Abstracts

Anxiety and mood disorders are highly prevalent in epilepsy, yet few studies have evaluated a comorbid treatment response. Epidiolex®, a pharmaceutical grade cannabidiol, is FDA-approved for the treatment of complex epilepsy syndromes and may be efficacious for a wide variety of seizure types. Similar to broad spectrum anti-seizure medicines, Epidiolex® may serve a “dual role” in treating both seizure disorders and mood and anxiety disorders. This open label, adjunctive, flexible dose study is actively recruiting and to date has reached approximately 70% of the intended recruitment goal, prompting interim analyses to identify trends. The aim of this clinical trial is to evaluate whether Epidiolex® may offer broad improvements in seizure control as well as comorbid neuropsychiatric symptoms in pediatric populations. A single treatment that offers dual benefits would have significant clinical implications in epilepsy care.

This study recruits participants ages six to seventeen, with active epilepsy requiring medication treatment, and with impairing anxiety symptoms. Titration occurred from 5 mg/kg/day to a target dose of 20 mg/kg/day over a four week period, but flexible dosing was allowed to more closely mimic clinical practice. Given this study’s observational nature, ratings from 20 completers will be used to assess primary outcome measures such as changes from baseline to end-of-study (EOS) scores in anxiety, as measured by Clinical Global Impression Improvement (CGI-I) ratings, where ratings of a one or two on a seven point scale will be considered positive responses.

A total of 13 participants have been enrolled at the time of abstract submission (mean age = 12.5 years; 61.5% female). Nine participants completed the study, and three terminated early. Of the 13 enrolled, all have presented with baseline CGI-Severity ratings of markedly ill (5) or higher in the overall (mean = 5.4, SD = 0.5) and anxiety (mean = 5.3, SD = 0.5) subcategories. Across the nine completers, the mean CGI-I scores at EOS were 1.7 (SD = 0.9) and 1.6 (SD = 0.9) for the overall and anxiety subcategories, respectively; seven completers (77.8%) demonstrated a final score of one or two indicative of a robustly positive response. In addition, most completers (88.9%) have shown improvement in anxiety from baseline to EOS visits on parent-reported anxiety measures such as the Screen for Child Anxiety Related Emotional Disorders with a mean decrease of 13.6 points across completers. This trend in improved anxiety was also reflected in the Behavioral Assessment Score for Children anxiety subcategory scores (baseline mean T-score = 68.7 [at-risk range from 60-69, clinically significant 70+], SD = 10.5; EOS mean = 55.7, SD = 7.5).

Given the study is actively recruiting, data analysis is ongoing and additional trends being interpreted include gender and concomitant medication differences accounting for variations in participant responsiveness to treatment. Overall, interim data suggest that Epidiolex® notably improves both seizure control and anxiety symptoms simultaneously and represents a potentially effective treatment option for anxiety comorbid with pediatric epilepsy.