Table I. Efficacy criteria for cannabidiol treatment. |
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Efficacy criteriaa, listed in descending order of relevance |
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% of reduction in drop seizures or seizures with motor a component (convulsions) |
It is the most important criteria, since convulsions or seizures with a motor component and drop seizures have a high impact on the quality of life of patients The efficacy goal of the reduction in seizures depends on the baseline situation of each patient In some cases (e.g. LGS patients with a high number of nocturnal seizures or drop seizures), a reduction of up to 50-70% in total seizures could be considered an excellent result even if total control of said seizures were not achieved. |
Reduction in generalised tonic-clonic seizures and drop seizures |
These are the most life- threatening seizures and the ones that have the highest impact on the quality of life of patients Generalised tonic-clonic seizures can lead to status epilepticus and can be associated with a higher risk of sudden unexpected death in epilepsy (SUDEP) in DS patients Controlling drop seizures is essential in LGS patients. The morbidity and mortality rates for trauma is very high and this gives rise to anxiety in patients’ family members and caregivers |
Reduction or improvement in the severity of other types of seizures |
Reduction in other types of seizures (atypical absences, minor motor seizures, or myoclonic seizures) and night tonic seizures:
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Changes in seizures semiology and reduction in rescue medication |
It is essential to reduce the ‘rescue medication’ (mainly benzodiazepines) administered by patients’ caregivers in order to avoid status epilepticus. Many AEs are reduced. The collection of this information weekly by caregivers is very relevant and helpful for the physicians when it comes to optimising the treatment |
Increase in seizure-free days |
The increase in seizure-free days is a parameter highly valued by caregivers. More seizure-free days allow them to carry out more activities, reassure the confidence of the patients’ families, and improve their QoL |
Cognitive improvement: improvement in alert or attention, which involves an improvement in the QoL |
Improvement in QoL: recovery of school days and daily living activities. Reinforcement of family confidence QoL scales needed to assess these changes (for example CAVE, LQOL scales) It is difficult to assess whether the patient is alert or more participative, by using scales because there are not specific scales for DS or LGS. The reports of the educational centre caregivers are very helpful |
Reduction in the number of concomitant ASMs or their doses |
DS or LGS patients are generally polymedicated If the dose or the number of concomitant ASMs got to be reduced, treatment-related AEs would be reduced |
AE: adverse event; ASMs: antiseizure medications; CAVE: quality of life scale in childhood epilepsy; CBD: cannabidiol; DS: Dravet syndrome; LGS: Lennox-Gastaut syndrome; QoL: quality-of-life. a They can be easily quantified/identified by physicians and/or caregivers. |
Table II. AEs commonly reported associated with the use of cannabidiol and recommendations on their management. |
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Common AEs and recommendations for their management |
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Transaminase’s elevation |
This is the AE that most concerns, since the underlying molecular mechanism is unknown at this time; it is mainly related to concomitant treatment with VPA These elevations of the liver enzymes are generally transient and dose-dependent, and they normalise after ASMs dose adjustment or, sometimes, spontaneously. Following two weeks from VPA dose adjustments, a blood test is repeated Recommendations:
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Somnolence |
It is the most common and easily detectable AE. In children, it can be expressed as irritability or motor coordination difficulties. It is mainly related to co-adjuvant treatment with CLB and brivaracetam The improvement in symptomatology guides dose adjustments |
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Gastrointestinal events |
Severe diarrhoea |
Diarrhoea is a difficult to manage AE Recommendation: Take CBD in combination with food in order to reduce the osmolarity effect of sesame oil |
Loss of appetite |
It is mainly detected in DS patients, since they often have anorexia and prior malnutrition, and they are prone to previous loss of appetite |
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Vomiting |
Mainly when combining CBD with VPA |
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Hyperammonaemia |
This AE has been mostly observed in patients on concomitant VPA treatment. In patients with CBD and VPA, it can be associated with encephalopathy +/- vomiting, regardless the transaminases elevation or VPA levels. It is essential to detect it. Recommendation:
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AE: adverse event; ASMs: antiseizure medications; CBD: cannabidiol; CLB: clobazam; DS: Dravet syndrome; LGS: Lennox-Gastaut syndrome; VPA: valproic acid. |
Cannabidiol para el tratamiento del síndrome de Lennox-Gastaut y del síndrome de Dravet: recomendaciones de expertos sobre su uso en la práctica clínica en España Introducción. El cannabidiol (CBD) es uno de los componentes principales de la planta del cannabis que ha demostrado efecto ante las crisis epilépticas. Tras su desarrollo clínico, obtuvo su aprobación por la Agencia Europea del Medicamento en septiembre de 2019 para el tratamiento de las crisis epilépticas asociadas con el síndrome de Lennox-Gastaut (SLG) y el síndrome de Dravet (SD), en combinación con el clobazam (CLB), en pacientes a partir de los dos años. Objetivo. Establecer unas recomendaciones de manejo del CBD derivado de la planta altamente purificado consensuadas por expertos españoles en el tratamiento de la epilepsia para su uso en pacientes con SD y SLG, basándose en su experiencia clínica y en la evidencia científica. Desarrollo. Reunión de consenso de un grupo de cuatro neurólogos y neuropediatras españoles expertos en el manejo de la epilepsia asociada al SD y el SLG y con experiencia clínica en el uso de CBD. Se debatió sobre diferentes áreas, incluyendo la posología (dosis de inicio, pauta de escalada), la eficacia (valoración de resultados e indicaciones para la suspensión del tratamiento) y la seguridad (evaluación, interacciones entre fármacos, manejo de efectos adversos). Conclusiones. Para optimizar el tratamiento con CBD, se recomienda una pauta lenta de escalada de dosis (de cuatro semanas o más) hasta alcanzar la dosis máxima recomendada o el efecto deseado, reducir los fármacos anticrisis epilépticas concomitantes si aparecen efectos adversos por interacciones y mantener el tratamiento al menos seis meses si se tolera. La eficacia y la seguridad del CBD deben evaluarse de forma individual, considerando el beneficio y el riesgo para cada paciente. Palabras clave. Cannabidiol. Efectos adversos. Eficacia. España. Recomendaciones. Síndrome de Dravet. Síndrome de Lennox-Gastaut. |