The high-cost, high-potency paradox of the new antidepressant nasal spray

Countries & Cities · Published 2 October 2026 Swipe more like this →

In short: Once a controversial anesthetic, esketamine is now a frontline tool for treatment-resistant depression. But as medical efficacy debates clash with a staggering US$32,400 annual price tag, scientists and insurers are questioning if the breakthrough is worth the cost.

Esketamine, the S(+) enantiomer of ketamine, functions primarily as an NMDA receptor antagonist. While it is roughly twice as potent as racemic ketamine as an anesthetic, its role in psychiatry is more complex. In the United States and Canada, the FDA-approved nasal spray Spravato is used for treatment-resistant depression (TRD) and major depressive disorder (MDD) with suicidal ideation. However, the drug's efficacy is a subject of intense scrutiny. While early small-scale studies suggested a massive effect size (Cohen's d of 1.3–1.7), larger, more rigorous studies showed much more modest results, with a standardized mean difference of only 0.28.

The drug's mechanism involves stronger dopamine inhibition than its counterpart, arketamine, contributing to its dissociative effects. This potency comes with significant physiological trade-offs. Patients may experience dizziness, sedation, nausea, and even visual disturbances, necessitating a strict REMS program where patients remain under medical supervision for at least two hours post-administration. Because of its potential for misuse and its psychotomimetic effects, it is classified as a controlled substance in the US and the UAE.

Economic and clinical debates remain unresolved. In 2020, the UK's NHS rejected the drug, citing high costs and questionable benefits. Similarly, the Institute for Clinical and Economic Review (ICER) declined to recommend it due to its steep cost and modest efficacy compared to cheaper alternatives like atypical antipsychotics. While esketamine offers a rapid-acting option for those who have failed at least two conventional antidepressants, the medical community continues to weigh its rapid onset against limited long-term safety data and the high financial burden on healthcare systems.

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