Posted by Hugh on April 12, 2021, at 12:55:06
Researchers from the Icahn School of Medicine at Mount Sinai have identified a drug that works against depression by a completely different mechanism than existing treatments.
Their study showed that ezogabine (also known as retigabine), a drug that opens KCNQ2/3 type of potassium channels in the brain, is associated with significant improvements in depressive symptoms and anhedonia in patients with depression. Anhedonia is the reduced ability to experience pleasure or lack of reactivity to pleasurable stimuli; it is a core symptom of depression and associated with worse outcomes, poor response to antidepressant medication, and increased risk of suicide.
Ezogabine was approved by the U.S. Food and Drug Administration in 2011 as an anticonvulsant for epilepsy treatment but had not been previously studied in depression. The research results, published March 3 in the American Journal of Psychiatry, provide initial evidence in humans for the KCNQ2/3 channel as a new target for novel drug discovery for depression and anhedonia.
"Our study is the first randomized, placebo-controlled trial to show that a drug affecting this type of ion channel in the brain can improve depression and anhedonia in patients. Targeting this channel represents a completely different mechanism of action than any currently available antidepressant treatment," says James Murrough, MD, PhD, Associate Professor of Psychiatry, and Neuroscience, Director of the Depression and Anxiety Center for Discovery and Treatment at the Icahn School of Medicine at Mount Sinai, and senior author of the paper.
The current study was a two-site, double-blind, randomized, placebo-controlled proof of concept clinical trial designed as a preliminary test of the hypothesis that increasing KCNQ2/3 channel activity in the brain is a viable new approach for the treatment of depression. Forty-five adult patients diagnosed with a depressive disorder were assigned to a five-week treatment period with daily dosing of either ezogabine or matching placebo. All participants underwent clinical evaluations and functional magnetic resonance imaging (fMRI) during a reward task at baseline and at the end of the treatment period. Compared to patients treated with placebo, those treated with ezogabine showed a significant and large reduction in several key measures of depression severity, anhedonia, and overall illness severity.
"The fundamental insight by Dr. Han's group that a drug that essentially mimicked a mechanism of stress resilience in the brain could represent a whole new approach to the treatment of depression was very exciting to us," said Dr. Murrough.
Complete article:
poster:Hugh
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URL: http://www.dr-bob.org/babble/20210120/msgs/1114538.html