PMID- 32903409 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 1664-2295 (Print) IS - 1664-2295 (Electronic) IS - 1664-2295 (Linking) VI - 11 DP - 2020 TI - Slow Titration of Cannabidiol Add-On in Drug-Resistant Epilepsies Can Improve Safety With Maintained Efficacy in an Open-Label Study. PG - 829 LID - 10.3389/fneur.2020.00829 [doi] LID - 829 AB - Objective: To assess adverse events (AEs) and efficacy of add-on cannabidiol (CBD) with a slower titration protocol in pediatric clinical practice. Methods: We conducted a prospective, open-label, multicenter study in seven French reference centers for rare epilepsies. Patients had slow titration to reach a target dose of 10 mg/kg/day within at least 1 month and then gradually increased to a maximum dose of 20 mg/kg/day. We analyzed AEs and efficacy at M1 (month 1), M2, and M6, comparing two sets of subgroups: Dravet syndrome (DS) vs. Lennox-Gastaut (LGS) and patients with clobazam (CLB+) vs. patients without (CLB-). Results: One hundred and twenty-five patients were enrolled (62 LGS, 48 DS, 5 Tuberous sclerosis, and 10 other etiologies). Median concomitant antiepileptic drugs (AEDs) was three (25th percentile: 3, 75th percentile: 4). Patients received a dose of 10 (10-12), 14 (10-20), and 15.5 mg/kg/day (10-20) at M1, M2, and M6, respectively. Twenty-six patients discontinued CBD, 19 due to lack of efficacy, 2 due to AEs, 4 for both, and 1 had a sudden unexpected death in epilepsy. AEs were reported in 61 patients (48.8%), mainly somnolence (n = 26), asthenia (n = 20), and behavior disorders (n = 16). Abnormal transaminases (>/=3 times) were reported in 11 patients receiving both valproate and clobazam. AEs were significantly higher at M2 (p = 0.03) and increased with the number of AEDs (p = 0.03). At M6, total seizure frequency change from baseline was -41% +/- 37.5% (mean +/- standard deviation), and 28 patients (37.8%) had a reduction >/=50%. AE and efficacy did not differ between DS vs. LGS and CLB+ vs. CLB- patients. Significance: A slower titration of CBD dose delivered better tolerance with comparable efficacy to previous trials. Concomitant CLB did not increase efficacy rates but in a few cases increased AEs. This slow titration scheme should help guide clinicians prescribing CBD and allow patients to benefit from its potential efficacy. CI - Copyright (c) 2020 D'Onofrio, Kuchenbuch, Hachon-Le Camus, Desnous, Staath, Napuri, Ville, Pedespan, Lepine, Cances, de Saint-Martin, Teng, Chemaly, Milh, Villeneuve and Nabbout. FAU - D'Onofrio, Gianluca AU - D'Onofrio G AD - Department of Pediatric Neurology, Reference Centre for Rare Epilepsies, Hopital Necker-Enfants Malades, APHP, Paris, France. AD - Pediatric Residency, Department of Women and Child Health, University of Padua, Padua, Italy. FAU - Kuchenbuch, Mathieu AU - Kuchenbuch M AD - Department of Pediatric Neurology, Reference Centre for Rare Epilepsies, Hopital Necker-Enfants Malades, APHP, Paris, France. AD - Laboratory of Translational Research for Neurological Disorders, INSERM UMR 1163, Imagine Institute, Universite de Paris, Paris, France. FAU - Hachon-Le Camus, Caroline AU - Hachon-Le Camus C AD - Department of Pediatric Neurology, Hopital des Enfants, Toulouse University Hospital, Toulouse, France. FAU - Desnous, Beatrice AU - Desnous B AD - AP-HM, Pediatric Neurology Department, Timone Children Hospital, Marseille, France. FAU - Staath, Veronique AU - Staath V AD - Department of Pediatric Neurology, Strasbourg University Hospital, Hopital de Hautepierre, Strasbourg, France. FAU - Napuri, Sylvia AU - Napuri S AD - Department of Pediatrics, Rennes University Hospital, University Rennes, Rennes, France. FAU - Ville, Dorothee AU - Ville D AD - Department of Pediatric Neurology, CNRS UMR 5304, Bron, France. FAU - Pedespan, Jean-Michel AU - Pedespan JM AD - Department of Pediatrics, Pellegrin University Hospital, Bordeaux, France. FAU - Lepine, Anne AU - Lepine A AD - AP-HM, Pediatric Neurology Department, Timone Children Hospital, Marseille, France. FAU - Cances, Claude AU - Cances C AD - Department of Pediatric Neurology, Hopital des Enfants, Toulouse University Hospital, Toulouse, France. FAU - de Saint-Martin, Anne AU - de Saint-Martin A AD - Department of Pediatric Neurology, Strasbourg University Hospital, Hopital de Hautepierre, Strasbourg, France. FAU - Teng, Theo AU - Teng T AD - Department of Pediatric Neurology, Reference Centre for Rare Epilepsies, Hopital Necker-Enfants Malades, APHP, Paris, France. FAU - Chemaly, Nicole AU - Chemaly N AD - Department of Pediatric Neurology, Reference Centre for Rare Epilepsies, Hopital Necker-Enfants Malades, APHP, Paris, France. AD - Laboratory of Translational Research for Neurological Disorders, INSERM UMR 1163, Imagine Institute, Universite de Paris, Paris, France. FAU - Milh, Mathieu AU - Milh M AD - AP-HM, Pediatric Neurology Department, Timone Children Hospital, Marseille, France. FAU - Villeneuve, Nathalie AU - Villeneuve N AD - AP-HM, Pediatric Neurology Department, Timone Children Hospital, Marseille, France. FAU - Nabbout, Rima AU - Nabbout R AD - Department of Pediatric Neurology, Reference Centre for Rare Epilepsies, Hopital Necker-Enfants Malades, APHP, Paris, France. AD - Laboratory of Translational Research for Neurological Disorders, INSERM UMR 1163, Imagine Institute, Universite de Paris, Paris, France. LA - eng PT - Journal Article DEP - 20200812 PL - Switzerland TA - Front Neurol JT - Frontiers in neurology JID - 101546899 PMC - PMC7434926 OTO - NOTNLM OT - Dravet OT - Lennox-Gastaut OT - adverse events OT - drug resistant OT - liver function OT - tolerability EDAT- 2020/09/10 06:00 MHDA- 2020/09/10 06:01 PMCR- 2020/08/12 CRDT- 2020/09/09 17:54 PHST- 2020/05/29 00:00 [received] PHST- 2020/07/02 00:00 [accepted] PHST- 2020/09/09 17:54 [entrez] PHST- 2020/09/10 06:00 [pubmed] PHST- 2020/09/10 06:01 [medline] PHST- 2020/08/12 00:00 [pmc-release] AID - 10.3389/fneur.2020.00829 [doi] PST - epublish SO - Front Neurol. 2020 Aug 12;11:829. doi: 10.3389/fneur.2020.00829. eCollection 2020.