Ketamine For Depression: A Starting Guide

Ketamine For Depression: A Starting Guide

According to the World Health Organization, depression is the leading cause of disability worldwide. A quarter of a billion people suffer its effects, from children to senior citizens. It can be extremely debilitating in its severe forms and may lead to a range of associated problems, from lack of productivity at work to suicide. While modern medications and various forms of talk therapy have proven invaluable in addressing the depression epidemic, some patients are resistant to conventional treatment. Given the severity of the effects of the disease, this is no small problem. And now using ketamine for depression is becoming a more popular and accepted therapy.

In recent years, an unexpected but highly promising new form of treatment has emerged: ketamine therapy.

Origins of Using Ketamine For Depression

In 1964, ketamine was first trialed on human prisoners. It found to have high effectiveness in reducing pain and in rendering patients unconscious for surgical procedures. Side effects dissipated rapidly upon emergence from anaesthesia. These findings led to its approval as an anaesthetic in 1970 and from that point it came into wide use. It was particularly important during the Vietnam War. Its fast action and relatively few side effects made it essential in treating injured soldiers on the battlefield.

Soon after its introduction as an anaesthetic, some began to use it as a recreational drug due to its pleasant side effects. (In fact, this tendency has resulted in a spate of veterinary clinic burglaries executed by criminals in search of ketamine.) Ketamine ingestion may produce visual and other sensory distortions. While it is more strictly a dissociative drug, its effects are similar to those of psychedelics. In clinical settings, ketamine is safe. However, without physician supervision, various street formulations — sometimes adulterated with other drugs — have resulted in death due to overdose. Therefore, ketamine is a schedule III illegal drug in the United States.

Beginning in the early 2000s, researchers began to investigate the use of ketamine in treating resistant forms of depression.

Mechanism Of Action

Drugs that help treat depression fall under the category of selective serotonin reuptake inhibitors (SSRIs). These drugs prevent the reuptake, or reabsorption of the neurotransmitter serotonin. Serotonin is responsible for the regulation of mood and plays a part in many other brain functions, notably cognition and memory. Serotonin deficiencies often associate with depression.

While the efficacy of SSRIs in a portion of depressed patients has been demonstrated, several other neurotransmitters also play a role in regulating mood and a sense of well-being. In fact, GABA and glutamate comprise some 80% of the neurotransmitters in the body and are, along with serotonin, responsible for brain plasticity and mood regulation, among other functions. SSRIs do not affect these.

Further, SSRIs do not affect the number of serotonin receptors in the brain. Depressed patients may have fewer serotonin receptors in the first place — or they may have an excess of certain types of serotonin receptors. In the former case, damage to the cells that contain the receptors may occur, due to high levels of stress hormones such as cortisol.

Interestingly, it seems that ketamine may facilitate the repair of the cells involved in serotonin reception. By increasing the number of these receptors, the brain may be able to process serotonin more normally. However, further research is necessary.

Ketamine’s Impact On The Brain

Ketamine may actually prompt the brain to produce more glutamate. It may also block the uptake of glutamate by NMDA receptors and thus reduce the firing of certain neurons. In doing so, it may reactivate the reward centers of the brain, leading to alleviation of depression by allowing the brain to react to positive stimuli in a healthy way.

Glutamate may also induce the formation of new connections between neurons. These new connections serve to make the brain more adaptable to negative events and stress, thus alleviating depression. In combination with cognitive behavioral therapy and other modalities, the treatment thus has the potential to break some of the patterns that lead to depression, though this has not been conclusively proven.

Ketamine may also affect the processing of other neurotransmitters in the brain on short- and long-term scales.

Administration

Many major cities in the United States now have ketamine therapy clinics that offer treatment for patients with depression. It is typically provided in one of two ways.

  • Intravenously. Administering ketamine often comes in a tapered fashion, with six doses or more in the course of three weeks to a month. They may then receive booster infusions once a month or as needed.
  • Nasally. Esketamine, a new form of ketamine as a nasal spray, gained approval by the FDA in 2019. Patients still need to go into a doctor’s office to receive the treatment. Typically prescribed in conjunction with a conventional oral antidepressant, it may enhance the effect of these drugs. Administering it comes in tapered doses, with twice-weekly doses to start and decreasing to once every several weeks for maintenance.

Please note that treatment protocols differ by practitioner and are likely to change as new research emerges. Here’s how to find the best ketamine therapy clinic near you.

Results

Some studies have shown that ketamine may begin acting upon depressive symptoms as soon as two hours after treatment. Patients have reported improved mood in addition to increased alertness, motivation, and mental clarity in the wake of their initial ketamine treatments. There have also been reports of reduced suicidal ideation following treatment. These improvements compare positively to the effects of SSRIs, which some patients have stated as having a “smoothing” effect on their negative emotions without necessarily alleviating the mental fogginess that often manifests in depression. SSRIs also typically take 6-8 weeks or longer to take effect.

These early improvements are by no means the rule for ketamine treatment. And they typically only last a week at most, underscoring the need for repeated administrations. Some patients may require multiple doses of ketamine before they see even minor improvement in their depressive symptoms. And some may not respond at all.

Side Effects When Using Ketamine For Depression

Even when a clinic is administering ketamine, like most drugs, it may cause side effects. In addition to psychedelic-like sensory distortions caused by its dissociative properties, ketamine may also have a number of negative physiological side effects.

  • Dizziness
  • Increased heart rate and blood pressure
  • Lethargy
  • Nausea
  • Sedation
  • Vertigo
  • Bladder problems

Ketamine for depression remains a promising treatment modality, as well as a number of other mental health problems such as PTSD and bipolar disorder. It is also effective in treatment of chronic pain.

Also read: What, exactly, is psychedelic therapy?

If an ongoing condition might benefit from ketamine therapy, talk to a licensed physician who can help assess your options.

Richard Pallardy

View all posts by Richard Pallardy

Richard Pallardy is a writer with some 15 years of experience. He has worked with a number of high-profile publishers. He was an editor for Encyclopedia Britannica for seven years and has bylines with Earth Island Journal, National Geographic Learning, Areo Magazine, Arc Digital, Earth.com, SavingforCollege.com, and The American Gardener. His work for Britannica has been cited in a number of publications. He is particularly interested in stories about the natural world: zoology, botany, evolution, conservation. He also writes about politics and culture.

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