Long-term safety and efficacy of highly purified cannabidiol for treatment refractory epilepsy.
Epilepsy Behav
; 117: 107862, 2021 04.
Article
in En
| MEDLINE
| ID: mdl-33667843
ABSTRACT
OBJECTIVE:
To evaluate the safety, efficacy, and tolerability of highly purified cannabidiol (CBD) for the treatment of seizures in children and adults with treatment-resistant epilepsy (TRE) in an open-label, expanded access program (EAP).METHODS:
One hundred sixty-nine participants (89 children and 80 adults) with TRE received plant-derived highly purified CBD (Epidiolex® in the U.S.; 100â¯mg/mL oral solution) with a starting dose of 5â¯mg/kg/day divided twice per day and titrated to a maximum dose of 50â¯mg/kg/day over the study period to seizure control and tolerability and followed for up to 2â¯years. Seizure frequency (calendars) and severity (Chalfont Seizure Severity Score; CSSS) were collected at every study visit. Adverse Events were reported at/between study visits as required, and participants also completed Adverse Events Profile (AEP) which generates a numerical representation of AEs. Response to CBD was defined as ≥50% reduction in seizure frequency. Given non-normal distribution of seizure frequency, a log transformation was applied after which the generalized least squares regression model for longitudinal data was used.RESULTS:
Evidence from the adjusted model revealed a significant mean reduction in seizure frequency compared to baseline in children and adults at all time points (1â¯month and 1 and 2â¯years). Percentage of children achieving ≥50% seizure frequency reduction was 44% at month 1, and 41% at year 1, and 61% reduction at year 2, while adult responder rates were 34% at month 1, 53% at year 1, and 71% at year 2 (all Pâ¯<â¯0.0001). CSSS showed a sustained reduction from baseline to all 3 time points. Children displayed 52% seizure reduction at month 1, a 51% reduction at year 1, and 75% reduction at year 2. Seizure reductions in adults were 60%, 81%, and 85%, respectively (all Pâ¯<â¯0.0001). While there were no significant differences between seizure frequency reduction between children and adults at all time points, there was a significant difference in seizure severity reduction at year 1, with adults reporting greater improvement in seizure severity (Pâ¯<â¯0.001). The most commonly reported adverse events in the study period were diarrhea, sedation, and decreased appetite. AEP revealed significant improvement from baseline at multiple time points in adults and children, and the mean AEP scores were always lower compared to baseline over the duration of the study.SIGNIFICANCE:
Our study provides further evidence of sustained seizure frequency and severity reduction over two years of treatment with highly purified CBD in TRE. In addition, CBD was generally well tolerated with minority of participants experiencing adverse events resulting in stopping CBD.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cannabidiol
/
Epilepsy
/
Drug Resistant Epilepsy
Type of study:
Prognostic_studies
Limits:
Adult
/
Child
/
Humans
Language:
En
Journal:
Epilepsy Behav
Journal subject:
CIENCIAS DO COMPORTAMENTO
/
NEUROLOGIA
Year:
2021
Document type:
Article