Even 31% Seizure Reduction with CBD Was Clinically Meaningful for Lennox-Gastaut Patients | Research

The takeaway

Post hoc analysis of two phase 3 trials found that a 31% reduction in drop seizures (not the traditional 50%) was the threshold for clinically meaningful improvement as rated by caregivers.

pediatric neurologists, epilepsy treatment teams, caregivers of LGS patients, insurance coverage decision-makers

What the researchers found

Using CGIC of 'slightly improved' or better, the threshold for clinically meaningful drop seizure reduction was 30.6%, with 57.7% of patients meeting this threshold. With 'much improved' or better, the threshold was 49.6% (40.5% of patients). 60% of CBD-treated patients were rated as 'slightly improved' or better, and 31% as 'much improved' or better after 14 weeks. Spearman's correlation between CGIC and seizure reduction was 0.47.

Why it matters

Clinical trials typically use 50% seizure reduction as the success cutoff, but this analysis shows that caregivers perceived meaningful benefit at much smaller reductions (31%), suggesting the 50% threshold may undercount patients who genuinely benefit from treatment.

The numbers in context

215 patients with LGS. 60% rated 'slightly improved' or better. 31% rated 'much improved' or better. Clinically meaningful threshold: 30.6% reduction (57.7% met it). 'Much improved' threshold: 49.6% (40.5% met it). Mean seizure reduction for 'slightly improved+': 46.9%. Spearman's correlation: 0.47.

How the study worked

Post hoc analysis of 215 LGS patients receiving CBD (Epidiolex) from two phase 3 randomized placebo-controlled trials (NCT02224690 and NCT02224560). Drop seizure reduction anchored to Caregiver Global Impression of Change scores to determine clinically meaningful thresholds.

What this study cannot tell us

Post hoc analysis with inherent limitations. CGIC is a single subjective rating. Only 14 weeks of data. Analysis of CBD-treated patients only (no placebo comparison for thresholds). Sample included wide age range (2-55 years). Exploratory nature limits definitive conclusions.

How to read the evidence

Post hoc analysis of two phase 3 RCTs with validated caregiver assessments and appropriate statistical methodology supports strong evidence.

When this study was published

Data from phase 3 trials conducted April-December 2015.

The bigger picture

By redefining what counts as a meaningful response, this analysis suggests CBD helps more LGS patients than traditional trial endpoints indicate. This has implications for insurance coverage, treatment continuation decisions, and regulatory assessments.

Questions still open

Should clinical trials adopt lower seizure reduction thresholds?
Do patients with 30-50% seizure reduction maintain benefits long-term?

Common questions

How much seizure reduction counts as helpful?

While clinical trials typically use a 50% reduction as the success benchmark, this analysis found caregivers perceived meaningful improvement at just 31% reduction in drop seizures, suggesting the traditional cutoff may be too strict.

Does CBD help most patients with Lennox-Gastaut syndrome?

60% of CBD-treated patients were rated as at least 'slightly improved' by caregivers, and 58% met the 31% seizure reduction threshold. This suggests a majority experience some meaningful benefit.

Read the original research

Clinically Meaningful Reduction in Drop Seizures in Patients with Lennox-Gastaut Syndrome Treated with Cannabidiol: Post Hoc Analysis of Phase 3 Clinical Trials.

CNS drugs, 39(10), 1025-1036

View on PubMed ↗Publisher’s paper ↗

Citation

Specchio, Nicola; Auvin, Stéphane; Greco, Teresa; Lagae, Lieven; Nortvedt, Charlotte; Zuberi, Sameer M. (2025). Clinically Meaningful Reduction in Drop Seizures in Patients with Lennox-Gastaut Syndrome Treated with Cannabidiol: Post Hoc Analysis of Phase 3 Clinical Trials.. CNS drugs, 39(10), 1025-1036. https://doi.org/10.1007/s40263-025-01201-8