Cannabidiol significantly reduces Tuberous sclerosis seizures, in lower doses;JAMA Neurology

Cannabidiol is approved as Epidiolex in the US for treatment of seizures associated with several syndromes. Efficacy of cannabidiol was first demonstrated against Dravet syndrome–associated and Lennox-Gastaut syndrome–associated seizures.

In a recently published study in JAMA Neurology, Cannabidiol significantly reduced Tuberous sclerosis (TSC-associated) seizures compared with placebo. Dosages of 25 mg/kg/day led to fewer adverse events than the 50-mg/kg/day, though both cannabidiol dosages were equally efficacious , reported the researchers.

On the basis of data from patients with TSC in an expanded-access program, a research team under Elizabeth A. Thiele,from the Pediatric Epilepsy Program, Massachusetts General Hospital, Boston ,conducted a placebo-controlled randomized clinical trial to assess efficacy and safety of add-on cannabidiol for the treatment of TSC-associated seizures (primarily focal seizures) in children and adults.

This was a phase 3, international, double-blind, parallel-group randomized clinical trial of add-on cannabidiol vs placebo in patients with TSC and drug-resistant epilepsy. The trial consisted of a 4-week baseline period, a 16-week treatment period (4 weeks for dose escalation [titration period] followed by 12 weeks of stable dosing [maintenance period]), a taper period of up to 10 days, and a 4-week safety follow-up.

Eligible patients (aged 1-65 years) with a definite clinical diagnosis of TSC¹ and medication-resistant epilepsy had at least 8 TSC-associated seizures during the 4-week baseline period with at least 1 seizure occurring in at least 3 of the 4 weeks and were taking at least 1 antiepileptic medication. The prespecified primary outcome was the change from baseline in number of TSC-associated seizures for cannabidiol vs placebo during the treatment period.

Data analysis revealed the following facts.

• Of 255 patients screened for eligibility, 31 were excluded and 224 were randomized. Of the 224 included patients (median [range] age, 11.4 [1.1-56.8] years; 93 female patients [41.5%]), 75 were randomized to CBD25, 73 to CBD50, and 76 to placebo, with 201 completing treatment.
• The percentage reduction from baseline in the type of seizures considered the primary end point was 48.6% (95% CI, 40.4%-55.8%) for the CBD25 group, 47.5% (95% CI, 39.0%-54.8%) for the CBD50 group, and 26.5% (95% CI, 14.9%-36.5%) for the placebo group; the percentage reduction from placebo was 30.1% (95% CI, 13.9%-43.3%; P < .001) for the CBD25 group and 28.5% (95% CI, 11.9%-42.0%; nominal P = .002) for the CBD50 group.
• The most common adverse events were diarrhea (placebo group, 19 [25%]; CBD25 group, 23 [31%]; CBD50 group, 41 [56%]) and somnolence (placebo group, 7 [9%]; CBD25 group, 10 [13%]; CBD50 group, 19 [26%]), which occurred more frequently with cannabidiol than placebo.
• Eight patients in CBD25 group, 10 in CBD50 group, and 2 in the placebo group discontinued treatment because of adverse events.
• Twenty-eight patients taking cannabidiol (18.9%) had elevated liver transaminase levels vs none taking placebo.

In patients with tuberous sclerosis complex (TSC), add-on cannabidiol reduces drug-resistant seizures compared with add-on placebo and has a good safety profile,the team concluded.

For the full article follow the link: Thiele EA, Bebin EM, Bhathal H, et al. Add-On Cannabidiol Treatment for Drug-Resistant Seizures in Tuberous Sclerosis Complex: A Placebo-Controlled Randomized Clinical Trial. JAMA Neurol Thiele EA, Bebin EM, Bhathal H, et al. Add-On Cannabidiol Treatment for Drug-Resistant Seizures in Tuberous Sclerosis Complex: A Placebo-Controlled Randomized Clinical Trial. JAMA Neurol. Published online December 21, 2020. doi:10.1001/jamaneurol.2020.4607. Published online December 21, 2020. doi:10.1001/jamaneurol.2020.4607

Primary source:JAMA Neurology