Role of Ketamine as Antidepressant: A Comprehensive Overview

Role of Ketamine as Antidepressant: A Comprehensive Overview

Anxiety & Depression, Mental Health |  May 11, 2023BY Sozo Centers

As the number of individuals struggling with mental illnesses increases, mental and behavioral health clinics are experiencing an influx of patients. Experts are searching for treatment techniques and drugs that can produce both short-term and long-term results without any negative effects.

When treating depression and other mental illnesses, cognitive and behavioral health professionals must exercise utmost caution. Integrating medications into mental health treatment necessitates complete supervision and a thorough understanding of their efficacy.

What is Ketamine?

Originally used as a general anesthetic, ketamine has now been approved by the FDA as a treatment for severe depressive disorder, thanks to its antidepressant properties. However, it’s important to use ketamine with caution, as it should only be administered in supervised medical settings. Recreational use of ketamine can lead to hallucinations and distorted perceptions of sight and sound, similar to LSD or PCP.

As a last resort, doctors may prescribe ketamine to patients who have not responded well to standard depression medications. Esketamine, a nasal spray medication derived from ketamine, is specifically used to treat patients with Treatment-Resistant Depression.

Studies have revealed that the combination of intranasal Esketamine and oral antidepressants has shown a remarkable 70% improvement rate in patients suffering from Treatment Resistant Depression (TRD).

The introduction of ketamine as a treatment for TRD has been a game changer, as it functions differently from other medications. For instance, drugs like Valium may alleviate anxiety temporarily, but once the effect wears off, patients may experience rebound anxiety. In contrast, ketamine has a unique effect on the cortex that allows the formation of new connections in the brain. Interestingly, the effects of ketamine are determined by how the body responds to it, rather than by the amount of the drug present in the system.

Ketamine is a unique treatment for depression that stands out for its distinctiveness. Despite its potential as a powerful tool in combating depression, concerns about its safety, effectiveness, and accessibility persist among patients who may be apprehensive about its use in their mental health treatment plans.

Role of Antidepressants in treating depression

In the 90s, depression was commonly referred to as the “black box disease” due to the limited understanding of its underlying causes. While there have been advancements in the field, the general perspective hasn’t changed much. However, doctors and scientists have made strides in developing new medications that can alleviate the symptoms of depression and other mental health issues.

One of the most widely accepted theories surrounding depression is the serotonin hypothesis. This hypothesis suggests that individuals who suffer from depression have lower levels of the neurotransmitter serotonin. Interestingly, this theory was discovered accidentally. Researchers found that some medications used to treat conditions like hypertension and tuberculosis had a notable impact on patients’ moods. Patients with decreased levels of serotonin displayed depressive symptoms, while those with increased serotonin levels experienced euphoric sensations.

The discovery of the serotonin hypothesis served as a crucial turning point in the development of medications for depression. This new class of drugs was called Selective Serotonin Reuptake Inhibitors or SSRIs, and the first medication developed to increase serotonin levels in depressed patients was Prozac.

However, as time passed, it became evident that serotonin only makes up a small fraction (less than 20%) of the overall neurotransmitters in the brain. The remaining 80% is composed of neurotransmitters like GABA and glutamate. Therefore, relying solely on SSRIs as antidepressants would have limited benefits for patients.

Recent research has revealed that neurotransmitters like GABA and glutamate play a significant role in regulating brain activity, including mood. In fact, conditions like seizures and schizophrenia have been shown to be significantly impacted by these neurotransmitters. The complex interplay between GABA and glutamate results in a delicate push-and-pull reaction that initiates and halts electrical signals in the brain.

Moreover, studies have shown that extreme stress can alter the signaling ability of glutamate, making them less adaptable and less responsive to neurons. This disruption in communication between neurons suggests that depression and anxiety can make it harder for individuals to cope with difficult events, leading to a vicious cycle of distress for those struggling with challenging life circumstances.

Ketamine – The Miracle Drug

Recent research has revealed that the drug ketamine has a promising impact on treating depression by stimulating glutamate synthesis. In a complex chain of events, this process triggers the brain to generate new synaptic connections, which makes the brain more receptive and prompts the development of new pathways for patients to incorporate positive thoughts. This groundbreaking treatment approach has shown more promising results than traditional antidepressants.

The idea of targeting this system with medication was inspired by mounting evidence that there might be some malfunction related to the glutamatergic mechanism in the brains of those suffering from depression. This discovery has opened up new avenues for the development of more effective treatments for depression that can help patients overcome their symptoms and improve their quality of life.

For almost two decades, Yale researchers have been delving into the potential benefits of subanesthetic doses of ketamine, carefully monitoring patients with severe depressive disorders who did not respond to standard treatments. Astonishingly, more than half of the patients experienced significant improvements in their depressive symptoms in just one day.

However, it is important to note that a single dose of ketamine is unlikely in healing depression. Rather, its effects are rapid but require a thorough treatment program, which may involve ongoing ketamine doses. Ketamine has the ability to facilitate the creation of neural pathways that can help patients develop resilience and protect against depression recurrence.

When combined with Cognitive Behavioral Therapy, ketamine has the potential to lead to groundbreaking advancements in helping patients better understand positive attitudes and productive behaviors.

Delivering a patient-friendly form of Ketamine

In this article, we have previously discussed Esketamine, an FDA-approved nasal spray drug. Compared to the anesthetic version of ketamine, this nasal spray contains only half the amount of ketamine but is up to 5 times more potent due to its chemical composition and easy binding with the glutamate receptors.

As a result, patients only need to take a smaller dosage of Esketamine, making it more convenient to administer in a medical setting under the supervision of a doctor. The nasal spray form also makes it more accessible than the anesthetic ketamine.

Despite its potential benefits, Esketamine has its own set of side effects, as is often the case with new medications. These side effects include hypertension, dizziness, and a sense of detachment from reality. Moreover, ketamine has a high potential for abuse, which could pose a threat if the drug ends up in the wrong hands. It is therefore essential to regulate its availability.

Esketamine is only prescribed by medical professionals as a last resort for patients who have not responded well to at least two other antidepressants. Additionally, Esketamine is only effective when taken in combination with oral antidepressants and is not typically the first line of treatment for depression and its associated symptoms.

In conclusion, the FDA‘s approval of Esketamine offers another powerful tool for doctors to combat depression and brings renewed hope to patients who were previously unable to receive treatment.


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