The US Foods and Drug Administration (FDA) lately approved Esketamine nasal spray, a reformulation of Ketamine, to ease severe behavioral health associated complications and reduce the risk of self-destruction. Esketamine differs substantially from ketamine and other antidepressants because of its novel way of treating depression. 

From the Archives: Ketamine vs. Esketamine

In the United States, ketamine was created in 1962, therapeutically evaluated in 1964, and licensed as an anesthetic in 1970. 

Ketamine was first employed as an anesthetic for soldiers dealing with post-traumatic stress disorder (PTSD) during the Vietnam War, and it has since become a standard in veterinary care. The mechanism of ketamine has developed over time, and researchers discovered its application in the treatment of major depressive disorder (MDD) in 2006. 

Ketamine is unique among antidepressants because it enters the brain quickly and effectively to relieve depression. In the year 2012, doctors began utilizing ketamine to treat depression. Individuals with persistent depression are given ketamine infusions orally, intravenously (IV), intramuscularly (IM), or nasally. 

Ketamine was added to the World Health Organization’s List of Essential Medicines due to its favorable results, which advance its broad use.

The FDA approved Esketamine as an intranasal antidepressant under the brand name Spravato on March 16th, 2019. Esketamine is approved to treat depression with self-destructive ideation (MDSI), major depressive disorder (MDD), and treatment-resistant depression (TRD). 

Esketamine varies from ketamine in several ways, as we’ll see later in this article. 

Why Esketamine When Ketamine Is Sufficient?

Why make Esketamine when we as of now have ketamine is an interesting point that merits an answer. Ketamine is an older medicine that has been used as an anesthetic for over 40 years. 

However, it likewise serves as an antidepressant by treating depressed indications within hours via intravenous infusions. Albeit, the FDA has only approved ketamine as an anesthetic, a low concentration, can treat depression. It is as yet not endorsed for treating MDD or TRD. 

The American Psychiatric Association (APA) also stated that there is deficient information on ketamine effectiveness for treating depression, which is why pharmaceutical corporations are unwilling to spend millions of dollars on clinical preliminaries to test its anti-depressive effect.

Ketamine vs. Esketamine: What’s the Difference?

Many people are confused about the differences between Esketamine and ketamine. Here’s what you should know.

Mechanism of Action (MOA)

Ketamine and Esketamine both function in the same way to treat depression, which sets them apart from other antidepressants. Both ketamine and Esketamine act as N-Methyl-D-aspartic acid (NMDA) inhibitors, increasing glutamate levels in the brain. 

Glutamate is one of the cerebrum’s most pervasive neurotransmitter, assisting with reestablishing neural associations and further improving mood, thoughts, behaviors, and analytical competence.

Disparities in Molecular Structure

Intravenous ketamine infusion is a mix of R and S molecules, commonly known as a racemic mixture of ketamine. As an off-label treatment for depression, clinicians utilize racemic ketamine. 

Esketamine, on the other hand, exclusively includes the S version of the molecule and has been licensed by the FDA to treat persistent depression manifestations.

Dosage

On a molecular level, ketamine and Esketamine are not the same. Orally administered, ketamine degrades quickly and has a reduced effect. The effect will be immediate if given as an intravenous infusion, but the patient would have to have it three times a week, which is expensive. 

Esketamine, on the other hand, is administered twice a week intranasally with an oral antidepressant and has a typical dose that ranges from 28 mg to 58 mg in adults. Each dose of 14 mg is delivered using the intranasal device. As a maintenance dose, Esketamine is given once a week or once every other week.

Evidence on Safety and Effectiveness

Ketamine’s utilization in the treatment of MDD and TRD is restricted, thus, it is not suggested as an antidepressant. Esketamine has a well-established safety and viability profile, with positive results in different clinical preliminaries to treat chronic depression. 

Apart from lithium, a popular prescription for bipolar disorder, Esketamine (Spravato) is the only medicine that has been shown to lessen self-destructive musings.

Effectiveness

There is a lack of data on how ketamine and Esketamine compare in terms of efficacy. Both are successful in treating depressed symptoms, but there are a few things to consider when deciding which is the best.

The Drug’s Bioavailability

Both ketamine and Esketamine are available to the body in different ways. For example, a person receiving a ketamine IV infusion receives 100 percent of the drug, whereas a person receiving Esketamine via intranasal route receives just 25-30 percent of the medication.

Drug Delivery Convenience 

Experts commonly administered ketamine by intravenous method, which necessitates careful monitoring and a consistent flow rate to distribute sufficient drugs throughout the day, which is a critical process. 

Esketamine, which is frequently delivered by the nose, does not require monitoring because it is a self-administered method of taking a drug that can be done in front of or without the presence of health care experts.

Side Effects

Esketamine is a more potent medicine than ketamine, that’s why therapists use it in lower dosages and have fewer incidental effects. 

Since both ketamine and Esketamine have a high potential to cause dependency, they are classified as Schedule III restricted substances by the FDA. Medical care experts regulate both ketamine and Esketamine administration. 

Esketamine and ketamine may cause the following adverse effects:

• Nausea/ vomiting
• Sluggishness
• Raised pulse/ blood pressure
• Dissociation/ Separation
• Encountering cerebral pains

The adverse effects of ketamine or Esketamine usually spike after 40 minutes and then go away after two hours of treatment.

Insurance

Insurance doesn’t cover ketamine since it is an experimental prescription that the FDA has not endorsed, thusly you should pay for it using cash on hand. 

Esketamine (Spravato), on the other hand, is covered because the FDA has approved it and has sufficient safety and viability data. You must have tried at least two antidepressants and failed to receive a response from them in order to be covered for Esketamine.

Esketamine is an advanced treatment alternative for depressive patients that can help them feel better rapidly. Nonetheless, extensive strategic snags keep the medication from being generally taken on, and uncertainties about the drawn-out adequacy of Esketamine in the treatment of depression persist. 

To achieve the best results, always utilize medicine under the supervision of a mental health expert.