Cannabinoids May Be Effective as Adjunctive Treatment for Refractory Epilepsy
Minor adverse events are likely with the use of cannabidiol for the treatment of refractory epilepsy.
A reasonable proportion of patients with epilepsy who have received treatment with pharmaceutical-grade cannabidiol (CBD) products along with antiepileptic drugs have experienced a decrease in seizure frequency, despite the likely occurrence of minor adverse events (AEs), according to the results of a systematic review of controlled and observational evidence published in the Journal of Neurology, Neurosurgery, and Psychiatry.
The primary study outcome was the proportion of patients who experienced a ≥50% reduction in seizure frequency. Secondary outcomes included the proportion of patients who attained complete seizure freedom, quality-of-life indicators (eg, changes in mood, behavior, sleep, attention, and speech, and cognitive, social, and motor skills), and study withdrawal (because of AEs and serious AEs [SAEs]). Of the studies analyzed, a total of 36 were identified — 6 randomized, controlled trials and 30 observational studies. Mean age of the participants was 16.1 years (range, 0.5-55 years).
In 2 of the randomized, controlled trials, treatment with CBD 50 mg/day was more effective than placebo in generating a >50% reduction in seizure frequency (relative risk [RR] 1.74; 95% CI, 1.24-2.43). The 2 randomized, controlled trials included a total of 291 patients, with a low Grades of Recommendation, Assessment, Development and Evaluation (GRADE) rating. The investigators estimated that the number needed to treat for 1 person using CBD to achieve a 50% reduction in seizure frequency was 8 (95% CI, 6-17).
In 3 randomized, controlled trials with a total of 306 patients, CBD was more effective than placebo in attaining complete seizure freedom (RR 6.17; 95% CI, 1.50-25.32; low GRADE rating) and improving quality of life (RR 1.73; 95% CI, 1.33-2.66). An increased risk for AEs and SAEs, however, was reported in these patients (RR 1.24; 95% CI, 1.13-1.36 and RR 2.55; 95% CI, 1.48-4.38, respectively).
Overall, an estimated 48.5% of the 970 patients enrolled in 17 observational studies achieved a ≥50% reduction in seizures with CBD therapy (95% CI, 39.0%-58.1%; mean age, 8.8 years [range, 6 months-46 years]; low GRADE rating). In 14 observational studies, 8.5% (95% CI, 3.8%-14.5%) of patients were seizure free. Moreover, in 12 observational studies (n=440; mean age, 12.7 years [range, 6 months-50 years]), 55.8% (95% CI, 40.5-70.6) of patients reported improved quality of life, 50.6% (95% CI, 31.7-69.4) reported AEs, and 2.2% (95% CI, 0.0-7.9) reported SAEs with CBD treatment.
The investigators concluded that pharmaceutical-grade CBD used as adjunctive therapy in patients with pediatric-onset drug-resistant epilepsy may reduce the frequency of seizures. Because the existing evidence from randomized, controlled trials is primarily in pediatric samples with rare and severe forms of epilepsy, randomized, controlled trials designed to examine the use of CBD in other syndromes is warranted.
Stockings E, Zagic D, Campbell G, et al. Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence [published online March 6, 2018]. J Neurol Neurosurg Psychiatry. doi:10.1136/jnnp-2017-317168