Ketamine, once primarily known as an anesthetic, has seen a remarkable shift in its use, particularly in mental health treatment. With its breakthrough application in treating depression and other mood disorders, two forms of ketamine have emerged in clinical discussions—esketamine and racemic ketamine.

Both are used to treat depression, but they differ in their chemical composition, delivery method, and effects. Understanding these differences can help patients and practitioners make more informed choices.

What is Ketamine?

Ketamine is a medication originally developed as an anesthetic and has been used widely in both human and veterinary medicine. However, in recent years, it has garnered attention for its rapid-acting antidepressant properties, particularly for treatment-resistant depression (TRD).

Ketamine works by blocking NMDA receptors in the brain, leading to increased glutamate activity, which promotes neural plasticity, rewires the brain and helps alleviate depressive symptoms.

Esketamine: The New Kid on the Block

Esketamine (brand name Spravato) is a newer, FDA-approved version of ketamine specifically designed for mental health treatment. Chemically, esketamine is one of the two mirror-image molecules (or isomers) found in ketamine. Esketamine is the "S" isomer of ketamine, whereas racemic ketamine contains both "R" and "S" isomers.

Key Features of Esketamine:

• FDA Approval: Esketamine is approved for use as a nasal spray for treatment-resistant depression (TRD) and major depressive disorder (MDD) with acute suicidal ideation. It is administered under medical supervision due to its potential side effects.
• Delivery Method: Administered via a nasal spray in a clinical setting, typically in combination with an oral antidepressant. This controlled environment ensures patient safety.
• Rapid Action: Esketamine's effects can be felt within hours, providing quick relief for individuals who have not responded to traditional antidepressants.
• Cost: As an FDA-approved treatment, esketamine tends to be more expensive due to its branded nature and the necessary medical supervision during administration.

Racemic Ketamine: The Traditional Approach

Racemic ketamine, on the other hand, contains both the "R" and "S" isomers. This form of ketamine has been used for many years, primarily in IV infusions, for both anesthetic and off-label mental health treatments.

Key Features of Racemic Ketamine:

• Off-label Use: Racemic ketamine has not received FDA approval specifically for depression, but it has been used off-label in intravenous (IV) treatments for TRD, anxiety disorders, and PTSD.
• Delivery Method: Racemic ketamine is typically administered via IV infusions, allowing more direct control over dosing and duration. However, in addition to IV treatments, racemic ketamine can also be administered intranasally or orally, especially in specialized treatments like rewire. At rewire, both intranasal and oral methods are used for administration, and remote patient monitoring technology ensures that each patient’s safety is prioritized during their treatment.
• Controlled Nasal Spray Delivery: Just like esketamine, rewire offers a controlled nasal spray delivery method. This method provides a predictable side effect profile, ensuring a safer experience for patients. However, rewire takes this a step further by offering weight-specific dosages, increasing the efficacy of the treatment and tailoring it to each individual’s unique needs.

Efficacy Comparison Between Esketamine and Racemic Ketamine

The efficacy between esketamine and racemic ketamine differs based on their composition and how each enantiomer (R- and S-ketamine) functions in the body.

Racemic Ketamine:

• Composition: Contains both R-ketamine and S-ketamine (esketamine) in equal proportions.
• Efficacy: Racemic ketamine is often used in clinical settings because both enantiomers contribute to its therapeutic effects. The S-ketamine part is more potent as an anesthetic and antidepressant, while R-ketamine has been shown to have longer-lasting antidepressant effects with fewer dissociative side effects.
• Use: Commonly used for anesthesia, pain management, and off-label for treatment-resistant depression.

Ketamine (Referring to R- or S-Ketamine Alone):

• R-ketamine: Research suggests it may have a more sustained antidepressant effect with fewer side effects like dissociation compared to S-ketamine. It is still being studied for broader clinical use.
• S-ketamine (Esketamine): Approved by the FDA in 2019 for treatment-resistant depression under the brand name Spravato. It is more potent on a milligram-per-milligram basis compared to racemic ketamine but may have more dissociative side effects in some patients.

Summary of Efficacy:

• Racemic ketamine offers a balanced therapeutic profile due to the combined effects of both enantiomers.
• S-ketamine (as part of racemic ketamine or alone) is faster-acting and more potent but might cause more dissociation.
• R-ketamine could offer longer-lasting relief with fewer side effects but is still under study.

In terms of your clinic’s offerings, the controlled nasal spray with weight-specific dosages provided by rewire allows for customized efficacy, which could maximize the benefits while minimizing side effects. This tailored approach ensures that patients receive the most effective and safe treatment possible.

Conclusion

Both esketamine and racemic ketamine represent groundbreaking advances in the treatment of treatment-resistant depression. Esketamine, with its FDA approval and nasal spray delivery, offers a more regulated and perhaps slightly faster route to relief. Racemic ketamine, with its broader use and different delivery options (IV, nasal, and oral), provides flexibility and accessibility. Ultimately, the choice between these two treatments should be guided by a patient's medical history, treatment preferences, and the expertise of their healthcare provider.

If you or someone you know is struggling with depression and traditional treatments have failed, exploring ketamine-based therapies could be a promising step forward.

Businesses like rewire, which prioritize patient safety through remote patient monitoring and offer cost-effective solutions, can be an ideal option to explore. Additionally, rewire’s weight-specific nasal spray dosing may provide an even more tailored and effective treatment for those seeking individualized care.

Note: Always consult with a healthcare professional before beginning any new treatment, particularly those involving ketamine or esketamine. Each individual’s response to treatment can vary, and medical supervision is essential.