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
This economic analysis (2022) finds that esketamine nasal spray (Spravato) is not cost-effective as compared to intravenous (racemic) ketamine for patients with treatment-resistant depression. The analysis uses quality-adjusted life years (QALYs), a common measure of added good years, and finds that esketamine and ketamine both add about two QALYs, but that the costs of the former are disproportionally higher.
Abstract
Objective
The aim of this study was to estimate the cost-effectiveness of esketamine nasal spray relative to intravenous ketamine for patients with treatment-resistant depression (TRD) in the US.
Methods
We used a Markov model with a 1-month cycle length, and we estimated quality-adjusted life years (QALYs), costs (2020 USD), and incremental cost-effectiveness ratios (ICER) of esketamine relative to ketamine over a 3-year time horizon, from both the healthcare sector and patient perspectives. We ran the model using efficacy estimates from both clinical trial and real-world effectiveness (RWE) data. One-way and probabilistic sensitivity analyses (PSAs) were performed to evaluate the robustness of findings.
Results
Over a 3-year time horizon, the use of esketamine yielded 1.98 QALYs (RWE/clinical trial efficacy), and the use of ketamine yielded 2.03 QALYs (clinical trial efficacy) or 1.99 QALYs (RWE). Esketamine was dominated by ketamine using the healthcare perspective. ICERs were above $150,000/QALY threshold with the patient perspective. Under the healthcare perspective, PSA showed there are no scenarios where esketamine was cost-effective compared to ketamine. With the patient's perspective, the probability that esketamine was cost-effective compared to ketamine was 0.0055 (clinical trial efficacy) and 0.35 (RWE).
Limitations
The data utilized for efficacy have limitations. The time horizon may fail to capture longer-term costs and benefits.
Conclusions
In this decision analytic model evaluating esketamine versus ketamine for TRD, we found esketamine unlikely to be cost-effective under a healthcare sector perspective. Under a patient perspective, esketamine had similar effectiveness and was less costly than ketamine due to insurance coverage.
Research Summary of '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'
Introduction
Brendle and colleagues frame treatment-resistant depression (TRD) as a substantial public-health and economic problem within major depressive disorder in the United States. They note that about one third of people with major depressive disorder meet common definitions of TRD and that this subgroup has higher rates of hospitalisation and suicide. Existing pharmacological and somatic therapies have limitations: many antidepressants take weeks to act, somatic therapies can be time consuming or have adverse effects, and there is an unmet need for more rapidly acting treatments. The study sets out to compare the cost-effectiveness of esketamine nasal spray (an FDA-approved, rapid-acting S-enantiomer formulation) with intravenous racemic ketamine (commonly administered off-label in clinics) for adults with TRD. Using both clinical trial efficacy estimates and real-world effectiveness (RWE) drawn from a private outpatient psychiatric clinic, the investigators aim to estimate incremental costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) from both a healthcare sector and a patient perspective over a multi-year horizon to inform decision making about these two treatment strategies.
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Study Details
- Study Typemeta
- Journal
- Compounds
- Topics
- APA Citation
Brendle, M., Robison, R., & Malone, D. C. (2022). 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. Journal of Affective Disorders, 319, 388-396. https://doi.org/10.1016/j.jad.2022.09.083
References (2)
Papers cited by this study that are also in Blossom
Bahji, A., Vazquez, G. H., Zarate, C. A. · Journal of Affective Disorders (2021)
Sanacora, G., Frye, M. A., McDonald, W. et al. · JAMA Psychiatry (2017)
Cited By (4)
Papers in Blossom that reference this study
Chatterton, M. L., Perez, J. K., Thai, T. et al. · Journal of Affective Disorders (2025)
Avancena, A. L. V., Vuong, L., Kahn, J. G. et al. · Translational Psychiatry (2025)
Clemens, K., Teeple, A., Rive, B. et al. · Journal of Comparative Effectiveness Research (2025)
Dougherty, R. F., Clarke, P., Kuc, J. et al. · Psychopharmacology (2023)
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