Cannabidiol Cuts Seizure Severity, Frequency in Resistant Epilepsy

Damian McNamara

April 24, 2018

LOS ANGELES — One of the main components of cannabis, cannabidiol, decreased seizure frequency by 50% to 60% in children and adults with treatment-refractory epilepsy.

Among the 70 children and 62 adults assessed at 12 weeks, biweekly seizure frequency significantly decreased from a mean of 144 at baseline to 52 (P < .001). The seizure control remained stable over time, with a mean of 67 seizures reported at 24 weeks and 47 seizures at 48 weeks. The differences between 12-, 24- and 48-week rates were not significant.

"Pharmaceutical-grade cannabidiol improves seizure frequency in children and adults, and also decreases their severity," Jerzy P Szaflarski, MD, PhD, professor and director of the UAB Epilepsy Center in Birmingham, Alabama, told Medscape Medical News.

"There was a dramatic seizure decrease in children, driven mainly by the patients with very high seizure frequencies," he added.

"We already know there is anecdotal evidence of cannabis efficacy in epilepsy, whether it's a purified product like cannabidiol or a plant extract," Szaflarski said during a poster discussion session here at the American Academy of Neurology (AAN) 2018 Annual Meeting. There are also three randomized controlled studies evaluating cannabidiol (Epidiolex, GW Pharmaceuticals), some of which are ongoing.

In addition, as reported by Medscape Medical News, an FDA Advisory Panel recently unanimously recommended Epidiolex for severe epilepsy.

The goal of the current, compassionate-use study was to look more at safety and adverse events than efficacy, "but I will address all three of them."

Severe Seizures

The mean baseline seizure severity was 80.7 points on the Chalfont Seizure Severity Scale (CSSS). "Eighty is a very high number," he said.

Scores at study entry were similar between pediatric (a mean of 78 points) and adult (84 points) patients.

At 12 weeks, seizure severity decreased to a mean 39 on the CSSS, a significant difference compared with baseline (P < .001). The mean seizure severity was 41 at 24 weeks and 35 at 48 weeks. Again, results at different assessments during the study were not statistically significant.

Patients had video-electroencephalography–proven epilepsy, had failure of at least four antiepileptic drugs (AEDs), and experienced at least four seizures per month. Patients were titrated to tolerability and seizure control. At 12 weeks, doses were about the same for the pediatric and adult groups up until 12 weeks, after which investigators continued to titrate adults more than they did with children.

Cannabidiol was generally well tolerated, with a "relatively low overall" side effect profile. "Some patients discontinued, mainly from lack of efficacy; in very few cases was it because of side effects," Szaflarski said.

The number of AEDs did not change significantly during the study, but investigators weaned some patients taking clobazam and valproic acid off those two medications because of interactions.

Pediatric patients tended to experience generalized seizures, whereas adults reported mainly partial or focal-onset seizures, "which may explain some of the differences we see." The accuracy of seizure counts in diaries prepared by patients and families was another potential limitation.

Additional details on the study, including information for referring neurologists, are available from the UAB Cannabidiol Program site.

Going forward, Szaflarski would like to determine whether cannabidiol, in combination with other cannabinoids such as tetrahydrocannabinol, is more efficacious than cannabidiol alone. He also would like to assess other cannabinoids that might have efficacy in seizure control. "We need to determine the effects of cannabidiol on the central nervous system, neuroimaging, cognition [and more]," he added.

"Important Study"

Commenting on the findings for Medscape Medical News, Gregory D Cascino, MD, Whitney MacMillion Jr professor of neuroscience at the Mayo Clinic College of Medicine, enterprise director of epilepsy for the Mayo Clinic (both in Rochester, Minnesota), and a fellow of the AAN, said it is "an important study."

"They looked at a composition of patients like those that we see in the real clinical practice setting — adults and pediatric patients. They also had patients who were refractory to four or more antiepileptic drugs, so [the patients] clearly had drug-resistant epilepsy," he said

"This is a well-done, open-label study," Cascino added. "What I found was helpful is there was benefit at 12 weeks, a sustained benefit as they followed patients out several months.

"As with many of the drug investigation studies, there was a moderate reduction in seizure tendency. It certainly compares very favorably to patients who are enrolled in adjunctive antiepileptic drug trials."

The State of Alabama funded the study. GW Pharmaceuticals provided cannabidiol for the study. Szaflarski has disclosed no relevant financial relationships. Dr Cascino is a co-investigator on studies performed by GW Pharmaceuticals but had no relevant financial disclosures.

American Academy of Neurology (AAN) 2018 Annual Meeting. Abstract PD030. Presented April 22, 2018.

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