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Dual studies highlight ketamine’s potential to treat anxiety and addiction

New evidence suggests ketamine can reduce anxiety related to major depression, and substance abuse depression
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Two new studies suggest the psychiatric benefits of ketamine treatment may extend beyond just the targeting of depression. The research demonstrates ketamine may be helpful in targeting both anxiety- and substance abuse-related depression.

Although ketamine is a relatively old drug, originally developed in the 1950s as an anesthetic, over the last decade a growing body of research has affirmed its unique, and rapid, antidepressant effects. The anecdotal effects of the drug on depression have raced ahead of scientific research so quickly that ketamine clinics have popped up all across the United States, where the drug can be administered for up to US$1,000 a dose.

Much is still unknown about how efficacious ketamine actually is for depression. We don’t know ideal dosages, how long the treatments last, or how safe long-term usage is. Two newly published studies are adding to our knowledge about ketamine’s psychiatric uses, adding weight to the drug’s burgeoning new potential.

The first study, led by a team from Massachusetts General Hospital and Harvard Medical School, set out to study how effective ketamine is at treating patients with anxiety-based treatment-resistant depression. This is an important question to resolve, as many traditional antidepressants do not consistently improve anxiety-based symptoms in cases of major depression.

The study took 99 subjects with treatment-resistant depression, half of whom suffered from high anxiety and half of whom displayed no anxious symptoms. The study randomly administered subjects either one of four different intravenous ketamine doses, or midazolam, a general sedative that could serve as a control.

As well as demonstrating ketamine’s novel antidepressant qualities, the study revealed the drug worked equally well in both anxious and non-anxious subjects. This suggests that ketamine’s antidepressant effects are uniquely effective across different types of treatment-resistant depression, something that cannot be said for many major antidepressant drugs.

“In contrast to reports from monoaminergic antidepressants, our data suggest that patients with anxious depression respond equally as well to ketamine compared to those with non-anxious depression,” write the researchers in the published study.

The second new study comes from a team at Yale University School of Medicine. This research investigated whether ketamine could be effective in treating addiction-related depression when administered in tandem with naltrexone.

A study in 2018 offered a small but significant finding, revealing that ketamine was ineffective in treating depression when administered alongside naltrexone. These results were important because they suggested that part of ketamine’s antidepressant effects may be related to the activation of opioid receptors, which would mean long-term ketamine use may potentially result in problems with addiction, something that many researchers have long argued against.

Naltrexone, an opioid receptor blocker, is often administered effectively to combat serious substance abuse problems, so if it rendered ketamine ineffective then that would cast doubt on much research into how ketamine actually works to reduce symptoms of depression. The new Yale research was small, with a sample of only five patients, but its results strongly suggest ketamine and naltrexone do not cancel each other out.

All five subjects suffering from alcohol use disorder and depression displayed significant depressive relief from ketamine dosages despite long-term naltrexone consumption. Senior author on the study, John Krystal, says although larger studies still need to be completed the research does suggest ketamine and naltrexone may be a complimentary combination that helps treat substance abuse and its related depression.

“[The results] raise the possibility that for people who have depression complicated by substance abuse disorders, the combination of ketamine and naltrexone may be a strategy to explore in the effort to optimally treat both conditions,” says Krystal.

Although this new study only consisted of five subjects, the prior research linking ketamine to the opioid system was generated from just 12 subjects. So we are still in uncharted territory regarding ketamine’s mechanistic effects of the brain. But the Yale research should assuage some fears that ketamine may be, “merely another opioid in a novel form.”

The ketamine anxiety study was published in the journal Depress Anxiety.

The ketamine naltrexone study was published in the journalJAMA Psychiatry.

Source: Yale News

Efficacy of intravenous ketamine treatment in anxious versus nonanxious unipolar treatment‐resistant depression

Abstract

Objective

To examine the effect of high baseline anxiety on response to ketamine versus midazolam (active placebo) in treatment‐resistant depression (TRD).

Methods

In a multisite, double‐blind, placebo‐controlled trial, 99 subjects with TRD were randomized to one of five arms: a single dose of intravenous ketamine 0.1, 0.2, 0.5, 1.0 mg/kg, or midazolam 0.045 mg/kg. The primary outcome measure was change in the six‐item Hamilton Rating Scale for Depression (HAMD6). A linear mixed effects model was used to examine the effect of anxious depression baseline status (defined by a Hamilton Depression Rating Scale Anxiety‐Somatization score ≥7) on response to ketamine versus midazolam at 1 and 3 days postinfusion.

Results

N = 45 subjects had anxious TRD, compared to N = 54 subjects without high anxiety at baseline. No statistically significant interaction effect was found between treatment group assignment (combined ketamine treatment groups versus midazolam) and anxious/nonanxious status on HAMD6 score at either days 1 or 3 postinfusion (Day 1: F(1, 84) = 0.02, P = 0.88; Day 3: F(1, 82) = 0.12, P = 0.73).

Conclusion

In contrast with what is observed with traditional antidepressants, response to ketamine may be similar in both anxious and nonanxious TRD subjects. These pilot results suggest the potential utility of ketamine in the treatment of anxious TRD.

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New Drug Combo Shows Promise for Treatment of Depression and Addiction

Drug Combo Shows Promise for Depression and Addiction
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The combination of naltrexone and ketamine can help treat both symptoms of addiction and depression, a preliminary study by Yale University researchers suggests.

Substance abuse and depression are common in many patients, and efforts to treat both conditions simultaneously have had limited success. One recent study suggested that the antidepressant effects of ketamine might blunted by administration of naltrexone, used to limit cravings of those addicted to opioid drugs and alcohol.

A preliminary study of five patients suffering from both depression and substance abuse disorders suggest that isn’t the case. The study was published Jan. 9 in the journal JAMA Psychiatry.

The results “raise the possibility that for people who have depression complicated by substance abuse disorders, the combination of ketamine and naltrexone may be a strategy to explore in the effort to optimally treat both conditions,” said senior author John Krystal, Yale’s Robert L. McNeil Jr. Professor of Translational Research; professor of psychiatry, neuroscience, and psychology; and chair of the Department of Psychiatry.

Krystal and lead author Gihyun Yoon, assistant professor of psychiatry, treated the five patients suffering from depression and alcohol use disorder with a long-lasting form of naltrexone and then administered ketamine. Four of the five responded to the first ketamine dose and all five found relief from depression after multiple doses.

The study also challenges the idea that ketamine might produce antidepressant effects by stimulating opiate receptors.

Krystal cautioned that larger studies are needed to confirm beneficial effects of the combination treatment.

Krystal and Yoon have provisional patents on the use of ketamine and naltrexone to treat comorbid depression and substance abuse.

The study was primarily funded by the U.S. Department of Veterans Affairs.

Publication: Gihyun Yoon, et al., “Association of Combined Naltrexone and Ketamine With Depressive Symptoms in a Case series of Patients With Depression and Alcohol Use Disorder,” JAMA Psychiatry, 2019; doi:10.1001/jamapsychiatry.2018.3990

At NOVA Health Recovery, we do use Ketamine and other combinations to treat Alcoholism and Opioid and Pain pill addiction using Ketamine Treatment. Dr. Sendi is Board Certified in Addiction Medicine. Call 703-844-0184 Today. Fairfax, Va 22304.



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Radical ketamine therapy could treat alcohol addiction

There is a growing body of research to support the idea that ketamine, a horse tranquiliser, can be used to disrupt harmful patterns of behaviour.
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A one-off dose of the drug could help alcohol addicts reduce their intake by ‘erasing’ drink-related memories, say psychologists testing treatment.
There is a growing body of research to support the idea that ketamine, a horse tranquiliser, can be used to disrupt harmful patterns of behaviour

Scientists believe that a radical treatment involving the tranquilliser ketamine could help overcome alcohol addiction by “erasing” drink-related memories.

Psychologists based at University College London are testing whether a one-off dose of the drug could help hazardous drinkers who are trying to reduce their alcohol intake. Alcohol addiction is notoriously difficult to treat, and there are few effective therapies available.

First ‘gold-standard’ trial of ketamine’s anti-depressant effects launched

 Read more

Using a recreational drug to treat addiction may sound counterintuitive, but the researchers say there is a growing body of research suggesting that ketamine can be used to disrupt harmful patterns of behaviour.

Ravi Das, one of the lead researchers, said: “There is evidence that it could be useful as a treatment for alcoholism.”

Crucially, ketamine can disrupt the formation of memories, and scientists believe that this property could be harnessed to over-write the memories that drive addiction and harmful patterns of behaviour.

“Memories that you form can be hijacked by drugs in some people,” said Das. “If you were an alcoholic you might have a strong memory of being in a certain place and wanting to drink. Those memories get continuously triggered by things in the environment that you can’t avoid.”Advertisement

For instance, seeing a glass of beer, hearing the clinking of glasses or even arriving home from work may trigger memories of the rewarding sensation of taking a drink – and might prompt a person to follow this urge.

“The main problem is the really high relapse rate after treatment,” said Das. “People can successfully quit using over the short term while they’re being monitored in the hospital … but when they return home they’re exposed to those environmental triggers again.”

There is increasing evidence, however, that memories are less stable than once assumed and may be open to manipulation.

Each time our brain accesses a memory, the neural connections that encode it are temporarily destabilised, meaning that our recollection can be slightly altered before it goes back into storage. This is one reason why, in everyday life, people can recall wildly different versions of the same events.

In the clinic, scientists believe this short period of instability, represents a window of opportunity. Ketamine blocks a brain receptor called NMDA, which is required for the formation of memories. So the logic is that giving someone the drug just as a memory has been destabilised could help weaken the memory, or even erase it.

 Read more

A similar approach with a different drug was shown to eradicate people’s phobia of spiders. And research in rats that were made to be addicted to cocaine showed that the memories underpinning their addiction could be completely wiped out using a similar strategy (although this involved injecting a chemical into the brain).

In the UCL trial, the scientists will intentionally trigger alcohol-related memories by placing a glass of beer in front of the participants, who are all heavy drinkers. They will then disrupt the memory, by surprising the participant (the team is not disclosing the exact details as this could bias the results).

Participants will then be given either a ketamine infusion, with a concentration equivalent to a high recreational dose, or a placebo. The team will follow up the people for a year and monitor whether their drinking has changed and by how much.

In total the scientists are aiming to include 90 people in the trial and more than 50 have already taken part. It involves people who drink harmful quantities of alcohol, but excludes anyone who meets the clinical criteria for alcoholism. The participants were drinking at least 40 units a week for men (equivalent to four bottles of strong wine) and 28 units for women, and drinking on at least four days. The UK needs common sense about ketamine

Nikki, 31, who works as a consultant in London said she decided to take part in the study when she had some time off between jobs and realised she was drinking more than she wanted to. “It’s just in the culture, that’s what all my friends are like. Everyone drinks to excess,” she said.

She described the experience of being given the ketamine as “overwhelming and intense”, but not unpleasant. “My body felt like it was melting away,” she said. “It was quite psychedelic, I felt untethered from my body.”

In the week after the session, she said, she felt in an “incredibly positive mood” and that since taking part she has been more conscious about deciding whether to have a drink, although said this could also be linked to starting a new job and taking up meditation. “In the past, there were occasions where I would be drinking and I’d be on autopilot ‘Let’s get another drink’,” she said.

If the trial yields promising results, the team hope that the approach could form the basis for therapy sessions targeted at alcoholics and people who are drinking unhealthily. However, they acknowledge that there may be resistance to the use of a recreational drug to treat people with addiction.

“There’s just the general social attitude that everything that’s illegal is terrible. There will obviously be that kind of narrow-sighted pushback,” said Das. “But if it’s safe and effective enough it should be recommended.”

Andrew Misell, a spokesman for Alcohol Concern, said: “The researchers have quite rightly highlighted what a lot of people in recovery from alcohol problems know from experience, namely that cues or triggers like the smell of beer can cause a relapse even after long periods of abstinence. Any work looking at how people can overcome these pitfalls is going to be useful.”

However, he added, no drug-based therapy is risk-free “and that certainly includes ketamine”.

Professor Michael Saladin, of the Medical University of South Carolina, is looking at similar approaches to help people quit smoking. “There is a vast animal research literature that suggests memories can be manipulated following reactivation,” he said. “I am convinced that there is sufficient evidence to believe that memory reconsolidation can be harnessed for clinical purposes.”

Problematic alcohol use is a big public health problem in the UK, but could ketamine help?
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January 2018 has come to an end and with it the month that people increasingly use to abstain from alcohol. It is still unknown whether Dry January has a lasting effect on drinking behaviours, and people with an alcohol dependency problem should always seek support from their GP before going through detox. Nonetheless, Dry January undoubtedly drives a critical conversation about alcohol use and provides an opportunity for us to reconsider our relationship with alcohol (one of the main goals of the charity Alcohol Concern, who support the challenge).

While overall alcohol consumption in the UK is falling, alcohol abuse still represents the fifth biggest risk factor for illness, death and disability across all ages. With current treatments often failing to prevent relapse in the long term, researchers are investigating the possibility of using ketamine combined with psychological therapy to help people stay dry, and not just for January. Despite its often cited use as a recreational drug and “horse-tranquilizer” ketamine is also the most widely used anaesthetic in humans. Administered appropriately in a controlled and safe medical environment, ketamine may also have benefits in the treatment of drug problems.

Say Why To Drugs – does alcohol put our health on the rocks?

Evidence for this originally came from a research group in Russia in the 1980s. In this study, patients who had alcohol problems were given three weekly ketamine treatments in conjunction with psychological therapy. After one year, 66% of patients who underwent this treatment regime were abstinent, in comparison to 24% of patients who received treatment as usual, without any ketamine. This abstinence rate is much greater than those documented with any other relapse prevention method.

Inspired by the promising results seen in Russia, we are now conducting the KARE trial (Ketamine for reduction of Alcoholic Relapse) at the University of Exeter and University College London. In this trial participants who have made the decision to abstain are administered ketamine once a week for three weeks. Participants also receive seven sessions of cognitive behavioural therapy to aid their quit attempt and are followed up for six months. Unlike the earlier study, this trial is placebo controlled, thus participants have an equal chance of receiving either ketamine or a matched placebo as well as either cognitive behavioural therapy or alcohol education as a placebo for therapy. It is also double-blind, meaning neither the participant nor the researcher know whether the active treatment or a placebo treatment are administered. This controls for placebo effects and bias due to expectancies of the researcher – putting the original findings to the test with a more rigorous research design.

 The media has a problem with alcoholism – and it’s stopping people getting help

James Morris Read more

Why might ketamine help people stay sober? Recent studies have demonstrated that ketamine has rapid and powerful anti-depressant properties, while people with alcohol problems often also experience symptoms of depression. The direction of the relationship between alcohol problems and depression is not clear, but depressive symptoms are thought to be a common trigger for relapse. Treating people who have alcohol problems with ketamine, therefore, could help them to remain abstinent for longer by lifting their mood.

Furthermore, laboratory research has demonstrated that ketamine promotes the growth of new neurons and connections in the brain. These processes are essential to learning and memory, and are suggested to be impaired in both depression and problematic alcohol use. Thus ketamine might make people more receptive to new information and able to plan effectively for the future, which in turn may enhance the effect of psychological therapy.

We do not yet know how effective the ketamine treatment will be. However, well-designed research studies, such as the KARE trial, could be critical in helping people achieve their abstinence goals.

https://www.pharmaceutical-journal.com/news-and-analysis/features/the-secret-life-of-ketamine/20068151.article?firstPass=false

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The Effects of Intranasal Ketamine on Treatment-Resistant Depression

As I have previously reported, off-label use of ketamine for treatment-resistant depression has resulted in numerous anecdotal reports regarding its unique mechanism of action and overwhelming success in symptom reduction among treatment-resistant and suicidal patients.

This is an important finding because approximately one-third of patients with major depressive disorder (MDD) do not respond to currently available antidepressants. As a result, The American Psychiatric Association (APA, 2016) had issued guidelines for psychiatrists who wish to use ketamine for this purpose. At the time, a slow intravenous infusion was the primary delivery system used to attain the reported results. There are of course numerous challenges and costs associated with this delivery system, including the use of a clinical facility with available advanced life support systems in place.

What Is Ketamine?

Ketamine was developed and FDA approved more than 50 years ago as a fast-acting anesthetic with an impressive safety profile. It is still used today in anesthesiology on both pediatric and adult patients and animals. Ketamine in higher doses also has unique dissociative properties, which explains its popularity as a club drug known as “Special K” in the U.S. It is currently a highly abused club drug in southern Asia today.

Intranasal Ketamine Clinical Trial

In this well-designed original research conducted by Daly and colleagues, a phase 2, double-blind, doubly randomized, placebo-controlled study was employed to assess the efficacy, safety and dose-response of intranasal esketamine hydrochloride (ketamine) in patients with treatment-resistant depression (TRD). The primary positive endpoint was a statistically significant change from baseline to day eight during each study period, measured by the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS).

This study consisted of four phases:

  1. Screening
  2. Double-blind treatment (days 1-15), composed of two 1-week periods
  3. Optional open-label treatment (days 15-74)
  4. Post-treatment follow-up at 8 weeks

The results are impressive. Change in MADRS total score in all three esketamine groups was superior to placebo (esketamine 28 mg: −4.2 (2.09), P = .02; 56 mg: −6.3 (2.07), P = .001; 84 mg: −9.0 (2.13), P < .001), with a significant ascending dose-response relationship (P < .001). Even more impressive is the continuous reduction of depressive symptoms despite reduced dosing frequency during the open-label phase.

Why Does This Matter?

First, the mortality rate for untreated and undertreated depression is between 15 and 20%. Moreover, depression and suicidality are increasing in the U.S., most notably among children and adolescents. Ketamine is thought to inhibit the N-Methyl-D-Aspartame (NMDA) system, which is unrelated to our 50-year-old catecholamine hypothesis, suggesting that the inhibition of NDMA is a viable, and perhaps primary, target for future intervention. In addition, there is growing anecdotal data suggesting that ketamine may also be a viable treatment for pain and perhaps even addictive disease.

Second, the results of this important study show that esketamine has a significant effect on symptom reduction among patients with TRD (Montgomery- Asberg Depression Rating Scale) after only one week of twice-weekly administration, which is substantially faster than the SSRIs or SSNRIs. It is also of interest that esketamine is well tolerated with few adverse effects, evidenced by the fact that a mere 5% of participants discontinued treatment during the double-blind phase. In addition, the use of an intranasal delivery system allows lower dosage compared to oral administration by avoiding first-pass hepatic metabolism.

Third, because of its low molecular weight (238 Daltons), esketamine is a good candidate for intranasal delivery because lower molecular weight improves nasal mucosa absorption. This route will get the dose to the brain rapidly, and for reasons that remain unclear, the therapeutic effect remains when using a twice-per-week dosing system.

All this is to say that compared to currently available oral antidepressant medications, which have a poor adherence rate, esketamine should vastly improve treatment adherence. Combined with few reported adverse effects, more people will get well. This is good day to be a neuroscientist.

Reference:
Ella J. Daly, MD; Jaskaran B. Singh, MD; Maggie Fedgchin, PharmD; Kimberly Cooper, MS; Pilar Lim, PhD; Richard C. Shelton, MD; Michael E. Thase, MD; Andrew Winokur, MD, PhD; Luc Van Nueten, MD; Husseini Manji, MD, FRCPC; Wayne C. Drevets, MD Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression. A Randomized Clinical Trial. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2017.3739. Published online December 27, 2017.

Additional resource for Gambling disorders. Financial costs for loss from this disorder as for any addiction add up quickly. Here is a link to a resource:

Financial strategies for loved ones of problem gamblers

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Can We stop Suicides?

The link above attached to the New York Times article opinion section that discusses Ketamine and its transforming ability for depression and related mood  disorders. Below is the excerpt:

In May of 2017, Louise decided that her life was just too difficult, so she’d end it. In the previous four years, three siblings and a half-sibling had died, two from disease, one from fire and one from choking. Close friends had moved away. She felt painfully, unbearably alone. It would be the fourth time Louise (I’m using her middle name to protect her privacy), then 68, would attempt suicide, and she was determined to get it right.

She wrote a letter with instructions on where to find important documents and who should inherit what. She packed up her jewelry and artwork, addressing each box to particular friends and family members. Then she checked into a motel — homes where people have committed suicide lose value and she didn’t want hers to sell below market — put a plastic sheet on the bed, lay down and swallowed what she figured was an overdose of prescription pills with champagne.

A few days later, she woke up in a psychiatric ward in Albuquerque. The motel maid had found her. “I was very upset I had failed,” she told me recently. So she tried to cut her wrists with a bracelet she was wearing — unsuccessfully.

The suicide rate has been rising in the United States since the beginning of the century, and is now the 10th leading cause of death, according to the Centers for Disease Control and Prevention. It’s often called a public health crisis. And yet no new classes of drugs have been developed to treat depression (and by extension suicidality) in about 30 years, since the advent of selective serotonin reuptake inhibitors like Prozac.

The trend most likely has social causes — lack of access to mental health care, economic stress, loneliness and despair, the opioid epidemic, and the unique difficulties facing small-town America. These are serious problems that need long-term solutions. But in the meantime, the field of psychiatry desperately needs new treatment options for patients who show up with a stomach full of pills.

Now, scientists think that they may have found one — an old anesthetic called ketamine that, at low doses, can halt suicidal thoughts almost immediately

Depression ran in Louise’s family. It had afflicted all her siblings, both of her parents and her grandmother. Prozac had helped Louise for a time, but stopped working for her in the late 2000s, as it sometimes does. No other drug seemed able to lift her dark moods.

After her suicide attempt, Louise’s psychiatrist suggested she try ketamine. She agreed, and received an infusion intravenously. Within hours, her sense of well-being improved. The hospital discharged her. Back home, she discovered that going to the market was no longer a “herculean task.” Getting her car washed wasn’t an insurmountable chore. “Life was better,” she said. “Life was doable.”

Using ketamine to treat depression and suicidality is somewhat controversial. Numerous small studies suggest that it holds great promise, but it’s only now being tested in placebo-controlled trials with hundreds of patients. It is also popular as a club drug in some circles. Like morphine, it may operate on the opioid system, and it can induce feelings of euphoria. Occasionally ketamine abusers develop severe symptoms, including brain damage, persistent hallucinations and a painful inflammation of the bladder called cystitis.

Nonetheless, if proven safe and effective in small doses, ketamine stands to transform how doctors deal with suicidal patients and depression generally.

The drug seems to address a longstanding problem in emergency psychiatry. Sedation and physical restraint aside, doctors have few ways to quickly stop suicidal ideation, or thoughts of killing oneself. The current crop of anti-depressants can take weeks and sometimes months to work, if they work at all. They may also, paradoxically, increase suicidality in some patients. Talk therapy takes time to help as well (assuming it does). Here’s a sobering fact: Some studies indicate that suicide risk peaks soon after patients have been discharged from a medical facility.

Antidepressants and Suicide Risk A Comprehensive Overview

Antidepressants and Suicide Risk A Comprehensive Overview

Suicide risk peaks in first week of psychiatric hospitalisation and post discharge  <, See commentary excerpt at bottom of this page

 

Researchers at Yale discovered ketamine’s potential as an antidepressant in the late 1990s and scientists at the National Institute of Mental Health confirmed it the mid 2000s. Numerous studies followed suggesting that the drug helps precisely with that subset of depressive patients — about a third — for whom nothing else works. It doesn’t work for everyone in this group, but when it does, it works within hours, not weeks.

A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression<<<Carlos Zarate

Suicidality doesn’t perfectly overlap with depression. Many people attempt suicide not because they’re clinically depressed, but rather impulsively, because they’ve been fired or they’ve broken up with girl- and boyfriends, or sometimes because they’re just really drunk. I’ve heard people who show up in the hospital in this state — despondent, angry and uninhibited more than depressed — described as “drunkicidal.”

Many are fine once they sober up. For those who aren’t, ketamine may help independent of its effect on depression. And because ketamine is already approved by the Food and Drug Administration, doctors can prescribe it off-label. Meaning that not only does a drug exist right now that could help with depression and suicidality, it’s theoretically available to patients.

I kept thinking about this during the recent spate of high-profile suicides: the chef Anthony Bourdain, the designer Kate Spade, the actress Margot Kidder. Could ketamine have saved any of them? Did they know about it? Did their psychiatrists?

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What are the uses of ketamine?

Ketamine is a medication that is used to induce loss of consciousness, or anesthesia. It can produce relaxation and relieve pain in humans and animals.

It is a class III scheduled drug and is approved for use in hospitals and other medical settings as an anesthetic.

However, it is also a commonly abused “recreational” drug, due to its hallucinogenic, tranquilizing and dissociative effects.

Controversy has arisen about using ketamine “off-label” to treat depression. Off-label uses of drugs are uses that are not approved by the the United States, (U.S.) Food and Drug Administration (FDA).

Ketamine is safe to use in controled, medical practice, but it has abuse potential. Used outside the approved limits, its adverse mental and physical health effects can be hazardous. Prolonged use can lead to tolerance and psychological addiction.

Fast facts on ketamine:Here are some key points about ketamine. More detail is in the main article.

  • Ketamine is similar in structure to phencyclidine (PCP), and it causes a trance-like state and a sense of disconnection from the environment.
  • It is the most widely used anesthetic in veterinary medicine and is used for some surgical procedures in humans.
  • It is considered a “club drug,” like ecstasy, and it has been abused as a date-rape drug.
  • Ketamine should only be used as prescribed by a doctor.

 

What is ketamine?

ketamine and dissociation
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Ketamine can produce feelings of dissociation when used as a drug of abuse.

Ketamine belongs to a class of drugs known as dissociative anesthetics. It is also known as Ketalar, Ketanest, and Ketaset.

Other drugs in this category include the hallucinogen, phencyclidine (PCP), dextromethorphan (DXM), and nitrous oxide, or laughing gas.

These types of drugs can make a person feel detached from sensations and surroundings, as if they are floating outside their body.

 

Therapeutic uses

Ketamine is most often used in veterinary medicine. In humans, it can induce and maintain general anesthesia before, during, and after surgery.

For medical purposes, ketamine is either injected into a muscle or given through an intravenous (IV) line.

It is considered safe as an anesthetic, because it does not reduce blood pressure or lower the breathing rate.

The fact that it does not need an electricity supply, oxygen, or highly trained staff makes it a suitable option in less wealthy countries and in disaster zones.

In human medical practice, it is used in procedures such as:

  • cardiac catheterization
  • skin grafts
  • orthopedic procedures
  • diagnostic procedures on the eye, ear, nose, and throat
  • minor surgical interventions, such as dental extractions

It has been used in a hospital setting to control seizures in patients with status epilepticus (SE), a type of epilepsy that can lead to brain damage and death. However, researchers point out that ketamine is normally used for this purpose after 5 to 6 other options have proven ineffective. Ketamine for the treatment of refractory status epilepticus

It is also an analgesic, and, in lower doses, it can relieve pain.

In 2014, researchers found that a ketamine infusion significantly reduced symptoms of post-traumatic stress disorder (PTSD) in 41 patients who had undergone a range of traumas.

Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder

Researchers are looking into other possible medical uses of ketamine, particularly in the areas of treatment-resistant depression, suicide prevention, and substance use disorders. However, this use is controversial.

 

Treating depression

Researchers for the American Psychological Association (APA) noted in April 2017 that a number of doctors prescribe ketamine “off-label,” for people with treatment-resistant depression.

However, they caution:

While ketamine may be beneficial to some patients with mood disorders, it is important to consider the limitations of the available data and the potential risk associated with the drug when considering the treatment option.”

The FDA has not yet approved it for treating depression.

In a study published in BMC Medical Ethics, researchers urge doctors to “minimize the risk to patients” by considering carefully the evidence before prescribing ketamine off-label for patients to treat depression and prevent suicide.

Citing “questionable practice” regarding the prescription of ketamine, they point out that there is not enough evidence to prove that ketamine is safe, and that some studies supporting its use have not been sufficiently rigorous in terms of research ethics.

They call for open debate, more research, and for doctors to try all other options first, before prescribing ketamine.

The National Institutes of Health (NIH) are currently supporting research into whether ketamine may help people with treatment-resistant depression.

 

Effects

Ketamine use can have a wide variety of adverse effects, including:

  • drowsiness
  • changes in perceptions of color or sound
  • hallucinations, confusion, and delirium
  • dissociation from body or identity
  • agitation
  • difficulty thinking or learning
  • nausea
  • dilated pupils and changes in eyesight
  • inability to control eye movements
  • involuntary muscle movements and muscle stiffness
  • slurred speech
  • numbness
  • amnesia
  • slow heart beat
  • behavioral changes
  • increased pressure in the eyes and brain

It can also lead to a loss of appetite, upset stomach, and vomiting.

When used as an anesthetic in humans, doctors combine it with another drug to prevent hallucinations.

Risks

Ketamine is considered relatively safe in medical settings, because it does not affect the protective airway reflexes, and it does not depress the circulatory system, as other anesthetic medications do.

However, some patients have reported disturbing sensations when awakening from ketamine anesthesia.

Ketamine can cause an increase in blood pressure and intracranial pressure, or pressure in the brain.

People with the following conditions cannot receive ketamine for medical purposes:

  • brain swelling
  • glaucoma
  • brain lesion or tumor

It is used with caution in those with:

  • coronary artery disease
  • increased blood pressure
  • thyroid disease
  • chronic alcohol addiction
  • acute alcohol intoxication
  • aneurysm
  • chest pain
  • mental illness

These effects may be stronger in people aged over 65 years.

Some people may have an allergy to the ingredients. Patients with any type of allergy should tell their doctor before using any medication.

Anyone who is using this drug for therapeutic purposes on a regular basis should have regular blood pressure checks.

As a drug of abuse

Ketamine is most often used in the dance club setting as a party drug. It produces an abrupt high that lasts for about an hour. Users report euphoria, along with feelings of floating and other “out of body” sensations. Hallucinations, similar to those experienced with LSD, are common.

In 2014, 1.4 percent of 12th graders reported using ketamine for recreational purposes. This was down from 2002, when 2.6 percent reported using it.

Street names include:

  • Cat Valium
  • KitKat
  • Special K
  • Vitamin K
  • The horse tranquilizer
  • Ket
  • Purple
  • Super K
  • Jet

It is taken orally as a pill, snorted, smoked with tobacco or marijuana, or mixed into drinks. Most often, it is cooked into a white powder for snorting. Taken orally, it can cause severe nausea and vomiting.

Regardless of how it is ingested, its effects begin within a few minutes and last for less than an hour.

Higher doses can produce more intense effects known as being in the “K-hole,” where users become unable to move or communicate and feel very far away from their body.

Some users seek out this type of transcendental experience, while others find it terrifying and consider it an adverse effect.

Adverse effects

Unwanted effects include:

  • addiction
  • psychosis
  • amnesia
  • impaired motor function
  • high blood pressure
  • respiratory problems
  • seizures

As the user can become oblivious to their environment, ketamine abuse puts the person at risk of accidental injury to themselves and vulnerable to assault by others.

Problems with co-ordination, judgment, and the physical senses can continue for up to 24 hours. If an individual is using ketamine in a recreational setting, a sober friend should remain with them to ensure their safety.

Long-term effects include bladder and kidney problems, stomach pain, and memory loss.

If addiction and dependence develop, there is also a risk of depression.

Frequent, illegal use of ketamine can lead to serious mental disorders and major physical harm to the bladder, known as ketamine-induced ulcerative cystitis.

Ketamine and alcohol

Ketamine toxicity alone is unlikely to lead to death, according to the WHO. However, combining it with other substances, such as alcohol, can increase the sedative effects, possibly leading to a fatal overdose.

In the U.S., 1,550 emergency department (ED) visits were due to illegal ketamine use, and 71.5 percent of these also involved alcohol.

Overdose

The risk of overdose is high, because, for a recreational user, there is only a slight difference in dosage between obtaining the drug’s desired effects and an overdose.

Addiction

Ketamine is a Class III controlled substance. Prolonged use can cause dependence, tolerance, and withdrawal symptoms. Quitting can lead to depression, anxiety, insomnia, and flashbacks.

Chronic users have been known to “binge” their ketamine use in an attempt to experience again the dissociative, euphoric effects of their early first use.

The complications of long-term use can be fatal.

A final word

Ketamine is an anesthetic drug, used in human and veterinary medicine. It is important to distinguish the valid medical uses from the non-medical, recreational use of the drug.

When properly administered by a trained medical professional, ketamine is a safe and valuable medication.

Used in recreational settings, however, ketamine abuse can produce unpredictable physical and mental health results. In the long term, it can lead to psychological damage and, in some cases, death.

Any drug use should be prescribed by a doctor who knows the patient’s full medical history.

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What is ketamine?

Ketamine Nasal Spray
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Ketamine is a drug currently approved by the FDA for use as a general anesthetic during minor surgical procedures such as biopsies. It is widely known as a recreational drug because of its ability to induce cognitive-dissociative, hallucinogenic, and euphoric states in humans. Recently, it has been implicated in research as a potential therapeutic agent in depression especially in patients who have failed previous standard therapies.

Why ketamine?

Standard pharmacologic therapies for depression take several weeks of treatment before patients experience relief. Ketamine is different in that it has been shown to reduce depression symptoms and suicidal ideation in as little as forty minutes. This is considered a potentially lifesaving breakthrough in the treatment of depression because ketamine can rapidly reduce symptoms especially in emergency situations.

How does it work?

The most common medications used in depression affect serotonin in the brain. Ketamine works by a different mechanism. It has been shown to block the glutamate receptors in the brain resulting in its famous hallucinogenic effects. Ketamine has been shown to act on several other receptors, but it is theorized that at low doses, blocking glutamate receptors in the brain may be the reason for its anti-depressive effects.

Who should (and shouldn’t) take ketamine?

Ketamine has not been approved by the FDA for treatment of depression. Although, because of new studies, psychiatrists have been prescribing ketamine “off-label” for patients who did not respond to selective serotonin reuptake inhibitors (SSRIs) such has Celexa (citalopram), Zoloft (sertraline), or Prozac (fluoxetine) for immediate treatment of symptoms.

Ketamine has been shown to transiently yet significantly increase blood pressure following administration. Patients with high blood pressure should use caution when using ketamine. Ketamine has also been shown to be associated with increases in psychosis or dissociative properties.

Ketamine nasal sprays offer a quick and convenient way to administer ketamine for patients who need immediate relief, although they are currently not available commercially, so you will not find them at your local community pharmacy. Compounding pharmacies have the proper experience, equipment, and personnel to safely compound and customize this medication for you.

References

  1. Ketalar [package insert]. Chestnut Ridge, NY 10977: Par pharmaceutical; 2017 https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/016812s043lbl.pdf
  2. Browne CA, Lucki I. Antidepresssant effects of ketamine: mechanisms underlying fast-acting novel antidepressants. Front Pharmacol December 2013.
  3. Lapidus K, Levitch CF, Perez AM, et al. A randomized controlled trial of intranasal ketamine in major depressive disorder. Biol Psychology 2014;76:970–976
  4. Sanacora G, Frye MA, McDonald W, et al. A consensus statement on the use of ketamine in the treatment of mood disorders. JAMA Psychiatry 2017;74(4):399-405.

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Ketamine for Delirium Tremens

This study suggests that ketamine can safely be used to avoid intubation and may decrease length of intensive care unit stay.

Severe alcohol withdrawal, or delirium tremens (DT), is a life-threatening condition that can require massive doses of benzodiazepines or barbiturates (GABA agonists), which can require intubation and prolonged intensive care unit (ICU) care. These authors studied a retrospective sample of adult patients admitted to a single ICU with DT to determine whether adjunctive therapy with ketamine improved outcomes.

They compared outcomes in 29 patients who received symptom-triggered therapy with GABA agonists with outcomes in 34 patients who were treated after initiation of a guideline that added an intravenous ketamine infusion (0.15–0.3 mg/kg/hour) to GABA agonist therapy. Using multivariable modeling that accounted for initial ethanol level and the total amount of GABA agonist required for treatment, patients who received ketamine had significantly lower rates of intubation (29% vs. 76% for patients who did not receive ketamine) and shorter ICU stay (5.7 days vs. 11.2 for patients who did not receive ketamine). There were no reported adverse events.

Adjunct Ketamine Use in the Management of Severe Ethanol Withdrawal

NOVA Health Recovery Ketamine Treatment Center

 

 

 

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703-844-0184 | Fairfax Ketamine Treatment Center for Depression | 

 

From street drug to depression therapy

Ketamine offers a new option for people with stubborn depression that doesn’t respond to other medications.

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Many people know of ketamine as a hallucinogenic and addictive street drug, which, when abused, can put people in medical peril. But today, doctors are increasingly looking to ketamine as a potentially lifesaving treatment for people with severe, treatment-resistant depression, who may be at high risk for suicide.

“Ketamine has been shown to be effective in people who have not responded to antidepressant treatment,” says Dr. Cristina Cusin, an assistant professor of psychiatry at Harvard Medical School. The fast-acting treatment has shown promise — sometimes improving depressive symptoms within hours of the first intravenous treatment.

While ketamine can offer hope to some, it’s not for everyone. The use of ketamine to treat depression is still controversial in some circles. “Some prescribers would never consider the use of a controlled substance for this purpose, because of the potential for abuse,” says Dr. Cusin. “But as with opiates, a drug is not good or bad, per se.” Still, ketamine does need to be carefully matched to the right patient for the right use to avoid harm, and treatment should be closely monitored over time.

A variety of uses

The use of ketamine in medicine isn’t new. It’s routinely used in hospitals both for anesthesia and for pain relief.

Currently, the use of ketamine for depression is “off label.” This means that although ketamine is approved by the FDA for some medical purposes, it’s not approved specifically to treat depression. However, that may soon change. Under its “fast track” drug approval process, the FDA is reviewing the results of clinical trials of esketamine, a ketamine-based nasal spray, to treat depression, says Dr. Cusin.

For now, people who undergo ketamine treatment for depression typically receive the drug at specialized clinics, either intravenously or as a nasal spray. Effects from the nasal spray last for a single day or a few days, while the intravenous treatment may last for a few weeks to a month. In both instances the dose is significantly lower than would be used for anesthesia or when used illicitly.

How ketamine works

Studies have shown that ketamine is effective in treating people whose depression has not responded to other interventions, says Dr. Cusin. Such treatment-resistant depression is estimated to affect from 10% to 30% of people diagnosed with the condition.

Experts believe that ketamine works through a unique mechanism, directly modulating the activity of a brain chemical called glutamate. Glutamate is believed to play a role in stimulating the growth of new brain connections that may help alleviate depressive symptoms.

People who have taken ketamine to treat their depression experience varying success, depending on their personal history—how long they’ve been depressed, how severe their symptoms are, and how many drugs they’ve tried without seeing improvement, says Dr. Cusin.

For people with less severe depression, ketamine may be effective in as many as 60% of those who try it. Among those with more persistent and significant disease, a smaller number, 30% to 40%, may experience relief, says Dr. Cusin. “The expectation should not be that it will magically cure depression in everybody,” she says. “Ketamine is not a perfect fix. It’s like any other medication.” In other words, it works for some people, and it won’t work for others.

To be effective, treatment with ketamine must typically continue indefinitely and involve careful monitoring. Clinicians who prescribe ketamine for depression should screen patients carefully to ensure the drug is appropriate for the individual, says Dr. Cusin. “Not everybody who wishes to try ketamine will be a good candidate,” she says.

Among those who should not use ketamine are people with

  • a history of substance abuse
  • a history of psychosis
  • elevated blood pressure
  • an uncontrolled medical condition.

Who can benefit?

Because ketamine is a newer treatment, there are still a lot of questions surrounding its use, says Dr. Cusin. For instance:

  • Which people respond best to treatment?
  • How much should be given, and how often?
  • What are the long-term effects of treatment?

Because the medication is being used off label for depression, there are no clearly defined safety recommendations either for home use or for its use in specialized clinics, she says. This means that it’s up to individual providers to guide the patient in making informed decisions about treatment. Choosing a qualified provider is essential. JAMA Psychiatrypublished a statement in 2017 outlining best practices for doctors to follow in ketamine treatment, such as performing a comprehensive assessment, obtaining informed consent, and documenting the severity of depression before starting the medication. These guidelines are aimed at increasing the safe use of ketamine for depression, and providers can use them to help ensure that the treatment is a good match for your condition.

As with any other medical intervention, anyone considering ketamine should also consider the drawbacks of treatment along with the potential benefits. Ketamine’s drawbacks include these:

Cost. It’s expensive and not covered by insurance. “The cost ranges from $400 to $1,200 per dose for the intravenous drug, and you may need as many as 12 to 18 doses a year,” says Dr. Cusin.

Unknowns. Ketamine hasn’t been used to treat depression for long enough for doctors to know whether there are any harmful long-term consequences of taking the medication. More time and study are needed to truly understand how it affects people over the long term.

Treatment failure. Many people with treatment-resistant depression view ketamine treatment as their last option, so if this therapy fails to improve their depression, they can be emotionally devastated. Realistic expectations and follow-up support are essential.

Even if ketamine does produce results, it’s still important to understand what it can and can’t do. “-Ketamine isn’t going to eliminate all frustrations and stress from your life. While it may lift some symptoms of depression, the life stressors will still be there,” says Dr. Cusin. You’ll still need support to help you manage them.

Side effects. While ketamine is viewed as safe in a controlled setting, it can frequently increase blood pressure or produce psychotic-like behavior, which may result in delusions or hallucinations. Serious adverse events are rare because the drug is used at such low doses, says Dr. Cusin.

However, provided you are an appropriate candidate for the treatment and your doctor monitors you closely, you could find that it improves your mood. “Ketamine could make a huge difference in the quality and duration of life and can be very effective for people who are thinking about suicide,” says Dr. Cusin.

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Seasonal Affective Disorder and Ketamine Infusions as a rapid treatment

 

Do you find yourself getting depressed and sad in the fall and wintertime despite your best efforts? Seasonal affective disorder is common and can disrupt your lifestyle and happiness. Consider Ketamine infusions as an option for immediate relief with follow through intranasal ketamine. We can provide these solutions for people suffering from this disorder. A series of 2- 6 infusions can manage the majority of patients with rapid recover, almost within a few days. 

Seasonal Affective Disorder, or SAD, is a type of recurrent major depressive disorder in which episodes of depression occur during the same season each year. This condition is sometimes called the “winter blues.”

Definition

Seasonal affective disorder (also called SAD) is form of depression in which people experience depressive episodes during specific times of the year. The most common seasonal pattern is for depressive episodes to being in the fall or winter and diminish in the spring. A less common type of SAD, known as summer depression, usually begins in the late spring or early summer. SAD may be related to changes in the amount of daylight a person receives.

SAD is not considered as a separate disorder, but rather is a type of depression that has a recurring seasonal pattern. To be diagnosed with SAD, an individual must meet criteria for major depression coinciding with specific seasons for at least two years. The individual must experience seasonal depressions much more frequently than any non-seasonal depressions.

Seasonal affective disorder is estimated to affect 10 million Americans. Another 10 percent to 20 percent may have mild SAD. SAD is four times more common in women than in men. The age of onset is estimated to be between the age of 18 and 30. Some people experience symptoms severe enough to affect quality of life, and 6 percent require hospitalization. Many people with SAD report at least one close relative with a psychiatric disorder, most frequently a severe depressive disorder (55 percent) or alcohol abuse (34 percent).

Symptoms

Not everyone with SAD has the same symptoms, but symptoms commonly associated with the “winter blues” include the following:

  • Feelings of hopelessness and sadness
  • Thoughts of suicide
  • Hypersomnia or a tendency to oversleep
  • A change in appetite, especially a craving for sweet or starchy foods
  • Weight gain
  • A heavy feeling in the arms or legs
  • A drop in energy level
  • Decreased physical activity
  • Fatigue
  • Difficulty concentrating
  • Irritability
  • Increased sensitivity to social rejection
  • Avoidance of social situations

Symptoms of summer SAD are:

  • Poor appetite
  • Weight loss
  • Insomnia
  • Agitation and anxiety

Either type of SAD may also include some of the symptoms that are present in major depression, such as feelings of guilt, a loss of interest or pleasure in activities previously enjoyed, ongoing feelings of hopelessness or helplessness, or physical problems such as headaches and stomach aches.

Symptoms of SAD tend to reoccur at about the same time every year. To be diagnosed with SAD, the changes in mood should not be a direct result of obvious seasonal stressors (like being regularly unemployed during the winter). Usually, this form of depression is mild or moderate. However, some people experience severe symptoms that leave them unable to function in their daily lives.

Seasonal affective disorder can be misdiagnosed as hypothyroidyism, hypoglycemia, or a viral infection such as mononucleosis.

Causes

The cause for SAD is unknown. One theory is that it is related to the amount of melatonin in the body, a hormone secreted by the pineal gland. Darkness increases the body’s production of melatonin, which regulates sleep. As the winter days get shorter and darker, melatonin production in the body increases and people tend to feel sleepier and more lethargic.

Another theory is that people with SAD may have trouble regulating their levels of serotonin, which is a major neurotransmitter involved in mood. Finally, research has suggested that people with SAD also may produce less Vitamin D, which is believed to play a role in serotonin activity. Vitamin D insufficiency may be associated with clinically significant depression symptoms.

There are several known risk factors that increase an individuals chance of developing SAD. For example, SAD is more frequent in people who live far north or south of the equator. Additionally, people with a family history of other types of depression are more likely to develop SAD than people who do not have this family history.

Treatments

Treatment approaches to alleviate the symptoms of SAD typically include combinations of antidepressant medication, light therapy, Vitamin D, and counseling.

Because winter depression may be caused by a reaction to a lack of sunlight, broad-band light therapy is frequently used as a treatment option. This therapy requires a light box or a light visor worn on the head like a cap. The individual either sits in front of the light box or wears light visor for a certain length of time each day. Generally, light therapy takes between 30 and 60 minutes each day throughout the fall and winter. The amount of time required varies with each individual. When light therapy is sufficient to reduce symptoms and to increase energy level, the individual continues to use it until enough daylight is available, typically in the springtime. Stopping light therapy too soon can result in a return of symptoms.

When used properly, light therapy seems to have few side effects. The side effects that do arise include eyestrain, headache, fatigue, irritability, and inability to sleep (when light therapy is used too late in the day). People with manic depressive disorders, skin that is sensitive to light, or medical conditions that make their eyes vulnerable to light damage may not be good candidates for light therapy.

When light therapy does not improve symptoms within a few days, then medication and behavioral therapies such as CBT should be introduced. In some cases, light therapy can be used in combination with one or all of these therapies.

Self-Care

  • Monitor your mood and energy level
  • Take advantage of available sunlight
  • Plan pleasurable activities for the winter season
  • Plan physical activities
  • Approach the winter season with a positive attitude
  • When symptoms develop seek help sooner rather than later
  • Light therapy and lamps for SAD
  • IV Vitamin Therapy for rapid recovery including Vitamin D injections