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Recent research has shown that ketamine has considerable promise for treating a wide range of treatment-refractory neuropsychiatric disorders, including obsessive compulsive disorder (OCD), post-traumatic stress disorder (PTSD), bipolar disorder, suicide ideation, addiction and, most notably, treatment-resistant major depressive disorder (MDD). Although this research has taken place almost exclusively within the past two decades, evidence of ketamine’s neuropsychiatric effects appeared long before this. For example, ketamine was used throughout the 1970s in Mexico as part of psychedelic therapy sessions that combined traditional healing practices with psychoanalytic techniques.

In 2000, researchers found that ketamine had strong, fast-acting, and long-term effects in depression. In a randomized, placebo-controlled, crossover design study, patients with depression received 0.5 mg/kg of ketamine or saline on the first day of testing. Treatments were switched 1 week later. Researchers found that the antidepressant effects of ketamine began within 4 hours, peaked at 72 hours, and lasted for 1 to 2 weeks thereafter.1 In a 2006 study, this finding was replicated in an independent group of 18 patients with major depressive disorder who were resistant to other treatments. Compared with participants who received placebo, those who received ketamine showed significant improvement in symptoms within 110 minutes, with 35% maintaining significant response for at least 1 week.

Many of today’s depression treatments are monoaminergic-based, including monoamine oxidase inhibitors, tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors. These treatments have been proven effective for a large number of patients. However, a significant subset of patients with major depressive disorder do not respond to these agents. Despite its undisputed value to the field, the monoamine hypothesis of depression cannot fully explain the heterogeneity of MDD. In the 1990s, animal models began to implicate glutamate – one of the major excitatory neurotransmitters in the mammalian central nervous system (CNS) – as well as its ionotropic NMDA receptor in the etiology and treatment of mood disorders .

Existing antidepressant treatments [MAOIs, TCAs, SSRIs, and serotonin-norepinephrine reuptake inhibitors (SNRIs)] are monoaminergic-based treatments. Although they have been in use for decades and have helped many patients, a significant subset of MDD patients showed little to no therapeutic benefit in response to these agents. For instance, the NIMH-funded, communitybased Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study of >4000 MDD patients found that, even after four unique medication trials, augmentation, or switch, 33% of the patients did not respond to standard monoaminergic-based treatments .

In 2000, Berman and colleagues discovered that ketamine exerted rapid, robust, and relatively sustained antidepressant effects in depressed patients . Using a randomized, placebo-controlled, crossover design, each patient received an i.v. infusion of 0.5 mg/kg of either ketamine or saline on the first test day. On the following test day, which took place at least 1 week later, treatments were switched. The authors found that ketamine exerted antidepressant effects that began within 4 h of the infusion, peaked at 72 h, and persisted for 1–2 weeks post-infusion. .Ketamine has also been shown to have distinct and independent antisuicidal and anti-anhedonic effects in patients with mood disorders .

Another limitation of currently available antidepressants is that their clinical effects take more time to reach their full therapeutic potential (for instance, the mean onset for paroxetine is 13 days). This is a substantial disadvantage during an acute depressive crisis. Furthermore, even when these agents do alleviate depressive symptoms, evidence regarding their ability to successfully reduce suicide ideation and behavior remains inconclusive . In contrast, a single dose (0.5 mg/kg) of i.v. ketamine exerts rapid and profound antidepressant effects within hours to days of administration . Ketamine also rapidly reduces suicidel ideation, an effect that appears to occur independently of its antidepressant properties . Ketamine has dose-dependent neuropsychological effects even at subanesthetic doses, with antidepressant properties peaking at 0.5–1.0 mg/kg.

Ketamine’s pan-therapeutic effects also include alleviating fatigue and anhedonia as well as improving sleep measures such as circadian rhythm and slow-wave activity in MDD patients .

The positive effects of Ketamine has led to research into other rapidly acting antisdepressants, including nasal ketamine. Lapidus and colleagues demonstrated that intranasal ketamine had antidepressant effects and led to sufficiently high ketamine plasma concentrations. We use a compounded intranasal ketamine miuxture in our office at NOVA Health Recovery. There is also an FDA approved version more recently, which has only the S-Ketamine in it . There are heavy restrictions and high costs to the FDA approved version, yet efficacy may not be any better.

Noitrois Oxide also has antidepressant effects. Like ketamine, it exhibits NMDA receptor antagonism, has partial agonism for mu, kappa, and delta opioid receptors, inhibits AMPA, kainite, and gamma-aminobutyric acid receptors A and C (GABAA, GABAC), affects serotonin-3 receptors (5-HT3), and releases dopamine . In a double-blind, placebo-controlled, crossover trial, depressive symptoms improved for participants receiving nitrous oxide within 2 h compared with those receiving placebo, an effect that remained significant at 1 day post-treatment. Phase I and II trials are ongoing to determine optimal dose, safety, and efficacy.

Sarcosine also has antidepressant effects. t, sarcosine (also known as N-methylglycine), is an amino acid that functions as a glycine transporter-1 inhibitor and a 6- week, double-blind, randomized, citalopram-controlled trial in 20 MDD patients found that sarcosine possessed superior antidepressant properties compared with citalopram after 2 weeks . Notably, and in contrast to ketamine, sarcosine did not result in rapid-acting effects on the timescale of several days. Sarcosine has co-agonistic properties at the NMDA receptor and is an agonist at the inhibitory glycine receptor. It also exhibits NMDA-enhancing properties, suggesting that AMPA-receptor-mediated or other downstream mechanisms might elicit antidepressant effects. NMDA receptor downregulation might also play a part .

Suboxone (Buprenorphine) also has antidepressant effects as well. Intrigued by the potential of nonaminergic antidepressant mechanisms, researchers have begun to re-evaluate the role of endogenous opioids in depression. For instance, buprenorphine (BUP), a drug currently used to treat opioid addiction and pain disorders, is being explored as a treatment for MDD. The compound has a wide variety of actions throughout the brain, including partial agonism at the mu opioid receptor and antagonism at the kappa and delta opioid receptors ; these are connected to intracellular signaling cascades that potentially mediate antidepressant effects Several open-label studies of BUP in MDD have shown promising preliminary results, and a double-blind, randomized, placebo-controlled trial examining the effect of low-dose BUP on suicidal ideation similarly yielded positive results .

NOVA Health Recovery has used buprenorphine succesfully in the treatment of depression.

Ketamine and Future Depression Treatments

1. Kraus C, Wasserman D, Henter ID, Acevedo-Diaz E, Kadriu B, Zarate CA Jr. The influence of ketamine on drug discovery in depression [published online August 2, 2019]. Drug Discov Today. doi: 10.1016/j.drudis.2019.07.007

2. Zarate CA Jr, Singh JB, Carlson PJ, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depressionArch Gen Psychiatry. 2006;63(8):856-64.

3. Nagele P, Duma A, Kopec M, et al. Nitrous oxide for treatment-resistant major depression: a proof-of-concept trialBiol Psychiatry. 2015;78(1):10-18.

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Treating Alcohol Use with Ketamine? New Research Finds It May Help

  • Results from new studies suggest that ketamine may be effective in treating alcohol use disorder.
  • Researchers found that when participants were treated with ketamine instead of midazolam, a sedative that helps with alcohol withdrawal, they had higher rates of stopping drinking following treatment.
  • They were also less likely to relapse, had fewer days of drinking, and had fewer days of heavy drinking.

Once derided as a “club drug,” the anesthetic ketamine is facing a surge of interest from doctors and researchers who say it could treat certain psychiatric disorders. The most prominent among them: depression.

However, a pair of new studies show promise for a new area of ketamine therapy: alcohol use disorder.

Both studies are early indicators that ketamine could, along with other alcohol interventions like therapy, some day help people decrease or stop drinking. But there’s a lot more research to be done.

The first study, published earlier this month in The American Journal of Psychiatry, was a pilot study, the first of its kind, to test the effects of ketamine and mindfulness practice against a control for alcohol use disorder.

The study included 40 participants who, on average, consumed about 5 drinks per day. Most of the participants were white, and most were employed.

Participants were randomly assigned to either receive a single infusion of ketamine along with a 5-week regimen of motivational enhancement therapy, or midazolam, a sedative that helps with alcohol withdrawal, and the same therapy.

Researchers found that participants who received ketamine rather than midazolam had higher rates of abstinence (stopping drinking) following treatment, were less likely to relapse, had fewer days of drinking, and had fewer days of heavy drinking.

The beneficial results of the ketamine also persisted for several weeks after the single dose infusion.

Call 703-844-0184 for home based ketamine treatment and Ketamine infusions for alcohol and depression

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‘Nothing less than transformational:’ Ketamine brings relief to people with severe depression

Ketamine gave Rachel Morgan her life back.

The 33 year old has struggled to beat back severe depression and post-traumatic stress disorder for much of her life. She’s tried more than 30 psychiatric medications, none of which helped. Her inner pain reached a level so unbearable that she retreated from the world. She stayed in bed. She stopped doing the dishes and taking out the trash, which piled up in her San Francisco apartment. She stopped socializing.

She lost the will to live.

“I had gotten to a point where I disappeared, mentally and physically,” Morgan said. “My psychiatrist kind of put his hands up in the air and said, ‘There’s nothing else I can do for you.'”

But he did suggest something different she could try, albeit not through him: ketamine. The only legally available psychedelic in the U.S., the drug is widely used as an anesthetic in hospitals and medical settings. But it has been found to give people with severe mood disorders, including treatment-resistant depression and suicidal ideation, almost unbelievably fast-acting relief from their symptoms — some with a single dose, though more commonly it takes several treatments.

Morgan received her first ketamine infusion in a Palo Alto psychiatry clinic in June. By her second treatment, she took out the trash for the first time in months. After several infusions, friends told her she was talking more than she had in a year.

For the first time in her life, “I felt like there is a future for me,” Morgan said. “It’s left me a different person than I was a year ago.”

Ketamine is starting to shed its reputation as a psychedelic club drug and experimental mental health treatment as more patients like Morgan see results and more research is conducted on the drug’s impact on the brain. A watershed moment came in March when the U.S. Food and Drug Administration (FDA) approved Spravato, or esketamine, a ketamine nasal spray for adults with treatment-resistant major depression. One short-term clinical trial showed the spray had a statistically significant effect on depression compared to a placebo, and patients saw some effect within two days, according to the FDA.

A handful of local private psychiatry clinics, including in Palo Alto, Menlo Park and Woodside, have in recent years started offering ketamine. They are working at the forefront of a promising new treatment in psychiatry, a field that has seen little medication innovation for decades.

Many of the psychiatrists who run these clinics said they were initially skeptical of the drug’s potential, with little still known about how exactly ketamine works as an antidepressant and its long-term effects, but became believers when they saw life-changing improvements in patients for whom nothing else had worked.

“I think we’re on the brink of an amazing revolution in psychiatry,” said Alex Dimitriu, who offers ketamine treatments at his Menlo Park private psychiatry clinic. “We’re on the brink of understanding that a lot of drugs that previously we thought were drugs of abuse are actually turning out to be some very powerful agents.”

Exploring ketamine’s potential

Ketamine was developed in 1962 as a fast-acting anesthetic and continues to be widely used as such today, particularly for surgery and pain relief, including with children and in veterinary medicine. The drug is a schedule III controlled substance, meaning its medical use is accepted and it has moderate to low potential for abuse. The World Health Organization has included ketamine on its list of essential medicines since 1985 and calls it “possibly the most widely used anesthetic in the world.” As an anesthetic, it is incredibly safe (it does not depress breathing or blood pressure) and is easy to administer, according to the World Health Organization.

In higher doses, ketamine produces a “dissociative” state that can include hallucinations and out-of-body experiences. The drug’s conscious-altering potential led to its recreational use in the psychedelic era of the 1960s and 1970s.

Reports of ketamine use to treat psychological or psychiatric disorders first emerged in the 1970s, including in Argentina, Mexico and Russia, according to a study co-authored by Jennifer Dore, who offers ketamine at her private Helios Psychiatry practice in Woodside.

In 2000, a group of Yale University researchers published a seminal but small-scale study that found seven patients with major depression who received ketamine showed significant improvement in their symptoms within 72 hours, suggesting the drug could be used as an antidepressant.

Six years later, a National Institute of Mental Health study showed that ketamine reduced depression symptoms more quickly than a placebo.

Dore, who trained as a resident at the Stanford University Department of Psychiatry, became curious about ketamine several years ago while treating patients with severe PTSD and treatment-resistant depression. They simply weren’t getting better.

Dore dug into the available research on the drug’s antidepressant effects, which suggested that ketamine inhibits the action of the brain’s NMDA receptors and triggers glutamate production, which causes the brain to form new neural connections. She reached out to Phil Wolfson, director of the Center for Transformational Psychotherapy in San Anselmo, who pioneered ketamine-assisted psychotherapy, in which ketamine is administered while simultaneously patients receive therapy. She was compelled by taking this approach rather than the more medical model of providing the drug in isolation.

The results with her early patients in 2016 were like nothing she had ever seen.

“They had immediate relief,” she said.

Dore said her clinic was the first on the Peninsula to offer ketamine-assisted psychotherapy. She now offers trainings for other providers and sits on the board of the Ketamine Research Foundation.

In March, Dore published a five-year study with two other psychiatry practices that found patients who received ketamine saw clinically significant improvements in depression and anxiety, particularly so for people who came in with more severe symptoms like suicidality and a history of psychiatric hospitalization. At their clinics, they saw the drug help people suffering from obsessive compulsive disorder, bipolar disorder, personality disorders, substance abuse, psychological reactions to physical illness and even relationship issues and social anxiety.

“Ketamine promotes a time-out from (the) ordinary, usual mind, relief from negativity, and an openness to the expansiveness of mind with access to self in the larger sense,” Dore’s study states. “These effects enhance a patient’s ability to engage in meaningful psychotherapy during and after administration.”

Dore is a staunch champion of combining ketamine with psychotherapy, which she believes is necessary to harness the full potential of the drug. She doesn’t see ketamine as a magic bullet, but rather one tool she can use in concert with others — talk therapy, medication, nutrition — to treat people in serious psychological pain.

Before patients start ketamine, Dore carefully evaluates them to determine if it’s an appropriate next step in their treatment, as recommended by the American Psychiatric Association, including through therapy sessions, psychological tests and a review of their medical history. If they choose to proceed, Dore requires patients to sign a lengthy consent form that explains how ketamine works and its potential benefits and risks.

During a patient’s initial treatment, Dore monitors their physical and emotional responses, including blood pressure and heart rate, to decide on an appropriate dose going forward. The highest doses can produce the dissociative state, or the dream-like sensation of disconnecting from reality, Dore said. (Some people believe they have died and are in a new reality, she said. One patient described it as being in a lucid dream.) At lower doses, it can feel more like having a glass of wine, she said. The peak effects last about 15 to 30 minutes, according to Dore.

Patients can take the ketamine via a small lozenge that dissolves under their tongues, intravenously or an intra-muscular injection.

They receive the ketamine in a large second-floor space at Dore’s practice. It resembles a homey living room more than a psychiatric setting — a reflection of the importance of creating “set and setting” for a psychedelic experience, including a comforting physical environment. A large, soft corner couch is strewn with pillows, including one that says “anger” and another, “love.” During treatments, Dore pulls down the blinds on the windows, adjusts the temperature and offers patients weighted blankets, eyeshades and quiet music. The sessions last two to three hours.

Gaining a new perspective

Andy Mathis was at the end of his mental rope when he found Dore. A father, husband and successful tech industry executive, he had quietly suffered from self-doubt and insomnia since he was a young child. By the time he reached his mid-40s, it had escalated to depression. He felt his well-being and very brain chemistry was at risk.

A friend of a friend referred him to Dore, who prescribed him antidepressant and anti-anxiety medications that finally helped him sleep. But she suspected there was more to understand about the root causes of his symptoms, he said, and suggested ketamine as a means for exploring that.

A former professional tennis player, Mathis said he had never taken any drugs before. He did his own research on ketamine and thought it sounded “groundbreaking.” He was more curious than fearful about embarking on a psychedelic experience.

He received his first infusion two and a half years ago and continues to get ketamine every four to eight weeks today.

“It was indeed transformational,” Mathis said. “Nothing less than transformational.”

Mathis described the experience as taking him out of his own ego, a “tilt(ing) of the prism on how I see things.”

“It allowed me to have a detached, philosophical view on all things — me, my place in the world, my relationships,” he said.

This helps him make sense of his emotions “in a way that can be extremely difficult and sometimes even impossible to do when I am inside of myself,” referring to his default, day-to-day mental state.

Over the course of the infusions, Mathis started feeling more comfortable in his own skin, which he said improved his relationships and even his work performance. He realized he has a love for music and at age 47, started to learn how to play the saxophone. He came to a better understanding of his relationship to food and how he had used it as a coping mechanism.

Combining the ketamine-induced realizations with therapy was crucial, Mathis said.

“It was the post-experience discussions that we would have that would also unravel and unwind some of the unhealthy habits,” he said. “I’m 47 now, almost 48. I am healthier now than I was probably, maybe, ever.”

Dore likened ketamine’s power as a catalyst for psychological change to “a year of psychotherapy in three hours.”

Unlike antidepressants, patients don’t have to take ketamine every day and do not experience significant side effects; they can become nauseous or slur their words during the treatment, psychiatrists said. They require patients to have someone to drive them home after the treatment.

Mathis, for his part, did not experience any negative side effects. A patient at another local psychiatry clinic, Lisa Ward, however, said her mind feels “foggy” if she has two infusions in a single week. According to the FDA, the most common side effects experienced by patients treated with Spravato, the esketamine nasal spray, in clinical trials including disassociation, dizziness, nausea, lethargy and increased blood pressure.

“It would be inhumane,” Dore said, to not offer ketamine to people in intractable mental anguish. “We need things that are transformative, that aren’t putting a Band-Aid on a problem.”

Psychiatrist calls it ‘life-changing’

When Rameen Ghorieshi first looked into ketamine as an option for a patient with treatment-resistant depression about five years ago, it was still “very much fringe,” he said. His colleagues at Stanford, where he completed his psychiatric training, knew about the drug but had no idea how to actually use it as a treatment.

He decided to offer ketamine at his small private practice in downtown Palo Alto, Palo Alto Mind Body. He trained with an anesthesiologist and started with two patients. One suicidal young woman who had dealt with a chronic illness since childhood and didn’t intend to live past 30 years old, he said, got to the point where she was working four days a week, socializing and planning to go back to school.

“That just blew my mind,” Ghorieshi said. “I knew it would help just reading the studies but seeing it firsthand was pretty incredible.”

He has done more than 1,000 ketamine infusions at his downtown Palo Alto practice. Eighty-seven percent of patients rated their improvements as significant and 35% of those described it as “life-changing.” It particularly helped suicidal patients, he said. About 13% of patients said the improvement in their symptoms was not worth the time and effort of the infusions.

“This is a bit of a departure for me. I’m a very conservative prescriber,” Ghorieshi said. “My patients tend to be on one, two, maybe three medications. … But it was so remarkable that it seemed hard not to offer it to people.”

Ghorieshi said his was the first clinic in the Bay Area to treat someone with the tightly controlled, FDA-approved nasal spray. A handful of his patients have since received it, with good results, he said.

Esketamine is attached to a federal Risk Evaluation and Mitigation Strategy, which the FDA “can require for certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks.” Providers and patients must register and the drug must be administered in a certified medical office under the supervision of a health care professional.

At Palo Alto Mind Body, patients receive eight ketamine infusions over several weeks. They are strongly encouraged to also pursue therapy but it’s not part of the treatment itself, Ghorieshi said.

He or a nurse supervises patients over the course of the 90-minute appointments. Morgan likes to sit upright on the couch in Ghorieshi’s office, covered by a blanket that keeps her warm and gives her a sense of emotional security. She listens to relaxing elevator music. After, she goes home and naps off the residual effects.

Years ago, she was given much higher doses of ketamine as a pain treatment for chronic physical illnesses and had horrible hallucinations, which she described as “having my head slammed against a wall repeatedly by a slime monster from a deep black bog.”

At the dose Ghorieshi gives her, she feels like the floor and ceiling switch. Her inhibitions dissolve. Afterwards, she feels more open to trying new experiences, from coping mechanisms for her depression to new foods. She feels her perfectionism, which for a long time had prevented her from being vulnerable with others, soften.

“To me, that’s the magic of ketamine,” Menlo Park psychiatrist Dimitriu said of the drug’s tendency to destabilize entrenched behaviors. “I think that speaks to the magic of future psychedelic research, which is down the pipeline, in that it increases our openness to new experience. The general belief here is if you’re depressed severely, you get stuck in maladaptive patterns.”

Lisa Ward didn’t see immediate relief from her life-long depression after her first ketamine infusion with Ghorieshi in March.

Then, a week later as the drug continued to work in her system, “the whole cloud just lifted,” she said. (It takes most patients several treatments to see results, according to Ghorieshi.)

She had more energy. She felt more productive. The benefits extended to her loved ones, as she’s engaged more with her two young children, husband, her parents and her sister.

“It’s enough for me to have more fun with my kids. It’s enough for me to spend more time with my husband instead of going to bed because I just can’t deal with the day anymore,” she said. “Being in depression you don’t realize it but it takes a big toll on other people.”

For Ward, a photographer, the effects of ketamine last about five weeks before she feels the cloud returning. There was one period where the ketamine seemed to stop working all together. Because she lives in Hollister — a three-hour round trip drive from Palo Alto, not including the time of the session itself — and pays out of pocket for the expensive treatment, gaps between her appointments stretch longer than she’d like.

She actually doesn’t enjoy the experience of being on ketamine, which she described as mind-bending and often intense. But she said the disruption of her depression allows her to focus on shifting the underpinning behavior and thought patterns.

Ketamine “doesn’t magically lift all … your problems away,” Ward said. “You’re more apt to make changes when you’re thinking clearly and you’re not so focused on the depression.”

While esketamine, the nasal spray, is covered by insurance because of the FDA approval, most other ketamine administrations are not. Morgan pays almost $1,000 out of pocket for each infusion, though Ghorieshi said some of his patients have been reimbursed for their treatments. Dore charges patients for her time as a provider, about $1,000 for a several-hour session, rather than for the drug itself.

Morgan felt strongly about using her full name in this article to dispel stigma around ketamine in the hopes it will be more widely accepted — and thus available to more people in need.

“Just because you hear something in one context, like ketamine being used as an illicit drug, doesn’t mean it doesn’t exist in another,” she said. “I think that’s what scares insurance companies away from covering it for patients. And that’s what makes me angry because I wish this treatment was out there for everybody to see. I’m lucky enough to be able to handle the financial portion, but the average person might not be.”

The as-yet-unknown risks

Despite the success stories, ketamine has not yet been fully accepted by the broader psychiatric community. The unanswered questions and possible risks that surround ketamine — how it works as an antidepressant, the long-term effects, the potential for abuse — are cause for caution, said Alan Schatzberg, a Stanford School of Medicine psychiatry professor and former president of the American Psychiatric Association.

“Rarely has there been so much anticipation for a new antidepressant as has been seen for intranasal esketamine,” he wrote in the American Journal of Psychiatry in May about the newly FDA-approved ketamine nasal spray.

“Do we have clear evidence of efficacy? Maybe. How strong is the efficacy? Apparently mild. Do we have a real sense of how long and how often to prescribe it? It’s not entirely clear.

“Taken together,” he wrote, “there are more questions than answers with intranasal esketamine, and care should be exercised in its application in clinical practice.”

In an interview, Schatzberg said he’s concerned about repetitive, extended use of any form of ketamine and the drug’s potential for dependence. The American Psychiatric Association has said that the literature on ketamine’s longer-term effectiveness and safety is so limited that the organization cannot “make a meaningful statement” on such use.

“The scarcity of this information is one of the major drawbacks to be considered before initiating ketamine therapy for patients with mood disorders and should be discussed with the patient before beginning treatment,” an American Psychiatric Association task force wrote in a consensus statement on ketamine in 2017.

Schatzberg co-authored a 2018 study that suggests ketamine’s antidepressant effects are tied to the brain’s opioid system and said the implications of this for dependency should be studied further.

“This is the same as any potential drug of abuse, any kind of opioid type drug. Serial use is less the issue. It’s when you get into repetitive use that one needs to be careful,” Schatzberg said. “That’s the clarion call that we’ve been sounding.”

One of his study co-authors, Carolyn Rodriguez, a Stanford associate professor of psychiatry and behavioral sciences, has been blown away by the rapid benefits of ketamine in studies she’s conducted with patients with obsessive compulsive order, or OCD. In the first-ever randomized clinical trial of ketamine compared to placebo in OCD, she found that a single low dose of ketamine prompted a decrease in OCD symptoms within hours for all participants.

Yet she remains cautious and said more research is needed to fully understand the powerful drug. She’s currently studying the mechanisms of how ketamine works so quickly on OCD patients, with funding from the National Institute of Mental Health.

“I believe that the state of the field of ketamine and how it works on OCD is not at the point yet where I would recommend it clinically because I always like to see science, (including) my own science, replicated,” Rodriguez said.

With pause about the long-term effects, she and other researchers have suggested a national registry be created to monitor side effects.

Ghorieshi said he is frank with his patients about the unknowns and potential downsides of ketamine, which must be weighed against other risks.

“We do know the immediate mortality and morbidity of things like suicide and depression.

I think that’s, as with anything, the risk-benefit. What are the risks of suicide, but also depression and anxiety in general?” he said. “You have to balance that versus these unknown risks of ketamine.”

Mathis, for his part, said he’s not concerned about the long-term effects of taking ketamine.

“What I worry about,” Mathis said, “is what my health would have done without it.”



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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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Is ketamine safe? What are some reasons I would not be eligible (contraindications)?

Ketamine is a unique among anesthetic medications in that it is extremely safe, having been used in various settings for more than fifty years, even in poorly monitored settings such as battlefield anesthesia and developing countries, “ketamine has a good safety profile and is easy to use, especially in under-resourced health systems and emergency settings where clinical conditions and medical equipment are generally not available” (World Health Organization).  Ketamine has an even higher margin of safety when used to treat depression because such doses are much lower than those used in surgery. Patients typically remain conscious the entire time, though may feel somewhat altered and experience perceptual changes.  When used in higher surgical and anesthetic doses, ketamine requires the presence of an anesthesiologist for full airway and cardiac monitoring, while the lower doses used in depression do not.  There are specific reasons you would not be eligible for ketamine, including recent myocardial infarction (heart attack), recent psychosis (hallucinations, delusions), or recent bladder inflammation (cystitis). Administration of ketamine and medical monitoring throughout the session is performed by Dr. Sendi, and not by nurses or personnel with less medical training.

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WHO Recommends against International Control of Ketamine

20160309_FactFile_Ketamine

What is the best route of administration for treatment of depression?

As noted above, ketamine can be administered in several different ways: by an intravenous infusion, an intramuscular injection, intranasally, sublingually, and orally. Intravenous ketamine infusions have been most studied because of their historical use and original FDA approval decades ago, though more and more studies are finding comparable efficacy with the other routes of administration.  It is not clear that intravenous ketamine infusions are more effective than other routes of administration, and further results in great patient discomfort, greater resource utilization, and ultimately result in a higher cost.  For this reason I typically offer ketamine via the intramuscular route, which appears to be non-inferior in terms of efficacy for depression.Here is a link to an article on Ketamine and depression:   the International Journal of Transpersonal Studies: Ketamine and depression: a review.

Am I a good candidate?  How are ketamine treatments structured?

Prior to initiating ketamine treatments, some  potential patients are scheduled for an initial psychiatric evaluation.  On this first meeting, we will determine a diagnosis, develop a treatment plan, and assess for any medical or psychiatric issues that may interfere with ketamine treatment. If we mutually agree that ketamine could be beneficial, then we can schedule a subsequent visit for the actual administration; with some planning, it is possible for both the intake and administration to be done on the same day.  The greatest benefit of ketamine is attained with multiple administrations over the first few weeks of treatment, which is then followed by periodic booster treatments to maintain freedom from depression.  I ask patients to commit to a series of 6 administrations over 3 weeks, and then return for periodic bimonthly to monthly booster treatments thereafter to prevent depression from returning. Please note, it is always your option to stop treatment at any time. Patients must have a friend or family member pick them up after the appointment, as ketamine temporarily impairs one’s ability to drive. Ketamine sessions are scheduled for 90 minutes in duration, and involve a brief medication management visit, the actual ketamine administration, followed by psychotherapy, all of which is integrated into one visit.

For individuals interested in ketamine treatments, please print out the informed consent  and bring it with you to our appointment.  I will have you sign it after an in depth discussion about the risks, benefits, and alternatives available to you.

Are there any precautions?

Individuals receiving ketamine should abstain from any food or drink for the 6 hours prior to receiving the medication, and furthermore, should not drive for the remainder of the day. This is a necessary precaution because the subtle after effects of ketamine can linger for hours after the treatment and impair the ability to drive.  Effects typically resolve by the following day, at which time driving is allowed. Typically patients arrange a ride home with a friend or family member, and once tolerability is established can later use a taxi or ride sharing service to return home.

What is the cost of ketamine treatments? Do insurance companies cover it?

I do not directly contract with insurance companies, but instead collect the full fee at time of the visit and provide patients with a superbill that can be submitted to their insurance provider for reimbursement.  Current fees can be found on the new patient intake form, available here.

Visits may be partially covered depending on your insurance plan.  The ketamine administration itself is generally not covered by insurance, however the typical 90 minute long ketamine treatment session involves several other components which may be reimbursed for: the brief medication management (99213, 99214, or 99215) and psychotherapy visit (90833 or 90834) are typically covered by insurance, though this cannot be guaranteed.  In addition, the initial psychiatric evaluation visit (99205) is also typically covered.  I suggest potential patients check with their insurance provider to see what their out-of-network coverage benefits are for the above procedures/CPT codes.  PPO type insurances usually allow for out-of-network benefits, while HMO plans do not.

What can you tell me about the use of ketamine for treatment of addiction or substance use disorders?

Ketamine has been studied for treatment of addiction, specifically to the opiate and street drug, heroin.  Findings suggest that ketamine, as part of a structured therapy program, is effective for the treatment of addiction, perhaps due to biochemical properties as an NMDA receptor antagonist. While studies examining this particular application of ketamine are more limited than those examining treatment of depression, work with compounds that create similar states of consciousness–such as the “classical hallucinogens”: LSD, psilocybin, mescaline, DMT, and ayahuasca–suggest a role for altered states independent of the biochemical effects of ketamine.  Such compounds seem to work to treat addiction via their ability to produce spiritual or mystical experiences. While such “classical hallucinogens” are not currently available for clinical use, there exists a growing literature detailing successful and robust treatment of tobacco and alcohol addiction. Use of the aforementioned compounds outside of a research setting is however illegal, except for ketamine which has been FDA approved for other indications and is consequently available for off-label use to treat such diagnoses as depression, post-traumatic stress disorder, and addiction / substance use disorders.

What other psychiatric conditions has ketamine been used for?

Treatment resistant depression is, by far, the most extensively studied psychiatric application of ketamine, and has a wealth of data to support its use.  Other indications (or reasons to use ketamine) include drug or alcohol use disorders (specifically for opioid or cocaine use disorders),  Post-Traumatic Stress Disorder (PTSD), and eating disorders such as anorexia or bulimia.  On the other hand, data suggests ketamine is less effective for treatment of Obsessive-Compulsive Disorder (OCD), but may be worth pursuing on a case by case basis.

Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder a randomized clinical trial.

Where can I learn more?

You are invited to read a review article on ketamine for depression.  The full text is available free of charge from the California Institute of Integral Studies [ full text ].  Ketamine and Depression_ A Review An updated version of this review is available as a book chapter in a larger publication on ketamine.  The book, entitled The Ketamine Papers–Science, Therapy and Transformation, is published by the non-profit Multidisciplinary Association for Psychedelic Studies (MAPS) and available for purchase through their website and amazon [ order the book via MAPS, or via amazon ].  Also available is a video recording of a presentation on ketamine that I gave for the Aware Project [ YouTube video ].

 

 

 

The Ketamine Papers

 

 2007 Mar;39(1):13-9.

Single versus repeated sessions of ketamine-assisted psychotherapy for people with heroin dependence.

Abstract

A prior study found that one ketamine-assisted psychotherapy session was significantly more effective than active placebo in promoting abstinence (Krupitsky et al. 2002). In this study of the efficacy of single versus repeated sessions of ketamine-assisted psychotherapy in promoting abstinence in people with heroin dependence, 59 detoxified inpatients with heroin dependence received a ketamine-assisted psychotherapy (KPT) session prior to their discharge from an addiction treatment hospital, and were then randomized into two treatment groups. Participants in the first group received two addiction counseling sessions followed by two KPT sessions, with sessions scheduled on a monthly interval (multiple KPT group). Participants in the second group received two addiction counseling sessions on a monthly interval, but no additional ketamine therapy sessions (single KPT group). At one-year follow-up, survival analysis demonstrated a significantly higher rate of abstinence in the multiple KPT group. Thirteen out of 26 subjects (50%) in the multiple KPT group remained abstinent, compared to 6 out of 27 subjects (22.2%) in the single KPT group (p < 0.05). No differences between groups were found in depression, anxiety, craving for heroin, or their understanding of the meaning of their lives. It was concluded that three sessions of ketamine-assisted psychotherapy are more effective than a single session for the treatment of heroin addiction.

How to use psychedelics

How to Take Ketamine to Treat Depression, Anxiety and PTSD

Ketamine is a legal prescription medication used for a variety of purposes– as a pain killer, sedative, anesthetic, and anti-depressant. It’s one of the safest anesthetics in the world and is available in every hospital. Ketamine’s use as an anti-depressant and PTSD treament is growing very quickly and research studies are expanding. Here’s a directory of US doctors offering ketamine treatment for depression, bipolar, PTSD, and other mood disorders.

As the BBC wrote in a 2014 article about ketamine, “Some patients who have faced incurable depression for decades have had symptoms disappear within hours of taking low doses of the drug.”

What makes Ketamine so remarkable for treating depression is that its positive effects begin almost immediately, within 1 – 12 hours, compared to SSRIs that may take weeks to start working, if they work at all. Ketamine also seems to have much fewer side effects than SSRIs (though it hasn’t been studied much for long term use) and is incredibly effective as a treatment for people who don’t respond well to SSRIs and other anti-depressants. If you’ve had limited success with other treatment methods you may respond very well to ketamine.

Before you begin, be sure to read our safety section and ensure that you aren’t taking any medication or supplements that interact with Ketamine.

Dosage

Dosage for ketamine varies depending on whether it’s taken intranasally, intravenously (IV), orally, or sublingually. We recommend taking ketamine orally or sublingually because it’s safe and easy. Many doctors and treatment centers will give ketamine in an IV. Treatment with a doctor / center can be quite expensive but you may be able to find a doctor or center in your area if you google around.

The anti-depressant effect of ketamine typically wears off after a while (a few days to a month), though the relief that is felt while it is active can often lead to lasting improvements. There are various protocols for using ketamine to treat depression– some people take small amounts daily, others weekly, and others monthly. We recommend starting with a moderate dose once a week and adjusting based on how it feels.

How to Take Ketamine Sublingually (Under the Tongue)

Sublingual ketamine seems much more potent than oral ketamine. We suggest starting with a very small “microdose” and trying a little more each session until you find the minimum amount that works for you. You should almost certainly see results using .3mg of ketamine per pound of body weight (or .75mg per kg of body weight). This works out to about 50mg for someone who weighs 160lbs (72kg). But start far below that.

  • STEP ONE
    Prepare your ketamine solution. You’ll want to use one of those little bottles that has an eyedropper in the lid. Maybe you have one around the house with some sort of herbal tincture. Boil some water, then let it cool. Using the eyedropper, wash out the dropper and the bottle with the water, just to get rid of any residue. Put a known amount of ketamine into the bottle. Then add water to the bottle using the eyedropper, carefully counting the drops. You want to use as few drops as possible to dissolve all the ketamine. In a lab you should be able to dissolve 5mg ketamine per drop. If you add this much water and you still see some undissolved ketamine in there, add just enough water to dissolve it all. Carefully swirl it around to speed things up. Now you can give yourself microdoses of ketamine. Just divide the amount of ketamine by the number of drops. If you had 1000mg of ketamine, and added 200 drops of water, you’d know there was 5mg ketamine per drop.
  • TWO
    Find a place where you can sit or lie down comfortably for an hour. Unlike traditional psychedelics like mushrooms, LSD, and even MDMA, the benefits of ketamine do not seem to derive from an exploratory experience while taking the medicine. In addition, the experience at an effective dose is much more gentle. You can read a book, watch TV, etc.
  • THREE
    Looking at yourself in a mirror, put one or two drops under your tongue. This is probably at most 5-10mg. Don’t swallow it, just leave it under your tongue. After 5 minutes or so, you can swallow.
  • FOUR
    The effects will be very subtle but you might feel a slight mellow or sleepy feeling in about 5-15 minutes.
  • FIVE
    The anti-depressant effects of the ketamine generally start to appear about two hours after taking the first dose. In some people the anti-depressant effect is strong right away and in some people it gradually grows over 1-4 days– so you might feel the most relief 4 days after taking the dose.
  • SIX
    See how you feel the next day. If you are less depressed, great! If not, the next time try the previous dose plus one more drop. Don’t take ketamine two days in a row. Once you find a dose that seems to work, see how many days you can wait between doses. Ideally, you would take a dose once a week or once a month. Worst-case, you’d take it every other day. If you get up to 50mg sublingually and it still doesn’t work, it might just not work for you in general.

How to Take Ketamine Orally

We suggest using .6mg of ketamine per pound of body weight (or 1.5mg per kg of body weight). This works out to about 100mg for someone who weighs 160lbs (72kg).

Remember these are oral doses– usually mixed with warm water and swallowed. If you are taking ketamine in an IV the doses should be much, much lower.

  • STEP ONE
    Find a place where you can sit or lie down comfortably for an hour. Unlike traditional psychedelics like mushrooms, LSD, and even MDMA, the benefits of ketamine do not seem to derive from an exploratory experience while taking the medicine. In addition, the experience at an effective dose is much more gentle. You can read a book, watch TV, etc.
  • TWO
    Make sure you have the right dose measured and ready. If you don’t have a mg scale, you can order them cheaply anywhere, including Amazon. They are about $20-$30.
  • THREE
    If it’s your first time, mix about 1/5th of the dose with about an inch of warm water in a mug. If you are taking about 100mg, that would be roughly 20mg. Once you mix it, drink it.
  • FOUR
    A 1/5th dose will be very subtle but you should be able to feel a nice mellow or sleepy feeling in about 5-15 minutes. After 15 minutes, if you feel comfortable with that test dose (and it’s fine if you don’t feel anything at all), then you can mix the rest of the dose with warm water and drink it.
  • FIVE
    As you feel the effects of the dose, again after 5-15 minutes, you will likely feel sleepy or mellow. You can rest, read, watch tv, etc. After about 45 minutes to an hour, the effects will be mostly gone, though you may still feel very relaxed or sleepy for a couple more hours.
  • SIX
    The anti-depressant effects of the ketamine generally start to appear about two hours after taking the first dose. In some people the anti-depressant effect is strong right away and in some people it gradually grows over 1-4 days– so you might feel the most relief 4 days after taking the dose.

Afterwards

The anti-depressant effects of ketamine last for days and sometimes weeks or even a month. We suggest starting with weekly re-dosing, using the same dose, and seeing how it goes. If you find that you don’t need to redose after a week, then wait longer and see how things go. It’s always good to err on the side of taking too little rather than too much. Some people need to redose more often, every few days. You’ll probably get a sense pretty quickly of what works for you.

Special Safety Considerations

Always research any supplements or other medicines that you may be taking to avoid interactions. Here’s a Medscape list of potential interactions. (Note that the dosing levels listed on that site are for inducing anesthesia, which is way way more than what is use for anti-depressant effects.)

Articles and Research on Ketamine for Anxiety and Depression

Research on ketamine is growing quickly and some drug companies are trying to create new versions of ketamine that they can patent.

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One more reason to treat your depression rapidly with Ketamine:

 

Depression Linked to Increased Risk of Developing Atrial Fibrillation

NEW YORK—Depression appears to be a risk factor for atrial fibrillation, the most common arrhythmia in the U.S., according to new observational data from the national Multi-Ethnic Study of Atherosclerosis (MESA) study.

Considering that 20% of U.S. adults report depressive symptoms, “our findings identify a large portion of the U.S. population that is potentially at an increased risk of developing atrial fibrillation and who may benefit from more targeted efforts to prevent atrial fibrillation,” Dr. Parveen Garg, from the Keck School of Medicine at the University of Southern California in Los Angeles, told Reuters Health by email.

He presented the study March 22 at the American Heart Association’s Epidemiology and Prevention/Lifestyle and Cardiometabolic Health Scientific Sessions in New Orleans.

The analysis included 6,644 adults (mean age, 62; 53% women, 38% white, 28% black, 22% Hispanic, 12% Chinese-American) with no known heart disease at baseline who were followed for a median of 13 years as part of the MESA study.

In the fully adjusted model, individuals with a Centers for Epidemiologic Studies Depression Scale (CES-D) score of 16 or higher (indicating clinically relevant depressive symptoms) had a 34% (P=0.039) higher risk of developing atrial fibrillation during follow-up compared with those with a CES-D score of less than 2. Similarly, individuals reporting antidepressant use had a significant 36% increase in their risk of developing atrial fibrillation compared with those not on the drugs.

“An important next step is to confirm these results in other studies, especially those with more comprehensive and clinically validated assessments of depression. If confirmed, then it will be important to determine if treating individuals with depression actually reduces their risk of atrial fibrillation,” Dr. Garg said.

Several mechanisms have been proposed to explain a possible link between depression and atrial fibrillation, Dr. Garg explained. Depression can increase systemic inflammation and activate the autonomic nervous system, which increases catecholamine levels, and the hypothalamic-pituitary-adrenal axis, which increases cortisol levels. Depression may also activate the renin-angiotensin-aldosterone system.

“Taken together, these changes may induce atrial fibrillation susceptibility either directly by disrupting the electrophysiologic properties of the atria or indirectly by promoting atrial fibrosis, increasing the atrial pressure,” Dr. Garg said, adding that further research is needed to fully understand the mechanisms involved.

Dr. Gordon Tomaselli, a spokesman for the American Heart Association, said this study “affirms the association between depression and atrial fibrillation in a population that I think is important because it’s a mixed population and not just the standard Caucasian population.”

“There are some associated risk factors in people with depression that might increase their risk of atrial fibrillation, including an increased incidence of hypertension in some patients who have depression as well as other disorders that might be driven by activation of the sympathetic nervous system like anxiety disorder. So there are several reasons why people might have depression and atrial fibrillation,” Dr. Tomaselli, who was not involved in the research, told Reuters Health by phone.

“One question is what should we do about it, and I’m not sure we have an answer from this study except to make sure that we are looking for symptoms of depression,” he said. “We don’t know whether treatment of depression will reduce the incidence of atrial fibrillation. There is some reason to think that it might, but there are other reasons to think that antidepressant drugs actually have some effects on the heart, the ion channels that determine the rhythm of the heart.”

The study had no commercial funding and the authors have no relevant disclosures.

SOURCE: https://bit.ly/2pCdkOA

AHA Epidemiology and Prevention – Lifestyle and Cardiometabolic Health Scientific Sessions 2018.

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What is ketamine?

Ketamine Nasal SprayKetamine 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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Trippy depression treatment? Hopes and hype for ketamine

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Lauren Pestikas sits as she receives an infusion of the drug ketamine during a 45-minute session at an outpatient clinic in Chicago on July 25, 2018. Pestikas struggled with depression and anxiety and made several suicide attempts before starting ketamine treatments earlier in the year. (AP Photo/Teresa Crawford)

CHICAGO (AP) — It was launched decades ago as an anesthetic for animals and people, became a potent battlefield pain reliever in Vietnam and morphed into the trippy club drug Special K.

Now the chameleon drug ketamine is finding new life as an unapproved treatment for depression and suicidal behavior. Clinics have opened around the United States promising instant relief with their “unique” doses of ketamine in IVs, sprays or pills. And desperate patients are shelling out thousands of dollars for treatment often not covered by health insurance, with scant evidence on long-term benefits and risks.

Chicago preschool teacher Lauren Pestikas long struggled with depression and anxiety and made several suicide attempts before trying ketamine earlier this year.

The price tag so far is about $3,000, but “it’s worth every dime and penny,” said the 36-year-old.

Pestikas said she feels much better for a few weeks after each treatment, but the effects wear off and she scrambles to find a way to pay for another one.

For now, ketamine has not received approval from the U.S. Food and Drug Administration for treating depression, though doctors can use it for that purpose.

Some studies show ketamine can provide relief within hours for tough-to-treat depression and suicidal behavior and clinics promising unproven benefits have popped up nationwide. But more research is needed to know long-term benefits and risks. (Oct. 31)

Ketamine has been around since the 1960s and is widely used as an anesthesia drug during surgery because it doesn’t suppress breathing. Compared to opioids such as morphine, ketamine isn’t as addictive and doesn’t cause breathing problems. And some studies have shown that ketamine can ease symptoms within hours for the toughest cases.

Its potential effects on depression were discovered in animal experiments in the late 1980s and early 1990s showing that glutamate, a brain chemical messenger, might play a role in depression, and that drugs including ketamine that target the glutamate pathway might work as antidepressants.

Conventional antidepressants like Prozac target serotonin, a different chemical messenger, and typically take weeks to months to kick in — a lag that can cause severely depressed patients to sink deeper into despair.

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A vial of ketamine, which is normally stored in a locked cabinet, on display in Chicago on July 25, 2018. AP Photo/Teresa Crawford)

Ketamine’s potential for almost immediate if temporary relief is what makes it so exciting, said Dr. Jennifer Vande Voort, a Mayo Clinic psychiatrist who has used ketamine to treat depression patients since February.

“We don’t have a lot of things that provide that kind of effect. What I worry about is that it gets so hyped up,” she said.

The strongest studies suggest it’s most useful and generally safe in providing short-term help for patients who have not benefited from antidepressants. That amounts to about one-third of the roughly 300 million people with depression worldwide.

“It truly has revolutionized the field,” changing scientists’ views on how depression affects the brain and showing that rapid relief is possible, said Yale University psychiatrist Dr. Gerard Sanacora, who has done research for or consulted with companies seeking to develop ketamine-based drugs.

But to become standard depression treatment, he said, much more needs to be known.

Last year, Sanacora co-authored an American Psychiatric Association task force review of ketamine treatment for mood disorders that noted the benefits but said “major gaps” remain in knowledge about long-term effectiveness and safety. Most studies have been small, done in research settings and not in the real world.

When delivered through an IV, ketamine can cause a rapid increase in heart rate and blood pressure that could be dangerous for some patients. Ketamine also can cause hallucinations that some patients find scary.

“There are some very real concerns,” Sanacora said. “We do know this drug can be abused, so we have to be very careful about how this is developed.”

Dr. Rahul Khare, an emergency medicine specialist in Chicago, first learned about ketamine’s other potential benefits a decade ago from a depressed and anxious patient he was preparing to sedate to fix a repeat dislocated shoulder.

“He said, ‘Doc, give me what I got last time. For about three weeks after I got it I felt so much better,’” Khare recalled.

Khare became intrigued and earlier this year began offering ketamine for severe depression at an outpatient clinic he opened a few years ago. He also joined the American Society for Ketamine Physicians, formed a year ago representing about 140 U.S. doctors, nurses, psychologists and others using ketamine for depression or other nonapproved uses.

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Dr. Rahul Khare poses for a portrait at his outpatient Chicago clinic on July 25, 2018. (AP Photo/Teresa Crawford)

There are about 150 U.S. ketamine clinics, compared with about 20 three years ago, said society co-founder Dr. Megan Oxley.

Khare said the burgeoning field “is like a new frontier” where doctors gather at meetings and compare notes. He has treated about 50 patients with depression including Pestikas. They’re typically desperate for relief after failing to respond to other antidepressants. Some have lost jobs and relationships because of severe depression, and most find that ketamine allows them to function, Khare said.

Typical treatment at his clinic involves six 45-minute sessions over about two weeks, costing $550 each. Some insurers will pay about half of that, covering Khare’s office visit cost. Patients can receive “booster” treatments. They must sign a four-page consent form that says benefits may not be long-lasting, lists potential side effects, and in bold letters states that the treatment is not government-approved.

At a recent session, Pestikas’s seventh, she leaned back on a reclining white examining-room chair as a nurse hooked her up to a heart and blood pressure monitor. She grimaced as a needle was slipped into the top of her left palm. Khare reached up with a syringe to inject a small dose of ketamine into an IV bag hanging above the chair, then dimmed the lights, pulled the window curtains and asked if she had questions and was feeling OK.

“No questions, just grateful,” Pestikas replied, smiling.

Pestikas listened to music on her iPhone and watched psychedelic videos. She said it was like “a controlled acid trip” with pleasant hallucinations. The trip ends soon after the IV is removed, but Pestikas said she feels calm and relaxed the rest of the day, and that the mood boost can last weeks.

Studies suggest that a single IV dose of ketamine far smaller than used for sedation or partying can help many patients gain relief within about four hours and lasting nearly a week or so.

Exactly how ketamine works is unclear, but one idea is that by elevating glutamate levels, ketamine helps nerve cells re-establish connections that were disabled by depression, said ketamine expert Dr. Carlos Zarate, chief of experimental therapies at the National Institute of Mental Health.

A small Stanford University study published in August suggested that ketamine may help relieve depression by activating the brain’s opioid receptors.

Janssen Pharmaceuticals and Allergan are among drug companies developing ketamine-like drugs for depression. Janssen leads the effort with its nasal spray esketamine. The company filed a new drug application in September.

Meanwhile, dozens of studies are underway seeking to answer some of the unknowns about ketamine including whether repeat IV treatments work better for depression and if there’s a way to zero in on which patients are most likely to benefit.

Until there are answers, Zarate of the mental health institute said ketamine should be a last-resort treatment for depression after other methods have failed.

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