Slow CBD titration in children with severe epilepsy achieved comparable efficacy with better tolerance | Research

The takeaway

In 125 children with drug-resistant epilepsy, a slower CBD titration protocol achieved 38% with 50%+ seizure reduction at 6 months while reducing side effects compared to faster titration in previous trials.

Neurologists prescribing CBD for epilepsy, parents of children with drug-resistant seizures

37.8% achieved 50%+ seizure reduction; slow titration improved tolerability

What the researchers found

At 6 months, mean seizure frequency decreased 41% from baseline, and 37.8% had 50%+ seizure reduction. Adverse events occurred in 48.8%, mainly somnolence (21%), asthenia (16%), and behavioral changes (13%). Abnormal transaminases occurred in 11 patients receiving both valproate and clobazam. Concomitant clobazam did not increase efficacy rates.

Why it matters

Slow titration may allow clinicians to achieve similar seizure control with fewer side effects, improving the risk-benefit profile of CBD therapy for severe childhood epilepsy.

The numbers in context

125 patients enrolled. Doses: 10 mg/kg/day at M1, 14 at M2, 15.5 at M6. 26 discontinued (19 for lack of efficacy). AEs in 48.8%. Somnolence 21%, asthenia 16%. 37.8% achieved 50%+ seizure reduction at M6. 1 SUDEP.

How the study worked

Prospective, open-label, multicenter study in 7 French reference centers. 125 patients (62 LGS, 48 Dravet, 15 other) with slow CBD titration to 10 mg/kg/day over at least 1 month, then gradual increase to max 20 mg/kg/day. Assessed at months 1, 2, and 6.

What this study cannot tell us

Open-label without control group; heterogeneous epilepsy types; variable follow-up; one SUDEP occurred (not necessarily related to CBD).

How to read the evidence

Multicenter prospective study but open-label without control group.

When this study was published

Published in 2020.

The bigger picture

This study offers practical guidance for clinicians prescribing CBD: slower dose escalation may deliver comparable seizure control with better tolerability, and clobazam co-administration may not add efficacy but does increase some adverse events.

Questions still open

Would even slower titration further improve tolerability? Can clinicians predict which patients will benefit without clobazam co-administration?

Common questions

Why does a slower titration help?

Gradually increasing the CBD dose gives the body time to adjust, reducing side effects like somnolence and fatigue. This study showed that seizure reduction was comparable to faster protocols in previous trials while side effects were more manageable.

Does adding clobazam to CBD improve results?

In this study, patients taking CBD with clobazam did not have better seizure outcomes than those without clobazam. However, the combination was associated with more side effects in some cases, particularly elevated liver enzymes when valproate was also present.

Read the original research

Slow Titration of Cannabidiol Add-On in Drug-Resistant Epilepsies Can Improve Safety With Maintained Efficacy in an Open-Label Study.

Frontiers in neurology, 11, 829

View on PubMed ↗Publisher’s paper ↗

Citation

D'Onofrio, Gianluca; Kuchenbuch, Mathieu; Hachon-Le Camus, Caroline; Desnous, Béatrice; Staath, Véronique; Napuri, Sylvia; Ville, Dorothée; Pedespan, Jean-Michel; Lépine, Anne; Cances, Claude; de Saint-Martin, Anne; Teng, Théo; Chemaly, Nicole; Milh, Mathieu; Villeneuve, Nathalie; Nabbout, Rima. (2020). Slow Titration of Cannabidiol Add-On in Drug-Resistant Epilepsies Can Improve Safety With Maintained Efficacy in an Open-Label Study.. Frontiers in neurology, 11, 829. https://doi.org/10.3389/fneur.2020.00829