Formulation of purified cannabidiol (CBD) may offer patients with tuberous sclerosis complex (TSC) a new treatment option for seizures, according to study results presented at the American Epilepsy Society 2019 Annual Meeting.
A purified oral solution form of CBD that contains only trace amounts of tetrahydrocannabinol, was recently approved by the Food and Drug Administration for the treatment of Dravet syndrome and Lennox-Gastaut syndrome, which are also associated with resistant epilepsy. As many patients with TSC struggle with therapy-resistant epilepsy, the goal of the current study was to assess the efficacy and safety of adjunctive CBD in this population.
The randomized, double-blind, controlled trial included patients with TSC treated at 46 sites in 6 countries. All patients were diagnosed with TSC-associated focal and generalized seizures and had previously tried and discontinued a median of 4 anti-epileptic drugs. The participants were randomized to receive CBD at 25 mg/kg/day (CBD25), 50 mg/kg/day (CBD50), or placebo for 16 weeks.
The primary outcome was percent change from baseline in TSC-associated seizure frequency for CBD, compared to placebo.
The study included 224 participants (median age 11 years): 75 treated with CBD25, 73 treated with CBD50 and 76 treated with placebo. The subjects were actively treated with a median of 3 anti-epileptic drugs, most commonly valproate (45%), vigabatrin (33%), levetiracetam (29%), and clobazam (27%).
Treatment with CBD was associated with a significantly greater decrease in TSC-related seizures, compared to placebo: 49% for CBD25 (P =.0009), 48% for CBD50 (P =.0018), compared to 27% decrease for placebo. A higher rate of participants treated with CBD had a 50% reduction in seizure frequency, compared to placebo: 36% for CBD25 and 40% for CBD50, compared to 22% for placebo.
Treatment with CBD was also associated with a significantly greater reduction in total seizure frequency, compared to placebo: 48% for CBD25 (P =.0013) and 48% for CBD50 (P =.0018), compared to 27% for placebo.
Caregivers reported an overall improvement in 69% of those treated with CBD25 (odds ratio [OR], 2.25; P =.0074), 62% of those taking CBD50mg (OR, 1.77; P =.0074) and 40% of those who had the placebo.
Adverse events were very common and documented in 93% of patients treated with CBD25, 100% of those treated with CBD50 and 95% of those in the placebo group. The common adverse events were diarrhea (31% of patients treated with CBD25; 56% of those treated with CBD50; 25% of those in the placebo group), decreased appetite (20%, 23%, 12%, respectively) and somnolence (13%, 26%, 9%, respectively).
Treatment discontinuation due to an adverse event was more common with CBD25 (8 patients) or CBD50 (10 patients), compared to placebo (2 patients).
Elizabeth Thiele, MD, PhD, senior author of the study, director of pediatric epilepsy and director of the Herscot Center for Tuberous Sclerosis Complex at Massachusetts General Hospital, and professor of neurology at Harvard Medical School, Boston concluded that these findings suggest “lower dose of 25 mg/kg (of weight) provides the same benefit with fewer side effects compared to a dose of 50 mg/kg and will likely be the recommended dose.” Dr Thiele also notes that “our findings suggest this formulation of purified CBD offers patients with TSC a new treatment option for their very difficult-to-manage seizures.”
Thiele E, Wong M. Cannabidiol (CBD) treatment in patients with seizures associated with tuberous sclerosis complex: A randomized, double-blind, placebo-controlled phase 3 trial (GWPCARE6). Presented at The American Epilepsy Society 2019 Annual Meeting; December 6-10, 2019; Baltimore, MD. Abstract 1.293.