Esketamine & How It Works to Treat Depression?

People who suffer from severe treatment-resistant depression have some positive news: Esketamine is an innovative treatment that can lift severe depression within hours. Adam Kaplin, M.D., Ph.D., a psychiatrist with Johns Hopkins Medicine, states, “For the first time in 60 years, we have a new antidepressant therapy that is not merely a spinoff of existing antidepressants.”

Esketamine therapy is a groundbreaking treatment for some patients, allowing them to live without depression for the first time in decades. Before discussing Esketamine, let’s first discuss the manifestations of clinical depression.

What is Depression?

Anxiety and depression frequently co-occur as one of the most prevalent mental health problems.

Depression can range from mild to severe. Sometimes it is transient, but can also be persistent. Depression can strike someone only one time or several times in their lifetime.

Suicide can be caused by depression, but it can be avoided by taking the appropriate medication. It is crucial to realize that many things may be done to treat severe depression.

Treatment-Resistant Depression

Treatment-resistant depression (TRD) is characterized by a poor outcome from at least one trial of an antidepressant treatment at the recommended dose and for the recommended amount of time. In clinical practice, TRD is a reasonably frequent occurrence, with up to 50% to 60% of patients not seeing an acceptable response to antidepressant medication.

Early treatment termination, insufficient medication dosage, incorrect diagnosis, and other psychiatric diseases are a few variables that lead to ineffective treatment. The most common cause of disability worldwide is major treatment-resistant depressive illness and oftentimes patients need another option besides standard antidepressants. Esketamine has been approved by the US Food and Drug Administration as the first rapid-acting medication for treatment-resistant depression (TRD). Now let’s get into the details of Esketamine and how it works to treat depression.

Read More: Psychedelics and Psilocybin Treatment For Depression

What is Esketamine?

Esketamine is produced from ketamine, an anesthetic agent that was historically used for sedation purposes. The S-enantiomer of ketamine, esketamine, is more effective at stimulating the N-methyl-D-aspartate (NMDA) glutamate receptor than the R-enantiomer. 

Ketamine’s antidepressant effects are thought to be produced by its action on the NMDA receptor, which results in the development of new neural connections (synapses). For this reason, the S-enantiomer was developed to treat Depression with the introduction of Spravato.

To specifically treat depression, the FDA recently approved an esketamine nasal spray. Esketamine has a higher potency, low doses still provide good clinical effects with minimal side effects.

Insurance companies do provide coverage for Spravato.

Esketamine Therapy for Depression

Esketamine is a special medicine that, when used for the first time, can momentarily alter your sensory perception. Psychiatrists administer Esketamine in a physical clinic to allow for monitoring. Five minutes must pass between each treatment as you administer three doses. Patients must stay in the clinic for two hours to be monitored and must be driven home by a friend or family member.

Additionally, esketamine can be prescribed alongside other antidepressant medications. Common choices for conventional antidepressants include selective serotonin reuptake inhibitors (SSRIs).

Who Is Eligible For Esketamine Treatment?

The FDA authorized esketamine for use in patients with depression who had failed previous treatments. You must have unsuccessfully tried two other antidepressants before being eligible. Most physicians will try additional treatments if you have not experienced total remission or at least a 50% improvement.

Esketamine gives patients hope, according to some experts, which is its best quality. It lets patients briefly experience what it is like to live without depression. They can have faith that slower treatments will finally be effective in the long run since they know that recovery is possible.

Esketamine Mechanism of Action

Ketamine, esketamine’s parent substance, is the subject of a great deal of interest. Esketamine and ketamine, a similar medication, are very effective antidepressants for a variety of reasons:

Esketamine’s antidepressant properties operate via a distinct mechanism from other medications. Traditional antidepressants elevate neurotransmitters such as serotonin, norepinephrine, and dopamine. These substances act as messengers, carrying messages between different brain cells. Theoretically, elevated neurotransmitter levels improve communication between neurons and benefit mood.

Esketamine elevates glutamate levels in neuronal synapses. Glutamate is the most readily available chemical messenger in the brain and is thus vital for brain function.

Clinical Trials that Proved Efficacy of Esketamine

Esketamine provides a tolerable safety profile and a long-lasting antidepressant effect, according to clinical studies, when used with an oral antidepressant. In patients with treatment-resistant depression, esketamine significantly decreased depressive symptoms.

Three four-week investigations, one maintenance study, and a long-term safety study: all assessed how well esketamine worked. In two of these investigations, it demonstrated that esketamine significantly lessens depressive symptoms in people with TRD.

One involved administering intranasal esketamine with an oral antidepressant to persons younger than 65 for a brief period. Approximately 70% of people who took esketamine reported at least a 50% improvement in depression symptoms after one month (compared to just over half in the placebo group).

The maintenance study, which evaluated relapse prevention, was the other encouraging study. Esketamine lowers the relapse rate, according to this experiment's results. Patients who received both an oral antidepressant and esketamine nasal spray had a 50% to 70% decreased risk of relapse than those who received only an oral antidepressant.

The effectiveness and patient acceptability of the available treatments for treatment-resistant depression has been limited for the past twenty years. Through the novel action of esketamine and quick onset of antidepressant efficacy, esketamine is anticipated to meet an unmet medical need in this population.

Depression Sufferers Obtain Quick Relief From Esketamine Therapy

Antidepressants are typically slow-acting and can take anywhere from four to six weeks to work. On the other hand, esketamine has an instantaneous effect on brain cells and provides relief from depression symptoms within days.

1. Reduction in Suicidal Thoughts

There is the worry that SSRIs may initially make people more suicidal in their thinking. The risk then gradually goes down over time.

With SSRIs, specific populations, particularly teens, may be more at risk for suicidality. However, there is conflicting evidence on SSRI use in kids and teenagers, and the advantages are typically thought to exceed the risks.

Esketamine is a secure alternative, nevertheless. It is one of the only medications, along with lithium, that has shown reduced suicidality rates in conventional research.

2. TRD Reinforcement

A third of all individuals with depression do not react to the first round of therapy. Despite trying medications for a sufficient amount of time, they still have symptoms. Olanzapine and fluoxetine are the only additional FDA-approved therapy options. Olanzapine, an antipsychotic, and an SSRI antidepressant are used in this treatment (fluoxetine).

3. Esketamine Aids in the Formation of New Brain Connections

The process of neuroplasticity involves the formation of new connections in the brain. It is a crucial method for the brain to keep learning and developing over time.

According to the data, depression can even increase the risk of dementia if it is not treated over time. Depression can harm the brain’s memory centers. For instance, the hippocampus is 20% smaller in those who suffer from depression. This is concerning given that the hippocampus controls memory and learning in the brain.

The positive news is that Esketamine may directly offset these effects. This may enhance the brain’s long-term health.

According to animal research, persistent stress weakens the connections between brain cells; however, esketamine rescues these stress-related alterations. Esketamine differs from other antidepressants in that it appears to have a growth-promoting impact in addition to protecting the brain from the neurotoxic effects of depression.

4. Esketamine can Aid in the Processing of Previous Events

It is typical for people to access and experience memories when entering this enlarging level of consciousness through dissociation. These memories may be pleasant, but they may also be unpleasant ones that have been walled off in some way as a defense. People are then able to process such memories and situations in a way that they have not been able to before with esketamine.

Long-Term Use of Esketamine

Esketamine use for an extended time is still a controversial topic. At the moment, esketamine use is frequently intended for short-term treatment but many patients may need extended therapy for months, typically at a lengthened cadence of treatment.

What is the Success Rate of Esketamine?

Antidepressants are beneficial in treating clinical depression and other mood disorders for many but not all will respond. Antidepressants do not alleviate symptoms in 10-15% of depressed patients, and they only partially relieve symptoms in 30% to 40% of them.

In a study that combined esketamine and an antidepressant for treating depression in a clinical environment, about 70% of patients experienced at least a 50% reduction in symptoms. A complete remission of symptoms, or the absence of all symptoms of depression, was experienced by around 50% of patients in the same trial.

While some people exhibit improvement after just one treatment, the entire course of treatments (12 sessions over two months) is typically necessary to get the greatest results.

It is crucial to realize that the frequency of treatments may vary by patient. As a result, for specific treatment plans to be most effective, they may take longer or call for various combinations of treatment options.

Patients must communicate adequately to their doctor regarding the effectiveness of their treatment plan. The outcomes of a patient’s wellness journey can be significantly impacted by patient and physician collaboration.

Final Words

Patients who have experienced difficulty finding relief from depression may want to think about nasal esketamine therapy (Spravato). Esketamine is an intriguing new medication for people with depression who have failed other therapies.

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