Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review.

Brain-derived neurotrophic factor (BDNF) supports neuroplasticity and neuronal survival, and its expression is reduced in depression-related brain regions. This narrative review summarizes human studies of BDNF changes in patients treated with ketamine or esketamine. Traditional antidepressants can increase BDNF levels, and ketamine and esketamine produce rapid antidepressant effects partly through glutamate pathways and neurotrophic mechanisms involving BDNF. Clinical findings are mixed; most studies report increased plasma BDNF after intravenous ketamine, but some contradict this. Few studies examine BDNF and esketamine. More research with larger samples and intranasal esketamine, approved for treatment-resistant depression, is needed.

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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.