Hess, Evan J.;
Moody, Kirsten A.;
Geffrey, Alexandra L.;
Pollack, Sarah F.;
Skirvin, Lauren A.;
Bruno, Patricia L.;
Paolini, Jan L.;
Thiele, Elizabeth A.
Cannabidiol as a new treatment for drug‐resistant epilepsy in tuberous sclerosis complex
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Medientyp:
E-Artikel
Titel:
Cannabidiol as a new treatment for drug‐resistant epilepsy in tuberous sclerosis complex
Beteiligte:
Hess, Evan J.;
Moody, Kirsten A.;
Geffrey, Alexandra L.;
Pollack, Sarah F.;
Skirvin, Lauren A.;
Bruno, Patricia L.;
Paolini, Jan L.;
Thiele, Elizabeth A.
Beschreibung:
<jats:title>Summary</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>Tuberous sclerosis complex (<jats:styled-content style="fixed-case">TSC</jats:styled-content>) is an autosomal‐dominant genetic disorder with highly variable expression. The most common neurologic manifestation of <jats:styled-content style="fixed-case">TSC</jats:styled-content> 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 (<jats:styled-content style="fixed-case">CBD</jats:styled-content>), a nonpsychoactive compound derived from the marijuana plant, as an adjunct to current antiepileptic drugs in patients with refractory seizures in the setting of <jats:styled-content style="fixed-case">TSC</jats:styled-content>.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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 <jats:styled-content style="fixed-case">TSC</jats:styled-content>. After an initial baseline period of 1 month, patients began treatment with <jats:styled-content style="fixed-case">CBD</jats:styled-content>. 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 <jats:styled-content style="fixed-case">CBD</jats:styled-content>.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The median weekly seizure frequency during the baseline period was 22.0 (interquartile range [<jats:styled-content style="fixed-case">IQR</jats:styled-content>] 14.8–57.4), which decreased to 13.3 (<jats:styled-content style="fixed-case">IQR</jats:styled-content> 5.1–22.1) after 3 months of treatment with cannabidiol. The median percent change in total weekly seizure frequency was −48.8% (<jats:styled-content style="fixed-case">IQR</jats:styled-content> −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 <jats:styled-content style="fixed-case">CBD</jats:styled-content>, respectively. In patients taking clobazam concurrently with <jats:styled-content style="fixed-case">CBD</jats:styled-content> (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 <jats:styled-content style="fixed-case">CBD</jats:styled-content>; the most common adverse events were drowsiness (n = 8, 44.4%), ataxia (n = 5, 27.8%), and diarrhea (n = 4, 22.2%).</jats:p></jats:sec><jats:sec><jats:title>Significance</jats:title><jats:p>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 <jats:styled-content style="fixed-case">TSC</jats:styled-content>.</jats:p></jats:sec>