By Marilynn Larkin
NEW YORK (Reuters Health) - Children with Dravet and Lennox-Gastaut syndrome may experience seizure relief from cannabidiol, and those with other forms of drug-resistant epilepsy might benefit, too, according to findings of a systematic review.
"Despite centuries of cannabis use for medicinal purposes, there have been relatively few clinical studies of its effectiveness and safety, especially among children," Jesse Elliott of the University of Ottawa said in an email to Reuters Health. "Our pooled analysis of studies involving children with severe forms of drug-resistant epilepsy suggests that cannabidiol is effective in reducing seizures in this group of children, with few serious side effects."
However, she added, "Most studies had a relatively short treatment duration, and we do not know whether these effects are maintained over a longer time."
Four randomized controlled trials (RCTs) and 19 nonrandomized studies involving children with epilepsy, primarily treated with cannabidiol, were included in the review. All RCTs were at low risk of bias.
The four RCTs included 550 participants with either Dravet or Lennox-Gastaut syndrome randomized to placebo or oral cannabidiol (5-20 mg/kg/d) for up to 14 weeks. The mean age in each study was between seven and 16 years, with about an equal number of male and female children taking multiple anti-epileptic drugs at baseline. The baseline frequency of total seizures varied across RCTs.
Of the nonrandomized studies, two were comparative cohort studies, 12 were single-arm cohort studies, four were cross-sectional surveys and one was a case series. Overall, they involved 1,115 patients with variable baseline seizure frequency and treatment duration.
As reported online December 4 in Epilepsia, among the RCTs, there was no statistically significant difference between cannabidiol and placebo in freedom from seizures, quality of life, sleep disruption or vomiting.
There was, however, a statistically significant reduction in median frequency of monthly seizures with cannabidiol versus placebo (−19.8% to −12.6%), as well as an increase in the number of participants with at least a 50% reduction in seizures (RR, 1.76) and diarrhea (RR, 2.25). Death and status epilepticus were infrequent.
Among the nonrandomized studies, the reduction in total seizures with use of a cannabis‐based product ranged from 30% to 90% (duration: 8 weeks to >16 months; very low certainty of evidence).
Elliott noted, "At this time, all of the evidence from RCTs is specific to cannabidiol in children with Dravet and Lennox-Gastaut syndrome, and the findings should not be extended to other cannabis-based products or preparations. Additional research is needed into the effects of cannabis-based products in different epilepsy syndromes."
Study coauthor Alexander Repetski, director of communications at a licensed cannabis producer and parent of a child with epilepsy, commented in the same email that while he's seen "enormous benefit" in his daughter's seizure control and quality of life during four years of treatment with cannabis oil, "we have only uncovered the tip of the iceberg and much more research is needed."
Dr. Orrin Devinsky, Director of NYU Langone Health's Comprehensive Epilepsy Center in New York City, commented, "The findings... mirror our experience leading several of these trials and open-label studies looking at cannabidiol for...Lennox-Gastaut syndrome and Dravet syndrome. Our research, which was included in this review, demonstrated that cannabidiol can reduce seizure burden in these conditions."
That said, "clinicians and the lay public should be aware cannabidiol is a drug and has side effects," he noted. "There is often a misperception that since these medications are derived from a natural plant, that they are completely safe. But our trials reported increases in tiredness, vomiting, diarrhea, fever, decreased appetite, and upper respiratory infection, and some patients developed elevated liver enzymes. In some cases, side effects led patents to withdraw from the study."
"One concern around consumer cannabidiol products found in smoke shops, stores and dispensaries is that the quality standards are either not regulated or regulated to variable degrees, and it's not a certainty that a patient (is) getting purified cannabidiol," he added.
"FDA approval of a cannabidiol medication this June (http://bit.ly/2rxEzdY) represented the first time the government had approved a compound derived from the cannabis plant to treat any disorder, and this approval enables patients to access consistent cannabidiol doses made to the highest quality standards," Dr. Devinsky concluded.
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