Reem Gebrekidan, Mercer University College of Pharmacy
Dravet Syndrome is a genetic epileptic encephalopathy beginning in infancy that is characterized by febrile, prolonged, and lateralized seizures. Epilepsy guidelines consider sodium valproate or topiramate as first-line treatment in children with Dravet syndrome while clobazam or stiripentol are supported as adjunctive therapy. Medications such as carbamazepine, gabapentin, lamotrigine, oxcarbazepine, phenytoin, pregabalin, tiagabine or vigabatrin were advised to be avoided. 
The U.S. Food and Drug Administration (FDA) has approved two synthetic cannabinoids based on a substance present in marijuana and a substance acting similarly to another compound in marijuana. Attempting to use components of marijuana is considered to be in the public’s best interest; however, safe and effective use has not been determined. 
|Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome |
|Design||Multinational, randomized, double-blind, placebo-controlled; N= 120|
|Objective||To assess the efficacy of cannabidiol for drug-resistant epilepsy in the Dravet syndrome|
|Study Groups||Cannabidiol (n = 61); placebo (n = 59)|
|Methods||Patients were eligible if they had Dravet syndrome, were taking one or more antiepileptic drugs, and had had four or more convulsive seizures during the 28-day baseline period. Patients received cannabidiol 100 mg/mL oral solution or placebo solution twice daily. The dose was escalated up to 20 mg/kg/day (or the equivalent volume of placebo) with a 14-day dosing regimen.
Caregiver Global Impression of Change (CGIC) score went from 0 (no change) to 7 (very much improved). Patients or their caregivers recorded the number and type of convulsive seizures. Percentage of convulsive-seizure frequency was analyzed every 4 weeks from baseline.
|Duration||18 weeks (14 weeks treatment, 4 weeks baseline)|
|Primary Outcome Measure||Percentage change of convulsive-seizure frequency|
|Secondary Outcome Measure||CGIC scale, reduction in total seizure frequency, reduction in nonconvulsive seizures, duration of seizure subtypes|
|Adverse Events||Common Adverse Events (cannabidiol, %): diarrhea (31), vomiting (15), fatigue (20), pyrexia (15), upper respiratory tract infection (11), decreased appetite (28), somnolence (36), lethargy (13), convulsion (11)|
|Serious Adverse Events (cannabidiol, n): any (10), status epilepticus (3), elevated liver aminotransferase enzymes (3)|
|Percentage that Discontinued due to Adverse Events: 3.33%|
|Study Author Conclusions||Cannabidiol reduced the frequency of convulsive seizures among children and young adults with Dravet syndrome over a 14-week period but was associated with adverse events including somnolence and elevation of liver-enzyme levels.|
End points, convulsive-seizure frequency and CGIC score, were subjective in nature and the degree of clinical improvement may have varied between providers. The ineffectiveness for nonconvulsive seizure suggests the antiepileptic effect of cannabidiol might be specific to convulsive seizures. Side effects such as elevated liver enzymes led to discontinuation of treatment which could limit its application.The duration of treatment was short, thus long term efficacy and safety of the drug cannot be concluded.
 Dravet-syndrome: what is Dravet-Syndrome. Available at: http://www.epilepsy.com/learn/types-epilepsy-syndromes/dravet-syndrome. Accessed June 2, 2017.
 The epilepsies: the diagnosis and management of the epilepsies in adults and children in primary and secondary care. National Institute for Health and Care Excellence (NICE); 2016 feburary. 111p. (clinical guideline cg137).
 Public health: FDA and Marijuana.Food and Drug Administration Web site. http://www.fda.gov/cder/approval/index.htm. Accessed June 2, 2017.
 Devinsky O, Cross JH, Laux L, et al. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med. 2017;376(21):2011-2020.