S-Ketamine in Adolescent Psychosis: Clinical and Policy Implications

Case Report Details: S-Ketamine in Adolescent Early-Onset Psychosis

A case report published on August 25, 2026 in PubMed (PMID: 42640420) documents the off-label use of S-ketamine to treat suicidal ideation and treatment-resistant depression in an adolescent diagnosed with early-onset psychosis. The patient, whose identity and demographic details are anonymized, had previously failed to respond to conventional antidepressants and antipsychotic medications. Following administration of S-ketamine, the report notes a rapid reduction in suicidal thoughts and depressive symptoms, with no immediate adverse effects observed during the monitored period.

This is the first published instance of S-ketamine being used in this specific adolescent population, and it provides a rare, detailed clinical narrative for a group with few evidence-based options. The report does not claim efficacy or safety beyond the single patient, but it does highlight the pressing need for more rigorous investigation.

Mechanism and Clinical Context: Why S-Ketamine?

S-ketamine, the S-enantiomer of ketamine, is an N-methyl-D-aspartate (NMDA) receptor antagonist with established rapid-acting antidepressant effects in adults. Its mechanism involves modulation of glutamatergic neurotransmission and downstream effects on synaptic plasticity. In the United States and European Union, intranasal esketamine (the S-enantiomer) is approved for treatment-resistant depression in adults, but not for adolescents or individuals with primary psychotic disorders.

Adolescents with early-onset psychosis and comorbid depression face elevated suicide risk and limited pharmacological options. Standard antidepressants often carry increased risk of exacerbating psychosis or suicidal ideation in this demographic. The case report’s rationale for S-ketamine use was its unique mechanism and rapid onset, which may bypass some limitations of serotonergic agents. However, the potential for ketamine to worsen psychotic symptoms remains a significant concern, and the report emphasizes close monitoring and multidisciplinary oversight.

Policy and Research Implications: A Call for Controlled Trials

The publication of this case report does not alter the legal or regulatory status of S-ketamine for adolescents with psychosis. Currently, no regulatory agency—including the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA)—has approved S-ketamine for this indication or population. Off-label use in minors, especially those with psychotic disorders, remains highly controversial and is generally discouraged outside of research settings.

However, the case underscores a critical research gap: there are no registered randomized controlled trials (RCTs) of S-ketamine in adolescents with early-onset psychosis and suicidal ideation as of August 2026 (see ClinicalTrials.gov). The report may prompt institutional review boards (IRBs) and funding agencies to prioritize feasibility and safety studies in this group, with a focus on stringent risk mitigation and informed consent protocols. A non-obvious implication is that ethics committees may need to revisit their frameworks for compassionate use in pediatric psychiatry, balancing lack of alternatives against poorly characterized risks.

Risks, Unknowns, and Ethical Considerations

S-ketamine’s safety profile in adolescents, especially those with psychosis, is not well established. Known risks in adults include dissociation, blood pressure elevation, and potential for misuse. In patients with psychotic disorders, ketamine can theoretically exacerbate psychosis or trigger manic symptoms. The case report did not observe such effects in the single patient, but this cannot be generalized. Long-term neurodevelopmental impacts of NMDA antagonists in the adolescent brain remain unknown, and there is a paucity of data on repeated dosing or sustained use in this age group.

Ethically, clinicians face a dilemma: the urgency of suicidal ideation may justify experimental interventions under compassionate use, but the lack of robust safety and efficacy data makes routine off-label use untenable. The case report’s authors call for “extreme caution” and emphasize that such interventions should only occur within tightly controlled research or emergency settings, with comprehensive monitoring and support.

Looking Forward: Next Steps for Research and Policy

This case report is unlikely to change clinical practice or regulatory policy in the near term, but it serves as a catalyst for dialogue among researchers, clinicians, and policymakers. The most immediate need is for phase 1 safety trials of S-ketamine in adolescents with complex psychiatric presentations, followed by carefully designed efficacy studies. Funding agencies and ethics boards should consider prioritizing this high-risk, underserved population while maintaining rigorous safeguards.

For now, S-ketamine remains an experimental option for adolescent psychosis with suicidal ideation, and its use should be limited to research protocols or exceptional compassionate circumstances. The case adds to a growing body of literature calling for nuanced, evidence-driven approaches to psychiatric emergencies in youth—a field where clinical urgency often outpaces available science.

How we research: This article was researched and written by Dr. Alex R. Klein, MD, PhD, clinical psychiatrist and policy analyst. Reviewed by Dr. Klein on 2026-08-27. Primary source: PubMed PMID: 42640420.