Seizure frequency, quality of life, behavior, cognition, and sleep in pediatric patients enrolled in a prospective, open-label clinical study with cannabidiol

Christopher L Anderson; Victoria Evans; Laura Gorham; Zhao Liu; Cynthia R Johnson; Paul R Carney

doi:10.1016/j.yebeh.2021.108325

Seizure frequency, quality of life, behavior, cognition, and sleep in pediatric patients enrolled in a prospective, open-label clinical study with cannabidiol

Epilepsy Behav. 2021 Sep 21:124:108325. doi: 10.1016/j.yebeh.2021.108325. Online ahead of print.

Authors

Christopher L Anderson¹, Victoria Evans², Laura Gorham³, Zhao Liu⁴, Cynthia R Johnson⁵, Paul R Carney⁶

Affiliations

¹ Department of Child Health, University of Missouri, Columbia, MO 65201, USA; Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611, USA; Department of Pediatrics, University of Florida, Gainesville, FL 32611, USA. Electronic address: christopher.anderson@health.missouri.edu.
² Department of Clinical and Health Psychology, University of Florida, Gainesville, FL 32611, USA.
³ School of Medicine, University of Florida, Gainesville, FL 32611, USA.
⁴ Department of Child Health, University of Missouri, Columbia, MO 65201, USA.
⁵ Department of Clinical and Health Psychology, University of Florida, Gainesville, FL 32611, USA; Cleveland Clinic Children's Center for Autism, Case Western Reserve University, Cleveland, OH, USA.
⁶ Department of Child Health, University of Missouri, Columbia, MO 65201, USA; Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611, USA; Department of Pediatrics, University of Florida, Gainesville, FL 32611, USA.

PMID: 34560358
DOI: 10.1016/j.yebeh.2021.108325

Abstract

Objective: To evaluate the effects of oral pharmacological cannabidiol (CBD) on seizures, side effects, quality of life, behavior, mood, and sleep in children with drug-resistant epilepsy (DRE) during a phase II, prospective, open-label clinical study.

Methods: During a phase II expanded access program (EAP) study to evaluate the safety and efficacy of using cannabidiol (CBD) for the long-term treatment of children with drug-resistant epilepsy, secondary outcome measures were also performed, including quality of life (QOLCE), behavior (aberrant behavior checklist ABC), and sleep (children's sleep habit questionnaire, CSHQ). Participants between the ages of 2 and 16 years of age with drug-resistant epilepsy (n = 35) were included in this EAP. Primary outcomes included change in parent-recorded seizure frequency relative to baseline, as well as the safety and tolerability over the course of 24 months of CBD treatment. Secondary outcomes observed in the first 12 months included changes in child behavior, and cognitive function, and sleep quality.

Results: The median change in overall seizure frequency decreased from baseline (n = 33) by -61.3% ([n = 33], Inter Quartile Range (IQR): 43-88%) at month 3, -62.9% at month 6 ([n = 29], IQR: 48-92%), -74.7% at month 12 ([n = 29], IQR: 64-96%), and finally -83.7% ([n = 28], IQR: 68-100%) at the conclusion of 24 months of treatment. Seven (20%) of the 35 patients enrolled withdrew from treatment and observation by month 24: 2 failed inclusion criteria at baseline, 4 due to lack of treatment efficacy, and 1 was lost to follow-up. The 12-month recording of secondary measures revealed a significant improvement in Irritability (-39.4%, [n = 28], ABC), Hyperactivity (-45.4%, [n = 28], ABC), Cognition in Quality of Life (+14.2%, [n = 28], QOLCE), Behavioral function (+14.7%, [n = 28], QOLCE), General Health (+14.7%, [n = 28], QOLCE), Sleep duration (-33.9%, [n = 28], CSHQ), Daytime sleepiness (-23.8%, [n = 28], CSHQ), and nocturnal arousals (-36.2%, [n = 28], CSHQ).

Significance: The results of this phase II open-label study demonstrate that pharmacological CBD significantly reduces seizure frequency, and improves QOL, behavior deficits, and sleep disruption, in children with drug-resistant epilepsy. The results also suggest that CBD is efficacious in controlled seizures over a 2-year period in childhood DRE.

Keywords: Behavior; Cannabidiol; Epilepsy; Quality of life; Seizures; Sleep.