Epidiolex, a cannabidiol add-on medication for treatment-resistant epilepsy, was safely given to children and teenagers for one year in a clinical trial that included youth with Lennox-Gastaut syndrome, a study reported.
Seizure control was improved with no adverse treatment effects on cognition or functioning after one year, its researchers reported, adding there were also no significant changes in patients’ thinking abilities or functional status.
The study, “Cognitive function and adaptive skills after a one-year trial of cannabidiol (CBD) in a pediatric sample with treatment-resistant epilepsy,” was published in the journal Epilepsy & Behavior.
Epidiolex, by GW Pharmaceuticals, is an oral cannabidiol approved to treat seizures in Lennox-Gastaut and Dravet syndrome patients ages 1 and older.
Clinical trials have found that Epidiolex to be safe and well-tolerated, with reported side effects that include sleepiness, decreased appetite, diarrhea, and fatigue. (Cannabidiol is a non-psychoactive extract from marijuana, meaning it does not have the characteristic “high” associated with marijuana use.)
With any new anti-epileptic therapy, a complete analysis of adverse events as well as benefits beyond seizure control is essential.
Studies investigating Epidiolex’s effects on cognition in adults with treatment-resistant epilepsy (TRE) — those whose seizures fail to respond to first-line medications or surgery — have also shown long-term use to be well tolerated.
However, “the potential [adverse events] or benefits of [Epidiolex] involving cognitive function have not been determined in pediatric populations with TRE,” the scientists wrote.
Researchers at Children’s of Alabama, along with colleagues at the University of Alabama at Birmingham, looked at cognitive and functional effects of Epidiolex use for one year in children and teenagers with TRE.
They enrolled patients between the ages of 3 and 19 in a pediatric arm of an open-label Phase 1 study (NCT02700412 for adults; NCT02695537 is listed for children) assessing the safety and tolerability of Epidiolex as an add-on medication.
TRE was defined as a failure to respond to four or more anti-seizure therapies, including at least one attempt at using two of these medications concurrently.
During the first visit (baseline visit), participants underwent physical, neurological, and laboratory testing. Treatment began with a daily dose of Epidiolex 5mg/kg, divided between the morning and evening, which was increased in 5 mg/kg increments over two weeks until a tolerable and effective dose was reached. The maximum dose was set at 50 mg/kg per day.
Seizure severity was assessed using the Chalfont Seizure Severity Scale (CSSS) questionnaire, along with seizure calendars completed by caregivers.
Cognitive skills were measured using the NIH Toolbox (NIHTB-CB), which includes seven tasks assessing attention, working memory, executive function, episodic memory, and language.
Many of these patients had cognitive problems that left them unable to complete the toolbox, and their caregivers completed the Adaptive Behavior Assessment System (ABAS-II), which measures the ability to perform various daily life skills.
Of the 87 children enrolled, 38 completed the cognitive or functional assessment given after one year of treatment. Of these, 14 were able to finish at least part of the NIHTB-CB questionnaire, while the other 24 were assessed using the ABAS-II.
No significant changes in cognitive performance or functional status after a yearlong stable dose of Epidiolex was seen in an analysis.
There was a trend indicating better performance in one cognitive subdomain of the NIHTB-CB questionnaire: the Flanker Inhibitory Control and Attention Test, which measures response inhibition and attention.
An improvement was also seen in one functional subdomain of the ABAS-II: the social domain, which measures the ability to engage in leisure and social activities.
A significant decrease in seizure severity, as measured by the CSSS questionnaire, was reported after the year of treatment, but a correlation analysis found no relationship between cognitive or functional status and seizure severity scores.
Likewise, the last Epidiolex dose had little or no association with changes in cognitive performance or overall functional status.
“Our findings suggest that [Epidiolex], as an add-on drug for the treatment of TRE in a pediatric sample, does not appear to cause [adverse effects] involving cognition or adaptive functioning in participants who completed one year of treatment,” the researchers wrote.
“The current findings indicate that improved seizure control can be obtained without adversely affecting cognitive or adaptive functioning,” they added, recommending further study of “cognitive performance in PWE [people with epilepsy] who are participating in randomized placebo-controlled trials.”