Why IV Ketamine-Assisted Psychotherapy Is Superior To Spravato Administration

‍Spravato Can increase Suicidality, Ketamine Significantly Reduces It

A critical concern with Spravato is the increased suicidality observed in the active arms of the Phase 3 trials. Patients receiving Spravato exhibited higher rates of suicidal ideation and behavior compared to those receiving placebo (Canuso et al., 2018; Daly et al., 2019). This alarming trend raises significant safety concerns, especially given that the treatment is intended for individuals with severe depression, who are already at an elevated risk of suicide.

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Higher Treatment Completion Rates

One significant issue with Spravato (esketamine) is that 58% of users do not complete the first phase of treatment (8 sessions) within the recommended 30 days, often extending to 45 days or more (Johnson & Johnson, 2023). This high dropout rate indicates that many patients find the treatment regimen difficult to adhere to, potentially reducing its effectiveness. 

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At Transcend, we have an initial series drop out rate of less than 3%. This is because we have licensed psychotherapists and a registered nurse at the patients side throughout every treatment. Nurses can adjust the level of Ketamine in real time to ensure it is never overwhelming, and therapists can ensure that patients are psychologically safe during. 

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Critique of Spravato Phase 3 Trials

The Phase 3 trials for Spravato that led to its FDA approval have faced significant criticism:

- Small Sample Sizes and Short Duration: The trials involved small sample sizes and had a short duration of only four weeks, limiting the ability to assess long-term efficacy and safety (Daly et al., 2019; Popova et al., 2019).

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-Poor Study Design: The trials allowed patients to continue or start other antidepressants during the study, which could confound the results and make it difficult to isolate the effects of Spravato (Canuso et al., 2018).

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-High Dropout Rates: There were high dropout rates in the trials, which can introduce bias and affect the reliability of the findings (Daly et al., 2019).

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-Subjective Outcome Measures: The studies relied on subjective outcome measures, such as patient self-reports and clinician assessments, which can be influenced by various factors and may not always accurately reflect the drug's efficacy.

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-Conflicts of Interest: Some researchers involved in the trials had financial ties to Johnson & Johnson, the pharmaceutical company that manufactures Spravato. This raises questions about the objectivity and impartiality of the research (Kim et al., 2019).

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Safety Concerns with Spravato

-Respiratory Depression: The FDA has reported cases of respiratory depression associated with Spravato, highlighting a significant safety concern. Unlike IV administered ketamine protocols, Spravato administration in clinics does not include cardiac, blood pressure, or blood oxygenation monitoring, which can increase the risk of undetected adverse events (Johnson & Johnson, 2023; Daly et al., 2019).

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Overwhelming Data for the Safety and Efficacy of Racemic Ketamine

Racemic ketamine, administered intravenously (IV), has a robust body (approximately 300 studies) of evidence supporting its efficacy and safety for treatment-resistant depression and PTSD. Numerous studies have demonstrated that IV ketamine can produce rapid and substantial improvements in depressive symptoms, often within hours of administration. This form of ketamine has been used extensively in clinical settings, with well-documented protocols and safety measures (Wilkinson et al., 2018).

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Conclusion

While Spravato offers a convenient nasal spray option, its higher dropout rates, safety concerns, and issues with the clinical trial data suggest that IV ketamine-assisted psychotherapy is clearly a superior treatment option. The robust data supporting racemic ketamine's efficacy, combined with comprehensive monitoring and structured treatment protocols, make it a more reliable and effective choice for treating treatment-resistant depression and PTSD. 

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References

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- Canuso, C. M., Singh, J. B., Fedgchin, M., Alphs, L., Lane, R., Lim, P., ... & Daly, E. J. (2018). Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression and suicidality in patients at imminent risk for suicide: Results of a double-blind, randomized, placebo-controlled study. *American Journal of Psychiatry, 175*(7), 620-630. 

doi:10.1176/appi.ajp.2018.17060720

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- Daly, E. J., Singh, J. B., Fedgchin, M., Cooper, K., Lim, P., Shelton, R. C., ... & Drevets, W. C. (2019). Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression: A randomized clinical trial. *JAMA Psychiatry, 76*(2), 139-148. doi:10.1001/jamapsychiatry.2018.3679

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- Johnson & Johnson. (2023). J&J warns of risk of respiratory depression with Spravato. *Managed Healthcare Executive*. Retrieved from https://www.managedhealthcareexecutive.com/view/j-j-warns-of-risk-of-respiratory-depression-with-spravato

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- Kim, J., Farchione, T., Potter, A., Chen, Q., & Temple, R. (2019). Esketamine for treatment-resistant depression — first FDA-approved antidepressant in a new class. *New England Journal of Medicine, 381*(1), 1-4. doi:10.1056/NEJMp1903305

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- Popova, V., Daly, E. J., Trivedi, M., Cooper, K., Lane, R., Lim, P., ... & Singh, J. B. (2019). Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression: A randomized double-blind active-controlled study. *American Journal of Psychiatry, 176*(6), 428-438. doi:10.1176/appi.ajp.2019.19020172

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- Wilkinson, S. T., Ballard, E. D., Bloch, M. H., Mathew, S. J., Murrough, J. W., Feder, A., ... & Sanacora, G. (2018). The effect of a single dose of intravenous ketamine on suicidal ideation: A systematic review and individual participant data meta-analysis. *American Journal of Psychiatry, 175*(2), 150-158. doi:10.1176/appi.ajp.2017.17040472

Reardon, S. (2021). Rapid and sustained symptom reduction with esketamine nasal spray and comprehensive standard of care in patients with treatment-resistant depression: SUSTAIN-3 results. Journal of Clinical Psychiatry, 82(1), 20m13644. https://doi.org/10.4088/JCP.20m13644