Ketamine: A Novel Cure For Depression?

It seems like Ketamine infusion clinics are the latest healthcare fad.

In 2019, President Trump was touting that he wanted ‘a lot’ of eskatamine, a derivative of Ketamine, administered intranasally. He ordered it to be purchased after the FDA approved it for treating depression in military veterans. 

Depression affects about 121 million people worldwide and about 17.3 million adults in the United States alone. Suicide can be a lethal consequence, with 50% of individuals who carry the diagnosis succumbing to it annually. Adults with a depressive disorder have a 64% greater chance of getting heart disease. Many patients are placed on antidepressants with no response, only to sink deeper into their illness. 

There’s no doubt something novel is needed and more research is essential to save lives in this arena. But, are Ketamine infusion clinics just another healthcare fad popping up on a local street corner in a strip mall? Can a drug with a ‘party drug’ reputation be the answer? Is it really the ‘golden ticket’ to cure depression? 

Horse Tranquilizer Turned Party Drug

“A couple of my friends have started doing Ketamine before they go to bed to relax. It’s like a horse tranquilizer” states female comedian Atsuko, on her Instagram comedy show “Let’s Go Atsuko.” Yes, it’s true. Ketamine was originally used as an animal tranquilizer, specifically for horses.

Initially named CI-581 and developed as a derivative of PCP, synthesized in 1926, as an anesthetic drug which acts, primarily, as an NMDA receptor antagonist. In 1956 chemists at Parke Davis Company, discovered that Phencyclidine, caused drunkenness in rodents, delirium in dogs, and anesthesia in monkeys. It was first used as a veterinary anesthetic and later discovered to be a safe anesthetic in humans. Researchers also noted that it caused a profound altered level of consciousness.  

In the 1970’s the FDA approved Ketamine to be used as an anesthetic on humans. Due to it’s hemodynamic benefits it was also used in the battlefield during the Vietnam war on septic patients with traumatic injuries. Ketamine started to gain popularity in the world and was used for both recreation and therapeutic purposes. Argentina used ketamine in regression therapy. New age spiritualists used it for mind exploration. 

The late 1990’s and early 2000’s, Ketamine was known as the ‘club drug’ popular with the rave club culture. It was known by names like ‘Special K’ and ‘Cat Valium.” In clubs, it has been dried to a powder and is smoked in a mixture of marijuana or tobacco, or is taken intranasally. A typical method uses a nasal inhaler, called a “bullet” or “bumper”; an inhalation is called a “bump”. Ketamine often is taken in “trail mixes” of methamphetamine, cocaine, sildenafil citrate (Viagra), or heroin. Due to it’s dissociative properties, Ketamine has also been used as a date rape drug. 

Off Label Use For Depression And PTSD

An unapproved use of an approved drug is termed “off-label.” What this means is that a drug is being used by a healthcare provider to treat a disease that a drug has not been approved for. It also can mean when a drug is administered in a different way or given as a different dose. 

Ketamine is FDA approved for use in anesthesia and procedural sedation. “off-label” Ketamine is not FDA approved for the treatment of depression and suicidal ideation, and such use is off label. The FDA has recently approved the esketamine (the S enantiomer) form for use in treatment-resistant depression in conjunction with another oral antidepressant. Recreational use of ketamine is not FDA approved. 

Subanesthetic doses of ketamine that are used to treat mood disorders have been found generally very safe in the limited studies that have been done. Typical peak plasma concentrations will not induce general anesthesia. However, systolic and diastolic blood pressure and heart rate elevations are not uncommon

Ketamine Used For Pain Management

The value of ketamine in the treatment of severe pain, including conditions such as trauma, fractures, abdominal and flank pain, low back pain, and extremity pain is pronounced. When used for pain management, sub-dissociative dosing, otherwise known as low dose ketamine (LDK), either alone or as an adjunct to other medications for pain relief, it is safe and effective to use in combination with injectable nonsteroidal pain medications as well as opioids.

Awakening The Brain

Ketamine relieves depression by blocking NMDA, a glutamate receptor. Glutamate makes the neruons more active since it is an excitatory neurotransmitter. It makes it’s receptors more active, more communicative and more likely to form connections. This makes neural activity stronger and awakens the brain. Ketamine provides a rapid and robust antidepressant effect with an onset of 40 mins after a single IV infusion. 1–2 weeks after infusion and its long-term effects are less reported.

Typical Ketamine clinics are set up with several stalls separated by curtains. Sometimes there is a sterile bed or a chair. The patients are screened through various questionnaires. They are hooked up to a monitor that keeps track of their vital signs. Once the Ketamine infusion starts, the patient is then left alone. 

Dr. Debra Gambrell, an anesthesiologist in Northern California and Oregon, usually stays present with her patients during a Ketamine infusion. She gives them various sensory experiences that include chimes, proprioceptive real touch, neural therapy, and various light therapies. She has even given Ketamine infusions during a sun set to allow for a more vivid experience during transitions of consciousness. 

“An accumulation of trauma prevents a patient’s natural unfolding which does not allow them to reach their true potential in life,” states Dr Debra Gambrell. Dr. Gambrell started to administer and study the effects of Ketamine on a private patient. She noticed that after she administered the Ketamine infusions to her patient, he was able to access things and start to get movement into areas of his subconscious. Dr. Gambrell describes it as giving her patient “space to move.” 

What’s It Like Getting A Ketamine Infusion? 

Many patient’s describe receiving Ketamine as having an out of body experience. People working in the tech industry describe their brains as always “pinging noise” with the inability to turn off. Ketamine was able to give them an experience of being in still water.

“It’s like when Wily E. Coyote gets run over by a bulldozer and you see his spirit floating up. That’s what getting a Ketamine infusion feels like.” States Emerson Dameron. Emerson suffered from treatment resistant depression for many years. He spent much of his life in and out of treatment, and also would self-medicate with alcohol. “Depression makes you feel small, and you don’t see how your actions affect others. 

Emerson had run across a research study where Ketamine was used in the treatment of PTSD on Military Veterans. He then had the opportunity to enter into UCLA’s Depression Grand Challenge Clinical Trials on Ketamine Infusions. Prior to the clinical trials, he filled out various surveys and completed MRI’s. 

Daily meditation, doing extensive research and consulting with professional practitioners who facilitate patients using psychedelics was how Emerson was able to prepare for his first Ketamine experience. He further describes his reality during the infusions as “seeing flashing lights, various images and diagrams,” while dissociating from his body. “During the treatment I was able to have a detached third-party perspective of my reality and my life. 

Does Spravato Have The Same Outcome As Infused Ketamine?

$437.34 for a 56-milligram dose, and $656.03 for an 84-milligram dose. The dose varies by patient. Patients receive two doses a week for the first month of treatment, once a week during the second month, and then are moved to either weekly or biweekly treatments for maintenance therapy.

By comparison, the wholesale acquisition cost of Spravato, or list price, is between $590 and $885 per treatment session. A review published in June by the Institute for Clinical and Economic Review — a nonprofit that reviews the cost-effectiveness of drugs — claimed that the drug was not cost-effective at Janssen’s chosen price.

The VA said it has spent $80,605.40 on Spravato as of Dec. 10.

Because of the risk of serious adverse outcomes resulting from sedation and dissociation caused by Spravato administration and the potential for abuse and misuse of the drug, it is only available through a restricted distribution system, under a Risk Evaluation and Mitigation Strategy (REMS).

Who Can Administer Ketamine & The Rise Of Ketamine Infusion Centers

From 2015 to 2018, the number of clinics increased from 60 to 300; that number is undoubtedly higher today. There are no standardized universal protocols that are offered for Ketamine clinics. Ketamine infusion protocols are up for debate, and many practitioners follow what they feel is appropriate for their practice.

Recommendations offered for each clinic is to have costs range from $300-$2000.00 depending on the clinic location.

In some states RN’s can administer Ketamine as long as it is ordered by a person who is lawfully qualified to prescribe it. 

Recommended  by the American Psychiatric Association, components include a comprehensive psychiatric diagnostic assessment, paying particular attention to substance use and psychosis history, if any; assessment of baseline symptom severity; history of prior antidepressant treatment; review of systems to assess risk factors; physical examination and laboratory screening that follows accepted guidelines for the anticipated level of sedation, with the recommended addition of a baseline urine toxicology screen; and records review and family corroboration with a particular eye to past substance use.

Finally, the informed consent process should ensure that the patient is aware not only of potential treatment risks, but also of the relatively limited data on the off-label use of ketamine for mood disorders. Thorough written documentation is recommended.

Standard operating procedures should include continued assessment of respiratory, cardiovascular, and mental status throughout the infusion. Stopping criteria should be clearly defined, as should a plan aimed at managing any cardiovascular or behavioral problems. Discharge procedures should include documentation of vital signs and mental status, ensuring that an adult caregiver can take the patient home, and a thorough review of discharge instructions.

Known risks of cognitive impairment and cystitis with more chronic high-frequency ketamine use, taken together with the significant potential for abuse, mean that ketamine should be discontinued if more than once-weekly dosing is required after 2 months of treatment. “The goal remains to eventually taper and discontinue treatment until more long-term safety data can be collected. The procedure should assess baseline vital signs, include criteria for acceptable vital signs, and incorporate a “time-out” procedure before initiating ketamine treatment.

Resources

https://adaa.org/sites/default/files/Ketamine%20JAMA%20Journal%20Article%20-%20Charlie%20Nemeroff.pdf

https://www.mdedge.com/psychiatry/article/133049/depression/apa-task-force-urges-caution-label-use-ketamine-mood-disorders

https://adaa.org/sites/default/files/Ketamine%20JAMA%20Journal%20Article%20-%20Charlie%20Nemeroff.pdf

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