In a new study, researchers found a drug that works against depression by a completely different mechanism than existing treatments.
They showed that ezogabine (also known as retigabine), a drug that opens KCNQ2/3 type of potassium channels in the brain, is linked to big improvements in depressive symptoms and anhedonia.
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.
The drug 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 provides initial evidence in humans for the KCNQ2/3 channel as a new target for novel drug discovery for depression and anhedonia.
The research was conducted by a team at Mount Sinai.
The new drug target, the KCNQ2/3 channel, is a member of a large family of ion channels that act as important controllers of brain cell excitability and function in the central nervous system.
The team had previously conducted a series of studies in mice showing that changes in the KCNQ2/3 potassium channel play an important role in determining if the animals show depression and anhedonic-like behavior.
The researchers viewed enhanced functioning of the KCNQ channel as a potential molecular mechanism of resilience to stress and depression.
In the study, 45 adult patients diagnosed with a depressive disorder were assigned to a five-week treatment period with daily dosing of either ezogabine or matching placebo.
The team found that compared to patients treated with placebo, those treated with ezogabine showed a large reduction in depression severity, anhedonia, and overall illness severity.
They say that the drug essentially mimics a mechanism of stress resilience in the brain and could represent a whole new approach to the treatment of depression.
They are greatly encouraged by these findings and the hope they offer for the prospect of developing novel, effective treatments for depression and related disorders.
One author of the study is James Murrough, MD, Ph.D., Associate Professor of Psychiatry, and Neuroscience.
The study is published in the American Journal of Psychiatry.
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