An Overview of Ketamine and Esketamine
Ketamine, a powerful anesthetic and pain reliever for both humans and animals, first surfaced in the early 1960’s. By 1970, it secured FDA approval as a human anesthetic and was frequently used during the Vietnam War to treat wounded soldiers. Ketamine also used as an anesthetic agent in the hospital setting as well.
Ketamine also found popularity as a recreational substance due to its hallucinogenic properties and dissociative experiences, going by various pseudonyms like “Special K” or just “K”.
Within the medical field, however, you might hear it referred to by another name: R/S-ketamine (racemic).
Ketamine’s utility extends beyond anesthesia applications; over the last decade, research has validated its effectiveness in helping patients with treatment-resistance depression.
How Does Ketamine Work and What Makes It Different To Antidepressants?
Ketamine, unlike traditional antidepressants (generally SNRIs or SSRIs), has been found to have antidepressant effects through a different route.
Ketamine engages with the brain by inhibiting NMDA (N-methyl-D-aspartate) receptors, and this blockade then triggers an uptick in glutamate – a neurotransmitter abundantly present in the brain that sends messages within nerve cells. This surge of glutamate sparks off activity in AMPA receptors, which then facilitates the release of additional molecules and enhances neural communication channels.
This entire chain reaction, known as synaptogenesis, influences areas of our brains linked to mood regulation, pleasure experience, and general cognitive processes.
Traditional antidepressants aim to boost the levels of certain neurotransmitters, such as serotonin, norepinephrine, and dopamine, to elevate an individual’s mood and emotional state.
The R/S-ketamine variant is still awaiting FDA approval for depression treatment but is currently being utilized “off-label”.
However, a new ground-breaking ketamine-based drug called Esketamine (Spravato) was given the green light from the FDA in March 2019 for treatment-resistant depression or major depressive disorder.
What is Esketamine (Spravato)?
Esketamine, marketed as Spravato, is a different form of ketamine, as it only contains the “S” molecule variant of ketamine and lacks the complete spectrum found in the anesthetic form.
This specific chemical makeup enables esketamine to bind more easily with NMDA glutamate receptors – making it nearly five times stronger than traditional ketamine.
This potent characteristic has piqued scientific interest in its potential use for treating extreme mental conditions – specifically depression unresponsive to standard treatments.
Research[1] conducted in 2017 suggested that administering esketamine through the nasal spray can offer quicker and more noticeable relief from major depressive disorders. In 2019, another study[2] also confirmed these findings by demonstrating a substantial reduction in symptoms among patients treated with esketamine compared to placebos.
Esketamine is specifically for use on patients deemed to have treatment-resistant depression. This means that the individual hasn’t experienced relief after taking at least two traditional antidepressants, each for a six-week session. They may have tried other widely recognized methods of battling depression, like therapy, Transcranial Magnetic Stimulation (TMS), or Electroconvulsive Therapy (ECT), with no notable success.
How Are These Treatments Administered?
Administering both IV ketamine and esketamine nasal spray (Spravato) requires the watchful eye of a medical professional in a clinical environment due to their potential influence on your perception post-treatment.
Ketamine is administered via a slow intravenous infusion (IV) into the bloodstream with treatment lasting around 40 minutes. Or via an intramuscular injection, which is quicker and perhaps more comfortable.
Esketamine (Spravato) is administered via a nasal spray, making it more accessible for those with anxiety related to needles or injections.
The recommended regimen for Spravato includes two treatments per week over four weeks (eight treatments in total). Following this intensive phase, one treatment session weekly spanning another four weeks should suffice before gradually reducing the frequency of doses.
A patient must combine esketamine with an antidepressant as it may also enhance the effects of antidepressants. Most studies on esketamine involved patients already taking an antidepressant, and researchers[3] found that esktamine, combined with a conventional antidepressant, enabled patients to remain in stable remission for up to 16 weeks once treatment began.
With IV (racemic) Ketamine for depression treatment, there are no specific recommendations as it’s still unapproved by the FDA. Nevertheless, medical practitioners often follow a similar technique involving two doses per week over one month.
What Are The Side Effects of Ketamine and Esketamine?
No drug comes without its potential drawbacks. Ketamine and esketamine could lead to complications like high blood pressure, unconsciousness, sedation, and slowed breathing.
More commonly observed effects are nausea and vomiting, light-headedness or dizziness, blurred vision, or anxiety.
Both drugs can impact your cognitive functions, which could result in:
· Altered Perception: You may feel time speed up or slow down or experience enhanced sensitivity towards colors. Sounds might also be overwhelming with accompanying pleasant or unpleasant feelings.
· Dissociation: You feel detached from your body as if you’re floating outside yourself, or you may even observe yourself lying down from above.
These cognitive shifts seem most intense during the first treatment session, usually peaking around the 40-minute mark before subsiding after about two hours. Fortunately, these side effects are temporary and typically occur under medical supervision. Therefore, you’ll most likely be able to return safely to your routine life post-treatment.
However, if you’ve been diagnosed with psychosis or schizophrenia, either currently or in the past, then ketamine’s dissociative properties could potentially amplify these conditions.
How Much Does This Treatment Cost?
IV ketamine treatment sessions can cost anywhere between $400 to $800. Securing insurance coverage can be a bit of a slippery slope, contingent on an array of conditions.
Medicare, Medicaid, and private insurance companies provide limited or no coverage at all for IV ketamine treatment for depression, as it’s considered ‘experimental’. Some may reimburse related expenses such as psychiatric assessments and consultations.
However, with Esketamine (Spravato) and its FDA approval, most major health insurers seem more inclined towards covering treatment costs.
Is Ketamine The Right Treatment For You?
When traditional treatments fall short, ketamine emerges as a beacon of hope and potentially offers a new lease of life for those with crippling depression. It may even be a lifesaver for those contemplating suicide.
Only by discussing this option with your healthcare professional will you discover if ketamine or esketamine is the next ideal option if you haven’t responded to traditional methods of treating severe depression.
References:
[1] Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression: https://pmc.ncbi.nlm.nih.gov/articles/PMC5838571/
[2] Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study: https://psychiatryonline.org/doi/10.1176/appi.ajp.2019.19020172
[3] Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial: https://pubmed.ncbi.nlm.nih.gov/31166571/