Introduction

Cannabidiol has been reported to improve patients’ overall quality of life (cognition and behavior) apart from seizure reduction in Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) in placebo-controlled phase 3 clinical trials. However, extensive data to support these effects is lacking.

Aim

• To characterize and quantify specific nonseizure outcomes (cognition, alertness, language, social interaction, behavioral regulation, mood, emotional function, physical function and motor skills, and sleep quality.), seizure frequency, seizure severity, and changes in caregiver burden in patients with LGS and DS

  Patient Profile

• 498 caregivers (97% parents) responded on behalf of patients with LGS (80%) or DS (20%)

Method

Study Design

• A 20-minute, cross-sectional, online caregiver survey based on questions from validated measures and previously published caregiver reports was used.
• Patients were treated with plant-derived highly purified cannabidiol (100 mg/mL oral solution) for ≥3 months.
• Caregivers were asked to compare the past month to the period before CBD initiation and rate their impression of changes.
• Caregiver responses were summarized as the percentage of respondents who assessed the changes in outcomes.
• Overall changes in seizure frequency and severity were ranked on a symmetric 7-point Likert scale, while changes in the frequency of seizure types and markers of seizure severity were assessed using a symmetric 5-point Likert scale.

Endpoints

• Nonseizure outcomes
• Overall change in seizure frequency and severity
• Change in the frequency of seizure types and markers of seizure severity
• Relationship between improvements in seizure frequency and nonseizure outcomes

Results

Efficacy

• Add-on cannabidiol significantly improved various domains of nonseizure outcomes in a substantial proportion of respondents in at least one survey question (Figure 1) including a net 85% improvement in cognition domain (alertness, awareness of their surroundings and executive function of learning new things)
• Caregivers noticed an 82% improvement and 25% worsening in at least one question of emotional and social functioning domain, 74% improvement in verbal and 79% in nonverbal patients for language and communication domain with cannabidiol treatment.
• A net 46% of respondents reported improvement in physical functioning and 51% in daily activities with cannabidiol
• Cannabidiol led to improvement in at least one aspect of the patient’s sleep patterns (time it takes to fall asleep, nighttime awakening, and the frequency of nighttime restlessness) as observed by 51% of caregivers

• Significant improvements were reported with cannabidiol in seizure outcomes, including seizure frequency domains (85%), seizure severity domains (76%), seizure-free days per week for ≥1 seizure type (67%), and seizure freedom during the past month (16%)
• Cannabidiol caused a net 84% improvement in at least one type of seizure; most common being drop seizures (71%) and convulsive seizures (72%) and 21% reported worsening in at least one seizure type
• Among respondents who reported reduction in seizure frequency, at least 50% also reported improvements across various domains of nonseizure-related outcomes, including cognition (80%), language (78%), and emotional (67%) domains
• However, cannabidiol led improvement in nonseizure outcomes were also reported in patients who either had no change or worsening of seizure frequency with 56% and 54% of respondents, respectively,
• Among caregivers, 71% noted improvement in at least one aspect of their burden; especially family stress (53%) and ability to get sound sleep (49%)
• Cannabidiol treatment was intended to be continued as reported by 93% of caregivers and most common reasons were reduced seizure frequency (78%), reduced seizure severity/duration (73%) and nonseizure-related reasons (77%) which included improved alertness (50%), cognition (43%), sleep (30%), and language/communication (30%)

Figure 1: Improvement in various domains of nonseizure outcomes with add-on cannabidiol

Conclusion

• Add-on CBD treatment significantly improved nonseizure outcomes, regardless of reduction in seizure frequency as reported by a substantial proportion of caregivers of patients with LGS and DS.
• These results support the need for future studies to confirm the effect of CBD treatment on nonseizure outcomes and distinguish whether the nonseizure effects are secondary to seizure control or a primary effect of treatment.

Epilepsy Res 2024; 200: 107280