KETAMINE THERAPY, DEPRESSION TREATMENT, AND A DISSOCIATING HIGH

Ketamine is a dissociative anesthetic and is used to induce a sleep-like state in humans and pets. It’s also a favorite party drug used by people seeking a psychedelic high, which varies on how much of the substance you take.

Ketamine is creating quite the buzz as a treatment for depression, with studies indicating that just two weeks of ketamine therapy can lead to a significant improvement in depression and anxiety.

Even though the treatment is getting growing attention from psychiatrists, people are confused about how the therapy works, and more importantly, can psychedelic drugs get you more than just a dissociating high.

Managing treatment-resistant depression: Patients whose depressive symptoms are not relieved after receiving adequate treatment have “harder-to-treat depression,” typically called treatment-resistant depression (TRD).

• The most common TRD definition is a major depressive disorder that has a minimum of two prior treatment failures despite adequate dosage and duration.
• 30 to 40 percent of people only notice a partial improvement in their symptoms with the use of antidepressants, and 10 to 15 percent don’t show any improvements at all.
• It is estimated that in the 5 years following remission, 80 percent of patients experience relapse.
• Depending upon your symptoms and length of depression, your doctor might advise you to try psychotherapy, such as cognitive behavioral therapy (CBT), alternative medications such as ketamine, or other treatments.

The effectiveness of ketamine: Studies have shown that a single dose of ketamine acts rapidly in reducing depressive symptoms, owing to its growing reputation as an effective therapy for treatment-resistant depression.

• A single ketamine IV infusion alleviates depressive symptoms in patients with TRD within hours. Some patients may even continue to show antidepressant-like effects for up to 2 weeks after the infusion.
• Patients have also exhibited significant improvement in symptoms following multiple infusions of ketamine.
• However, most of the patients in such studies eventually relapse in under a month after their final infusion.

While ketamine’s potential as an antidepressant has enraptured researchers and patients alike, the subject still needs long-duration studies before its efficacy as a treatment for depression can be established.

How ketamine therapy treats depression: Ketamine was approved by the U.S. Food and Drug Administration (FDA) on March 5, 2019, as a medication for treating major depression. The drug is a nasal spray called esketamine.

• Nearly one-third of depression patients do not respond to conventional antidepressant treatments, which is known as treatment-resistant depression (TRD).
• Several studies are now suggesting that ketamine is an effective treatment for TRD, with results showing that ketamine acts as a rapid antidepressant.
• Ketamine (likely) works by binding to NMDA receptors in the brain. This leads to the production of glutamate, a neurotransmitter that scientists believe is involved in mood regulation.
• Depression has been widely associated with inflammation and is believed to contribute to the development of major depressive disorder (MDD). Ketamine has also shown anti-inflammatory properties, which might contribute to its activity as a rapid-acting antidepressant.

What it treats: Major depression is defined as a period of at least two weeks where a person experienced a depressed mood, loss of interest, or pleasure in their daily activities.

• Estimates from 2020 suggest that nearly 14.8 million U.S. adults had at least one major depressive episode with severe impairment in the span of a year.
• Globally, an estimated 5 percent of adults suffer from depression.
• Between 1999 and 2016, suicide rates increased by over 30 percent in 25 U.S. states.
• The suicide rates in 2021 were 4 percent higher for males and 2 percent higher for females compared to 2020.

The initial clinical use of ketamine: Ketamine has only gained a reputation as an antidepressant over the last two decades despite being used in clinical practice for over half a century.

• Ketamine first gained a reputation in clinical practice in the 1960s as an anesthetic for animals.
• While effective in humans as well, using ketamine resulted in a prolonged lack of awareness, which made it undesirable for use on humans.
• The first clinical trial reporting the antidepressant action of ketamine was published in 2000.

Ketamine rapidly moves from a party drug to something that could be at the forefront of treating the symptoms of depression, but the subject is still not as well researched. People have reported both positive and adverse side effects to ketamine therapy, with some even reporting the experience as “terrifying.”

What to expect from your first ketamine infusion: Ketamine therapy is typically conducted through intravenous infusions, with doses lower than what is used for sedation.

• Ketamine infusion treatments generally last for 45 minutes to an hour when treating depression, PTSD, or other mood disorders. It usually takes 5-10 minutes to feel the effects of ketamine infusion.
• Patients are typically provided with a comfortable clinical setting, such as a reclining chair, soft blankets, and music.
• Healthcare providers report that you might experience a mild feeling of euphoria during the ketamine infusion treatment, with some patients describing a “dissociation” effect.
• Esketamine (Spravato) nasal spray is self-administered by the patient in three doses, each spaced five minutes apart, under the supervision of a doctor.

What happens after you complete the treatment: After the administration of ketamine IV or esketamine, your healthcare provider monitors you anywhere from about half an hour to at least two hours in some cases.

• The patient is monitored in a comfortable setting, often while listening to music.
• The doctor monitors temporary increases in blood pressure, which may last for at least four hours.
• Other common side effects of esketamine include dizziness, anxiety, lethargy, vomiting, and feeling drunk or very happy.

What comes after: The treatment protocols for ketamine therapy vary from patient to patient and depend upon the mode of treatment you are receiving.

• Ketamine IV infusions typically consist of 6 to 10 infusions administered over several weeks.
• After the initial treatment is complete, the doctor may suggest getting monthly booster doses.
• The patient can take anywhere from 4 weeks to over a few months to be relieved of depressive symptoms.
• Under the Spravato treatment plan for TRD, you receive the esketamine nasal spray twice a week for the first month. This is done in conjunction with your oral antidepressants. It may be given once a week for a second month. If required after that period, it is typically taken once a week or once every two weeks.

If you feel your current treatment for depression isn’t working for you, the first step should be to consult your psychiatrist about whether ketamine therapy is a viable option for you.

Dissociation and a happier existence: A 2021 study interviewed 13 patients aged between 30 and 60 years diagnosed with treatment-resistant depression about their experience of receiving ketamine treatment for depression.

• They stated that they decided to try ketamine therapy due to being desperate, receiving advice, or after making the “risk-rewards” assessment.
• Participants stated that they felt a feeling of dissociation during infusions, feeling like an “out-of-body experience.” Others described the feeling as a “trippy experience,” similar to that of consuming alcohol.
• Patients also described the experiences of heightened senses, feeling an overall brightened mood, and feeling like their true selves.
• The participants reported shifts in their mindset, with an increase in positive thoughts, reduced suicidal thoughts, improved self-worth, and a desire to make things turn around.

“People on maintenance ketamine are in a cycle of reduced or no depression symptoms (a return to ‘normal’) and then a decline over a period of 5-7 days until their next ketamine infusion. Some participants were able to use ketamine to experience longer remission and return to a socially engaged, active and purposeful life,” stated the authors of the study.

Adverse events: The same study reported that a few participants described their experiences as unpleasant.

• A participant reported that they always had low blood pressure during the treatment. Other adverse reactions included nausea and headaches.
• Three of the participants experienced horrific hallucinations or exceptionally high temperatures.
• Some exhibited an “outpouring of grief and crying,” with one participant stating that the experience was “almost like an impending doom.”

Another study involved 54 participants to study the safety and efficacy of ketamine for treatment-resistant depression. During the infusion, the most common side effects of ketamine reported were a feeling of being sick, decreased energy, increased blood pressure, nausea, vomiting, and anxiety.

The ethical dilemma: Many people who have received ketamine therapy recommend that others should try the treatment. However, people are still skeptical of the therapeutic effects of ketamine and other psychedelic drugs.

• A concern regarding the effects of psychedelics as the future of “greener psychiatric medications is how different expectations of people have produced substantially different psychedelic experiences.
• The approval of esketamine came based on a set of weak evidence-based studies, none of which evaluated the nasal spray alone.

Despite how ketamine has come into play as a viable therapeutic drug for treating depression, psychiatrists are positive about the outcomes of this form of therapy.

A growing body of research is not studying how ketamine may benefit in treating a number of disorders besides depression, including:

• anxiety
• acute suicidality
• post-traumatic stress disorder (PTSD)
• obsessive-compulsive disorder (OCD)
• chronic pain
• eating disorders

Talking to your psychiatrist: The first step in deciding any form of treatment for depression, including ketamine therapy, requires you to have a thorough discussion with your psychiatrist. It might be the right form of treatment for you if:

• you suffer from treatment-resistant depression and have already tried other medications without any relief in symptoms
• you haven’t had the best response to cognitive behavioral therapy (CBT) or other forms of therapy

Is ketamine therapy the right choice for you: If your depression isn’t the treatment-resistant kind, conventional forms of treatment might be the more comfortable choice. You should also consider how much you are willing to spend, and if you’re fairly risk intolerant to ketamine use.

The risks associated with ketamine therapy: Most healthcare practitioners considered the therapeutic use of ketamine to be safe when after proper screening and under medical supervision.

However, just like anything, there are certain risks associated with ketamine therapy.

• A study investigating the safety of repeated ketamine treatments involved the analysis of 6,630 patients who took parenteral ketamine for depression.
• One-third of the patients received over 10 treatments, and only 0.7 percent had to discontinue ketamine due to adverse side effects.
• These adverse events included psychological distress, bladder decline (0.1 percent), cognitive decline (0.03 percent), and psychotic symptoms (0.03 percent).

Where experts stand: The American Journal of Psychiatry published a report on the available evidence for ketamine and esketamine in treatment-resistant depression.

• It noted how concerns regarding the long-term efficacy, safety, and tolerability of ketamine and esketamine therapy have been raised.
• Short-term randomized controlled studies have established the rapid and significant effect of both.
• Studies have reported the rapid reduction of suicidal ideation with ketamine, which lasts for up to 7 days from the administration. However, there is a lack of evidence showing a more persistent reduction in suicidal ideation beyond 6 weeks.
• In healthy volunteers, ketamine infusions have been associated with an increased likeness for ketamine, raising concerns of potential misuse and addiction. However, no evidence suggests either ketamine or esketamine increases the risk of substance use disorders.

The report notes that although the therapy is effective in “providing hope to affected persons,” there is still an “urgent need to clarify the long-term efficacy of these agents” along with answering significant questions such as dosage, frequency, and adverse events.

The nasal spray medication approved by the FDA for treating depression is esketamine, which is derived from ketamine.

The efficacy of the medication was evaluated in three short-term clinical trials and one longer-term maintenance-of-effect trial, according to the FDA press release.

The most common side effects experienced by patients using the drug were:

• dissociation
• dizziness and nausea
• lethargy
• vertigo
• anxiety
• increased blood pressure
• vomiting
• feeling of being drunk

According to a 2021 review, the most common side effects of esketamine include:

• nausea
• dizziness
• dissociation
• headache
• vertigo
• somnolence, or a feeling of drowsiness
• dysgeusia, or an altered sense of taste

Rarer but more severe side effects include:

• panic attacks
• mania
• self-harm ideation
• loquacity, or talkativeness
• ataxia, or loss of muscle control
• akathisia, or the inability to remain still
• out-of-body experiences

According to a 2019 study, the most common side effect of ketamine therapy was a “strange or loopy” feeling. This is in conjunction with what various other trials report.

However, another recent study showed that ketamine infusions over a course of two weeks led to a significant worsening of depressive symptoms in several patients.

When it comes to ketamine therapy, you can receive it in several different forms, including:

• intravenous (IV) therapy
• nasal spray
• intramuscular (IM) injections
• sublingual tablets

Depending upon the approach you chose, a single session could cost you anywhere from $400 to $2,000, depending on your location, condition, ketamine dose, and other factors.

Since the Spravato nasal spray is the only FDA-approved treatment for depression right now, insurance companies won’t cover other forms of treatment in most cases.

The cost for the first month of treatment with Spravato would cost an estimated $4,800 to $6,800, while maintenance therapy would cost between $1,200 and $3,600 per month.

However, the cost of Spravato is covered to a certain extent by some insurance companies, about which you can learn more here.

On the other hand, ketamine infusions can cost between $400 to $800 per treatment, with most patients requiring 6 treatments over a few weeks. Depending upon the cost of a single infusion, the entire IV treatment can cost up to $4,800.