said that it starts patients at around 400 milligrams and that some patients graduate to doses of around 1,000 milligrams.
Doses of around 1,000 milligrams heighten risks for severe side effects including rare seizures, hemorrhages or strokes, said
Ari Aal,
a psychiatrist in Boulder, Colo., who prescribes ketamine at lower doses to patients who take it under supervision at his clinic.
“That’s way too much of a dose to be doing at home and probably at all, and way too much without a practitioner watching you,” Dr. Aal said.
Mindbloom and Wondermed said they provide blood-pressure monitors for patients to use before and during treatment. Nue Life said it instructs patients with controlled hypertension to monitor their blood pressure.
A ketamine kit provided by Mindbloom for Courtney Gable.
Photo:
Courtney Gable
Timothy Mitchell,
a 40-year-old patient advocate from Ballston Lake, N.Y., said Mindbloom started him on an 800-milligram dose last year. He said he is undergoing his third course of a six-dose regimen with Mindbloom at 1,200 milligrams a dose. The treatment helped quiet suicidal thoughts, he said.
Wondermed said it charges $399 for a month of ketamine tablets or lozenges and telemedicine treatment. Mindbloom said it charges around $1,000 for around three months of ketamine and telemedicine care. Nue Life said it charges as much as $2,999 for ketamine tablets and telemedicine treatment over four months. Health insurers usually don’t reimburse people for the off-label treatments.
Amanda Itzkoff,
a psychiatrist and chief executive of Curated Mental Health, which administers ketamine in clinics, said she declined to be on Mindbloom’s advisory board in part because she was concerned that at-home use might not include enough patient supervision.
Making a comparison with a crackdown on psychedelic-drug research decades ago, she said that if companies recklessly prescribe ketamine for home use, they could set back adoption of a valuable treatment. “We could blow it again,” Dr. Itzkoff said.
A spokesman said that Mindbloom ended its relationship with Dr. Itzkoff and that she didn’t raise safety concerns. Mindbloom’s medical director, Dr.
Leonardo Vando,
said striking the right balance between expanding access to ketamine and safe prescribing practices is critical to Mindbloom.
Courtney Gable,
47, said her husband checked on her when she took ketamine that Mindbloom prescribed for her this year to treat chronic pain and depression. The 400-milligram dose was higher than initial doses prescribed at a clinic where she works in Philadelphia, she said.
“There’s a safety net, but the spaces between the net are a little wider,” Ms. Gable said.
Leon New Valentine,
a 32-year-old actor and videogame model in Los Angeles, was prescribed 100 milligrams of ketamine online last year by Peak Health Global Inc., and took the medication with someone nearby. Mx. Valentine, who uses they as a pronoun, said they graduated to 150-milligram doses and took that alone. Ketamine alleviated symptoms of treatment-resistant depression and PTSD, Mx. Valentine said.
“Things are joyful again even though I’m in pain,” Mx. Valentine said. Peak said it would close in November because it expects rules allowing controlled substances to be prescribed remotely to be tightened soon.
Write to Brianna Abbott at brianna.abbott@wsj.com and Daniela Hernandez at daniela.hernandez@wsj.com
Copyright ©2022 Dow Jones & Company, Inc. All Rights Reserved. 87990cbe856818d5eddac44c7b1cdeb8
Mechanism for the Antidepressant Effect of Ketamine Revealed
Summary: Those with treatment-resistant depression showed significant improvement in symptoms and became more receptive to positive experiences following a one-week ketamine treatment regimen.
Source: Paris Brain Institute
Researchers from Inserm, CNRS, Sorbonne University and clinicians from the AP-HP and at Paris Brain Institute identified one of the mechanisms explaining ketamine effect as an antidepressant.
Ketamine, usually used as an anesthetic, was administered to patients with severe resistant depression. This treatment led patients to present an increased ability to overcome their negative beliefs about themselves and the world when researchers presented them positive information.
These results, published in JAMA Psychiatry, open new therapeutic avenues for the management of antidepressant-resistant mood disorders.
Depression is the most common psychiatric disorder: it is estimated that 5 to 15% of the French population will experience a major depressive episode during their lifetime. All age groups and all social backgrounds are affected.
The disease is characterized by sadness and loss of hedonic feelings that positive events do not improve. Depressed patients progressively develop negative beliefs about themselves, the world, and the future, that may develop into suicidal thoughts. These negative beliefs remain even when the patient receives positive information.
About one-third of people with depression do not respond to the most prescribed antidepressants, leading to a diagnosis of treatment-resistant depression (TRD). For these people, finding new and effective therapies is a priority.
Ketamine, a commonly used anesthetic, has been shown to influence resistant depression. While conventional antidepressant treatments take time to be efficient (on average three weeks), ketamine has a rapid antidepressant effect, only a few hours after administration. The mechanisms associated with this fast-acting antidepressant effect are still unknown.
To identify these mechanisms, Dr. Hugo Bottemanne and the research team co-led at the Paris Brain Institute by Pr Philippe Fossati and Liane Schmidt, Inserm researcher, coordinated a clinical study involving 26 antidepressant-resistant patients (TRD) and 30 healthy controls.
During the protocol, patients and healthy subjects were first asked to estimate the probability of 40 “negative” events which could occur in their lives (e.g., have a car accident, get cancer, or lose their wallet).
After being informed of the actual occurrence risks in the general population, patients and healthy subjects were again asked to estimate the probability of these events occurring in their lives. The research team was interested in the updating of beliefs after getting information.
Results showed that healthy subjects tended to update their initial beliefs more after receiving factual and positive information, which was not the case in the depressed patient population.
In the suite of the study, TRD patients received three administrations of ketamine at a subanesthetic dose (0.5 mg/kg over 40 minutes) in one week.
Only four hours after the first administration, patients’ ability to update their beliefs after receiving a positive information was increased. They became less sensitive to negative information and recovered an ability to update their knowledge com parable to that of control subjects.
Moreover, improvement in depressive symptoms after ketamine treatment was associated with these changes in belief updating, suggesting a link between clinical improvement and changes in this cognitive mechanism. “In other words, the more patients’ belief updating ability was increased, the greater the improvement in symptoms was”.
In conclusion, in this study, patients with antidepressant-resistant depression showed a significant decrease in symptoms and became more receptive to “positive” experiences after one week of ketamine treatment.
This work highlights for the first time a cognitive mechanism potentially involved in the early effect of ketamine. It paves the way to new research on antidepressant therapies modulating the mechanisms of belief updating.
About this psychopharmacology research news
Author: Nicolas Brard
Source: Paris Brain Institute
Contact: Nicolas Brard – Paris Brain Institute
Image: The image is in the public domain
Original Research: Open access.
“Evaluation of Early Ketamine Effects on Belief-Updating Biases in Patients With Treatment-Resistant Depression” by Hugo Bottemanne et al. JAMA Psychiatry
Abstract
Evaluation of Early Ketamine Effects on Belief-Updating Biases in Patients With Treatment-Resistant Depression
Importance
Clinical research has shown that persistent negative beliefs maintain depression and that subanesthetic ketamine infusions induce rapid antidepressant responses.
See also
Objective
To evaluate whether ketamine alters belief updating and how such cognitive effects are associated with the clinical effects of ketamine.
Design, Setting, and Participants
This study used an observational case-control protocol with a mixed-effects design that nested 2 groups by 2 testing time points. Observers were not blinded. Patients with treatment-resistant depression (TRD) and healthy volunteer participants aged 34 to 68 years were included. Patients with TRD were diagnosed with major depressive disorder or bipolar depression, had a Montgomery-Åsberg Depression Rating Scale score greater than 20, a Maudsley Staging Method score greater than 7, and failed to respond to at least 2 prior antidepressant trials. Exclusion criteria were any other psychiatric, neurological, or neurosurgical comorbidities, substance use or addictive disorders, and recreational ketamine consumption. Data were collected from January to February 2019 and from May to December 2019, and data were analyzed from January 2020 to July 2021.
Exposures
Patients with TRD were observed 24 hours before single ketamine infusion, 4 hours after the infusion, and 4 hours after the third infusion, which was 1 week after the first infusion. Healthy control participants were observed twice 1 week apart without ketamine exposure.
Main Outcomes and Measures
Montgomery-Åsberg Depression Rating Scale score and belief updating after belief updating when patients received good news and bad news measured by a cognitive belief-updating task and mathematically formalized by a computational reinforcement learning model.
Results
Of 56 included participants, 29 (52%) were male, and the mean (SEM) age was 52.3 (1.2) years. A total of 26 patients with TRD and 30 control participants were included. A significant group × testing time point × news valence interaction showed that patients with TRD updated their beliefs more after good than bad news following a single ketamine infusion (controlled for age and education: β = −0.91; 95% CI, −1.58 to −0.24; t216 = −2.67; P = .008) than controls. Computational modeling showed that this effect was associated with asymmetrical learning rates (LRs) after ketamine treatment (good news LRs after ketamine, 0.51 [SEM, 0.04]; bad news LRs after ketamine 0.36 [SEM, 0.03], t25 = 3.8; P < .001) and partially mediated early antidepressant responses (path a*b: β = −1.00 [SEM, 0.66]; t26 = −1.53; z = −1.98; P = .04).
Conclusions and Relevance
These findings provide novel insights into the cognitive mechanisms of the action of ketamine in patients with TRD, with promising perspectives for augmented psychotherapy for individuals with mood disorders.
Inside one of NYC’s ketamine clinics where hotshots and average Joes are given IV of psychedelic
Stepping inside the Jeff Ditzell Psychiatry clinic in the financial district of Manhattan, it feels more like a luxury spa than a medical facility.
But customers come here for something far more powerful than a deep tissue massage or hot yoga session — they come for the ketamine.
A medical loophole means facilities like this one can offer the hallucinogen, which was first developed as a horse tranquilizer and has become popular among ravers, for people with depression.
Far from the party atmosphere that typically surrounds ketamine, the person receiving the infusion at Dr Ditzell’s clinic is taken into a dimly-lit room where they are surrounded by plants and colorful abstract art.
They are put in a leather reclining chair whose back is enveloped in a white pod reminiscent of an Elon Musk SpaceX invention. It puts the patient in partial darkness to induce relaxation while they get hooked up to an IV for a roughly 40-minute infusion.
Patients spend the next hour outfitted with a sleeping mask and headphones playing theta brain waves, which are at the dominant frequency in healing, high creative states, and remembering emotional experiences.
Dr Jeff Ditzell told DailyMail.com: ‘Essentially, the music and the aromatherapy that we have going as well as the calm setting, warm lights and all that, the comfortable space that’s dedicated to the ketamine infusion is really key in getting a good response.’
His clinic, which is just a stone’s throw away from Wall Street, has attracted bankers with deep pockets looking to escape from the madness of the trading floor.
Ket clinics have been appearing across New York at a rapid rate and they are now staring to crop up in other major US cities like Houston, Miami, Los Angeles and Seattle.
There are estimated to be over 100 nationwide now compared to just a handful a decade ago. It comes after several recent studies indicated a low dose of the drug may help treat depression and PTSD.
Patients undergoing ketamine treatments recline in a leather lounge chair that resembles a SpaceX device designed by Elon Musk, a feature meant to cocoon the user and foster introspection. Ditzell is committed to providing clients with a good trip, he told DailyMail.com. The office is festooned with abstract art, ambient lights, and potted plants
Ketamine infusions are for people with debilitating depression who have tried several other courses of treatment including antidepressant medications with little or no relief. Before it was known as a party drug that could produce out-of-body experiences, ketamine was used as an anesthetic in surgical procedures. Since then, it has been prescribed ‘off-label’ for treatment-resistant depression
Ditzell’s office, which is just a stone’s throw away from Wall Street, has attracted bankers with deep pockets looking to escape from the madness of the trading floor. But not just anyone can receive a ketamine treatment, Ditzell says. There is a lengthy screening process that considers the person’s psychiatric history before determining if they qualify
In a treatment room at Ditzell’s clinic, patients spend an hour outfitted with a sleeping mask while listening to theta brain waves, which are at the dominant frequency in healing, high creative states, and remembering emotional experiences. Patients report feeling ‘stoned’ with many saying they’ve had out of body experiences
People undergoing ketamine infusions report sedating or relaxing effects. Some gain a heightened sensory awareness while many report feeling outside of their bodies.
‘I wouldn’t quite call it psychedelic,’ said David Hogberg, 52, a journalist who underwent five treatments in Washington, DC. ‘But you’re definitely you are, for lack of a better word, stoned.’
Ketamine is a schedule III drug under the Controlled Substances Act in the same category as codeine and anabolic steroids.
The consequences of possessing recreational ketamine vary by state but fines can range from the hundreds to tens of thousands of dollars, with jail time of up to 20 years.
But it is approved in the US and UK as a surgical anesthetic and can be prescribed ‘off-label’ for depression in private clinics.
This loophole guarantees that providers who administer ketamine treatments for treatment-resistant depression are on the right side of the law.
But experts Dailymail.com spoke to were split over the growing practice.
Some argue that administering the infusions is reckless and seeks to oversimplify the recovery process, which typically takes years of hard work in cognitive therapy and adherence to an effective medication regimen.
Ketamine infusions are for people with debilitating depression who have tried several other courses of treatment including antidepressant medications with little or no relief.
‘Complex mental health is not a situation where there is a quick fix,’ said Dr Zak Waqar-Uddin, a general practitioner in the UK.
He went on: ‘It relies on sympathetic trained experts including psychiatrists and psychologists, who use medications and counselling techniques that even when successfully applied, take months if not years for their results to show.’
On the other side of the debate, Dr Michel Thase, a psychiatry professor at University of Pennsylvania’s Perelman School of Medicine told this website: ‘The way we administer it is in no way shape or form the way people use it as as a party drug.’
‘And the doses that are used to treat depression are one quarter of the doses used as an anesthetic.’
Prescribing medications off label is a common practice for numerous treatments. The drug topiramate, for instance, is federally approved to treat epilepsy and prevent seizures.
But topiramate is commonly used to treat myriad other issues including alcohol and nicotine dependence, bulimia nervosa, borderline personality disorder, obsessive-compulsive disorder, and Tourette syndrome.
During the Covid pandemic the controversial Donald Trump-backed malaria drug hydroxychloroquine was allowed to be used ‘off-label’ to treat the virus after showing some early promise in the lab. But larger studies discovered it was not able to treat Covid and may have caused nasty side effects.
At Dr Ditzell’s clinic, clients undergo a consultation and screening process before they can be prescribed the infusions. The practice is meant to weed out people who are just looking for a trip.
But the screening process for prospective ketamine clients is not uniform across the US. And the infusions are not cheap and can cost anywhere from $400 to $2,000 a pop, which raises ethical issues.
Defending his clinic, Dr Ditzell said: ‘A ketamine clinic is never the first stop for a person looking to treat their depression. It’s more like a last resort.
‘You start looking at what [treatment is] left? Transcranial magnetic stimulation, electroconvulsive therapy, deep brain stimulation. We’re talking about some serious stuff.’
Before it was known as a party drug that could produce out-of-body experiences, ketamine was used as an anesthetic in surgical procedures.
David Hogberg, 52, and his son at National’s Park in Washington, DC. Hogberg underwent a series of five ketamine infusions. He reported feeling exceptionally well for a short period of time before his depression symptoms came rushing back. While he said the treatments were not the cure he was hoping for, he did not dissuade other people from trying them.
Credit Field Trip Health. Ketamine infusion clinics have cropped up nationwide. They have the same ingredients as Ditzell’s clinic: comfortable chairs, meditative lighting, plants and other earthy accoutrements, and supervision from a medical professional.
Credit Point Ketamine Malibu. There went from being a smattering of clinics in select major cities to a booming wellness industry trend that has reached all corners of the US. There are estimated to be over 100 nationwide now compared to just a handful a decade ago. It comes after several recent studies indicated a low dose of the drug may help treat depression and PTSD.
A patient at the Ketamine Clinic of Seattle. Depression is believed to be linked to a loss of synaptic connections between nerve cells, but ketamine has been shown to bolster frayed neural connections caused by chronic stress that contribute to severe emotional distress, depression, and mood disorders.
Credit Field Trip Ketamine Clinic in Houston. There is a growing body of evidence pointing to low-dose IV ketamine’s fast-acting antidepressant effects, but opponents argue that the new craze is a quick fix for severe depression. But clinical research into ketamine as a treatment for mood disorders is scarce and there remain concerns about long-term effects of repeated infusions of ketamine.
It was introduced in the 1960s and is still used today to induce sedation before operations.
In the intervening years, ketamine, nicknamed in certain circles ‘special K’ was embraced by the rave-going community as a popular party drug for its hallucinatory and psychoactive effects.
In the last few years, several studies have highlighted ketamine, sometimes known as ‘ket’, ‘K’ or ‘special K’, as a potential antidepressant, along with other psychedelic drugs such as psilocybin and MDMA.
A group of psychiatrists in India, for example, reported in 2019 that a group of 25 males using a low-dose infusion saw significant improvement in depression and anxiety symptoms immediately one hour after single dose.
The positive effect was sustained with six doses over two weeks with an overall decrease in illness severity after two weeks.
Depression is believed to be linked to a loss of synaptic connections between nerve cells, but ketamine has been shown to have nerve healing properties.
It is believed to bolster frayed neural connections caused by chronic stress that contribute to severe emotional distress, depression, and mood disorders.
But clinical research into ketamine as a treatment for mood disorders is scarce and there remain concerns about long-term effects of repeated infusions of ketamine.
Most of the data supporting the use of ketamine as a treatment for depression and mood disorders are based on trials that followed up on patients after just one treatment. Patients are typically encouraged to complete five or six.
A handful of studies have determined the relative safety of undergoing a series of treatments, but data to back up their efficacy and safety long term are lacking
Ketamine’s therapeutic effects stem from its ability to change the levels of a neurotransmitter called glutamate, which is crucial in certain concentrations to a fully functioning brain.
Overactivation of glutamate receptors may lead to long-term depression, and ketamine works by blocking those receptors. The result is a greater production and synaptic release of glutamate, which can result in new connections between neurons in areas of the brain that regulate mood and behavior.
The drug, when administered in low doses and monitored by healthcare providers, can provide instant antidepressant effects.
Dr Ditzell claims between six and eight out of 10 of his patients see ‘immediate’ improvements to their mood after the therapy.
Ketamine works differently than the antidepressants that have been on the market for decades, such as Prozac and Zoloft, which are prescribed for a wide range of mental health conditions including depression, panic disorder, obsessive compulsive disorder, and PTSD.
In order to qualify for the treatments, the would-be client has to prove they have already tried other treatments for their clinical depression without success.
Many clinics require a detailed list of prescription medications the person as tried as well as coordination with other mental health providers.
But the screening process for ketamine treatments across clinics is not uniform and some experts worry that anyone with money could get them.
David Hogberg completed five treatments starting in the spring of 2021. While he benefited from the treatments at first, the positive effects were not permanent.
‘After the fifth treatment, suddenly, boom, all my depression and anxiety was gone,’ he said. ‘And I am not even sure that lasted a week before my symptoms came back.’
He added, ‘I checked the research that afternoon and apparently it works for about 75% of patients. So that means for one in four it’s not going to work. That’s high, so I have no reason to think that I wasn’t one of those one in four.’
When all was said and done, David paid about $1,500 for the series of treatments. ‘For anyone thinking about it, I wouldn’t tell them not to do it because you may be one of those three out of the four, but I would say don’t go into it with high expectations and have a backup plan which unfortunately I didn’t have.’
Elijah McClain died of ketamine shot from medics in 2019, report says
Though it still lists the manner of death as “undetermined” — as opposed to a homicide or an accident — the report could bolster the prosecution of the police and first responders charged in McClain’s death and reignite calls for greater accountability from the city.
McClain, a massage therapist and self-taught musician, was walking home in August 2019 when he was detained by police responding to a 911 call that someone was acting “sketchy.” Officers tackled him and put him in a carotid chokehold, which restricts blood flow to the brain. Paramedics injected him with ketamine, a powerful sedative. He went into cardiac arrest on the way to the hospital and died several days later.
In the amended autopsy report, forensic pathologist Stephen Cina said the ketamine injection was excessive for McClain, who stood about 5-f00t-7 and weighed 140 pounds.
A review of body-camera footage that police did not provide during the initial autopsy showed that McClain was “extremely sedated” within minutes, according to Cina. He said he thought McClain was struggling to breathe as he lay on a stretcher and that respiratory arrest was “imminent.”
“Simply put, this dosage of ketamine was too much for this individual and it resulted in an overdose, even though his blood ketamine level was consistent with a ‘therapeutic’ blood concentration,” Cina wrote. “I believe that Mr. McClain would most likely be alive but for the administration of ketamine.”
It was not clear whether the carotid hold contributed to his death, Cina said, noting that medical literature suggested it would not have. He said that he saw nothing on McClain’s neck that showed he died of asphyxiation and that McClain could speak after the officers let him up.
Cina also noted that McClain was “alive and responsive to painful stimuli” up to the point that he received the ketamine shot.
“It is my opinion that he likely would have recovered if he did not receive this injection,” he said.
Deaths related to ketamine toxicity are usually classified as accidents, according to the report, but Cina said the manner would remain “undetermined” because other factors could have played a role.
He added: “I acknowledge that other reasonable forensic pathologists who have trained in other places may have developed their own philosophy regarding deaths in custody and that they may consider the manner of death in this type of case to be either homicide or accident.”
In an emailed statement to The Washington Post, an Aurora police spokesman said the department “fully cooperated with the investigation.” A representative for Aurora emergency services did not immediately respond to a message seeking comment Saturday morning.
Prosecutors initially declined to charge anyone in McClain’s death, citing the lack of evidence in the original autopsy.
Some officials, medical experts and criminal justice advocates criticized prosecutors for not seeking a second medical opinion to avoid an “undetermined” manner of death.
Colorado Gov. Jared Polis (D) appointed a special prosecutor to reopen the case, and a grand jury was empaneled to consider criminal charges.
During the proceedings, the investigation of McClain’s death came under greater scrutiny when Colorado Public Radio reported that the county coroner had met with police before the autopsy was released and that police investigators were present during the examination.
In September 2021, charges were announced against three Aurora police officers and two paramedics. The defendants are expected to enter pleas in November.
Evidence that emerged during the grand jury proceedings prompted the coroner to alter the original autopsy report, but the changes remained secret for more than a year.
The amended version released Friday was made public under a court order after Colorado Public Radio and several other media outlets sued to get access to it.
McClain’s case drew little interest outside Colorado until the May 2020 murder of George Floyd by then-Minneapolis police officer Derek Chauvin. McClain’s death became a rallying cry in the months of protests that followed. Friends and family remembered him as a gentle person who would use his lunch break to play violin for animals at a local shelter.
Aurora last year agreed to pay $15 million to settle a lawsuit by McClain’s family. The city also banned the chokehold used in his arrest and is considering a ban on ketamine.
Elijah McClain’s death attributed to ketamine administrated by paramedics
NEWYou can now listen to Fox News articles!
Elijah McClain died after being administrated ketamine while forcibly detained, according to a recently published autopsy report.
Denver District Court Chief Judge Christopher Baumann ordered Thursday that McClain’s autopsy report be published unredacted for the public.
The report was published Friday afternoon. According to the coroner, McClain’s 2019 cause of death was an overdose of ketamine administered by paramedics.
“Simply put, this dosage of ketamine was too much for this individual, and it resulted in an overdose, even though his blood ketamine level was consistent with a ‘therapeutic’ blood concentration,” said coroner Dr. Stephen Cina.
ELIJAH MCCLAIN DEATH: COLORADO GRAND JURY INDICTS 3 POLICE OFFICERS, 2 PARAMEDICS
FILE – A makeshift memorial stands at a site across the street from where Elijah McClain was stopped by Aurora, Colo., Police Department officers while walking home, before family members hold a news conference, Friday, July 3, 2020, in Aurora, Colo. Three Aurora Police Department officers have left the force after photographs surfaced of them reenacting the chokehold used on McClain across the road from the memorial, which sits in the shadow of Interstate 225. (AP Photo/David Zalubowski, File)
( (AP Photo/David Zalubowski, File))
“I believe that Mr. McClain would most likely be alive but for the administration of ketamine,” Cina added.
In September, a Colorado grand jury indicted three officers and two paramedics in the death of Elijah McClain, a black man who was put in a chokehold and injected with a powerful sedative two years ago in suburban Denver.
Aurora police stopped McClain, a 23-year-old massage therapist, as he walked home from a store on Aug. 24, 2019, after a 911 caller reported a man wearing a ski mask and waving his hands who seemed “sketchy.”
AURORA, CO – JUNE 27: Elijah McClain protesters close to the Aurora place line at the Aurora Municipal Center June 27, 2020. Elijah McClain died August 30, 2019 several days after a struggle with Aurora police. Elijah became unconscious during the encounter with police August 24, 2019 and had a heart attack while being transported to a hospital. McClain died after being taken off life support. (Photo by Andy Cross/MediaNews Group/The Denver Post via Getty Images)”n”n
( (Photo by Andy Cross/MediaNews Group/The Denver Post via Getty Images)”n”n)
Officers put McClain in a chokehold and pinned him down.
Paramedics injected him with 500 milligrams of ketamine, an amount appropriate for someone 77 pounds heavier than McClain’s 143-pound frame, according to the indictment. He fell unconscious, was pronounced brain-dead at a hospital, and was taken off life support.
AURORA POLICE IN COLORADO QUESTIONED ON USE OF FORCE DURING ELIJAH MCCLAIN PROTEST: REPORT
LOS ANGELES, CALIFORNIA – JUNE 28: A view of BEAR THE TRUTH Protest: A Pop-Up Art Curation of Teddy Bears for Children and Families in honor of #BlackLivesMatter at Los Angeles City Hall on June 28, 2020 in Los Angeles, California. (Photo by Chelsea Guglielmino/Getty Images)
((Photo by Chelsea Guglielmino/Getty Images))
The city of Aurora has released bodycam footage and the 911 call that preceded the incident.
CLICK HERE TO GET THE FOX NEWS APP
In portions of it, McClain, in a sobbing voice, denies having done anything wrong. He tells officers he’s “just different” and can be heard saying, “I can’t breathe, please stop.”
“When we showed up, he was wearing a ski mask,” someone can be heard saying.
Elijah McClain’s death caused by complications from ketamine injection following restraint, coroner says in amended autopsy report
CNN
—
The autopsy report for Elijah McClain, an unarmed Black man who died while in police custody in Colorado three years ago, has been changed to update the cause of death from “undetermined” to “complications of ketamine administration following forcible restraint,” Adams County Chief Coroner Monica Broncucia-Jordan said Friday.
In August 2019, McClain, a 23-year-old massage therapist, was walking home from a store when he was apprehended by Aurora police officers responding to a “suspicious person” call. Police said McClain had resisted and he was placed into a carotid hold.
Paramedics diagnosed McClain with “excited delirium” and administered the powerful sedative ketamine. He suffered a heart attack on the way to the hospital. Three days later, he was declared brain dead.
The original autopsy report listed the cause of McClain’s death as “undetermined.”
The coroner’s office received body camera footage, witness statements and additional records that were part of a grand jury investigation and not available before the autopsy was performed, pathologist Dr. Stephen Cina wrote in the amended autopsy report.
Man tranquilized during police stop calls for ban on practice
“Simply put, this dosage of ketamine was too much for this individual and it resulted in an overdose, even though the blood ketamine level was consistent with a ‘therapeutic’ concentration,” CIna wrote. “I believe that Mr. McClain would most likely be alive but for the administration of ketamine.”
Cina, who was assisted at the autopsy by Broncucia-Jordan, wrote that based on his training and experience, he still believes the manner of death is “Undetermined.”
“I acknowledge that other reasonable forensic pathologists who have trained in other places may have their philosophy regarding deaths in custody and that they may consider the manner of death in this type of case to be either HOMICIDE or ACCIDENT,” the pathologist added.
CIna could not determine whether the carotid hold contributed to McClain’s death, he added.
But “I have seen no evidence that injuries inflicted by the police contributed to death,” he wrote.
The amended autopsy report was signed in July 2021. It was released Friday after a Denver District Court judge approved the coroner’s emergency motion.
McClain’s death days after his interactions with police brought renewed scrutiny of the use of carotid holds and ketamine during law enforcement stops. His case gained renewed attention during Black Lives Matter protests in the wake of the police killings of George Floyd and Breonna Taylor.
Last year a grand jury indicted three police officers and two paramedics involved in the McClain case. They face charges of manslaughter, criminally negligent homicide and other charges.
In 2021, the city settled a civil rights lawsuit with the McClain family for $15 million, and the Aurora police and fire departments agreed to a consent decree to address a pattern of racial bias found by a state investigation.