Treatment of Anxiety Overlapping with Epilepsy: Interim Results from a Clinical Trial of Epidiolex® (EAPE)

Abstract Title: Treatment of Anxiety Overlapping with Epilepsy: Interim Results from a Clinical Trial of Epidiolex® (EAPE)

Background: Anxiety and mood disorders are highly prevalent in epilepsy and even more pronounced in complex epilepsy syndromes, yet few studies have evaluated a comorbid treatment response. Broad spectrum anticonvulsants are highly effective treatments both for mood disorders and for seizure disorders. Cannabidiol may be an anticonvulsant treatment with a similar “dual role.” The FDA approval of Epidiolex® for the treatment of complex epilepsy syndromes suggests pharmaceutical grade cannabidiol may benefit a wide variety of seizure types.

Purpose/Objectives: The aim of this study is to take advantage of the unique pharmacologic profile of Epidiolex® and evaluate whether it may similarly offer broad improvements in seizure control as well as neuropsychiatric symptoms. This open label, adjunctive, flexible dose clinical trial seeks to assess whether Epidiolex® improves anxiety as well as epilepsy in pediatric populations. Specifically;

1.  Assess whether Epidiolex® may yield benefits in terms of anxiety symptoms that are comorbid with pediatric epilepsy. Mood symptoms will also be assessed because of the marked overlap with anxiety.


2.  Assess the utility of Epidiolex® for seizure control in patients with medically refractory epilepsy, e.g. failure to achieve adequate seizure control with two AED trials. 


3. Assess whether treatment with Epidiolex® will yield improvement in quality of life. 

A single product that simultaneously offers benefits for epilepsy as well as for mood and anxiety comorbidity would immediately change practice patterns in epilepsy care. 

Methods: Participants ages 6-17, with an epilepsy diagnosis requiring medication treatment, and with anxiety symptoms impairing function at baseline were recruited to this study. Titration of 5 mg/kg/day over 4 weeks was implemented to reach a target dose of 20 mg/kg/day, but flexible dosing was allowed to more closely approximate clinical practice. Given the observational nature of this study, ratings from 20 completers will be used to assess primary outcome measures such as changes from baseline to end-of-study scores in anxiety, as measured by Clinical Global Impression Improvement (CGI-I) ratings, where ratings of a 1 or 2 (on a 7-point scale) will be considered positive responses.

Results: 12 participants have been enrolled at the time of abstract submission (5 males, 7 females, ages 9-17 [mean = 12.5 SD = 2.81]). Of the 12 participants enrolled, all have presented with overall baseline CGI-S ratings of markedly ill (5) or higher (mean = 5.4). Five participants have completed the study, and two terminated early. Of the 7 completer participants thus far, nearly all report final CGI-I scores indicative of a positive response (mean CGI-I = 2.28). Adjusting for early terminations, the mean end of study CGI-I score is 1.8, where lower scores indicate greater improvement. Anxiety measures such as the Screen for Child Anxiety Related Emotional Disorders (SCARED) have shown significant improvement with mean scores down-trending from screening visit to end of study visit for all 7 participants (mean change of score = 11.7) and an even greater difference in score for the 5 study completers (mean change of score = 18.2), suggesting fewer self-reported symptoms of anxiety at the end of the study and even fewer for those who completed the entire trial.

Conclusions: 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 results suggest that Epidiolex® notably improves anxiety and epilepsy symptoms simultaneously.

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