The anticonvulsant ezogabine (also known as retigabine) significantly reduced depressive symptoms, anhedonia, and increased resilience to stress in a small open-label study of patients with major depressive disorder (MDD). The results of this study are exciting because we haven’t had a new medicine to treat depression in decades. Most antidepressants are in the same class of drugs and work by increasing serotonin. This new research suggests a different molecular target that works through other brain mechanisms and could be helpful for patents.
Ezogabine is a first-in-class KCNQ-selective potassium channel opener approved by the US Food and Drug Administration as adjunctive treatment for partial-onset seizures. By activating (or opening) KCNQ transmembrane potassium ion channels, ezogabine is thought to reduce brain excitability likely leading to its anticonvulsant effect, but there hasn’t really been any study to see if it can affect a mood disorder until now. In the open-label study, they tested the effects on patients with MDD experiencing a major depressive episode. Patients received up to 900 mg/day ezogabine orally for 10 weeks. Treatment with ezogabine was associated with a significant reduction of depressive symptoms and, after 10 weeks of treatment, patients showed a 45% reduction in MADRS score from baseline.