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Cannabidiol as a new treatment for drug‐resistant epilepsy in tuberous sclerosis complex
Author(s) -
Hess Evan J.,
Moody Kirsten A.,
Geffrey Alexandra L.,
Pollack Sarah F.,
Skirvin Lauren A.,
Bruno Patricia L.,
Paolini Jan L.,
Thiele Elizabeth A.
Publication year - 2016
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.13499
Subject(s) - cannabidiol , tuberous sclerosis , tolerability , medicine , epilepsy , interquartile range , adjunctive treatment , drug resistant epilepsy , refractory (planetary science) , neurology , pediatrics , anesthesia , adverse effect , cannabis , psychiatry , physics , astrobiology
Summary Objective Tuberous sclerosis complex ( TSC ) is an autosomal‐dominant genetic disorder with highly variable expression. The most common neurologic manifestation of TSC is epilepsy, which affects approximately 85% of patients, 63% of whom develop treatment‐resistant epilepsy. Herein, we evaluate the efficacy, safety, and tolerability of cannabidiol ( CBD ), a nonpsychoactive compound derived from the marijuana plant, as an adjunct to current antiepileptic drugs in patients with refractory seizures in the setting of TSC . Methods Eighteen of the 56 patients who have enrolled in our current expanded‐access study of cannabidiol for patients with treatment‐resistant epilepsy carry a diagnosis of TSC . After an initial baseline period of 1 month, patients began treatment with CBD . The initial dose of 5 mg/kg/day was increased by 5 mg/kg/day every week up to a maximum dose of 50 mg/kg/day, if tolerated. Weekly seizure frequencies, percent change in seizure frequencies, and responder rates were calculated during the 2nd, 3rd, 6th, 9th, and 12th month of treatment with CBD . Results The median weekly seizure frequency during the baseline period was 22.0 (interquartile range [ IQR ] 14.8–57.4), which decreased to 13.3 ( IQR 5.1–22.1) after 3 months of treatment with cannabidiol. The median percent change in total weekly seizure frequency was −48.8% ( IQR −69.1% to −11.1%) after 3 months of treatment. The 50% responder rates over the course of the study were 50%, 50%, 38.9%, 50%, and 50% after 2, 3, 6, 9, and 12 months of treatment with CBD , respectively. In patients taking clobazam concurrently with CBD (n = 12), the responder rate after 3 months of treatment was 58.3%, compared to 33.3% in patients not taking clobazam (n = 6). Twelve (66.7%) of 18 patients in this study experienced at least one adverse event thought possibly related to CBD ; the most common adverse events were drowsiness (n = 8, 44.4%), ataxia (n = 5, 27.8%), and diarrhea (n = 4, 22.2%). Significance Although double‐blind, placebo‐controlled trials are still necessary, these findings suggest that cannabidiol may be an effective and well‐tolerated treatment option for patients with refractory seizures in TSC .