Esketamine Monotherapy: An Expanded Option, Not a Suicide-Prevention Claim

Separate indications matter

Current Spravato labeling permits esketamine nasal spray for treatment-resistant depression in adults either alone or with an oral antidepressant. Its separate indication for depressive symptoms in major depression with acute suicidal ideation or behavior requires an oral antidepressant. The label states that effectiveness in preventing suicide or reducing suicidal ideation or behavior has not been demonstrated. A depression-score improvement is not proof of suicide prevention.

Evidence without an oral antidepressant

A JAMA Psychiatry trial published in July 2025 evaluated monotherapy in adults with treatment-resistant depression without psychotic features. Conducted from November 2020 through January 2024 at 51 U.S. centers, it found greater symptom improvement than placebo over four randomized treatment weeks. Those research dates are distinct from today’s article date. The comparison does not determine whether esketamine is better than ECT, TMS, psychotherapy or a particular medication strategy.

Monotherapy does not mean at-home treatment

Spravato remains under a restricted risk-management program with supervised administration and monitoring for at least two hours. Its boxed warning addresses sedation, dissociation, respiratory depression and abuse or misuse potential. Blood-pressure effects and individual medical circumstances matter. Approved esketamine should not be conflated with intravenous ketamine or compounded products: formulation, indication and safeguards differ.

The questions that remain

Short trials cannot settle maintenance duration or predict sustained benefit for everyone. Eligibility criteria limit generalizability, and noticeable acute effects may complicate blinding and expectations. The publication includes Johnson & Johnson-affiliated authors, reinforcing the value of independent comparisons and patient-centered outcomes. The evidence supports an approved monitored option, not superiority over every alternative or a reason to delay urgent psychiatric assessment.

Sources

• Official Spravato label
• 2025 monotherapy randomized trial

Editorial disclosure: The accompanying image is a generated editorial illustration, not a photograph of study participants. This reporting is educational, not individualized medical advice.