Related Experiment Video
Updated: Aug 5, 2026
08:20
MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder
Published on: August 11, 2015
Esketamine in Treatment-Resistant Depression: Clinical and Translational Perspectives
Zofia Śledzikowska1, Agata Marianna Pasternak1, Ksawery Wojciechowski1
1Department of Psychiatry, Medical University of Bialystok, Białystok, Poland.
Current Neuropharmacology
|July 28, 2026
Summary
Intranasal esketamine offers rapid relief for treatment-resistant depression (TRD) by targeting NMDA receptors. While effective, ongoing research is needed for optimal patient selection and long-term outcomes.
Area of Science:
- Neuroscience
- Pharmacology
- Psychiatry
Background:
- Intranasal esketamine, an NMDA receptor antagonist, is a novel treatment for Major Depressive Disorder (MDD), especially Treatment-Resistant Depression (TRD).
- Its mechanism involves rapid glutamatergic enhancement and activation of the AMPA-BDNF-mTOR pathway, crucial for synaptic plasticity.
Purpose of the Study:
- To synthesize current clinical and translational evidence on intranasal esketamine for TRD.
- To provide an overview of its efficacy, safety, and therapeutic potential.
Main Methods:
- An integrative review of clinically relevant and translational studies.
- Focused search of PubMed and Scopus databases, including clinical trials, meta-analyses, mechanistic studies, and regulatory documents.
Main Results:
- Randomized controlled trials show rapid antidepressant effects within hours, significantly reducing depressive symptoms.
- Adverse events are typically transient, including dissociation and dizziness; effects on suicidality were variable.
- Esketamine demonstrates a favorable benefit-risk profile for TRD under clinical supervision.
Conclusions:
- Intranasal esketamine is an effective, rapid-acting treatment option for TRD patients unresponsive to traditional therapies.
- Further research is essential for optimizing patient selection, maintenance strategies, and understanding long-term outcomes.
- Development of predictive biomarkers and integration with psychotherapy are key areas for future investigation.
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