Long-term Efficacy of Cannabidiol in Children With Epilepsy

In a single center, open-label prospective study,³ there were 26 participants refractory to treatment despite an average of two AEDs:

•Mean age 9 years, 50% female•23% with Dravet syndrome•15% with Lennox-Gastaut syndrome

Add-on CBD was titrated to target of 25 mg/kg/day. Lab tests/clinical assessments were taken at regular intervals. Daily seizure frequency was recorded using patient diaries. Mean CBD duration: 21 months.

Results: 57.7% (n=15) discontinued CBD for lack of efficacy

•Most discontinued within first six months

At two years, only 34.6% (n=9) were still on CBD

>50% reduction in motor seizures (primary efficacy outcome):

•Sustained by 26.9% (n=7) over 2-4 years•11.5% (n=3) became seizure free

Adverse events were common: 80.8% (n=21) 

Most common:

• Decreased appetite: 38.4% (n=10)

• Diarrhea: 34.6% (n=9)

• Weight loss: 30.7% (n=8)

Serious adverse events in 23.1% (n=6)

• Status epilepticus: 21% (n=3)

• Catatonia: 7% (n=2)

• Hypoalbuminemia: 4% (n=1)

Clinically significant weight loss in 30.7% (n=8)

Which patients are more likely to respond to CBD?

• Generalized seizures appear to respond better than focal or epileptic spasms

• Best response with concomitant benzodiazepines and/or topiramate

• Further study needed

Adverse events with CBD very common

• Providers should be aware of rare treatment emergent status epilepticus

26.9% of children with treatment refractory epilepsy sustained treatment response to CBD over four years

• Most discontinued CBD due to lack of efficacy

80.8% experienced adverse events

• Providers should be aware of rare treatment emergent status epileptics with CBD

Determinants of response to CBD need further study

1. US Food and Drug Administration. FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm611046.htm. Accessed January 4, 2018.

2. Szaflarski JP, Bebin EM, Comi AM, et al. Long-term safety and treatment effects of cannabidiol in children and adults with treatment-resistant epilepsies: Expanded access program results. Epilepsia. 2018;59:1540-1548.

3. Sands TT, Rahdari S, Oldham MS, et al. Long-Term Safety, Tolerability, and Efficacy of Cannabidiol in Children with Refractory Epilepsy: Results from an Expanded Access Program in the US. CNS Drugs. 2018 Nov 20 [Epub ahead of print].