Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review.
Simone Pardossi, Andrea Fagiolini, Alessandro Cuomo
International Journal of Molecular Sciences December 5, 2024 DOI: 10.3390/ijms252313098 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Narrative review Peer reviewed |
|---|---|
| Population | Patients with depression |
| Interventions | Ketamine Esketamine |
| Topics | Depression Esketamine Ketamine |
| Keywords | Bdnf Depression therapy Neuroscience research Antidepressant medication Brain chemistry Mental health treatment |
| Citations | 43 |
| Key findings | Most human studies indicate an increase in plasma BDNF in patients treated with intravenous ketamine, though some findings contradict this, and few studies examine BDNF with esketamine. |
Abstract
Brain-derived neurotrophic factor (BDNF) is critical for neuroplasticity, synaptic transmission, and neuronal survival. Studies have implicated it in the pathophysiology of depression, as its expression is significantly reduced in brain areas such as the prefrontal cortex and hippocampus in patients with depression. Our narrative review focuses on the relationship between BDNF, ketamine, and esketamine, specifically by summarizing human studies investigating BDNF variations in patients treated with these two drugs. BDNF plays a pivotal role in neuroplasticity and neurotrophic mechanisms that can be enhanced by traditional antidepressants, which have been shown to increase BDNF levels both peripherally and in targeted brain regions. Ketamine and its S-enantiomer, esketamine, exert both rapid and sustained antidepressant effects through activation of glutamate-related pathways, with neurotrophic effects involving BDNF, as demonstrated in experimental studies. However, clinical findings have shown mixed results, with most indicating an increase in plasma BDNF in patients treated with intravenous ketamine, although some studies contradict these findings. In addition to this, there are few studies of BDNF and esketamine. Currently, the limited number of studies suggests the need for further research, including larger sample sizes and investigations of BDNF and intranasal esketamine, which has been approved by several regulatory agencies for the treatment of treatment-resistant depression.
Comparable studies
Other narrative reviews on esketamine for depression, most cited first.
Citations in the library
Cited by 19
- Effectiveness of repeated Esketamine nasal spray administration on anhedonic symptoms in treatment-resistant bipolar and unipolar depression: A secondary analysis from the REAL-ESK study group. Psychiatry Research July 26, 2025
- Risk of manic switch and suicidal outcomes in bipolar depression treated with esketamine: A one-year retrospective cohort study of 2126 patients. European Neuropsychopharmacology August 6, 2025
- Brain-derived neurotrophic factor (BDNF) changes in rodent models of schizophrenia induced by ketamine: a systematic review. Naunyn-Schmiedeberg's Archives of Pharmacology February 20, 2025
- Lack of relationships between ketamine treatment and peripheral neurotrophic and inflammatory factors in a randomized controlled ketamine trial of major depressive disorder. Brain, Behavior, and Immunity April 4, 2025
- Esketamine Optimized the Efficacy of Dexmedetomidine in Treating Sleep Disorders with Comorbid Depression. Neuropsychiatric Disease and Treatment 2025
and 14 more in the library
Cites 34
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) CNS Neuroscience & Therapeutics April 10, 2013
- BDNF Release Is Required for the Behavioral Actions of Ketamine The International Journal of Neuropsychopharmacology October 31, 2014
and 29 more in the library