Open-label use of highly purified CBD (Epidiolex®) in patients with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes

• Published in: Epilepsy & behavior Vol. 86; pp. 131 - 137
• Main Authors: Devinsky, Orrin, Verducci, Chloe, Thiele, Elizabeth A., Laux, Linda C., Patel, Anup D., Filloux, Francis, Szaflarski, Jerzy P., Wilfong, Angus, Clark, Gary D., Park, Yong D., Seltzer, Laurie E., Bebin, E. Martina, Flamini, Robert, Wechsler, Robert T., Friedman, Daniel
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2018
• Subjects: Adolescent; Adult; Aicardi syndrome; Aicardi Syndrome - diagnosis; Aicardi Syndrome - drug therapy; Anticonvulsants - chemistry; Anticonvulsants - therapeutic use; Cannabidiol; Cannabidiol - chemistry; Cannabidiol - therapeutic use; CDKL5 deficiency disorder; Child; Child, Preschool; Chromosomes, Human, 13-15 - genetics; Doose syndrome; Dup15q syndrome; Epilepsies, Myoclonic - diagnosis; Epilepsies, Myoclonic - drug therapy; Epileptic Syndromes - diagnosis; Epileptic Syndromes - drug therapy; Female; Humans; Infant; Male; Middle Aged; Prospective Studies; Protein-Serine-Threonine Kinases - deficiency; Spasms, Infantile - diagnosis; Spasms, Infantile - drug therapy; Trisomy - genetics; Young Adult; Cannabidiol; Doose syndrome; CDKL5 deficiency disorder; Dup15q syndrome; Aicardi syndrome
• ISSN: 1525-5050; 1525-5069
• DOI: 10.1016/j.yebeh.2018.05.013

We studied our collective open-label, compassionate use experience in using cannabidiol (CBD) to treat epilepsy in patients with CDKL5 deficiency disorder and Aicardi, Doose, and Dup15q syndromes. We included patients aged 1–30 years with severe childhood-onset epilepsy who received CBD for ≥10 weeks as part of multiple investigator-initiated expanded access or state access programs for a compassionate prospective interventional study: CDKL5 deficiency disorder (n = 20), Aicardi syndrome (n = 19), Dup15q syndrome (n = 8), and Doose syndrome (n = 8). These patients were treated at 11 institutions from January 2014 to December 2016. The percent change in median convulsive seizure frequency for all patients taking CBD in the efficacy group decreased from baseline [n = 46] to week 12 (51.4% [n = 35], interquartile range (IQR): 9–85%) and week 48 (59.1% [n = 27], IQR: 14–86%). There was a significant difference between the percent changes in monthly convulsive seizure frequency during baseline and week 12, χ2(2) = 22.9, p = 0.00001, with no difference in seizure percent change between weeks 12 and 48. Of the 55 patients in the safety group, 15 (27%) withdrew from extended observation by week 144: 4 due to adverse effects, 9 due to lack of efficacy, 1 withdrew consent, and 1 was lost to follow-up. This open-label drug trial provides class III evidence for the long-term safety and efficacy of CBD administration in patients with treatment-resistant epilepsy (TRE) associated with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes. Adjuvant therapy with CBD showed similar safety and efficacy for these four syndromes as reported in a diverse population of TRE etiologies. This study extended analysis of the prior report from 12 weeks to 48 weeks of efficacy data and suggested that placebo-controlled randomized trials should be conducted to formally assess the safety and efficacy of CBD in these epileptic encephalopathies. •CBD is a favorable adjuvant to antiseizure medication in patients with intractable genetic epilepsy.•Safety profile is tolerable; common adverse events are diarrhea, somnolence, and fatigue.•CBD reduced the median number of seizures by half at 12 and 48 weeks of follow-up.•Randomized, controlled trials of CBD are warranted given maintained efficacy and safety.