Drug-resistant epilepsy (inadequate response to two or more trials of appropriate antiepileptic drugs [1]) affects between 28% and 37% of people with epilepsy [2] and can have profound consequences for affected children and their families, with affected children at increased risk of severe morbidity (e.g., cognitive delay, behavioral problems, autism) and mortality [3]. Pediatric epilepsy is associated with increased contacts with the healthcare system, including neurologist visits, visits to the emergency department, and admissions to hospitals [4, 5], and children with uncontrolled seizures use more health resources than children with controlled seizures, with costs correlated with epilepsy severity [4, 6]. Taken together, resource use by children with epilepsy contributes major costs to the healthcare system [6, 7].

Drug-resistant epilepsy comprises multiple types of pediatric epilepsies, frequently with underlying genetic causes (e.g., Dravet syndrome, Lennox-Gastaut syndrome, West syndrome) [3]. Pediatric epilepsy may also be caused by structural or metabolic (e.g., structural abnormality or chronic metabolic condition) or unknown causes [3]. Because of this variation, and variation in seizure types, there is no standard of care for treatment of pediatric drug-resistant epilepsy, with treatment dependent on the nature of a child’s individual disease, which drugs are available in a given jurisdiction, and local practice [8]. Individual antiepileptic drugs may benefit only small groups of patients because of the rare nature of some epilepsy syndromes, and some antiepileptic drugs have designated orphan drug status (e.g., stiripentol for Dravet syndrome [9]). In addition to pharmacologic treatments (i.e., antiepileptic drugs), other treatment options include non-pharmacologic interventions (e.g., surgery to resect the seizure focus, vagus nerve stimulation, deep brain stimulation therapy, ketogenic diet therapy) [3], with increasing interest in the use of alternative therapies, including cannabinoids [10, 11].

Interest in the use of cannabis for the treatment of pediatric epilepsy has increased over the last decade, with recent clinical studies suggesting that cannabidiol, one of two main cannabinoids in cannabis, reduces seizure burden in some epilepsy syndromes [12, 13]. The first pharmaceutical-grade cannabidiol product intended to treat Dravet syndrome and Lennox-Gastaut syndrome was recently approved by the US Food and Drug Administration [14], and it is expected that public payers will soon be faced with decisions as to whether to include such products on their formularies. Economic evaluations can provide important information to decision-makers as they make such reimbursement and funding decisions [15]. As such, the objective of this systematic review is to provide a comprehensive overview of the cost-effectiveness of cannabis-based treatments for pediatric drug-resistant epilepsy and to search for inputs for a de novo cost-utility analysis to address this decision problem in the Canadian context.