Heterogeneous condition
In contrast, there were notable improvements from baseline to the final outcome visit in clinical measures of depression and anhedonia in the ezogabine group, compared with the placebo group. Mean (SD) differences in depression scores, based on the MADRS (Montgomery-Åsberg Depression Rating Scale) from baseline to endpoint as follows: mean difference, –7.9 (3.0); effect size, 0.76; response rate, 61.9% (ezogabine) and 37.5% (placebo); remission rate: 38.1% (ezogabine) and 20.8% (placebo)
Compared with placebo, there were also large improvements in hedonic capacity, as measured by the Snaith-Hamilton Pleasure Scale and the anticipatory subscale of the Temporal Experience of Pleasure Scale (t, –4.1; df, 212; P < .001 and t, 3.4; df, 213; P < .001, respectively).
Compared with placebo, ezogabine was associated with “significant benefit” in global illness severity and improvement (Clinical Global Impression–Severity: t, –2.2; df, 214; P = .026 and CGI-Improvement: t, –2.9; d, 214; P = .004, respectively).
Ezogabine was well tolerated. Dizziness and headache were the most common adverse events.
Depression is a “heterogeneous condition” with a single diagnosis encompassing a “large, multifaceted” array of symptoms, Dr. Murrough noted. A growing body of research is focusing on specific components as potential treatment targets. “Our study looked specifically at patients with a diagnosis of depression but high scores on the anhedonia scale and we found that boosting the function of the KCNQ2/3 channel may have a beneficial antidepressant effect by improving anhedonia.”
Potential gain
In a comment, Alan Schatzberg, MD, professor in the department of psychiatry and behavioral sciences at Stanford (Calif.) University, said that “anytime there’s a new treatment with a new mechanism of action for a given condition, there’s a potential gain for the field.”
Dr. Alan Schatzberg
Dr. Schatzberg, who was not involved with the study, said that ezogabine, with its “potentially new mechanism of action, seems to have an effect and reasonable safety and could be important for patients who may not respond to traditional medications. It might also be important for all sorts of patients, depending on findings of later trials.”
Dr. Murrough said that ezogabine in still in “early stages” of research. “We hope that future studies will look at other agents that would also affect this channel,” he added.
This research was supported by the National Institute of Mental Health. Additional funding was provided by the Friedman Brain Institute at the Icahn School of Medicine at Mount Sinai and the Ehrenkranz Laboratory for Human Resilience, a component of the Depression and Anxiety Center for Discovery and Treatment at the Icahn School of Medicine at Mount Sinai. Dr. Murrough is an inventor of a pending patent application for the use of ezogabine and other KCNQ channel openers to treat depression and related disorders. Dr. Schatzberg disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.