Skip to main content
Search
Search
Advanced Search
Skip main navigation
Open access
Short Report
9 June 2025

Cost-per-remitter for esketamine nasal spray versus quetiapine for treatment-resistant depression

Authors: Kristin Clemens, Amanda Teeple, Benoit Rive, Noam Kirson https://orcid.org/0000-0001-5200-6883, Urvi Desai https://orcid.org/0000-0001-5196-7201 [email protected], Jason Doran https://orcid.org/0000-0002-5501-9433, Diab Eid, Alice Qu, Hannah Bowrey, and Kruti JoshiAuthor Info & Affiliations
Volume 14, Number 7
https://doi.org/10.57264/cer-2024-0092
PDFFormats

Abstract

Aim: Estimate the cost-per-remitter with esketamine nasal spray plus an oral antidepressant (ESK NS + OAD) versus quetiapine extended release plus an oral antidepressant (QTP XR + OAD) among adults with treatment-resistant depression (TRD). Materials & methods: An Excel-based model was developed to estimate the cost-per-remitter for ESK NS + OAD and QTP XR + OAD from the perspective of a US commercial insurance plan and Medicaid. Remission and response rates were estimated in 4-week intervals over 32 weeks using data from the ESCAPE-TRD phase IIIb clinical trial comparing ESK NS + OAD versus QTP XR + OAD in adults with TRD. Direct healthcare costs were sourced from health economic literature and the RED BOOK® drug pricing database. Indirect costs were derived from a separate analysis of ESCAPE-TRD using the Work Productivity and Activity Impairment: Depression questionnaire. Adults not remitting/responding either stayed on current treatment or discontinued current treatment and initiated either augmented therapy with antipsychotics or repetitive transcranial magnetic stimulation. In a scenario analysis, all individuals who did not achieve response and discontinued treatment initiated repetitive transcranial magnetic stimulation. Results: The remission rate at 32 weeks was 50% for adults receiving ESK NS + OAD and 33% for adults receiving QTP XR + OAD. The cost-per-remitter for ESK NS + OAD compared with QTP XR + OAD was $3102.17 lower in the commercial setting and $456.12 lower in the Medicaid setting. Under the scenario analysis, the cost-per-remitter for ESK NS + OAD compared with QTP XR + OAD was $15,133.66 lower in the commercial setting and $12,487.62 lower in the Medicaid setting. Conclusion: The findings suggest that ESK NS + OAD is a cost-effective treatment for adults with TRD compared with QTP XR + OAD in the commercial and Medicaid settings.

Plain language summary: Comparison of cost and benefits of esketamine nasal spray versus quetiapine XR for treatment-resistant depression

What is this article about?

Esketamine nasal spray plus oral antidepressant (ESK NS + OAD) and quetiapine extended release plus oral antidepressant (QTP XR + OAD) are treatments for adults with treatment-resistant depression. This study uses an Excel-based model to determine whether treatment with ESK + OAD delivers more benefit for the money spent compared with treatment with QTP XR + OAD under commercial and Medicaid insurance coverage. Our model leveraged treatment efficacy results from the ESCAPE-TRD clinical trial and considered overall healthcare costs associated with treatment use, inpatient and outpatient visits and reduced work productivity.

What were the results?

We find that although ESK NS + OAD has higher annual costs, these are more than offset by the better clinical outcomes achieved by this treatment compared with QTP XR + OAD.

What do the results mean?

Our findings suggest that, under commercial or Medicaid insurance, more patients treated with ESK NS + OAD achieved remission compared with those on QTP XR + OAD, leading to lower related medical costs.

Supplementary Material

File (supplementary materials.docx)

References

Papers of special note have been highlighted as: • of interest
1.
National Institute of Mental Health. Major Depression Definitions. (2023). Accessed: 28 November 2023: https://www.nimh.nih.gov/health/statistics/major-depression
Google Scholar
2.
Jain S, Gupta S, Li VW, Suthoff E, Arnaud A. Humanistic and economic burden associated with depression in the United States: a cross-sectional survey analysis. BMC Psychiatry 22(1), 542 (2022).
PubMed
Google Scholar
3.
Greenberg PE, Fournier AA, Sisitsky T et al. The economic burden of adults with major depressive disorder in the United States (2010 and 2018). Pharmacoeconomics 39(6), 653–665 (2021).
PubMed
Google Scholar
4.
Chow W, Doane MJ, Sheehan J, Alphs L, Le H. Economic burden among patients with major depressive disorder: an analysis of healthcare resource use, work productivity, and direct and indirect costs by depression severity. Am. J. Manag. Care (2019). (Supplements and Featured Publications. February 2019). Available at: https://www.ajmc.com/view/economic-burden-mdd
Google Scholar
5.
Zhdanava M, Pilon D, Ghelerter I et al. The prevalence and national burden of treatment-resistant depression and major depressive disorder in the United States. J. Clin. Psychiatry 82(2), 20m13699 (2021).
PubMed
Google Scholar
• Reports the prevalence of treatment-resistant depression (TRD) and the considerable economic, clinical and societal burden of individuals with TRD in the USA.
6.
Sussman M, O'Sullivan AK, Shah A, Olfson M, Menzin J. Economic burden of treatment-resistant depression on the U.S. Health care system. J. Manag. Care Spec. Pharm. 25(7), 823–835 (2019).
PubMed
Google Scholar
7.
Mrazek DA, Hornberger JC, Altar CA, Degtiar I. A review of the clinical, economic, and societal burden of treatment-resistant depression: 1996–2013. Psychiatr. Serv. 65(8), 977–987 (2014).
PubMed
Google Scholar
8.
Voineskos D, Daskalakis ZJ, Blumberger DM. Management of treatment-resistant depression: challenges and strategies. Neuropsychiatr. Dis. Treat. 16, 221–234 (2020).
PubMed
Google Scholar
9.
Delaloye S, Holtzheimer PE. Deep brain stimulation in the treatment of depression. Dialogues Clin. Neurosci. 16(1), 83–91 (2014).
PubMed
Google Scholar
10.
Forma F, Liberman JN, Rui P, Ruetsch C. Adherence to augmentation therapy for the treatment of major depressive disorder. Expert Rev. Pharmacoecon Outcomes Res. 23(3), 327–335 (2023).
PubMed
Google Scholar
11.
Simpson GM. Atypical antipsychotics and the burden of disease. Am. J. Manag. Care 11(Suppl. 8), S235–S241 (2005).
PubMed
Google Scholar
13.
Reif A, Bitter I, Buyze J et al. Esketamine nasal spray versus quetiapine for treatment-resistant depression. N. Engl. J. Med. 389(14), 1298–1309 (2023).
PubMed
Google Scholar
• Clinical trial of esketamine nasal spray (ESK NS) versus extended-release quetiapine for individuals with TRD showing superior efficacy in ESK NS compared to extended-release quetiapine. Results from this trial were used as clinical inputs for our study.
14.
National Library of Medicine. A long-term comparison of esketamine nasal spray versus quetiapine extended release, both in combination with a selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor, in participants with treatment resistant major depressive disorder (ESCAPE-TRD). (2023). Accessed: 28 November 2023: https://clinicaltrials.gov/study/NCT04338321
Google Scholar
15.
Desai U, Kirson NY, Guglielmo A et al. Cost-per-remitter with esketamine nasal spray versus standard of care for treatment-resistant depression. J. Comp. Eff. Res. 10(5), 393–407 (2021).
PubMed
Google Scholar
• Used an approach similar to ours and reported the superior cost-efficiency of ESK NS in conjunction with an oral antidepressant for individuals with TRD compared to standard of care.
16.
Teeple A, Zhdanava M, Shah A et al. Costs associated with work productivity loss of patients with treatment-resistant depression treated with esketamine nasal spray versus quetiapine extended release: ESCAPE-TRD subgroup analysis [poster presentation]. Psych Congress, Nashville, TN, USA (6–10 September 2023).
Google Scholar
• Examined the productivity costs associated with clinical outcomes for ESK NS and extended-release quetiapine from the ESCAPE-TRD trial. Productivity loss results from this study were considered economic costs in the model of this study.
17.
McIntyre RS, Mattingly G, Godinov Y et al. Esketamine nasal spray versus quetiapine XR in adults with treatment-resistant depression: A secondary analysis of the ESCAPE-TRD randomized clinical trial. CNS Spectr. 30(1), e26 (2025).
PubMed
Google Scholar
• Presented the efficacy results from the ESCAPE-TRD clinical trial using the same subgroup population as this study.
18.
Merative. Micromedex REDBOOK. https://www.micromedexsolutions.com/micromedex2/librarian. (Accessed: 28 November 2023).
Google Scholar
19.
United States Census Bureau. Current Population Survey (CPS). 2022. (2022). Accessed: 28 November 2023: https://www.census.gov/programs-surveys/cps.html.
Google Scholar
20.
Bureau of Labor Statistics, U.S. Department of Labor. American Time Use Survey — 2021 results. (2022). Accessed: 28 November 2023
Google Scholar
21.
Centers for Medicare & Medicaid Services. Unit rebate amount calculation for non-innovator multiple source drugs. Accessed: 20 December 2023: https://www.medicaid.gov/medicaid/prescription-drugs/medicaid-drug-rebate-program/unit-rebate-calculation/unit-rebate-amount-calculation-for-non-innovator-multiple-source-drugs/index.html
Google Scholar
22.
Johnson & Johnson Innovative Medicine Scientific Affairs. Data on File.
Google Scholar
23.
Centers for Medicare & Medicaid Services. Unit rebate amount calculation for single source or innovator multiple source drugs. Accessed: 20 December 2023: https://www.medicaid.gov/medicaid/prescription-drugs/medicaid-drug-rebate-program/unit-rebate-calculation/unit-rebate-amount-calculation-for-single-source-or-innovator-multiple-source-drugs/index.html
Google Scholar
24.
Ross EL, Zivin K, Maixner DF. Cost-effectiveness of electroconvulsive therapy vs pharmacotherapy/psychotherapy for treatment-resistant depression in the United States. JAMA Psychiatry 75(7), 713–722 (2018).
PubMed
Google Scholar
25.
Voigt J, Carpenter L, Leuchter A. Cost effectiveness analysis comparing repetitive transcranial magnetic stimulation to antidepressant medications after a first treatment failure for major depressive disorder in newly diagnosed patients – a lifetime analysis. PLoS ONE 12(10), e0186950 (2017).
PubMed
Google Scholar
26.
Amos TB, Tandon N, Lefebvre P et al. Direct and indirect cost burden and change of employment status in treatment-resistant depression: a matched-cohort study using a US commercial claims database. J. Clin. Psychiatry 79(2), 17m11725 (2018).
PubMed
Google Scholar
• Shows that individuals with TRD have greater costs compared to individuals with non-TRD major depressive disorder (MDD) and non-MDD.
27.
Pilon D, Sheehan JJ, Szukis H et al. Medicaid spending burden among beneficiaries with treatment-resistant depression. J. Comp. Eff. Res. 8(6), 381–392 (2019).
PubMed
Google Scholar
• Supports similar conclusions as Amos (2018) within the Medicaid population.
28.
Guth M, Drake P, Rudowitz R, Mohamed M. Understanding the intersection of Medicaid & work: a look at what the data say. (2023). Accessed: 28 November 2023: https://www.kff.org/medicaid/issue-brief/understanding-the-intersection-of-medicaid-work-a-look-at-what-the-data-say/
Google Scholar
29.
Jiang Y, Du Z, Shen Y, Zhou Q, Zhu H. The correlation of esketamine with specific adverse events: a deep dive into the FAERSdatabase.Eur. Arch. Psychiatry Clin. Neurosci. (2023).
Crossref
Google Scholar
30.
McIntyre RS, Bitter I, Buyze J et al. Safety and tolerability of esketamine nasal spray versus quetiapine extended release in patients with treatment resistant depression. Eur. Neuropsychopharmacol. 85, 58–65 (2024).
PubMed
Google Scholar
31.
Brendle M, Robison R, Malone DC. Cost-effectiveness of esketamine nasal spray compared to intravenous ketamine for patients with treatment-resistant depression in the US utilizing clinical trial efficacy and real-world effectiveness estimates. J. Affect. Disord. 319, 388–396 (2022).
PubMed
Google Scholar
|