Treatment-Resistant Depression: Cost-Effectiveness of Esketamine Nasal Spray

The use of esketamine nasal spray for the management of patients with treatment-resistant depression is unlikely to be cost-effective at its current US price of $240 per dose, according to a study published in the journal Psychiatric Services.

The researchers aimed to evaluate the cost-effectiveness of the novel intranasally dosed antidepressant esketamine for patients in the United States with treatment-resistant depression. A decision-analytic model that was parameterized with efficacy data from four phase 3, randomized, controlled trials (RCTs) of esketamine was utilized to simulate the effects of treatment with esketamine nasal spray compared with oral antidepressants over 5 years, from both a societal and a health care sector perspective.

Outcomes of the study included remission and response of depression, quality-adjusted life-years (QALYs), costs in 2015 US dollars, and incremental cost-effectiveness ratios (ICERs) for esketamine. They calculated value-based prices, which were defined as the per-dose price at which esketamine would become cost-effective, based on cost-effectiveness thresholds of $50,000 per QALY, $100,000 per QALY, and $150,000 per QALY. The efficacy of esketamine was based on the results of 3 short-term phase 3 RCTs—TRANSFORM-1, TRANSFORM-2, and TRANSFORM-3—and the long-term phase 3 SUSTAIN-1 trial.

Over a 5-year period, esketamine was predicted to increase the fraction of time patients spent in remission from 25.3% to 31.1% of life-years, which translated to a gain of 0.07 QALYs. It was projected that total costs would increase by $16,617 from a societal perspective and by $16,995 from a health care sector perspective. The increase in cost was driven mainly by the cost of esketamine itself ($16,352), with smaller contributions from physician and medical assistant service costs ($2062), and patient time costs ($2074).

Moreover, other health care costs and lost productivity costs both decreased with the use of esketamine. Additionally, intranasal esketamine was not cost-effective based on either perspective, with predicted ICERs of $237,111 per QALY from the societal standpoint and $242,496 per QALY from the health care sector standpoint.

The use of probabilistic sensitivity analysis demonstrated a >95% likelihood that the ICER of esketamine would be $150,000 per QALY. Based on a cost-effectiveness threshold of $150,000 per QALY, the value-based price of esketamine was approximately $140 per dose, compared with the current price of $240 per dose.

The investigators concluded that intranasal esketamine is unlikely to be cost-effective for the management of treatment-resistant depression in the United States unless its price declines by >40%; a drop from its current price of $240 per dose to ≤$140 per dose. In order to achieve such price reductions while ensuring continued access for those patients who stand to benefit from esketamine would require careful, concerted efforts on the part of both payers and policymakers.


Ross EL, Soeteman DI. Cost-effectiveness of esketamine nasal spray for patients with treatment-resistant depression in the United States [published online July 7, 2020]. Psychiatr Serv. doi: 10.1176/