Novel Depression Treatment Approach

Researchers have discovered that ezogabine (a drug used to treat epilepsy) can also be used to treat depression.

Ezogabine (retigabine) was approved in 2011 as an anticonvulsant for treating epilepsy. It opens the KCNQ2/3 type of potassium channels in the brain.

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‘Changes in the KCNQ2/3 potassium channel determine if the animals show depressive and anhedonic behavior’
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Anhedonia, a core symptom of depression, is the reduced ability to experience pleasure or lack of reactivity to pleasurable stimuli. It is associated with worse outcomes, increased risk of suicide, and poor response to antidepressant medication.

Ezogabine was found to be associated with substantial improvements in anhedonia and depressive symptoms.

James Murough, senior author, comments, "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."

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The KCNQ2/3 channel belongs to the large family of KCNQ (or Kv7) ion channels that are important controllers of brain cell excitability and function in the central nervous system. These channels control the electrical charge flow across the cell membrane as potassium (K+) ions.

In a previous mice study, the researchers had found that changes in the KCNQ2/3 potassium channel determine if the animals show depressive and anhedonic behavior following chronic stress. They also found that mice with increased amounts of KCNQ2/3 channels were resistant to developing depression in the face of stress.

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Dr. Ming-Hu Han, co-author, says, "We viewed enhanced functioning of the KCNQ channel as a potential molecular mechanism of resilience to stress and depression."

The previous study also found that when a drug that increases this channel's activity (like ezogabine) was given to the depressed mice, they no longer showed depressive and anhedonic behaviors, i.e., the drug acted as an antidepressant.

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The current study involved 45 adult patients diagnosed with a depressive disorder. They were assigned to a five-week treatment period with daily dosing of either ezogabine or a matching placebo. All participants were asked to undergo clinical evaluations and functional magnetic resonance imaging (fMRI) during a rewarding task at baseline and the end of the treatment period.

Findings showed that patients treated with ezogabine showed a substantial and large reduction in various measures of depression severity, anhedonia, and overall illness severity. When the patients were tested using various depression scales, results showed significant improvements. These patients also showed increased responses to reward anticipation in the brain compared to placebo.

"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.

Source-Medindia

Novel Depression Treatment Approach - Brain Ion Channel