On March 5, 2019, the FDA approved esketamine CIII nasal spray as a “new option” for treatment-resistant depression under the brand name SPRAVATO®. This has led many to ask, “What is esketamine?” Equally common is the desire to understand the differences between ketamine vs. esketamine and what that means for available depression treatments.
Esketamine, commonly referred to as “S-ketamine,” constitutes one part of ketamine, which has a 52+ year history as a safe, effective, and fast-acting anesthetic and analgesic used in both human and veterinary medicine. Ketamine was approved by the FDA in 1970. For the last 22 years, IV infusions of ketamine, also known as IV ketamine therapy, have become increasingly common as one of the fastest-acting and most effective ways to treat depression, suicidal ideation, and other mental health conditions. Since ketamine is an old, generic drug with an expired patent, pharmaceutical companies sought to create a variation that could be patented for profitability, hence the introduction of esketamine, the ketamine nasal spray.
When comparing ketamine vs. esketamine, it's crucial to recognize that esketamine is essentially one part of ketamine. Ketamine, a racemic mixture, is composed of two mirror-image molecules known as R-ketamine and S-ketamine. Separating this mixture results in esketamine (S-ketamine), literally one-half of the molecular compound ketamine.
Both drugs are believed to stimulate relief from depressive symptoms by acting as N-methyl-D-aspartate (NMDA) receptor antagonists. This means they help restore the brain’s proper levels of the neurotransmitter glutamate, which in turn re-establishes the correct balance of other neurotransmitters required for a healthy, well-functioning brain. Both ketamine and SPRAVATO® for depression work similarly on a molecular level, though the route of administration (ROA) is one of the biggest differences between the two.
Ketamine Infusion Therapy: This method delivers a precisely controlled dose of ketamine directly into the bloodstream via an IV, ensuring 100% bioavailability. This means all of the drug enters the bloodstream without being broken down into metabolites.
SPRAVATO®: This is administered intranasally (through the nose) as a spray, and its bioavailability range is 25-50%. Factors such as nasal congestion can affect absorption, making the effectiveness vary more from one administration to the next.
While both clinical ketamine therapy and SPRAVATO® can produce rapid results, ketamine has generally proven to be faster-acting and more effective. Clinical research and real-world applications show IV ketamine infusions have a ketamine therapy success rate of about 70%, compared to SPRAVATO®'s approximately 40%. At Ketamine Clinics Los Angeles, IV ketamine shows an efficacy rate of 83%.
Because SPRAVATO® is a newer treatment, and its research is funded by its manufacturer, there are no direct comparative studies between SPRAVATO® and infusion-based treatments. However, ketamine infusions have demonstrated higher efficacy rates. The differences in effectiveness are less about chemical composition and more about the delivery method.
For more information about Ketamine Infusion Therapy, SPRAVATO® (esketamine/S-ketamine), and other treatments for depression, bipolar disorder, anxiety, PTSD, PPD, OCD, and other mental health conditions, contact Ketamine Clinics Los Angeles. Book a free phone consultation or call 310-270-0625 today. All inquiries are strictly confidential.