Treatment-resistant major depressive disorder (TRD) commonly refers to major depressive disorder for which there is an inadequate response to two or more anti-depressant (AD) treatments of adequate dosing and duration. Many individuals with TRD do not respond to or tolerate available therapies, emphasizing the need for new treatment options such as esketamine, which was recently approved in the United States.

OBJECTIVES: To evaluate the lifetime cost-effectiveness of adding esketamine nasal spray to a regimen of background AD treatment compared with AD alone in patients with TRD.

METHODS: A semi-Markov model with time-dependent mortality was developed, employing 3-month cycles over a lifetime horizon from a health care sector perspective. Included Markov states were effective initial treatment (esketamine plus AD or AD alone), partly effective initial treatment, discontinuation for long-term effectiveness, treatment with up to three subsequent therapies, and death. Outcomes, utility, and cost inputs were obtained through systematic literature reviews and clinical expert opinion. Total costs and quality-adjusted life years (QALYs) gained, discounted at 3% per year, were combined to generate incremental cost/QALY gained. One-way and probabilistic sensitivity analyses were conducted to evaluate uncertainty.

RESULTS: Given base-case inputs and assumptions, patients remained on esketamine plus AD for an average of 1.4 years. Discounted lifetime costs and QALYs were $448,600 and 12.66 for esketamine plus AD versus $410,200 and 12.47 for AD alone. The base-case incremental cost-effectiveness ratio was $198,000 per QALY gained. The model was most sensitive to the probability of esketamine continuing to have long-term effectiveness and utility associated with severe depression. Probabilistic sensitivity analyses resulted in 1% and 15% of simulation runs being cost-effective at thresholds of $100,000 and $150,000 per QALY gained.

CONCLUSIONS: Given the limited availability of information regarding esketamine’s long-term effectiveness and current price, esketamine does not provide value at established cost-effectiveness thresholds.