Updated: Aug 1, 2024
Ketamine vs Esketamine (Spravato): A Comparison
Updated: Aug 1, 2024
Ketamine therapy has emerged as a groundbreaking treatment for individuals suffering from depression, anxiety, and other mental health conditions. Originally used as an anesthetic, ketamine administered off-label has shown rapid antidepressant effects, providing relief for patients who have not responded to traditional antidepressants. Ketamine has been studied primarily in two forms: intravenous ketamine (KIT) and intranasal esketamine (IN-ESK), marketed under the brand name SpravatoⓇ. This page delves into the molecular differences, effectiveness, and cost between these two forms of ketamine therapy.
Ketamine is a mixture containing equal parts (racemic mixture) of two molecules that are mirror images of each other (enantiomers): Esketamine (S-ketamine) and Arketamine (R-ketamine). Esketamine and arketamine are chiral compounds, which means they are mirror images of each other with the same chemical formula but different spatial arrangements of their atoms. Common examples of chiral objects include hands, gloves, and shoes. Esketamine is the S-enantiomer of ketamine and has been found to have three to four times more affinity for N-methyl-D-aspartate (NMDA) receptors than the R-enantiomer.
Understanding the comparative effectiveness of KIT and IN-ESK is important, especially given the substantial cost differences and the growing calls for insurance coverage for KIT. Several real world studies have examined the comparative efficacy of these treatments for treatment resistant depression.
Nikayin et al. 2022 studied 210 patients and found no significant differences in the Montgomery-Åsberg Depression Rating Scale (MADRS) scores by treatment end between KIT and IN-ESK. However, KIT showed better outcomes in Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR) scores after eight treatments and in both MADRS and QIDS-SR scores after the first six treatments.
Singh et al. 2023 evaluated 62 adults and found no significant differences in baseline-to-endpoint changes in QIDS-SR scores or response/remission rates between the groups. However, the time to remission was faster for KIT compared to IN-ESK, adjusting for various factors.
D’Andrea et al. 2024 combined data from two cohorts and found that KIT showed larger effect sizes and higher response rates compared to IN-ESK, although remission rates were not significantly different. Despite more reported side effects, KIT did not cause more discontinuations for adverse events than IN-ESK.
McInnes & colleagues recently reported data at the ASCP meeting on the comparative effectiveness of KIT vs IN-ESK using data gathered from a very large sample of real-world patients (~7000 KIT and 541 IN-ESK) that showed that response to KIT had basically the same amplitude as that to IN-ESK but that the response to KIT was twice as fast. They acknowledged a major study limitation which was that the majority of patients were treated at sites offering only a single modality but they performed a propensity score weighting to control for co-variates. It should be noted the real-world KIT doses (~1 mg/kg) are higher than ESK.
Research on ketamine vs esketamine is ongoing. Yale was recently awarded $12.6 million in funding for a head to head “Comparative Effectiveness of Racemic Ketamine versus S-Ketamine (Spravato) for Depression” study.
The cost of ketamine therapy is a significant factor when considering KIT and IN-ESK. Esketamine (Spravato) is notably more expensive, with prices ranging from approximately $546 to $819 per dose and treatment protocols requiring more doses than is typical of KIT. This cost includes the drug and the mandatory monitoring required during administration, which can make the overall treatment cost significantly higher.
In contrast, generic ketamine is much more affordable, a sampling of clinics from Meeko Health’s clinic directory found a typical ketamine infusion for a mental health condition costs between $375-$500.
A cost-effectiveness study found that esketamine is unlikely to be cost-effective compared to ketamine from a healthcare sector perspective. From a patient perspective, esketamine has similar effectiveness but can be less costly due to insurance coverage for qualified patients.
Both ketamine and esketamine have shown effectiveness in treating treatment-resistant depression, but KIT appears to have a slight edge in terms of response rates and speed to remission. The cost of esketamine is significantly higher than that of generic ketamine, but can be less costly for some qualified patients because of insurance coverage. The molecular differences between the two drugs influence their pharmacological effects, with esketamine having a higher affinity for NMDA receptors. However, the racemic mixture of ketamine may provide a more comprehensive treatment option for some patients.
Given these factors, patients and healthcare providers must weigh the benefits, costs, and individual patient needs when choosing between ketamine and esketamine.
Ketamine therapy is revolutionizing mental health treatment, offering hope for those struggling with depression, anxiety, and other mental health condionts. This innovative approach works by enhancing neuroplasticity and promoting psychological healing and new growth. Discover if ketamine treatment is right for you.
