New findings from the phase 3/4 EpiCom study (NCT05864846) indicate that cannabidiol (CBD; Epidiolex; Jazz Pharmaceuticals) may offer benefits for neuropsychiatric disorders associated with tuberous sclerosis complex (TSC), a rare genetic condition often linked to epilepsy. The study, presented at the 2024 American Epilepsy Society (AES) Annual Meeting, evaluated the impact of CBD on psychiatric and behavioral issues in TSC patients.
The trial included participants aged 1-65 with TSC who experienced moderate to severe behavioral changes. These individuals received CBD (100 mg/mL oral solution) at doses up to 25 mg/kg/day, adjusted for response and tolerability, alongside standard of care (SOC) for 26 weeks. Following this, participants could continue CBD with SOC or SOC alone for up to 52 weeks.
TSC-associated neuropsychiatric disorders (TAND) were assessed using the TAND Self-Report Quantified Checklist (TAND-SQ) and Aberrant Behavior Checklist (ABC) at week 13, along with Caregiver Global Impression of Severity (CareGI-S) and Clinician Global Impression of Severity (CGI-S) scales at weeks 4 and 13. The study initially enrolled 24 patients, with 19 starting CBD treatment and 5 completing assessments within the initial 13-week period.
According to Dr. Agnies van Eeghen, an intellectual disability physician at Amsterdam University Medical Center and lead investigator, patients completing the 13-week trial showed a notable change of –4.6 (95% CI, –8.1 to –1.1) in the most problematic behavior (MPB) numerical rating scale (NRS) after CBD treatment. Among the 7 TAND-SQ clusters, the most significant changes were observed in dysregulated behavior (change, –3.5; 95% CI, –6.5 to –0.5) and overactive/impulsive scores (change, –2.9; 95% CI, –7.1 to 1.3).
Baseline data indicated a mean MPB numerical NRS value of 8.8 (SD, 1.01), with mood swings (24%) and aggressive outbursts (18%) being the most common manifestations. Additionally, 47% of participants experienced seizures, averaging 4 per 28 days, and were using a median of 3 antiseizure medications, including lamotrigine, topiramate, and everolimus.
Efficacy results from the ABC at week 13 showed the greatest changes related to irritability (change, –12.2; 95% CI, –22.3 to –2.1) and hyperactive noncompliance (–11.0; 95% CI, –25.1 to 3.1). Caregivers and clinicians also rated behavioral problems as less severe at weeks 4 and 13 on the CareGI-S and CGI-S scales.
CBD, which received FDA approval for TSC in 2020, demonstrated a consistent safety profile in this analysis. Adverse events (AEs) occurred in 12 of 19 (63%) participants, including diarrhea (42%), vomiting (11%), decreased appetite (11%), and lethargy (11%). Four patients discontinued the study due to AEs such as diarrhea, hypersomnia, increased transaminase, and rash.
Epidiolex was initially approved in June 2018 for treating seizures associated with Lennox-Gastaut syndrome and Dravet syndrome. Its indication was later expanded to include TSC, covering patients aged 1 and older. The efficacy of CBD in TSC was previously confirmed in the phase 3 GWPCARE6 trial (NCT02544763), a randomized, double-blind, placebo-controlled study involving 224 patients with drug-resistant seizures.
