40% of Epidiolex prescriptions in the US were for off-label conditions, with common drug interactions | Research

The takeaway

Among 4,214 Americans prescribed Epidiolex (pharmaceutical CBD) in 2022, 40% did not have FDA-approved diagnoses in their medical record, and nearly half were co-prescribed benzodiazepines known to interact with CBD.

Neurologists, psychiatrists, pharmacists, and FDA policy researchers

40% off-label; 47% co-prescribed interacting benzodiazepines

What the researchers found

Of 4,214 Epidiolex recipients, 40% lacked FDA-approved diagnostic indications (Lennox-Gastaut, Dravet, or tuberous sclerosis) in their records. Off-label use was primarily for other epilepsy syndromes (53.8%), sleep disorders (25.7%), anxiety (25.9%), mood disorders (18.6%), and autism (10.8%). Co-prescribing of interacting benzodiazepines was prevalent: clobazam 47.2%, diazepam 47.4%, clonazepam 40.7%.

Why it matters

Widespread off-label CBD prescribing and concurrent use of interacting medications create potential safety concerns that may not be well-studied or monitored.

The numbers in context

4,214 Epidiolex recipients in 2022; 40% off-label; co-prescribed clobazam 47.2%, diazepam 47.4%, clonazepam 40.7%; off-label uses: epilepsy 53.8%, sleep 25.7%, anxiety 25.9%, mood 18.6%, autism 10.8%

How the study worked

Analysis of the TriNetX database of de-identified electronic health records from over 110 million US patients, examining 4,214 individuals prescribed Epidiolex in 2022 for diagnostic indications and co-occurring prescriptions.

What this study cannot tell us

EHR data may have incomplete diagnostic coding; off-label use may be clinically appropriate even if evidence is limited; cannot determine if interactions resulted in adverse events; co-prescribing does not mean simultaneous use; 2022 single-year snapshot

How to read the evidence

Large real-world database analysis capturing prescribing patterns, but limited by EHR coding accuracy and inability to assess clinical outcomes.

When this study was published

2024 publication analyzing 2022 prescribing data

The bigger picture

The substantial off-label use of prescription CBD for conditions like anxiety, sleep, and autism reflects a gap between patient/provider interest in CBD and the available evidence base for these conditions.

Questions still open

Are prescribers monitoring for CBD-benzodiazepine interactions? Should off-label Epidiolex prescribing trigger additional safety monitoring? What outcomes are patients experiencing with off-label use?

Common questions

What is Epidiolex prescribed for beyond its FDA approval?

The most common off-label uses were other epilepsy syndromes (53.8%), sleep disorders (25.7%), anxiety disorders (25.9%), mood disorders (18.6%), and autism spectrum disorders (10.8%). Epidiolex is only FDA-approved for Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex.

Why is the drug interaction concern important?

Nearly half of Epidiolex recipients were also prescribed benzodiazepines (clobazam, diazepam, clonazepam) that are known to interact with CBD. CBD can increase blood levels of these drugs, potentially intensifying their sedative effects and side effects.

Read the original research

Cannabidiol prescribing in the United States: An analysis of real-world data.

Drug and alcohol dependence reports, 13, 100303

View on PubMed ↗Publisher’s paper ↗

Citation

Lin, Binx Yezhe; Lessard, Chloe; Li, Yifan; Gong, Lisa; Ling, Ruth; Jyotsana, Pallawi; Steinle, Jacob; Borodovsky, Jacob T; Nascimento, Fábio A; Xu, Kevin Y. (2024). Cannabidiol prescribing in the United States: An analysis of real-world data.. Drug and alcohol dependence reports, 13, 100303. https://doi.org/10.1016/j.dadr.2024.100303