“Esketamine [nasal spray] is a novel and fast-acting treatment, but its economic value comÂpared with treatments used in routine clinical practice remains unclear,” noted the researchers. “Previous economic studies mainly compared esketamine with less realistic alternatives, rather than with the broader range of treatment strategies commonly used in clinical care.” [PLoS Med 2026;23:e1005047]
The researchers therefore conducted a Markov cohort model simulation study to compare the projected costs and health benefits of esketamine plus antidepressant (AD) with six other commonly used third-line TRD treatments in Hong Kong, including: 1) combination therapy with ADs; 2) augmentation therapy with AD and antipsychotic or lithium; 3) psychotherapy alone; 4) psychotherapy plus AD; 5) rTMS plus AD; 6) ECT plus AD.
“Unlike previous studies that primarily compared esketamine with AD monotherapy or only a single comparator, our model incorporates a broader spectrum of both pharmacological and nonpharmacological comparators, better reflecting actual clinical practice,” highlighted the researchers.
The primary outcome was incremental cost-effectiveness ratios (ICERs) calculated as cost per quality-adjusted life-year (QALY) gained. A 5-year time horizon was used to capture long-term costs while minimizing uncertainty from extrapolated effectiveness, from the perspective of Hong Kong’s public healthcare payer, to reflect resource allocation and reimbursement decisions within the publicly funded healthcare system.
In the base-case analysis, esketamine outperformed rTMS by being both less costly and more effecÂtive. Compared with esketamine, ECT had a higher ICER (USD 322,407 per QALY), exceeding the willingness-to-pay threshÂold, indicating that esketamine is more cost-effective than ECT.
However, esketamine was not found to be cost-effective vs other third-line treatment strategies, including augmentation (ICER, USD 234,109 per QALY), AD combination (ICER, USD 274,426 per QALY), psychotherapy alone (ICER, USD 134,127 per QALY), or psychotherapy plus AD (ICER, USD 312,750 per QALY).
The results indicated that routine use of esketamine may not be economically viable at the existing price and reimbursement levels. “However, esketamine remains a potentially valuable option due to the rapid onset of action and relapse prevention benefits for patients with severe TRD who have not responded to other therapies,” pointed out the researchers.
Beyond evaluating the value of esketamine, the analysis also identified the most cost-effective option among multiple realistic alternative comparators. AD combination therapy was the most cost-effective strategy among all comparator strategies evaluated, but it remains underused in real-world clinical practice.
“[Our] findings help inform clinical guidelines and healthcare policy deciÂsions by supporting more cost-effective treatment sequencing strategies,” wrote the researchers.
“Although esketamine offers clinical benefits, its high cost currently limits its ecoÂnomic value compared with other widely used treatments,” commented the researchers. “Improving its cost-effectiveness may require price reductions or more efficient delivery.”
The study is limited by its modelling approach and dependence on data from multiple sources rather than direct patient comparisons.