22 Apr Pronounced State Variation in Population-Corrected Prescriptions of Esketamine—Even During Increased National Use

MedicalResearch.com with:

Luke Cavanah B.S.

Luke Cavanah, BS
Department of Medical Education
Geisinger College of Health Sciences
Scranton, PA, 18509

MedicalResearch.com: What is the background for this study?

Response: Almost a third of patients with medication-treated major depressive disorder will fail at least two depressants—many patients failing more.¹ Esketamine is an intranasal medication that was FDA-approved in 2019 for such patients when used in conjunction with an oral antidepressant.² Esketamine also is unique from the more traditional oral antidepressants in its mechanism of action, quick onset, and evidence for treatment of acute suicidality.³ While esketamine has been of much interest for these last few years, a recent study found low and geographically variable use of this medication within the Medicaid population.⁴ We were interested in investigating esketamine treatment utilization among Medicare patients in 2019 and 2020.

MedicalResearch.com: What are the key points of your research?

Response:  There were three main findings in this study.

• First, there was an average 55-fold variation in esketamine prescriptions (corrected for population) for 2019 and 2020.
• Second, Kansas and Nebraska had significantly higher number of prescriptions of esketamine than the national average in both years even when adjusting for population-size differences.
• Third, population-corrected prescription rates and spending for esketamine significantly increased from 2019 to 2020.

MedicalResearch.com: What should readers take away from your report?

Response:  While esketamine has gained a lot of attention due to its novel mechanism of action, quick onset, efficacy, and anti-suicide effects, there seems to be important barriers preventing it from reaching many patients. The significant increase in esketamine use between the two years may reflect the overcoming of some of these barriers. Despite the increase in esketamine prescriptions between 2019 and 2020, the high state-level variation continued, which is concerning for persistent regional care disparities.

MedicalResearch.com: What further questions remain to be answered in this answer? What further research is indicated?

Response:  While there have been many ideas posited about why esketamine use may be low, further research is needed to assess what truly are the underlying causes. For example, is there an association between the present findings and availability of psychiatrists and advanced psychiatric practitioners? Is there an association between the prescribing patterns of esketamine to Medicare patients and those with other insurances, such as Medicaid or private insurance? It would also be fruitful to better understand what the effects of the observed increased state level use of esketamine have been. For example, did greater state level use of esketamine lead to reductions in suicide rates?

Read the full study here: https://psychiatryonline.org/doi/10.1176/appi.ajp-rj.2025.200302

Cavanah LR. Increased use with continuing state-level variation in esketamine use among Medicare patients. Am J Psychiatry Resid J. 2025;20(3).

References

1. McIntyre RS, Alsuwaidan M, Baune BT, et al. Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions. World Psychiatry. 2023;22:394-412. doi:10.1002/wps.21120
2. Office of the Commissioner. FDA approves new nasal spray medication for treatment-resistant depression; available only at a certified doctor’s office or clinic. FDA. March 5, 2019. Accessed March 21, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-new-nasal-spray-medication-treatment-resistant-depression-available-only-certified
3. Stahl SM. Prescriber’s Guide: Stahl’s Essential Psychopharmacology. Cambridge University Press; 2020.
4. Aguilar AG, Beauregard BA, Conroy CP, et al. Pronounced regional variation in esketamine and ketamine prescribing to US Medicaid patients. J Psychoactive Drugs. Published online March 1, 2023:1-7. doi:10.1080/02791072.2023.2178558

• If you or someone you know is struggling or in crisis, help is available. Call or text 988 or chat at org. To learn how to get support for mental health, drug or alcohol conditions, visit FindSupport.gov. If you are ready to locate a treatment facility or provider, you can go directly to FindTreatment.govor call 800-662-HELP (4357).
• US. veterans or service members who are in crisis can call 988 and then press “1” for the Veterans Crisis Line. Or text 838255. Or chat online.
• The Suicide & Crisis Lifeline in the U.S. has a Spanish language phone line at 1-888-628-9454 (toll-free).

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Last Updated on April 22, 2025 by Marie Benz MD FAAD