Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review.
International journal of molecular sciences – December 05, 2024
Source: PubMed
Summary
A protein called BDNF acts like brain fertilizer, helping neurons grow and connect. Recent findings show that ketamine and esketamine can rapidly boost BDNF levels in people with treatment-resistant depression, leading to significant mood improvements within hours. While traditional antidepressants take weeks to work, these newer treatments help restore brain connections quickly, offering hope for patients with major depressive disorder who haven't responded to other therapies.
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.