Almost a third of patients with epilepsy have a treatment-resistant form, which is associated with severe morbidity and increased mortality. Cannabis-based treatments for epilepsy have generated much interest, but scientific data are scarce. We aimed to establish whether addition of cannabidiol to existing anti-epileptic regimens would be safe, tolerated, and effi cacious in children and young adults with treatment-resistant epilepsy.

22 AUTHORS, INCLUDING:

Orrin Devinsky*, Eric Marsh*, Daniel Friedman*, Elizabeth Thiele, Linda Laux, Joseph Sullivan, Ian Miller, Robert Flamini, Angus Wilfong, Francis Filloux, Matthew Wong, Nicole Tilton, Patricia Bruno, Judith Bluvstein, Julie Hedlund, Rebecca Kamens, Jane Maclean, Srishti Nangia, Nilika Shah Singhal, Carey A Wilson, Anup Patel, Maria Roberta Cilio

Summary

Background

Almost a third of patients with epilepsy have a treatment-resistant form, which is associated with severe morbidity and increased mortality. Cannabis-based treatments for epilepsy have generated much interest, but scientifi c data are scarce. We aimed to establish whether addition of cannabidiol to existing anti-epileptic regimens would be safe, tolerated, and effi cacious in children and young adults with treatment-resistant epilepsy.

Methods

In this open-label trial, patients (aged 1–30 years) with severe, intractable, childhood-onset, treatmentresistant epilepsy, who were receiving stable doses of antiepileptic drugs before study entry, were enrolled in an expanded-access programme at 11 epilepsy centres across the USA. Patients were given oral cannabidiol at 2–5 mg/kg per day, up-titrated until intolerance or to a maximum dose of 25 mg/kg or 50 mg/kg per day (dependent on study site). The primary objective was to establish the safety and tolerability of cannabidiol and the primary effi cacy endpoint was median percentage change in the mean monthly frequency of motor seizures at 12 weeks. The effi cacy analysis was by modifi ed intention to treat. Comparisons of the percentage change in frequency of motor seizures were done with a Mann-Whitney U test.

Results

Between Jan 15, 2014, and Jan 15, 2015, 214 patients were enrolled; 162 (76%) patients who had at least 12 weeks of follow-up after the fi rst dose of cannabidiol were included in the safety and tolerability analysis, and 137 (64%) patients were included in the effi cacy analysis. In the safety group, 33 (20%) patients had Dravet syndrome and 31 (19%) patients had Lennox-Gastaut syndrome. The remaining patients had intractable epilepsies of diff erent causes and type. Adverse events were reported in 128 (79%) of the 162 patients within the safety group. Adverse events reported in more than 10% of patients were somnolence (n=41 [25%]), decreased appetite (n=31 [19%]), diarrhoea (n=31 [19%]), fatigue (n=21 [13%]), and convulsion (n=18 [11%]). Five (3%) patients discontinued treatment because of an adverse event. Serious adverse events were reported in 48 (30%) patients, including one death—a sudden unexpected death in epilepsy regarded as unrelated to study drug. 20 (12%) patients had severe adverse events possibly related to cannabidiol use, the most common of which was status epilepticus (n=9 [6%]). The median monthly frequency of motor seizures was 30·0 (IQR 11·0–96·0) at baseline and 15·8 (5·6–57·6) over the 12 week treatment period. The median reduction in monthly motor seizures was 36·5% (IQR 0–64·7).

Interpretation

Our findings suggest that cannabidiol might reduce seizure frequency and might have an adequate safety profi le in children and young adults with highly treatment-resistant epilepsy. Randomised controlled trials are warranted to characterise the safety profi le and true effi cacy of this compound. Funding GW Pharmaceuticals, Epilepsy Therapy Project of the Epilepsy Foundation, Finding A Cure for Epilepsy and Seizures.

A continuación: El análisis de la Dra. Silvia Kochen

Considero muy interesante la publicación “Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial “, liderado por el Dr Orrin Devinsky y sponsoreado por el Laboratorio GW Pharmaceuticals, y por la Fundacion Epilepsy Therapy Project de Nueva York, Estados Unidos.

Los hallazgos de los autores sugieren que el cannabidiol puede reducir la frecuencia de las crisis y podría tener un perfil de seguridad adecuado en niños y adultos jóvenes con epilepsia altamente resistente al tratamiento.

Y plantean que es necesario realizar Ensayos controlados aleatorios o en ingles Randomised controlled trials (RCT) para caracterizar el perfil de seguridad y eficacia real de este compuesto. Este tipo de Ensayos representan la mayor garantía para probar si un nuevo tratamiento es efectivo y seguro. Consisten en que se elige al azar a un grupo de pacientes para ser tratado y se lo compara con un grupo de pacientes de iguales características a quien no se le da el tratamiento, grupo control, y se le da un placebo, es decir algo que parece un tratamiento pero no contiene ningún producto. Esta información no la conocen ni los pacientes ni los profesionales que participan en la investigación, se denomina “doble ciego”.

Prof. Dra Silvia Kochen

Prof. Dra Silvia Kochen, Directora Centro de Neurociencias Clínicas y Aplicadas. Epilepsia, Cognición y Conducta

Sección de Epilepsia, Div Neurología, Hosp “R.Mejía” – Inst. de Biología Celular y Neurociencias, 

Fac. Medicina, Univ. Buenos Aires –Consejo Nacional de Investigación Científico y Tecnológico (CONICET)

Neurociencias, Hosp El Cruce, Florencio Varela