Ketamine has existed since the 1960s when it was first developed as an anesthetic. Since then, its use has expanded to include a wide range of medical treatments, including depression and anxiety. In recent years, its use has become increasingly popular as a fast-acting antidepressant in people who have not responded to traditional therapies. 

Recently, a new form of ketamine called esketamine has emerged as a new effective treatment option for those suffering from depression and anxiety. This article will explore the history of ketamine and esketamine, their differences, their effectiveness, and how to decide which is right for you. 

History of Ketamine

Ketamine was first synthesized in 1962 by chemist Calvin Stevens at Parke-Davis Laboratories in Detroit. Originally developed as an anesthetic alternative to phencyclidine (PCP), it quickly became an essential medicine for surgeries and pain management, especially in children and challenging environments like battlefields. However, its dissociative and hallucinogenic effects led to its adoption as a recreational drug known as "Special K." Early anecdotal evidence and preliminary research in the mid-1970s hinted at ketamine's potential antidepressant properties. Still, rigorous investigation did not take place until the late 1990s and early 2000s.

The year 2000 marked a turning point when researchers at Yale found that a single low dose of ketamine could rapidly alleviate depression symptoms. This sparked a series of studies throughout the 2000s and 2010s that reinforced ketamine's potential as a fast-acting antidepressant, particularly for treatment-resistant depression. 

History of Esketamine 

Esketamine, a promising antidepressant developed by Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson, is actually the S-enantiomer of ketamine. This means it is one of the two mirror-image forms in which ketamine exists and has been around as long as ketamine itself.

In a breakthrough moment in 2019, the U.S. Food and Drug Administration (FDA) gave its seal of approval to a nasal spray formulation of esketamine, marketed under the brand name Spravato, for the treatment of adults grappling with treatment-resistant depression (TRD) ^[1]. This was a landmark decision that transformed ketamine from being primarily an anesthetic and recreational drug to an innovative and valuable option in the treatment of mental health disorders.

Differences Between Ketamine and Esketamine

Ketamine and esketamine are related, but they do have differences. Esketamine is a part of ketamine but is generally believed to be stronger in helping to fight depression. While standard ketamine is usually given as an injection at a clinic, esketamine comes in a nasal spray form. This means that, with the proper guidance, it could be used at home, making it more convenient for many patients.

When it comes to side effects, both ketamine, and esketamine can have similar ones, like feeling disoriented or dizzy. Although esketamine might seem stronger than ketamine, it doesn't necessarily mean it will cause more side effects. People react differently, and a lot depends on the dosage and the person's overall health.

Effectiveness Comparison Between Ketamine Versus Esketamine

When it comes to treating hard-to-beat depression, known as TRD (Treatment-Resistant Depression), both ketamine and esketamine have been shown to help. However, there are differences in how long the relief lasts and how strong it is. Ketamine, usually given through an injection, often provides relief from depression symptoms for a more extended period. On the other hand, esketamine, which is a nasal spray, may wear off a bit quicker, meaning that people might need to use it more often to keep the benefits.

Studies also suggest that esketamine might significantly reduce depression symptoms compared to regular ketamine ^[2]. This means that some people might find it more helpful in lifting their mood and improving their day-to-day life. 

How Do I Decide Between Ketamine vs. Esketamine?

When deciding between these two treatment options, there are several factors you should consider. These include your preferred setting (clinic vs. home), cost, insurance coverage availability, and potential side effects. 

If you prefer convenience, then esketamine may be best suited since you only need one weekly dose. In contrast, traditional infusions require multiple visits over several weeks or months, depending on your needs and symptoms. In addition, if cost is an issue, traditional infusions may be more suitable since they tend to cost less than esketamine due to their longer duration. Lastly, if you're concerned about potential side effects, then discussing these issues with your doctor before beginning any treatment is essential so that you can make an informed decision based on your individual needs.

Ketamine and esketamine offer promising solutions for those suffering from TRD; however, discussing both options with your doctor before beginning any treatment is essential. With proper research into all available options and appropriate guidance from healthcare professionals, finding the right solution can help bring much-needed relief.

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