Keywords
Drug Resistant Epilepsy
Child
How to Cite
Abstract
Introduction: there is evidence of the use of medicinal cannabis derivatives (DCM) as a therapeutic alternative for Refractory Epilepsy (RE).
Objectives: describe the profile of use, benefits and risks of DCM in the treatment of children and adolescents (NNA) with RD, assisted at the Pereira Rossell Hospital Center between July/2021 and February/2024.
Methodology: descriptive, longitudinal, retrospective study through review of histories and interviews with family members at two moments (t1: July/2022 and t2: February/2024). All children under 19 years of age who received DCM were included. The benefits were assessed according to the reduction in frequency and duration of epileptic seizures (EC). Adverse events and accessibility were researched.
Results: 15 children and adolescents were included, median age 8 years, 9/15 male, 13/15 carriers of severe chronic encephalopathies. At the beginning of treatment, 12/15 used DCM of industrial origin. The median initial dose was 0.5 mg/kg/day, then 3.5 and 3.7 mg/kg/day at t1 and t2, respectively. All caregivers reported a greater than 50% reduction in the frequency of CE and half of them reported a reduction in the duration of the crises. Even though the hospital pharmacy was the most frequent means of obtaining it, most of them expressed difficulties having access to it. Adverse effects, even though mostly mild, were identified in 8 cases.
Conclusions: the majority of children and adolescents presented a good response to treatment with DCM, which was maintained during follow-up. The safety profile was adequate. Treatment accessibility problems were identified.
References
De Santis A, Speranza N. Uso de cannabis medicinal en las epilepsias. Tend Med 2019; 28(55):152-6. Disponible en: https:// www.farmacologia.hc.edu.uy/images/publicaciones/2019/De_ Santis_A_Speranza_N_-_Cannabis.pdf. (Consulta: 19 abril 2024).
World Health Organization. Cannabis recommendations. 2019. Disponible en: https://www.who.int/publications/m/item/ecdd-41-cannabis-recommendations. (Consulta: 19 abril 2024).
Liu J, Chen H, Newmaster S, Wang S, Liu C. Global trends in cannabis and cannabidiol research from the year 1940 to 2019. Curr Pharm Biotechnol 2021; 22(5):579-91. doi: 10.2174/1389201021666200601152118.
Devinsky O, Cross J, Laux L, Marsh E, Miller I, Nabbout R, et al. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med 2017; 376(21):2011-20. doi: 10.1056/NEJMoa1611618.
Devinsky O, Patel A, Cross J, Villanueva V, Wirrell E, Privitera M, et al. Effect of cannabidiol on drop seizures in the Lennox-Gastaut syndrome. N Engl J Med 2018; 378(20):1888-97. doi: 10.1056/NEJMoa1714631.
Thiele E, Marsh E, French J, Mazurkiewicz M, Benbadis S, Joshi C, et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2018; 391(10125):1085-96. doi: 10.1016/S0140-6736(18)30136-3.
Miller I, Scheffer I, Gunning B, Sánchez R, Gil A, Perry M, et al. Dose-ranging effect of adjunctive oral cannabidiol vs placebo on convulsive seizure frequency in Dravet syndrome: a randomized clinical trial. JAMA Neurol 2020; 77(5):613-21. doi: 10.1001/jamaneurol.2020.0073.
Thiele E, Bebin E, Bhathal H, Jansen F, Kotulska K, Lawson J, et al. Add-on cannabidiol treatment for drug-resistant seizures in tuberous sclerosis complex: a placebo-controlled randomized clinical trial. JAMA Neurol 2021; 78(3):285-92. doi: 10.1001/jamaneurol.2020.4607.
Lattanzi S, Brigo F, Cagnetti C, Trinka E, Silvestrini M. Efficacy and safety of adjunctive cannabidiol in patients with Lennox-Gastaut syndrome: a systematic review and meta-analysis. CNS Drugs 2018; 32(10):905-16. doi: 10.1007/s40263-018-0558-9.
Chen J, Borgelt L, Blackmer A. Cannabidiol: a new hope for patients with Dravet or Lennox-Gastaut syndromes. Ann Pharmacother 2019; 53(6):603-11. doi: 10.1177/1060028018822124.
Devinsky O, Patel A, Thiele E, Wong M, Appleton R, Harden C, et al. Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome. Neurology 2018; 90(14):e1204-e1211. doi: 10.1212/WNL.0000000000005254.
Ley N° 19172. Regulación y control del cannabis. Montevideo, 7 de enero de 2014. Montevideo: IMPO, 2014. Disponible en: https://www.impo.com.uy/bases/leyes/19172-2013/8. (Consulta: 19 abril 2024).
Ley N° 19847. Declaración de interés público las acciones tendientes a proteger, promover y mejorar la salud pública mediante productos de calidad controlada y accesibles, en base a cannabis o cannabinoides, así como el asesoramiento médico e información sobre beneficios y riesgos de su uso. Montevideo, 8 de enero de 2020. Montevideo: IMPO, 2020. Disponible en: https://www.impo.com.uy/bases/leyes/19847-2019. (Consulta: 19 abril 2024).
Decreto N° 56/023. Montevideo, 27 de febrero de 2023. Montevideo: IMPO, 2023. Disponible en: https://www.impo.com. uy/bases/decretos-originales/56-2023. (Consulta: 19 abril 2024).
Decreto N° 298/017. Autorización de "venta bajo receta profesional" para las especialidades farmacéuticas con cannabidiol como principio activo. Montevideo, 24 de octubre de 2017. Montevideo: IMPO, 2017. Disponible en: https://www.impo. com.uy/bases/decretos/298-2017. (Consulta: 19 abril 2024).
Uruguay. Ministerio de Salud Pública. Listado de Medicamentos. Consulta de medicamentos. Montevideo: MSP, 2024. Disponible en: https://listadomedicamentos.msp.gub.uy/ListadoMedicamentos/servlet/com.listadomedicamentos.listadomedicamentos. (Consulta: 19 abril 2024).
Álvarez F, Guido A, Morandi M, Oliveira V, Rivas G, Vega L, et al. Uso de derivados de cannabis medicinal en una población pediátrica en Uruguay durante 2019-2021. An Fac Med 2022; 9(S1). Disponible en: https://revistas.udelar.edu.uy/OJS/index.php/anfamed/article/view/696. (Consulta: 19 abril 2024).
De Santis A, Galarraga F, Acosta D, Alcarraz M, Fernández T, Ferrari T, et al. Caracterización y seguimiento de una población de uruguayos usuarios de derivados de cannabis medicinal artesanal. Rev Méd Urug 2023; 39(2):e201. doi: 10.29193/rmu.39.2.1.
Notejane M, Zunino C, Rodríguez A, Speranza N, Giachetto G, Bernadá M, et al. Derivados cannábicos para uso medicinal en niños y adolescentes: aportes para un uso responsable y seguro. Arch Pediatr Urug 2018; 89(3):187-93. doi: 10.31134/ap.89.3.6.
Arias, T. Glosario de medicamentos: desarrollo, evaluación y uso. Washington, D.C.: OPS, 1999. Disponible en: https://iris.paho.org/bitstream/handle/10665.2/751/9275323054.pdf. (Consulta: 29 noviembre 2024).
Alvarado L, Ivanovic F. Adherencia a tratamiento en la epilepsia: una cuestión por resolver. Rev Méd Chile 2013; 141(8):1085-6. doi: 10.4067/S0034-98872013000800021.
Caraballo R, Demirdjian G, Reyes G, Huaman M, Gutiérrez R. Effectiveness of cannabidiol in a prospective cohort of children with drug-resistant epileptic encephalopathy in Argentina. Seizure 2020; 80:75-80. doi: 10.1016/j.seizure.2020.06.005.
Talwar A, Estes E, Aparasu R, Reddy D. Clinical efficacy and safety of cannabidiol for pediatric refractory epilepsy indications: a systematic review and meta-analysis. Exp Neurol 2023; 359:114238. doi: 10.1016/j.expneurol.2022.114238.
Treves N, Mor N, Allegaert K, Bassalov H, Berkovitch M, Stolar O, et al. Efficacy and safety of medical cannabinoids in children: a systematic review and meta-analysis. Sci Rep 2021; 11(1):23462. doi: 10.1038/s41598-021-02770-6.
Pawliuk C, Chau B, Rassekh S, McKellar T, Siden H. Efficacy and safety of paediatric medicinal cannabis use: A scoping review. Paediatr Child Health 2020; 26(4):228-33. doi: 10.1093/pch/pxaa031.
Johnson D, Funnell M, Heaney L, Cable T, Wheeler P, Bailey S, et al. Cannabidiol oil ingested as sublingual drops or within gelatin capsules shows similar pharmacokinetic profiles in healthy males. Cannabis Cannabinoid Res 2024; 9(5):e1423-e1432. doi: 10.1089/can.2023.0117.
Hausman M, Menascu S, Kramer U. Efficacy of CBD-enriched medical cannabis for treatment of refractory epilepsy in children and adolescents: an observational, longitudinal study. Brain Dev 2018; 40(7):544-51. doi: 10.1016/j.braindev.2018.03.013.
Tzadok M, Uliel S, Linder I, Kramer U, Epstein O, Menascu S, et al. CBD-enriched medical cannabis for intractable pediatric epilepsy: The current Israeli experience. Seizure 2016; 35:41-4. doi: 10.1016/j.seizure.2016.01.004.
McCoy B, Wang L, Zak M, Al-Mehmadi S, Kabir N, Alhadid K, et al. A prospective open-label trial of a CBD/THC cannabis oil in dravet syndrome. Ann Clin Transl Neurol 2018; 5(9):1077-88. doi: 10.1002/acn3.621.
Nixon A, Kerr C, Breheny K, Wild D. Patient Reported Outcome (PRO) assessment in epilepsy: a review of epilepsy-specific PROs according to the Food and Drug Administration (FDA) regulatory requirements. Health Qual Life Outcomes 2013; 11:38. doi: 10.1186/1477-7525-11-38.
Mohanraj R, Brodie M. Measuring the efficacy of antiepileptic drugs. Seizure 2003; 12(7):413-43. doi: 10.1016/s1059-1311(03)00047-5.
Golyala A, Kwan P. Drug development for refractory epilepsy: the past 25 years and beyond. Seizure 2017; 44:147-56. doi: 10.1016/j.seizure.2016.11.022.
Patel S, Grinspoon R, Fleming B, Skirvin L, Wade C, Wolper E, et al. The long-term efficacy of cannabidiol in the treatment of refractory epilepsy. Epilepsia 2021; 62(7):1594-603. doi: 10.1111/epi.16936.
Thiele E, Bebin E, Filloux F, Kwan P, Loftus R, Sahebkar F, et al. Long-term cannabidiol treatment for seizures in patients with tuberous sclerosis complex: an open-label extension trial. Epilepsia 2022; 63(2):426-39. doi: 10.1111/epi.17150.
Organización Mundial de la Salud. Adherencia a los tratamientos a largo plazo: pruebas para la acción. Ginebra: OMS. 2004. Disponible en: https://www3.paho.org/spanish/ad/dpc/nc/adherencia-largo-plazo.pdf. (Consulta: 19 abril 2024).
Neale M. Efficacy and safety of cannabis for treating children with refractory epilepsy. Nurs Child Young People 2017; 29(7):32-7. doi: 10.7748/ncyp.2017.e907.
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