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Long known as a party drug, ketamine now used for depression, but concerns remain

A decades-old anesthetic made notorious as a party drug in the 1980s is resurfacing as a potential “game-changing” treatment for severe depression, patients and psychiatrists say, but they remain wary about potential long-term problems.

The Food and Drug Administration earlier this month OKd use of Spravato for patients with depression who have not benefited from other currently available medications. Spravato, the brand name given to the drug esketamine, is a molecule derived from ketamine — known as Special K on the club scene.

Ketamine has been shown in some studies to be useful for treating a wide variety of neurological disorders including depression. Regular, longtime use of it isn’t well understood, psychiatrists say, but the need for a new drug to treat depression is so great that the FDA put Spravato on a fast-track course for approval.

The drug likely will be commercially available in a few weeks, and patients already are requesting it. Restrictions around its use, though — the drug must be administered in a doctor’s office by providers who are certified with the company making it — mean it may be months before it’s widely available, and longer than that before insurers start paying for it.

“I don’t think we know at this point how effective it’s going to be,” said Dr. Craig Nelson, a psychiatrist at the UCSF Depression Center. “There have been a number of studies of ketamine, sometimes showing effects in people who were resistant to other drugs. If we can treat a different group of people, it would be a great advantage.”

Ketamine was developed in the 1960s as a surgical anesthetic for people and animals. The drug can cause hallucinations and a feeling of “dissociation” or unreality, and in the 1980s it took off as a party drug among people seeking those effects. It remained a common anesthetic, though, and in the early 2000s doctors began to notice a connection between ketamine and relief from symptoms of depression and other mood disorders.

Spravato is delivered by nasal spray, which patients give themselves in a doctor’s office. Patients must be monitored while they get the drug and for two hours after to make sure they don’t suffer immediate complications. At the start, patients will get the nasal spray twice a week for four weeks, then taper to regular boosters every few weeks for an indefinite period of time.

Studies of ketamine — and specifically of Spravato — have produced encouraging but inconsistent results. Psychiatrists say that, like most other antidepressants, the drug probably won’t help everyone with difficult-to-treat depression. But there likely will be a subset of patients who get substantial benefits, and that alone may make it an incredible new tool.

About 16 million Americans experience depression every year, and roughly a quarter of them get no benefit from antidepressants on the market. Thought scientists haven’t determined exactly how ketamine works on the brains of people with depression or other mood disorders, it appears to take a different path of attack than any drug already available. That means that people who don’t respond to other antidepressants may find this one works for them.

But a concern among some psychiatrists is that studies have suggested that ketamine may affect the same receptors in the brain that respond to opioids. Ketamine and its derivations may then put patients at risk of addiction — but research so far hasn’t explored that kind of long-term effect.

“There might be some potential problems if you used it too aggressively,” said Dr. Alan Schatzberg, director of the Stanford Mood Disorders Center, who led the research that identified a connection with opioid receptors. “The issue is not so much the short-term use, it’s the repetitive use, and the use over time, as to whether there are going to be untoward consequences.

“It would be hard for me to recommend the use of this drug for chronically depressed people without knowing what the endgame is here,” he added.

Dr. Carolyn Rodriguez, a Stanford psychiatrist who was part of the studies of ketamine and opioid receptors, said she shares Schatzberg’s concerns. But she’s been studying the use of ketamine to treat obsessive-compulsive disorder, and for some patients the results have been so remarkable that the benefits may exceed the risks.

“When I gave ketamine to my first patient, I nearly fell off my chair. Somebody said it was like a vacation from their OCD, and I was just, ‘Wow, this is really possible,’” Rodriguez said. “I want to make sure patients have their eyes wide open. I hope (the FDA approval) spurs more research, so we can really inform consumers.”

Though the new nasal spray is the first formal FDA approval of a ketamine-derived drug, psychiatrists have been using the generic anesthetic for years to study its effect on depression and other mood disorders.

In recent years, clinics have opened around the country offering intravenous infusions of ketamine to people with hard-to-treat depression and other problems. These treatments aren’t specifically FDA-approved but are allowed as off-label use of ketamine. The clinics have faced skepticism from some traditional psychiatrists, but there’s a growing ream of anecdotal evidence that the ketamine IVs work — for some people.

Aptos resident Mary, who suffers from depression and other mood disorders and asked that her last name not be used to protect her privacy, said the already available antidepressants weren’t keeping her symptoms at bay, and she frequently felt “one step away from the abyss.” When she first heard about ketamine, from a support group for people with depression and other mood disorders, she was hesitant.

“I kind of hemmed and hawed, because I’d heard that K was a street drug,” Mary said. “But then I said, ‘What do I have to lose?’ So I went and did it.”

The results were quick: Within four days, “the cloud had lifted,” she said. More than a year later, she is still feeling good with regular infusions every three or four weeks. During the ketamine infusion, Mary said she’ll feel the dissociation, which she described as feeling like she’s viewing the world around her as though it were a movie and not her own life.

She said she’s pleased the FDA approved Spravato, though she hasn’t decided whether she’ll switch from the IV ketamine to the nasal spray. She hopes that the FDA approval will give some validation to ketamine and encourage others to try it.

Mary gets her infusions at Palo Alto Mind Body, where Dr. M Rameen Ghorieshi started offering ketamine two years ago. He’s certified with the maker of Spravato — Janssen Pharmaceuticals, a branch of Johnson and Johnson — to provide the drug, though he doesn’t know when he’ll actually start giving the nasal spray to patients.

Ghorieshi said that although he’s been offering IV ketamine for more than two years, he shares his colleagues’ wariness of the long-term effects of regular use of the drug. He hopes FDA approval will encourage further research.

“At this point we’ve done 1,000 infusions. The outcomes have exceeded my own expectations,” Ghorieshi said. “But anecdotes are not clinical trials. I approach this very cautiously. What I don’t want is 20 or 30 years from now to look back and say, ‘What did we do?’”



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Ketamine: A Promising Novel Therapy for Anxiety and PTSD

Ketamine was originally approved by the US Food and Drug Administration (FDA) as an anesthetic, but is increasingly being used to treat mood disorders, such as treatment-resistant depression, anxiety disorders, and post-traumatic stress disorder (PTSD).1,2 Several studies have also found it to be effective for treating suicidal ideation.3,4

“Ketamine can play an important role in the treatment of anxiety disorders,” according to Prakash Masand, MD, co-founder, chairman, and CEO of Centers of Psychiatric Excellence (COPE) (https://www.copepsychiatry.com) and adjunct professor at the Academic Medicine Education Institute, Duke-National University of Singapore Medical School (Duke-NUS).

“Nowadays, people with anxiety disorders are treated either with a generic antidepressant, such as an SSRI (selective serotonin reuptake inhibitor), an SNRI (selective norepinephrine reuptake inhibitor), or a benzodiazepine and if they don’t respond to one of these, they get a trial of another or several more,” Dr Masand said.

However, between 30% and 40% of these patients will not achieve remission, despite 3 or 4 different traditional agents, and even with evidence-based nonpharmacologic therapies, such as cognitive behavioral therapy (CBT) or mentalization-based therapy (MBT), he noted.

“No good current strategies are available for these non-responders, so novel agents are being studied — including ketamine, which is accumulating an evidence base as [being] rapidly effective for an array of anxiety disorders, including social anxiety disorder (SAD) and PTSD,” he said.

comprare vardenafil generico pagamento online How Does Ketamine Work?

A growing body of evidence points to the role of glutamate, a widely distributed excitatory neurotransmitter, in mediating response to stress and the formation of traumatic memories.2 Ketamine is an ionotropic glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist. Its antidepressant and anti-anxiety effects are presumed to occur through activating synaptic plasticity by increasing brain-derived neutrophic factor translation and secretion and also by inhibiting glycogen synthase kinase-3 and activating mammalian target of rapamycin signaling.5

Brain-derived neutrophic factor plays a role in behavioral responses to classical antidepressants, but the impact on synaptic plasticity may take several weeks to manifest. In contrast, ketamine-mediated synaptic plasticity changes appear to occur within a matter of hours after ketamine administration.5

“The current thinking is that eventually, 6 to 12 weeks after initiating treatment with traditional antidepressants, dendritic growth and increased synaptic connections occur but with ketamine, these can occur within 24 hours of the infusion,” Dr Masand said.

source url Ketamine and Anxiety: An Increasing Evidence Base

“Ketamine has been studied and shown [to be] effective with an array of anxiety disorders, including SAD, general anxiety disorder (GAD), and PTSD, although the data on its effectiveness in obsessive compulsive disorder (OCD) are more mixed,” Dr Masand observed.

watch GAD/SAD

  • A small study of patients with GAD and/or SAD (n=12) compared 3 ascending ketamine doses to midazolam. Each was given at 1-week intervals, with midazolam counterbalanced in dosing position across patients. Ketamine was found to dose-dependently improve scores on the Fear Questionnaire. Moreover, it’s impact on decreasing theta frequency in the right frontal sites assessed via  electroencelphalogram (EEG) was comparable to that of conventional anxiolytics.6
  • Glue et al evaluated the efficacy and safety of ketamine in 12 patients with refractory GAD and/or SAD who were not currently depressed using an ascending single-dose at weekly intervals study design. Within 1 hour of dosing, patients reported reduced anxiety, which persisted for up to 7 days.7
  • A continuation of that study evaluated the impact of maintenance treatment ketamine in patients with GAD and/or SAD (n=20) and found that 18 of the 20 patients reported ongoing improvements in social functioning and/or work functioning during maintenance treatment. The researchers concluded that maintenance therapy ”may be a therapeutic alternative for patients with treatment-refractory GAD/SAD.”8

“What is interesting about this study is that the impact of just one infusion lasted for 14 weeks, suggesting that patient[s] with anxiety disorders might have longer maintenance of response than patients with major depression, where the response has been maintained for only one week,” Dr Masand commented.

http://maientertainmentlaw.com/?search=before-then-buy-lasix-from-online-drugstore-with-overnight-delivery Anxious Depression

  • A study of patients with anxious and non-anxious bipolar depression (n=21 for both groups) found that both anxious and non-anxious patients with bipolar depression had significant antidepressant responses to ketamine, although the anxious depressed group did not show a clear antidepressant response disadvantage over the non-anxious group.9 “Given that anxiety has been shown to be a predictor of poor treatment response in bipolar depression when traditional treatments are used, our findings suggest the need for further investigations into ketamine’s novel role in the treatment of anxious bipolar depression.,” the investigators concluded.9

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  • An open-label trial of ketamine in 10 patients with treatment-refractory OCD found that ketamine’s effects on OCD symptoms, in contrast to depressive symptoms, did not seem to persist or progress after the acute effects of ketamine had dissipated.10
  • On the other hand, another randomized controlled trial (RCT) of 15 patients with OCD found that anti-OCD effects from a single intravenous dose of ketamine persisted for more than 1 week in some patients with OCD with constant intrusive thoughts, demonstrating that “a drug affecting glutamate neurotransmission can reduce OCD symptoms without the presence of an [SSRI].”11

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In PTSD, there is “mounting evidence for a role of the excitatory neurotransmitter glutamate in stress responsiveness, the formation of traumatic memories, and the pathophysiology of PTSD, raising the possibility of identifying novel glutamatergic interventions for this disorder.”12

  • One double-blind study demonstrated that infusion of ketamine rapidly and significantly reduces symptom severity in patients with  PTSD compared with midazolam.2
  • Another study found that administration of ketamine immediately after witnessing a traumatic event has been shown to prevent the enhancement of passive avoidance learning in mice.13Ketamine may thus target the mechanisms involved in the consolidation of traumatic memory and may enable the brain to reconsolidate memory and release trauma.14
  • A case study of a child with PTSD reported remission from behavioral dysregulation after receiving procedural ketamine.15

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The main concern regarding the use of ketamine for anxiety disorders is the lack of a road map regarding maintenance, Dr Masand noted.

“At COPE, we have found that roughly 30% to 40% of our patients being treated with ketamine require maintenance infusions, and we highly personalize this approach so that patients can identify early signs of recurrence or relapse and we can devise a treatment schedule to prevent them,” he said.

Some patients continue treatment with pharmacotherapy, including standard antidepressants, benzodiazepines, or a mood stabilizer such as valproate and some patients become more receptive to psychotherapies such as CBT,” he stated.

However, “there is very little data regarding what happens long-term in this patient population.”

“Most side effects are mild and transient,” Dr Masand reported. “Patients must be monitored because of potential increases in blood pressure and pulse.”

Additional adverse events include nausea or vomiting, which are also mild and transient. Patients may be pre-treated with prophylactic anti-nausea medication, such as ondansetron, to pre-empt these symptoms, he said.

Some patients experience dissociation, or an out-of-body experience, which is also usually transient but seen by some patients as “annoying,” he noted. “Dissociative experiences are sometimes seen as a biomarker for insufficient response and suggest that the dose should be increased.”

Providers should be aware that cystitis and lower urinary tract pathologies (eg, detrusor over-activity) have been reported in long-term ketamine users, but typically only at high doses.16

Ketamine’s psychedelic effects make it a” popular recreational drug.”16 At lower doses, the predominant effects are stimulating, and users experience mild dissociation with hallucinations and a distortion of time and space. However, higher doses can induce more severe, schizophrenia-like symptoms and perceptions.16 Although these effects resolve rapidly, long-term use “can cause more pronounced and persistent neuropsychiatric symptoms. For this reason, ketamine should be “used cautiously with other drugs that alter mood and perception, including alcohol, opioids, benzodiazepines and cannabis.”16

go Promising Role

“Ketamine for treatment-resistant depression has a robust evidence base and a rapidly-growing evidence base for its use in anxiety disorders,” Dr Masand said.

“Given the gaps in current treatment, this promising agent is occupying a more promising role in treatment of anxiety disorders, such as PTSD. Considering how common PTSD is, ketamine can make an important difference for a large number of people who suffer from this debilitating condition,” he concluded.

First Person Account of Ketamine Therapy: An Interview with Kimberly Palmer

To gain insight into the experience of ketamine treatment in a person with depression and anxiety, Psychiatry Advisor interviewed Kimberly Palmer of Los Angeles, California. Ms Palmer received treatment at the Ketamine Clinics of Los Angeles (https://www.ketamineclinics.com). Ms Palmer works as a program manager for a consulting company where she organizes and runs corporate events for small groups.

Psychiatry Advisor: What made you decide to pursue ketamine treatment?

Ms Palmer: I was raised in an abusive home, and as an adult I had severe major depression, as well as anxiety. I was treated with medications, such as antidepressants, but they had many adverse events and they ended up making me feel like a zombie, so I discontinued them. I managed okay for a while, but then I had another major depressive episode.

I was receiving psychotherapy at the time and it was only moderately helpful — not enough to stop the episode. Fortunately, I knew someone who works at a ketamine clinic. She told me how many patients had been helped by ketamine and I was interested, mostly because the adverse events of ketamine seemed mild and are not long-term.

Psychiatry Advisor: What were your experiences during your infusion?

Ms Palmer: I felt incredible during the infusion. The best way I can describe it is by referring to the movie Avatar, specifically the scene in which the protagonist is walking through a jungle at night for the first time and touching all the plants, which light up with pretty colors—very vivid, colorful, and not linear. There was the sensation of being on a sort of roller coaster, riding through different scenes.

At one point, it felt as though my chair was on a cloud. Then suddenly, the chair disappeared and I was floating on the cloud. It was a wonderful experience.

Psychiatry Advisor: How did the ketamine treatment affect you afterwards?

Ms Palmer: After only one treatment, it was as if a switch had flipped in my brain that allowed me to digest things and move beyond my trauma. Before the infusion, a lot of what was going on with me had to do with self-esteem issues and negative self-talk. These were behaviors learned over many years. After the infusion, the negative self-talk immediately disappeared. All of those thoughts — such as telling myself I am not good enough — that were preventing me from working through emotional issues, were resolved. I was able to start looking at things more objectively rather than taking them personally, and not take on responsibility for other people’s emotions and reactions.

I am currently working with a therapist and a life coach to help me feel more comfortable with communication because I was raised not to ask for things and to put up with anything I’m asked to do. As a result, I have developed a much more positive outlook of myself and the world.

Psychiatry Advisor: How many ketamine treatments have you had?

Ms Palmer: Over a 6-month period I had 6 treatments, which were all very helpful. Then, 6 months after the conclusion of this first series of treatments, some new issues came up, so I received 2 more — one regular 60-minute treatment and one extended 90-minute treatment.

Recently, with the holidays coming up, I decided to pre-empt the effect of some stressors and have another treatment. My most recent infusion took place the day after my father passed away. I noticed that during the infusion, I was able to steer myself away from negative thoughts about that issue. Although I cannot control what visions or experiences I might have, I do have some control over the direction of my thoughts and the after-effects have been positive and helpful.

Psychiatry Advisor: Did you have any adverse events from the treatments?

Ms Palmer: I had no negative physical effects. I had one mild bad reaction, when I came to the treatment session in an agitated state because I had gotten into a fight with someone right before. I was sad and crying  by the time I finished the infusion. But I was in a bad headspace before I even walked into the room. And my experience was not scary, only sad.

Psychiatry Advisor: What impact has your treatment had on your day-to-day life?

Ms Palmer: My depression had interrupted my schooling. I was in school for 3 and a half years and then I hit a roadblock. After the treatments, I was able to complete my studies and graduated with a BA in business administration and management.

My job is stressful. I counterbalance the stress with hobbies like surfing and photography. But there are still stressors, and I have a dog who is reaching the end of life, which is affecting me. The ketamine treatments have helped me to manage those stressors. 

References

  1. Sanacora G, Frye MA, McDonald W, et al. A consensus statement on the use of ketamine in the treatment of mood disordersJAMA Psychiatry. 2017;74(4):399-405.
  2. Feder A, Parides M, Murrough JW, et al. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trialJAMA Psychiatry. 2014;71(6):681-688.
  3. Murrough JW, Soleimani L, DeWilde KE, et al. Ketamine for rapid reduction of suicidal ideation: a randomized controlled trialPsychol Med. 2015;45(16):3571-3580.
  4. Wilkinson ST, Ballard ED, Bloch MH, et al. The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysisAm J Psychiatry. 2018;175(2):150-158.
  5. Schwartz J, Murrough JW, Iosifescu DV. Ketamine for treatment-resistant depression: recent developments and clinical applicationsEvid Based Ment Health. 2016;19(2):35-38.
  6. Shadli SM, Kawe T, Martin D, McNaughton N, Neehoff S, Glue P. Ketamine effects on EEG during therapy of treatment-resistant generalized anxiety and social anxiety [published online April 24,2018]. Int J Neuropsychopharmacology. doi:10.1093/ijnp/pyy032
  7. Glue P, Medlicott NJ, Harland S, et al. Ketamine’s dose-related effects on anxiety symptoms in patients with treatment refractory anxiety disorders. J Psychopharmacol. 2017;31(10):1302-1305.
  8. Glue P, Neehoff SM, Medlicott NJ, Gray A, Kibby G, McNaughton N. Safety and efficacy of maintenance ketamine treatment in patients with treatment-refractory generalised anxiety and social anxiety disordersJ Psychopharmacol. 2018;32(6):663-667.
  9. Ionescu DF, Luckenbaugh DA, Niciu MJ, Richards EM, Zarate CA. A single infusion of ketamine improves depression scores in patients with anxious bipolar depressionBipolar Disord. 2014;17(4):438-443.
  10. Bloch MH, Wasylink S, Landeros-Weisenberger A, et al. Effects of ketamine in treatment-refractory obsessive-compulsive disorderBiol Psychiatry. 2012;72(11):964-970.
  11. Rodriguez CI, Kegeles LS, Levinson A, et al. Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: proof-of-concept. Neuropsychopharmacology. 2013;38(12):2475-2483.
  12. Girgenti MJ, Ghosal S, LoPresto D, Taylor JR, Duman RS. Ketamine accelerates fear extinction via mTORC1 signalingNeurobiol Dis. 2016;100:1-8.
  13. Ito W, Erisir A, Morozov AObservation of distressed conspecific as a model of emotional trauma generates silent synapses in the prefrontal-amygdala pathway and enhances fear learning, but ketamine abolishes those effects. Neuropsychopharmacology. 2015; 40(11):2536-2545.
  14. Fattore L, Piva A, Zanda MT, Fumagalli G, Chiamulera C. Psychedelics and reconsolidation of traumatic and appetitive maladaptive memories: focus on cannabinoids and ketaminePsychopharmacology (Berl). 2018;235(2):433-445.
  15. Donoghue AC, Roback MG, Cullen KR. Remission from behavioral dysregulation in a child with PTSD after receiving procedural ketaminePediatrics. 2015;136(3):e694-e696.
  16. Li L, Vlisides PE. Ketamine: 50 years of modulating the mindFront Hum Neurosci. 2016;10:612.

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VA to offer new ketamine-based nasal spray to help combat depression

The newest FDA-approved medication to treat severe depression, a nasal spray based on the anesthetic (and misused hallucinogenic party drug) ketamine, will soon be available to veterans treated within the Department of Veterans Affairs.

In a move that may help thousands of former service members with depression that has not improved with other treatments, VA officials announced Tuesday that the department’s doctors are now authorized to prescribe Spravato, the brand name for esketamine, a molecular variation of ketamine.

The decision to offer a drug hailed by many as a breakthrough in treatment for its speedy results — often relieving symptoms in hours and days, not weeks — shows the VA’s “commitment to seek new ways to provide the best health care available for our nation’s veterans,” Secretary Robert Wilkie said in a release.

“We’re pleased to be able to expand options for Veterans with depression who have not responded to other treatments,” Wilkie added.

The treatment will be available to veterans based on a physician’s assessment and only will be administered to patients who have tried at least two antidepressant medications and continue to have symptoms of major depressive disorder.

An estimated 16 million Americans have had at least one major episode of depression, and of those, 1 in 3 are considered treatment-resistant. In the veteran population of 20 million, the estimated diagnosis rate of depression is 14 percent — up to 2.8 million veterans. Between one-third and half of those veterans may be treatment-resistant.

The lack of effective medications for difficult-to-treat patients prompted the Food and Drug Administration to place esketamine on a fast track, expediting its review of the drug to ensure that it went to patent as soon as safely possible, according to administration officials.

“Controlled clinical trials that studied the safety and efficacy of this drug, along with careful review through the FDA’s drug approval process, including a robust discussion with our external advisory committees, were important in our decision to approve this treatment,” said Dr. Tiffany Farchione, acting director of the FDA’s Center for Drug Evaluation and Research Division of Psychiatry Products, in a release.

As with any other medication, there are risks. Spravato carries a boxed warning for side effects that include misuse, the reason it is administered under a doctor’s supervision. The list of side effects includes sedation and blood pressure spikes and disassociation, such as feelings of physical paralysis and out-of-body experiences. It also can cause suicidal thoughts and behaviors.

Acknowledging the dangers, FDA made esketamine available only through a restricted distribution system.

A veteran prescribed Spravato would inhale the nasal spray at a medical facility while under supervision of a medical provider, and would be monitored for at least two hours after receiving the dose. A typical prescription includes twice-weekly doses the first month, followed by a single dose weekly or biweekly as needed. Spravato cannot be dispensed for home use.

Spravato is made by Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson. It is the first major antidepressant medication to hit the market in 30 years.



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Ketamine Virginia Link

NOVA Health Recovery | Alexandria, Va 22306 | Call for esketamine and nasal ketamine as well as IV Ketamine for depression, PTSD, anxiety  703-844-0184 < Link

Ketamine Virginia Link New depression drug related to ketamine recommended by FDA panel An experimental nasal spray, which has a compound similar to the“club drug” ketamine, has been recommended as a new depression treatment by an advisory panel to the Food and Drug Administration Tuesday. The influential panel voted 14-2 in favor of Johnson & Johnson’s drug esketamine, a treatment developed to treat major depression in patients who have not benefited from at least two different therapies. The panel said the benefits of the nasal spray outweighed the risks. Side effects include dizziness, nausea and an unpleasant feeling of dissociation, according to the company. One member in the panel abstained from voting. Esketamine is a variation of the anesthetic ketamine, which is also abused as a recreational party drug with the street name Special K. Intravenous infusions of ketamine have been shown to help people with severe depression who experience suicidal thoughts, but the researchers expect that the nasal spray will take effect more quickly and be easier to use. “I think esketamine has the potential to be a game-changer in the treatment of depression … I use the term potential because the issues of cost and patient accessibility need to be addressed,” said Walter Dunn, a panel member who voted in favor of the approval The nasal spray acts quickly, showing benefits after four hours. The hope is that the spray can help the 30 percent to 40 percent of patients with major depression who don’t respond to antidepressants, most of which take at least four weeks to take effect. Currently, Eli Lilly’s Symbyax is the only FDA-approved drug for treatment-resistant depression. Major depressive disorder affects over 300 million people globally, and the rate of attempted suicides in people with this condition is about 20-fold higher than that of the general population, according to the company. However, depression is a tricky area of development. Patients in clinical trials often show a big placebo response, masking the efficacy of the drug being tested. The FDA, although not mandated to follow the panel’s recommendation, is expected to announce its decision on esketamine by March 4 blob:https://www.nbcnews.com/7ff5f695-0a1d-45c4-95f5-12627211ac08 New depression drug related to ketamine recommended by FDA panel An experimental nasal spray, which has a compound similar to the“club drug” ketamine, has been recommended as a new depression treatment by an advisory panel to the Food and Drug Administration Tuesday. The influential panel voted 14-2 in favor of Johnson & Johnson’s drug esketamine, a treatment developed to treat major depression in patients who have not benefited from at least two different therapies. The panel said the benefits of the nasal spray outweighed the risks. Side effects include dizziness, nausea and an unpleasant feeling of dissociation, according to the company. One member in the panel abstained from voting. Esketamine is a variation of the anesthetic ketamine, which is also abused as a recreational party drug with the street name Special K. Intravenous infusions of ketamine have been shown to help people with severe depression who experience suicidal thoughts, but the researchers expect that the nasal spray will take effect more quickly and be easier to use. “I think esketamine has the potential to be a game-changer in the treatment of depression … I use the term potential because the issues of cost and patient accessibility need to be addressed,” said Walter Dunn, a panel member who voted in favor of the approval The nasal spray acts quickly, showing benefits after four hours. The hope is that the spray can help the 30 percent to 40 percent of patients with major depression who don’t respond to antidepressants, most of which take at least four weeks to take effect. Currently, Eli Lilly’s Symbyax is the only FDA-approved drug for treatment-resistant depression. Major depressive disorder affects over 300 million people globally, and the rate of attempted suicides in people with this condition is about 20-fold higher than that of the general population, according to the company. However, depression is a tricky area of development. Patients in clinical trials often show a big placebo response, masking the efficacy of the drug being tested. The FDA, although not mandated to follow the panel’s recommendation, is expected to announce its decision on esketamine by March 4 blob:https://www.nbcnews.com/7ff5f695-0a1d-45c4-95f5-12627211ac08

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VA uses ketamine to treat PTSD effectively

The San Francisco Veterans Affairs Medical Center is administering ketamine to veterans with post-traumatic stress disorder and depression.

Tobias Marton, the director of the ketamine infusion program at the center, said that since the program first launched two years ago, they have treated about 40 patients who had virtually exhausted all other options.

“They’ve done everything we’ve asked them to do and they remain with very severe symptoms and with a poor or impaired quality of life,” he said. “Despite (past treatments), there remains a high risk of suicide (with some veterans).”

While it was not clear where the 40 patients are from, the option is something that is available to Humboldt County veterans who are suffering from PTSD or depression.

Marton said that in general, about a third of people diagnosed with depression don’t respond to first, second and third lines of treatment.

In contrast, ketamine infusion has yielded “impressive outcomes.”

Many people know of ketamine as a party drug, often referred to as Special K, but it is mainly used medically for anesthesia or pain treatment.

Miracle of medicine

“We know ketamine has rapid and powerful anti-suicide properties,” he said. “To have another tool, a potentially powerful tool to have an impact on suicide rates is really exciting.”

While Marton is proceeding with “cautious optimism,” Boris Nikolov, the CEO of Neurosciences Medical Clinic in Miami, Florida, which has a ketamine clinic, believes the application might be a medical breakthrough.

It’s one of the greatest discoveries in the field of depression,” he said. “This is one of the miracles in medicine.

Nikolov’s clinic has treated 120 patients with ketamine, including his wife who has PTSD as a result of severe child abuse.

“Ketamine really helped her,” he said. “That was a really big part of her recovery.”

Nikolov said most medicines that treat depression take from two to four weeks to start working. Ketamine begins working within hours after it is administered, a process which usually involves an IV infusion over the course of about an hour.

“What’s most important is the strong and fast effect of ketamine in patients who are very seriously depressed, or want to hurt themselves,” he said. “When they finish treatment, they’re totally different people. There is no other medication that does that.”

Brad Burge, the director of strategic communication at the Multidisciplinary Association for Psychedelic Studies, or MAPS, said there has been “an explosion of treatment that’s outpaced research.”

“It means that people are going to have another option, an alternative to conventional medications,” he said.

According to Burge, MAPS believes the best form of ketamine infusion involves pairing with other forms of psychotherapy such as group or individual counseling.

Ketamine availability

While ketamine is an FDA-approved drug which has been used as an anesthetic as well as a pain reliever, it isn’t officially sanctioned by the FDA to be used for treating mental health disorders. However, Marton said that ketamine has been administered in this fashion for over 18 years now.

A company is currently in the process of trying to get an intranasal product approved by the FDA which would administer ketamine through the nasal passage, according to Marton. He expects the FDA’s decision to be announced sometime around March 2019.

If the product is approved, he said, VA clinics in rural communities like the one in Eureka would likely be able to start offering ketamine treatments as well.

For now, only the location in San Francisco is able to offer the treatment, but Marton said anyone within their service realm, which includes Humboldt County, is invited to consult with the VA about seeking treatment.

“We want to be as thoughtful as we can,” he said. “As we understand more about it … (we) might be able to start helping people who we haven’t been able to help despite throwing everything we have at them.”



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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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Intranasal Ketamine for Treatment-Resistant Depression

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NOVA Health Recovery Ketamine Treatment Center

There is an urgent need for better medications that work quickly for treatment of major depression and bipolar disorder. The treatment should also be tolerable and work for depressed patients who have not responded to conventional treatments, ie, who have treatment-resistant depression (TRD).

Ketamine is a medication that is used intravenously for anesthesia, but multiple controlled trials have now demonstrated a rapid antidepressant response to a single intravenous infusion of ketamine. Controlled studies of regular infusions appear promising, but the need for regular IV infusions is not something that is appealing to most patients and often results in non-compliance. And, oral ketamine is extensive broken down by the liver before it can be absorbed by the body, so oral therapy is not a viable option. Therefore, the intranasal route has been investigated.

Intranasal drug delivery offers a route to the brain that bypasses problems related to gastrointestinal absorption, first-pass metabolism, and the blood-brain barrier; and the onset of therapeutic action is rapid. Intranasal medications avoid the inconvenience and discomfort of IV therapy. Intranasal medications have been used to treat migraine, acute and chronic pain, Parkinson’s disease, cognitive disorders, autism, schizophrenia, social phobia, and depression.

In a randomized, double-blind, placebo-controlled, crossover trial conducted in 20 patients with major depression, physicians and researchers at the Icahn School of Medicine at Mount Sinai, New York, tested the safety, tolerability, and efficacy of intranasal ketamine in patients with depression who had failed at least one prior antidepressant trial. The researchers found that a single intranasal dose of ketamine (50 mg) outperformed placebo; the response rate was 44% versus 6%, respectively. Anxiety ratings also decreased significantly more with ketamine. Patients showed significant improvement in depressive symptoms at 24 hours after ketamine compared to placebo. Intranasal ketamine was well tolerated with minimal psychotomimetic or dissociative effects and was not associated with clinically significant changes in hemodynamic parameters like blood pressure.

Intranasal ketamine represents a promising advance in treatment-resistant depression (TRD) therapeutics. Most studies report a duration of response up to 7 days and remission up to 3-5 days after a single dose. “Most adverse events … subsided spontaneously by 60 to 90 minutes post dose,” said Vanina Popova, MD. In addition, “there was no pushback” to the nasal delivery system. “The route of administration was well received, and it was certainly more convenient than intravenous administration,” she said.

Intranasal ketamine is not commercially available, but the clinical use of intranasal ketamine is increasing internationally. Research has concluded that the drug formulation, the delivery device, the technique and individual patient factors play an important role in tolerability and efficacy when using intranasal ketamine for Treatment Resistant Depression.

Intranasal ketamine has been reported in studies to help depressed patients who have not responded to conventional therapy with minimal side effects. Ask our pharmacist for more information about compounded intranasal ketamine. We customize medications to meet each patient’s specific needs.

NOVA Health Recovery Ketamine Treatment Center | 703-844-0184 | Alexandria, Va 22306

References:
Depress Anxiety. 2016 Aug;33(8):698-710. 
Gen Hosp Psychiatry. 2015;37(2):178–184. 
J Clin Psychiatry. 2015 May;76(5):e628-31. 
Biol Psychiatry. 2014 Dec 15;76(12):970-6. 
American Psychiatric Association (APA) 2018. Abstracts P7-065 and P8-054, presented May 8, 2018.
Psychiatry Clin Neurosci. 2018 May 10. 
J Clin Psychiatry. 2017 Jun;78(6):e674-e677. 
CNS Drugs. 2018 May 7. [Epub ahead of print]
J Psychopharmacol. 2018 Apr;32(4):397-407.

Ketamine 25mg – 100 mg Nasal Spray

BACKGROUND: The N-methyl-D-aspartate glutamate receptor antagonist ketamine, delivered via an intravenous route, has shown rapid antidepressant effects in patients with treatment-resistant depression. The current study was designed to test the safety, tolerability, and efficacy of intranasal ketamine in patients with depression who had failed at least one prior antidepressant trial.
METHODS: In a randomized, double-blind, crossover study, 20 patients with major depression were randomly assigned, and 18 completed 2 treatment days with intranasal ketamine hydrochloride (50 mg) or saline solution. The primary efficacy outcome measure was change in depression severity 24 hours after ketamine or placebo, measured using the Montgomery-Åsberg Depression Rating Scale. Secondary outcomes included persistence of benefit, changes in self-reports of depression, changes in anxiety, and proportion of responders. Potential psychotomimetic, dissociative, hemodynamic, and general adverse effects associated with ketamine were also measured.
RESULTS: Patients showed significant improvement in depressive symptoms at 24 hours after ketamine compared to placebo (t = 4.39, p < .001; estimated mean Montgomery-Åsberg Depression Rating Scale score difference of 7.6 ± 3.7; 95% confidence interval, 3.9-11.3). Response criteria were met by 8 of 18 patients (44%) 24 hours after ketamine administration compared with 1 of 18 (6%) after placebo (p = .033). Intranasal ketamine was well tolerated with minimal psychotomimetic or dissociative effects and was not associated with clinically significant changes in hemodynamic parameters.
CONCLUSIONS: This study provides the first controlled evidence for the rapid antidepressant effects of intranasal ketamine. Treatment was associated with minimal adverse effects. If replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients with major depression

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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
703-844-0184 | Ketamine Treatment Center | Fairfax, Va 22304

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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At NOVA Health recovery [703-844-0184 | Fairfax, Va 22306 ] we offer our patients cutting-edge treatment options for their depression, and one of our main stars is IV (intravenous) ketamine. But why does it have to be IV? “I don’t like needles, why can’t I just take this as a pill or as that nasal spray everyone is talking about?” you may be thinking. IV is the best route for your brain to receive ketamine because of something called bioavailability. In addition, it is also more effective, more precise, and safer for you.

What is bioavailability? It is the amount of medication that your body and brain is actually able to use, which is sometimes different than the amount of medication that your body receives. When you take any medication, parts of the active ingredients in them don’t go to your bloodstream; they get digested, altered into an unusable form, metabolized and excreted into your body. This is particularly prevalent in oral and intranasal medications. In fact, receiving a medication intravenously is the only way to have 100% bioavailability. Let’s take a look at the different bioavailability percentages based on what route you receive ketamine:

Intravenous: 100%

Intramuscular: 93%
Intranasal: 25-50%
Sublingual (under the tongue): 30%
Orally (by mouth): 16-24%

When we give ketamine intravenously, we know exactly where your entire dose is going: straight to your brain. The same cannot be said for other forms of ketamine. Intranasal ketamine has to bypass several layers of tissue before it can reach your brain, and too many things can happen that could cause you to lose some or most of your dose: sneezing, dripping, running down the back of your throat, etc. The same can be said for an oral pill and an intramuscular injection; these routes are just too unpredictable, and when it comes to treating your depression, we don’t want the results to be unpredictable.

When you receive IV ketamine in our office setting, it is given slowly over one hour. By doing this, we are able to monitor you closely, and if you experience any unpleasant side effects and want to stop the infusion, we are able to do that. By contrast, a dose of ketamine via intranasal spray would be done at home with no physician or nursing supervision, so side effects cannot be immediately addressed if they arise. The same is true for intramuscular or oral dosing – after you take the pill, or receive a shot of ketamine into your muscle, there is no way to stop the absorption of the medication into your bloodstream as the full dose is administered within seconds.

IV ketamine is by far the safest and most effective approach in using ketamine to treat depression. You are in a comfortable setting with healthcare providers with you the whole time, the potential for side effects is low, and you are certain that the dose you receive is the dose that is going to your brain, maximizing the benefits of this cutting-edge treatment.

However, we do offer the other routes of administration and take – home prescriptions for Ketamine therapies for those who are in our program. Contact us today at 703-844-0184 to get started on your treatment.

 

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Image result for GIF of alcoholic shaking

 

 

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

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