1. Seizures associated with tuberous sclerosis complex (TSC) were reduced by 30% with add-on cannabidiol treatment compared to placebo.
2. Oral cannabidiol at 25 mg/kg/day and 50 mg/kg/day were equally efficacious, although the lower dosage resulted in fewer adverse events.
Evidence Rating Level: 1 (Excellent)
Study rundown: Tuberous sclerosis complex (TSC) is a genetic condition with an incidence of 1 in 6000 live births: It involves excess cell growth and proliferation in numerous organ systems, with epilepsy affecting 85% of TSC patients. TSC-associated seizures often start in infancy, and include focal seizures and infantile spasms. However, more than 60% have epilepsy that is drug and treatment-resistant. Despite other epileptic conditions such as Lennox-Gastaut and Dravet syndromes having sufficient evidence showing the efficacy of cannabidiol, there has been a paucity of research investigating its efficacy for TSC. To address this, this double-blind, randomized, placebo-controlled trial investigated cannabidiol’s efficacy in reducing TSC-associated seizures over 16 weeks. The study population included 224 patients from Europe and the United States, randomized into three groups: Placebo, oral cannabidiol 25 mg/kg/day (CBD25), and oral cannabidiol 50 mg/kg/day (CBD50). The results found a 27% reduction in seizures for placebo, 49% reduction for the lower cannabidiol dosage, and 48% reduction for the higher dosage, demonstrating similar efficacy but a lesser prevalence of adverse events in the lower dosage group. Despite the promising findings however, the generalizability of the findings may be limited by the fact that the study had a limited age range in the study population, where 70% of participants were under the age of 17. Nonetheless, study findings are promising for cannabidiol for reduction of seizures for TSC, and should warrant further validation for the purpose of potentially finding a new therapeutic agent for the condition.
In-Depth [randomized controlled trial]: The study population consisted of patients aged 1-65 years with a diagnosis of TSC and epilepsy that was medication-resistant. There were 224 participants: 41.5% were female, the median age was 11.4 years, and the age range was 1.1-56.8 years. 76 were in the placebo group, 75 in CBD25, and 73 in CBD50. In the CBD groups, participants began with a dose of 5 mg/kg/day, reaching 25 mg/kg on the 9th day and 50 mg/kg on the 29th day. The primary outcome was the reduction in TSC-associated seizures compared to baseline. The results showed that the CBD25 and CBD50 groups had significantly higher rates of seizure reduction compared to placebo. CBD25 had a 30.1% reduction from placebo (95% CI 13.9-43.3%, p < 0.001) and CBD50 had a 28.5% reduction from placebo (95% CI 11.9-42.0%, nominal p = 0.002). Furthermore, the percentage of patients with a 50% or greater reduction in seizures was 36% in CBD25, 40% in CBD50, and 22% in the placebo. Adverse events were reported by nearly all patients in the study, with 93% in CBD25, 100% in CBD50, and 95% in placebo, although 88% of events were mild to moderate. The most common adverse events in the CBD groups were diarrhea and somnolence. Serious adverse events were reported in 21% of CBD25 patients, 14% of CBD50 patients, and 3% of placebo patients, with elevations of liver enzyme levels as the most frequent serious event. Overall, this study demonstrated the efficacy of add-on cannabidiol treatment: This has implications for informing clinical guidelines on patients with TSC-associated medication-resistant seizures, and further adds to the growing list of medical conditions that can be benefitted from cannabinoid treatments.
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