Background: Since 2014, patients with severe treatment-resistant epilepsies (TREs) have been receiving add-on cannabidiol (CBD) in an ongoing, expanded access program (EAP), which closely reflects clinical practice. We conducted an interim analysis of long-term efficacy and tolerability in patients with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) who received CBD treatment through December 2016.
Methods: Children and adults with LGS/DS taking stable doses of antiepileptic drugs (AEDs) at baseline were included from 25 EAP sites across the United States. During the 4-week baseline period, parents/caregivers kept diaries of all countable seizure types. Patients received a pharmaceutical formulation of highly purified CBD (Epidiolex®; 100 mg/mL) in oral solution at 2-10 mg/kg/day, titrated until tolerability limit or a maximum dose of 25-50 mg/kg/day. Patient visits were every 2-4 weeks. The percentage change from baseline in median monthly convulsive (ie, major motor) and total seizures was evaluated at 12-week intervals through 96 weeks. The percentages of patients who had ≥50%, ≥75%, and 100% reduction in monthly seizures relative to the baseline period were also evaluated. Adverse events (AEs) were monitored and summarized for the safety analysis set (SAS) through 144 weeks.
Results: Of the 607 patients in the SAS, 58 had DS and 94 had LGS (N = 152); 455 patients had other TREs. Twenty-eight percent of LGS/DS patients withdrew, primarily owing to lack of efficacy (20%). LGS/DS patients were taking a median of 3 (0-10) concomitant AEDs. Median treatment duration was 78.3 (range, 4.1-146.4) weeks. Between weeks 12 and 96, median CBD dose ranged from 21 to 25 mg/kg/day. At 12 weeks, add-on CBD reduced median monthly major motor seizures by 50% and total seizures by 44%, with consistent reductions in both seizure types through 96 weeks. At 12 weeks, the proportions of patients with ≥50%, ≥75%, and 100% reductions in major motor seizures were 53%, 23%, and 6%; the proportions with corresponding reductions in total seizures were 46%, 26%, and 5%. Responder rates for both seizure types were consistent through 96 weeks. CBD had an acceptable safety profile; the most common AEs were somnolence (30%) and diarrhea (24%).
Conclusions: Results from this interim analysis support add-on CBD as an effective long-term treatment option in LGS or DS.
Keywords: Cannabidiol; Dravet syndrome; Efficacy; Expanded access program; Lennox-Gastaut syndrome; Seizures; Tolerability; Treatment-resistant epilepsy.
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.
Don't Fear the Reefer-Evidence Mounts for Plant-Based Cannabidiol as Treatment for Epilepsy.Epilepsy Curr. 2019 Mar-Apr;19(2):93-95. doi: 10.1177/1535759719835671. Epilepsy Curr. 2019. PMID: 30955420 Free PMC article.
Long-term safety and treatment effects of cannabidiol in children and adults with treatment-resistant epilepsies: Expanded access program results.Epilepsia. 2018 Aug;59(8):1540-1548. doi: 10.1111/epi.14477. Epub 2018 Jul 12. Epilepsia. 2018. PMID: 29998598 Free PMC article.
Cannabidiol in patients with Lennox-Gastaut syndrome: Interim analysis of an open-label extension study.Epilepsia. 2019 Mar;60(3):419-428. doi: 10.1111/epi.14670. Epub 2019 Feb 11. Epilepsia. 2019. PMID: 30740695 Free PMC article. Clinical Trial.
Cannabidiol: A New Hope for Patients With Dravet or Lennox-Gastaut Syndromes.Ann Pharmacother. 2019 Jun;53(6):603-611. doi: 10.1177/1060028018822124. Epub 2019 Jan 8. Ann Pharmacother. 2019. PMID: 30616356 Review.
Cannabidiol as adjunctive treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome.Drugs Today (Barc). 2019 Mar;55(3):177-196. doi: 10.1358/dot.2019.55.3.2909248. Drugs Today (Barc). 2019. PMID: 30938373 Review.
Cited by 7 articles
A Balanced Approach for Cannabidiol Use in Chronic Pain.Front Pharmacol. 2020 Apr 30;11:561. doi: 10.3389/fphar.2020.00561. eCollection 2020. Front Pharmacol. 2020. PMID: 32425793 Free PMC article. Review.
Terpenoids From Cannabis Do Not Mediate an Entourage Effect by Acting at Cannabinoid Receptors.Front Pharmacol. 2020 Mar 25;11:359. doi: 10.3389/fphar.2020.00359. eCollection 2020. Front Pharmacol. 2020. PMID: 32269529 Free PMC article.
Cannabidiol Drugs Clinical Trial Outcomes and Adverse Effects.Front Pharmacol. 2020 Feb 25;11:63. doi: 10.3389/fphar.2020.00063. eCollection 2020. Front Pharmacol. 2020. PMID: 32161538 Free PMC article. Review.
Is cannabidiol a drug acting on unconventional targets to control drug-resistant epilepsy?Epilepsia Open. 2020 Jan 17;5(1):36-49. doi: 10.1002/epi4.12376. eCollection 2020 Mar. Epilepsia Open. 2020. PMID: 32140642 Free PMC article. Review.
Medical Cannabis in Children.Rambam Maimonides Med J. 2020 Jan 30;11(1):e0003. doi: 10.5041/RMMJ.10386. Rambam Maimonides Med J. 2020. PMID: 32017680 Free PMC article. Review.