Several small clinical trials have shown that low doses of ketamine, an anesthetic drug, can act rapidly as an antidepressant. The quickness of its action meant that ketamine, or compounds that share its mechanism of action, could be a much-needed alternative to current antidepressant therapies, many of which require several weeks to take effect. Fast-acting antidepressant therapies are especially valuable for treating people with depression who may be at risk of suicide. Previous work had stopped short of explaining the mechanism underlying ketamine's rapid action. But now, new research in mouse models shows that ketamine exerts its rapid antidepressant effects by boosting levels of brain-derived neurotrophic factor (BDNF).
In the studies, led by Ege T. Kavalali and Lisa M. Monteggia (University of Texas Southwestern Medical Center, Dallas), one low dose of ketamine reduced depressive behavior in mice within 30 minutes, an effect that lasted up to 1 week (Nature doi:10.1038/nature10130; published online 15 June 2011). These effects were initiated by rapid, transient increases in translation of BDNF. The results suggest that higher levels of BDNF may trigger changes in synaptic plasticity that result in long-term antidepressant responses. More studies are needed to fully understand ketamine's effects in people.
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