Ketamine: This drug may finally change the way we study depression

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Alternative Therapies, Health

Ketamine: This drug may finally change the way we study depression

On a recent drive to the Home Depot on 2100 South, a billboard with simple blocked letters caught my eye. “Fight Depression, KetamineSLC.com.” I had to look twice. Fight depression. Ketamine. These were three words I never would have imagined seeing together. On a billboard. In Salt Lake City.

Introduced in the early 1960s, ketamine is known mainly for its medical use as an anesthetic, but also known infamously for its recreational use as the party drug “Special K.”

In 1970, the FDA approved ketamine for human anesthesia and it was used extensively for battlefield surgeries in the Vietnam War. Back in the United States, it began to appear in recreational circles when users discovered its powerful dissociative and psychedelic effects. Through the early 1980s, use increased among certain subcultures, as well as by underground psychotherapists who believed in its potential for psychological healing.

One strikingly public exposure of the drug came from neuroscientist-psychonaut John Lilly who was running some particularly unorthodox studies on dolphin-human communication. Lilly used high doses of ketamine on both himself and the dolphins, claiming that the drug aided in telepathy between them.

Medical research into ketamine specifically as an antidepressant began in the 1990s at the Yale School of Medicine. In 2006, a breakthrough study from the National Institute of Mental Health showing positive results on patients diagnosed with treatment-resistant depression fully re-ignited the interest of both doctors and the mainstream population.

As I’ve since learned, dozens of free-standing ketamine clinics have opened up in cities across the country in recent years, administering the drug to patients as a hopeful new treatment for conditions from depression to PTSD, anxiety disorders and chronic pain. Despite the drug lacking FDA approval for mental health treatment, doctors (and nurse practitioners with the right licensure and experience) can prescribe ketamine in Utah off-label.

People have long realized that drugs such as LSD, ketamine and psilocybin are capable of altering the mind in ways that bring about psychological healing. The resurgence in ketamine into the mainstream is understandable given that many people are not benefitting from conventional mental health treatments and are in desperate need of relief.

Perspectives from a mental health professional

To get a better read on the drug itself, I turned to Dr. Jeremy Kendrick from the University of Utah. Dr. Kendrick, a pediatrician and psychiatrist, works in the Treatment Resistant Mood Disorders Clinic at the University, where he was a pioneer in starting the University’s ketamine program.

“The reason why I’m involved with ketamine is because patients get better,” Dr. Kendrick said confidently. “These are patients who have been on every SSRI, every SNRI—they’ve been through years of therapy. They’ve come to us hopeless and overwhelmed and feeling like nothing is ever going to work. And the fact of the matter is that we see them get better.” (An SSRI—selective serotonin reuptake inhibitor—is a type of antidepressant that works by increasing levels of serotonin in the brain. Some examples are Prozac, Zoloft and Paxil. SNRIs —selective serotonin and norepinephrine reuptake inhibitors—increase serotonin and norepinephrine and are often used for anxiety and pain control. Examples include Cymbalta and Effexor.)

Ketamine’s class is completely different than any other antidepressant that the medical profession has used for the past 40 years, says Dr. Kendrick. Ketamine acts on the receptor that regulates glutamine levels, a neurological phenomenon that was not previously considered a major player in depressive illness. While scientists and researchers are now confident about the clinical effectiveness of the drug, there are still many ongoing hypotheses of why the drug actually helps depression.

Dr. Kendrick’s clinic strictly bases its ketamine treatment procedure on the research protocols that were established and proven in prior research trials. This means they only administer ketamine intravenously at a dosage based on a patient’s weight and always at a 40-minute interval. First and foremost, a rigid consultation must establish that a patient meets the inclusion criteria of suffering from a treatment-resistant major depressive disorder.

This treatment, which is not covered by insurance, can be arduous for patients in time and cost.

“We would love nothing more than to have a safe and effective delivery mechanism for ketamine that was less burdensome. You can get ketamine in an oral form and people have been compounding ketamine as a nasal spray and sending it home with patients to be self-administered every day.” Dr. Kendrick says these alternatives, though cheaper, compromise the drug’s effectiveness and safety.

The average cost of clinically administered IV ketamine typically ranges from $300 to $800 per infusion. According to the consumer mental health site HealthyPlace.com, “While the cost of ketamine depression treatments may seem high, it is on par with other procedures that require an IV drip. The ketamine itself may only be $10, but the cost of the qualified staff, equipment and the facility needed to administer it are expensive.” No insurance pays for depression-related ketamine treatment, as it is not FDA-approved for this use, according to the Ketamine Advocacy Network.

This past March the FDA did approve the use of the nasally administered Spravato (esketamine) for depression-related purposes. However, Dr. Kendrick is unimpressed with Spravato as the research shows it is not nearly as effective as IV ketamine.

“We would love for IV ketamine to be FDA approved for the treatment of depression, and, frankly, it should be if FDA approvals were sought on efficacy alone. Unfortunately, it’s the drug companies which lead that process.”

Though he understands that without insurance coverage IV ketamine is simply too expensive for most people, Dr. Kendrick encourages patients to  look less at the cost and more at how ketamine is being administered by alternative clinics. Right now, he says, the research shows that the safest and most effective administration of ketamine is through an IV and outcomes can vary wildly depending on how else it is administered.

“There are a number of clinics out in the community doing this right… But the point where you deviate from the established protocol— say, instead of IV I’m going to give it to you in your muscle, or instead of a dose of half

a milligram per kilogram I’m going to go up—whenever you deviate from any one of the established variables, you’re outside the parameters which supported the initial outcomes of ketamine.”

Some clinics in Utah administer IV for one hour instead of 40 minutes. Others treat patients suffering from conditions beyond depression (chronic pain, anxiety, even obsessive- compulsive disorder). Of course, the successes at these clinics are not any less real. The difference is that their patients are ultimately a part of an experiment without established efficacy and safety backed by randomized, controlled clinical trials, he says. Dr. Kendrick believes patients should be made aware of this and use it to help inform their decisions.

Plus, there may be something else special about IV ketamine that other ketamine treatments compromise. Dr. Kendrick is aware of the possibility that the “mystical” experience of the IV-infusion, the out-of-body feeling that people can have, as well as the supportive environment around them, may lead to further changes and improved depression.

“The study of mental illness and depression continues to be an ongoing search for its biologic basis, but we also know that depression is much more complex than just biology,” Dr. Kendrick says.

Still the Wild, Wild West

Ketamine success stories are numerous and exciting. But when one SLC resident was prescribed a daily-use intranasal ketamine spray for pain, she experienced a different side of the “new wonder drug.”

Alice has been dealing with chronic pain for some time now. Around three years ago, the multitude of stressors that filled her life caused her physical pain to spiral out of control.

“Doctors all wanted to diagnose me with fibromyalgia. Basically, my response was f*** that,” Alice said, flashing both middle fingers up to an invisible medical establishment.

Alice was wary of accepting SSRI antidepressants and opioid pain killers. She ended up with a doctor who recommended her an intranasal, low-dose version of ketamine. She used the nasal spray for about a year and a half until her body suddenly developed an extreme reaction to it.

“In the beginning, I’d take it every couple of days. But by the end, it was more like three to four times a day. This was in my prescription, but it definitely led to a habituation until finally my body just shut down. My nervous system was wracked with a new pain that nothing seemed to help.”

Alice had no choice but to quit the ketamine immediately, making her very unstable.

“I thought I was going to end up in UNI [University Neuropsychiatric Institute]. I was paranoid… suicidal… My neurotransmitters were anything but balanced and there was nothing I could do. I was just stuck like this.”

Alice went back to her doctor, accepting a prescription for Valium, a benzodiazepine antianxiety drug to get her through her ketamine withdrawals. After a couple of weeks, though, she became stuck again, now struggling to withdraw from the Valium.

Having had enough, Alice did what few can. She quit most of her prescription meds, taking the next year to wean herself off of Valium. She started weightlifting and seeing a pain therapist. Against the pain, against the complications and all of her suffering, she survived.

Intranasal ketamine sent Alice through a medical nightmare. Nonetheless, she retains hope for ketamine as a treatment for depression in some cases. Before her prescription, she actually did have one session of IV ketamine infusion that worked wonders for her.

“My feeling about ketamine is that it needs to be guided. Someone needs to be there working with you so that you go into it with the mindset of ‘I’m going to do this to learn about my body, my feelings, and release some of what’s feeding into my condition.’ I’m a supporter of ketamine in this sense. But definitely not on a daily basis.”

Alice is not alone in her sentiment. Countless users in online ketamine forums remark on their dissatisfaction with the direction the drug may be headed. These individuals focus on the experiential side of ketamine, advocating that ketamine be treated less like an antidepressant medication and more like a vehicle for consciousness exploration and psychological healing in a psychotherapeutic setting.

“If you have experienced depression, you understand that there are traumas in your history that are feeding into the chronic state of anxiety that you are feeling,” Alice said.

“If all you’re doing is taking a little daily dose of this molecule and hoping for a miraculous new balance, you’re not relieving any of your trauma and it’s not going to actually help you.”

Alice no longer yearns for immediate solutions to her chronic pain. Her journey has led her, finally, to a place where she can live and work without daily drugs.

“I believe that ketamine is a really promising therapy. But it needs regulation and it needs more study.”

When it works

Tyler has a movement disorder. His condition is called Willis-Ekbom Disease, also known as  restless leg syndrome.

Tyler had been taking a dopamine agonist, Mirapex, to help control his pain and movement until, two years ago, he experienced a rare side effect. His body had suddenly habituated to the drug and developed a physical dependency on it. Tyler was under even more neurological pain and restless leg movement than ever before.

Pain was now seriously interfering with his life. He was sleeping less than three hours a night and struggled to make it to work. His depression worsened. As Tyler tried other medications for his restless leg, his anxiety and depression only intensified until a new diagnosis made his list: treatment-resistant depression.

Exasperated, Tyler began his own search for a solution. He had seen advertisements for ketamine but could not afford their high prices. His hope nearly vanished until, months later, he ended up at the mental health institute at the University of Utah Health. It was determined that he was a prime candidate for their ketamine treatment, which, at $350 per treatment, also happened to be much more financially realistic.

Just hours after his first infusion, Tyler’s wife noticed a dramatic change in his energy and demeanor.

“The first thing I noticed was my major solemnness and despair just kind of go away,” says Tyler. “When I woke up the next day, I had more energy. I wanted to go do something. To listen to music again and do art again and… smile.”

When asked to describe the actual experience of undergoing an infusion, Tyler shared the experience of his first appointment:

“There was this ’80s playlist on,” he began. “It immediately put me in a place of my youth. It was like I was watching my younger self and could see that the emotional blockages I was having were tied to this kid. I could see my anxiety and depression and all of the severe emotions that were most present in my life, and I could see that they weren’t me.”

Tyler believes the most helpful part of his ketamine treatment has been this therapeutic edge.

“They’re keeping you at this place where you’re still totally conscious but you’re conscious in a different way and you’re removed from your everyday thought patterns.”

Now after 10 sessions, Tyler feels more optimistic about ketamine than any other treatment he has been on. The greatest hurdle continues to be cost, however, and he worries about having to take longer breaks between appointments due to the financial burden.

And what about that billboard?

Undoubtedly the biggest barrier most treatment-seeking individuals like Tyler face regarding ketamine is its cost.

While the hope is that, with repeated exposure to the drug, its effects will last longer, the fact is that a single dose for an average patient will only result in up to 48 hours of strong response and effects that typically fade in five to seven days. With most clinics recommending at least a six-session series, committed individuals are paying around $3,000-plus for a baseline treatment of two to three weeks.

One local clinic has made it their mission to provide the drug at the lowest cost in the valley. Ketamine SLC, the clinic I originally saw advertised on a billboard, offers treatment as low as $250 per session.

“I am not here for buy-low sell-high capitalism; my price is low for two reasons. Reason one: To get people out of the depression hole who could not normally afford it. Reason two: To bring down the price of ketamine across the country so that it is less burdensome on those who can afford it,” Robert C. Hiemstra, MD and former emergency medicine physician, writes on his clinic’s website.

Ketamine SLC administers ketamine through intramuscular injections (IM). IM is innately less expensive than IV; it requires less equipment, staff, clinic space and time.

It does, however, deviate from the research protocols that Dr. Kendrick and other IV ketamine clinicians swear by.

The route of ketamine’s administration—oral, IV, IM, or intranasal—affects a characteristic of the drug known as its bioavailability. A high bioavailability guarantees dosage precision. When administered via IV, the drug immediately enters the bloodstream, leading to  100% bioavailability and the most control over the amount of medication one is receiving.

Via IM injection, ketamine enters the muscle and then must find its way to blood vessels to become absorbed by the body. This means it has a slightly lower bioavailability and lesser controllability.

Zachery Taylor, a Certified Registered Nurse anesthetist from Utah Ketamine Clinic, explains why the variability of IM ketamine administration worries some professionals in regard to safety. “What happens if you get a shot of IM ketamine and it isn’t enough to get you to a therapeutic range? You get a second shot— what if that’s too much? Now you are nauseated and possibly having a nightmare dissociation…With an IV you can titrate a patient’s dose as well as stop it if needed… IV ketamine is the gold standard for treatment.”

Nonetheless, Dr. Hiemstra, who has been administering ketamine for depression for three years, stands by the drug and his method of delivery. His claims of success with IM sound remarkable and his mission bold.

The emergence of ketamine speaks to a broader revolution taking place in mental health treatment and understanding. Doctors, therapists and people suffering from mental health conditions alike are beginning to turn away from daily drugs for symptom suppression and instead toward alternative treatments that help deal with root causes. Ketamine’s potential for altering states of consciousness has interested psychologists into looking for ways to integrate it into their psychotherapy.

For example, Innate Path is a growing research and training organization that provides psychedelic psychotherapy and therapist training in Lakewood Colorado. They use both cannabis and ketamine, collecting data that shows a significant difference between ketamine treatment with psychotherapy and treatment without it.

Recent research from Stanford School of Medicine shows a significant portion of the biological anti-depressant effect has to do with ketamine acting upon an individual’s opioid receptors, essentially by numbing pain. Those at Innate Path have a problem with using ketamine in this way, simply to increase dissociation in people.

By contrast, they say, ketamine-assisted psychotherapy has a completely different focus from just the anti-depressant, pain management effect. “In this type of therapy we make use of ketamine’s psychedelic response where memories, feelings, sensations, beliefs and life experiences that were hidden in the subconscious all come to the surface. Even painful or overwhelming experiences that the mind has hidden in dissociation, which nevertheless generate symptoms of depression, anxiety and trauma, will make themselves known. Because there is much less fear during the ketamine session, your system will let you see and engage these memories directly,” according to their online literature. They claim to have successfully treated anxiety, trauma and even severe cases of dissociative identity disorder with such an approach.

Is it just a question of ideal dose and delivery system? Can a psychotherapeutic approach enable ketamine to access the underlying causes of depression, for a more sustainable outcome?  These and many other questions remain.

While some researchers believe ketamine’s purely biochemical response should not be the focus of treatment, others are forging ahead, making use of the ketamine studies to investigate other drugs with seemingly similar mechanisms.

Its medical success in research trials has also helped legitimize the work of therapists eager to explore the benefits of integrating safe, psychoactive drugs into their psychotherapy practices.

Among clinicians and patients alike, there is a lot of understandable frustration about the way we approach mental health in our current healthcare system. The story of ketamine’s newfound prominence may go to show that despite these frustrations, people haven’t given up their personal searches for health and recovery.

 

Emily is a recent college graduate from California.

Since August she has found home in Salt Lake City at CATALYST and as a junior high after-school teacher.

 

 
 
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