Esketamine moves from off-label ketamine infusions to a standardized treatment for resistant depression
A Freiburg practice update explains how intranasal esketamine has replaced off-label ketamine infusions in treatment-resistant depression, and how to use it safely.
Summary
Ketamine, long used as an anesthetic, was shown around 2000 to relieve treatment-resistant depression at subanesthetic doses. This launched the idea of glutamate-based antidepressant therapy. For years, intravenous ketamine was given off-label at specialized centers. Now that intranasal esketamine is approved, a standardized and reimbursable option exists, and off-label infusions matter less in routine care. This German-language practice update from Freiburg reviews how esketamine works, who it is for, who should avoid it, the approved dosing schedule, safety requirements, and where it fits in the treatment algorithm. Esketamine is approved only alongside an SSRI or SNRI and must be given in a structured setting with defined monitoring. Only the abstract was available, so specific data are not summarized here.
Detailed Summary
Treatment-resistant depression is a major clinical challenge, and conventional monoaminergic antidepressants often fail these patients. Ketamine's discovery as a rapid antidepressant opened a new, glutamate-based therapeutic route and is widely described as a paradigm shift in psychiatry.
This article is a practice-oriented narrative update, not a new trial. The authors, from the Department of Psychiatry and Psychotherapy at the University Hospital Freiburg, trace the history from ketamine as a long-established anesthetic to the first studies showing antidepressant effects at subanesthetic doses. They then cover mechanism of action, indications, contraindications, the approved treatment regimen, safety requirements, and the place of esketamine in the therapeutic algorithm.
The abstract's main message concerns the change in care. Intravenous ketamine was used off-label for many years in specialized centers. With approval of intranasal esketamine, a standardized, reimbursable option is available, and off-label infusion has lost importance in routine practice. Esketamine is approved only in combination with an SSRI or SNRI. It also requires a structured treatment setting with defined monitoring.
For clinicians, this means esketamine should be delivered as a protocolized service rather than an ad hoc intervention. Prescribers should attend to patient selection, contraindication screening, and monitoring infrastructure.
Several caveats apply. Only the abstract was available, so dosing schedules, efficacy figures, adverse-event rates, and algorithm positioning cannot be reported here. This is an expert review rather than a systematic analysis, so selection of evidence may reflect the authors' views. Several authors disclose financial relationships with Johnson & Johnson/Janssen, the manufacturer of esketamine (Spravato), and two are co-inventors on a patent for GluN2D inhibitors in depression. Readers should consult the full text and current regulatory labeling before applying the details.
Key Findings
- Subanesthetic ketamine doses showed antidepressant effects in treatment-resistant depression, establishing glutamatergic antidepressant therapy as a concept.
- Intranasal esketamine now offers a standardized, reimbursable option, reducing the role of off-label intravenous ketamine infusions in routine practice.
- Esketamine is approved only in combination with an SSRI or SNRI.
- Treatment requires a structured setting with defined monitoring and specific safety requirements.
- The update covers mechanism, indications, contraindications, approved regimen, and positioning in the treatment algorithm.
Methodology
This is a German-language narrative practice update (CME-style review), not a primary study. The abstract describes no systematic search, data extraction, or quantitative synthesis. Only the abstract was available for this summary.
Study Limitations
Only the abstract was reviewed, so dosing, efficacy and safety data, and algorithm details are not available here. As a narrative review, it may reflect author selection of evidence. Several authors report industry ties, including Johnson & Johnson/Janssen (esketamine's manufacturer), and patent interests in related depression therapeutics.
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