Objective: The aim of our study was to estimate the incremental cost, benefits, and cost-effectiveness of esketamine nasal spray relative to intravenous ketamine for treatment-resistant depression (TRD) in the United States.

Methods: We used a Markov model with a 1-month cycle length to assess the cost-effectiveness ratios (ICER) of esketamine relative to ketamine for adults with TRD. Four health states were utilized (TRD, non-response/relapse, response, and all-cause mortality). We estimated the percentage of the cohort in each health state, quality-adjusted life years (QALYs), costs, and ICERs of esketamine relative to ketamine over a 3-year time horizon, from both the payer and patient perspectives. We ran the model using efficacy data from clinical trials and real-world effectiveness (RWE) data from a private outpatient psychiatric clinic. We performed one-way and probabilistic sensitivity analyses.

Results: Over a 3-year time horizon utilizing clinical trial efficacy, 10% more of the cohort was in response for ketamine compared to esketamine (+0.05 QALYs). Utilizing patient-level efficacy, 1.5% more of the cohort was in response for ketamine compared to esketamine (+0.01 QALY). Using clinical trial efficacy, esketamine costs were $176,320 higher (payer perspective) or $42,532 lower (patient perspective) than for ketamine. With RWE, esketamine costs were $172,919 higher (payer perspective) or $47,606 lower (patient) than for ketamine. Esketamine was dominated by ketamine under the payer perspective. For the patient perspective, base-case ICERs were above $150,000/QALY threshold. The probability that esketamine being cost-effective compared to ketamine was 0.0055 (clinical trial efficacy) and 0.35 (RWE).

Conclusions: In this decision analytic model evaluating esketamine versus ketamine for TRD, we found that esketamine is unlikely to be cost-effective under a payer perspective. Under a patient perspective, esketamine has similar effectiveness and is less costly compared to ketamine due to insurance coverage and manufacturer assistance program covering most of the cost of esketamine.