RESUMO
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 16â¯years of age with drug-resistant epilepsy (nâ¯=â¯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 24â¯months of CBD treatment. Secondary outcomes observed in the first 12â¯months included changes in child behavior, and cognitive function, and sleep quality. RESULTS: The median change in overall seizure frequency decreased from baseline (nâ¯=â¯33) by -61.3% ([nâ¯=â¯33], Inter Quartile Range (IQR): 43-88%) at month 3, -62.9% at month 6 ([nâ¯=â¯29], IQR: 48-92%), -74.7% at month 12 ([nâ¯=â¯29], IQR: 64-96%), and finally -83.7% ([nâ¯=â¯28], IQR: 68-100%) at the conclusion of 24â¯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%, [nâ¯=â¯28], ABC), Hyperactivity (-45.4%, [nâ¯=â¯28], ABC), Cognition in Quality of Life (+14.2%, [nâ¯=â¯28], QOLCE), Behavioral function (+14.7%, [nâ¯=â¯28], QOLCE), General Health (+14.7%, [nâ¯=â¯28], QOLCE), Sleep duration (-33.9%, [nâ¯=â¯28], CSHQ), Daytime sleepiness (-23.8%, [nâ¯=â¯28], CSHQ), and nocturnal arousals (-36.2%, [nâ¯=â¯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.