Efficacy and safety of cannabidiol as add-on therapy in drug-resistant epilepsy, a single center experience

Abstract

Objective: To assess efficacy and side effects of cannabidiol (CBD) as add-on therapy in children with drug resistant complex epilepsy. Methods: In an open label add-on compassionate use program oral CBD (Epidiolex, GW Pharma) was given as follows: 2 mg/kg/day in two divided doses, increased to 16 mg/kg/day by 2 mg/kg/week over 8 weeks, further up-titration as tolerated individually. Full blood count, electrolytes, renal and liver function were monitored every two weeks. Seizure frequency, added benefits and tolerability were assessed by weekly telephone calls and a parent questionnaire. Results: Between December 2014 and June 2016 24 children aged 2–19 (mean 10) years were enrolled who had previously failed 3–11 antiepileptic drugs. Etiologies were structural (7), genetic (5), metabolic (1), inflammatory (3) and unknown (8). One patient was excluded, who only received 5 days of CBD add-on treatment as part of his acute treatment for ultimately fatal refractory status epilepticus (presumed FIRES). Eleven (47.8%) of the remaining 23 patients reported >50% seizure reduction. Twelve (52.1%) patients reported clinical side effects, namely diarrhea (n=5, 21.7%), somnolence (n=5, 21.7%), loss of appetite (n=2, 8.7%), weight loss (n=1, 4.3%), behavior deterioration (n=3, 13%) and respiratory depression due to increased clobazam levels (n=1, 4.3%). Of 21 patients 14 (67%) reported added benefits in form of increased alertness (n=11, 52%), better sleep (n=2, 9.5%) and better mood (n=6, 28.6%). Transaminases increased in 4 patients (17.4%), transiently in three, but leading to CBD discontinuation in one. One patient died of pneumonia unrelated to the drug. Treatment was discontinued in 11 patients (47.8%) after 1–19 months due to lack of efficacy (n=6, 26%) and side effects (n=5, 21.7%). Conclusion: 47.8% of patients reported an >50% reduction in seizures on CBD with the medication being reasonably well tolerated in this challenging patient cohort. Study limitations are the open label design and absence of a control cohort.