Pediatrik Epilepsi Tedavisinde Tıbbi Kannabinoidlerin Kullanımı
Özet
Tıbbi kannabidiol (CBD) preparatı olan Epidiolex, Dravet sendromu, Lennox-Gastaut sendromu ve tüberoz skleroz kompleksi gibi ilaca dirençli pediatrik epilepsilerde nöbet sıklığını belirgin şekilde azaltan güvenli bir tedavi seçeneğidir. Tedaviye genellikle günlük 5 mg/kg dozunda başlanıp ihtiyaca göre maksimum 20 mg/kg doza kadar çıkılabilirken, karaciğer yetmezliği olan hastalarda dozun hassas şekilde düşürülmesi gerekir. Tedavi sürecinde en sık somnolans (uyku hali), iştah azalması, ishal ve karaciğer enzimlerinde yükselme gibi yan etkilerle karşılaşılmaktadır. Bu nedenle tedavi boyunca karaciğer fonksiyonlarının düzenli olarak izlenmesi, özellikle klobazam ve valproat gibi diğer antiepileptik ilaçlarla etkileşimlerin yakından takip edilmesi kritik önem taşır.
Epidiolex, a purified pharmaceutical cannabidiol (CBD), serves as an effective and safe treatment option in reducing seizure frequency for children with drug-resistant epilepsies such as Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex. While the standard dosage starts at 5 mg/kg/day and can be titrated up to a maximum of 20 mg/kg/day, precise dose adjustments are mandatory for patients with hepatic impairment. Somnolence, decreased appetite, diarrhea, and elevated transaminase levels represent the most common adverse effects associated with this therapy. Consequently, regular monitoring of liver function and careful management of potential drug interactions, particularly with clobazam and valproate, are crucial throughout the treatment.
Referanslar
Kachru R, Perry-Lunardo C, Thompson LA. CBD Use in Children-Miracle, Myth, or Mystery? JAMA Pediatr. 2021 Jun 1;175(6):652. doi: 10.1001/jamapediatrics.2021.0367.
Huntsman RJ, Tang-Wai R, Alcorn J, Vuong S, Acton B, Corley S, Laprairie R, Lyon AW, Meier S, Mousseau DD, Newmeyer D, Prosser-Loose E, Seifert B, Tellez-Zenteno J, Huh L, Leung E, Major P. Dosage Related Efficacy and Tolerability of Cannabidiol in Children With Treatment-Resistant Epileptic Encephalopathy: Preliminary Results of the CARE-E Study. Front Neurol. 2019 Jul 3;10:716. doi: 10.3389/fneur.2019.00716.
Reithmeier D, Tang-Wai R, Seifert B, Lyon AW, Alcorn J, Acton B, Corley S, Prosser-Loose E, Mousseau DD, Lim HJ, Tellez-Zenteno J, Huh L, LeungE, Carmant L, Huntsman RJ. The protocol for the Cannabidiol in children with refractory epileptic encephalopathy (CARE-E) study: a phase 1 dosage escalation study. BMC Pediatr. 2018 Jul 7;18(1):221. doi: 10.1186/s12887-018-1191-y.
Raucci U, Pietrafusa N, Paolino MC, Di Nardo G, Villa MP, Pavone P, Terrin G, Specchio N, Striano P, Parisi P. Cannabidiol Treatment for Refractory Epilepsies in Pediatrics. Front Pharmacol. 2020 Sep 29;11:586110. doi: 10.3389/fphar.2020.586110.
Campbell CT, Phillips MS, Manasco K. Cannabinoids in Pediatrics. J Pediatr Pharmacol Ther. 2017 May-Jun;22(3):176-185. doi: 10.5863/1551-677622.3.176.
Maa E, Figi P. The case for medical marijuana in epilepsy. Epilepsia. 2014 Jun;55(6):783-6. doi: 10.1111/epi.12610. Epub 2014 May 22.
WEED: a Dr. Sanjay Gupta investigation [transcript]. Sanjay Gupta MD. CNN television. August 11, 2013. https://edition.cnn.com/2013/08/08/health/gupta-changed-mind-marijuana/index.html
Lattanzi S, Trinka E, Striano P, Rocchi C, Salvemini S, Silvestrini M, Brigo F. Highly Purified Cannabidiol for Epilepsy Treatment: A Systematic Review of Epileptic Conditions Beyond Dravet Syndrome and Lennox-Gastaut Syndrome. CNS Drugs. 2021 Mar;35(3):265-281. doi: 10.1007/s40263-02100807-y. Epub 2021 Mar 22.
Treves N, Mor N, Allegaert K, Bassalov H, Berkovitch M, Stolar OE, Matok I. Efficacy and safety of medical cannabinoids in children: a systematic review and meta-analysis. Sci Rep. 2021 Dec 6;11(1):23462. doi: 10.1038/s41598-021-02770-6.
O’Shaughnessy, W. B. On the Preparations of the Indian Hemp, or Gunjah (Cannabis Indica), Their Effects on the Animal System in Health, and Their Utility in the Treatment of Tetanus and Other Convulsive Diseases. Br Foreign Med Rev. 1840 Jul;10(19):225228. PMID: 30161735; PMCID: PMC5592602.
Lazarini-Lopes W, Do Val-da Silva RA, da Silva-Júnior RMP, Leite JP, Garcia-Cairasco N. The anticonvulsant effects of cannabidiol in experimental models of epileptic seizures: From behavior and mechanisms to clinical insights. Neurosci Biobehav Rev. 2020 Apr;111:166-182. doi: 10.1016/j.neubiorev.2020.01.014. Epub 2020 Jan 16.
Devinsky O, Marsh E, Friedman D, Thiele E, Laux L, Sullivan J, Miller I, Flamini R, Wilfong A, Filloux F, Wong M, Tilton N, Bruno P, Bluvstein J, Hedlund J, Kamens R, Maclean J, Nangia S, Singhal NS, Wilson CA, Patel A, Cilio MR. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016 Mar;15(3):2708. doi: 10.1016/S1474-4422(15)00379-8. Epub 2015 Dec 24. Erratum in: Lancet Neurol. 2016 Apr;15(4):352.
Devinsky O, Cross JH, Wright S. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med. 2017 Aug 17;377(7):699-700. doi:10.1056/NEJMc1708349.
Devinsky O, Patel AD, VanLandingham KE. Cannabidiol in the Lennox-Gastaut Syndrome. N Engl J Med. 2018 Aug 23;379(8):795. doi: 10.1056/NEJMc1807878.
Thiele EA, Marsh ED, French JA, Mazurkiewicz-Beldzinska M, Benbadis SR, Joshi C, Lyons PD, Taylor A, Roberts C, Sommerville K; GWPCARE4 Study Group. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018 Mar 17;391(10125):1085-1096. doi: 10.1016/S0140-6736(18)30136-3. Epub 2018 Jan 26.
Thiele EA, Bebin EM, Bhathal H, Jansen FE, Kotulska K, Lawson JA, O’Callaghan FJ, Wong M, Sahebkar F, Checketts D, Knappertz V; GWPCA-RE6 Study Group. Add-on Cannabidiol Treatment for Drug-Resistant Seizures in Tuberous Sclerosis Complex: A Placebo-Controlled Randomized Clinical Trial. JAMA Neurol. 2021 Mar 1;78(3):285-292. doi: 10.1001/jamaneurol.2020.4607.
Herlopian A, Hess EJ, Barnett J, Geffrey AL, Pollack SF, Skirvin L, Bruno P, Sourbron J, Thiele EA. Cannabidiol in treatment of refractory epileptic spasms: An open-label study. Epilepsy Behav. 2020 May;106:106988. doi: 10.1016/j.yebeh.2020.106988. Epub 2020 Mar 10.
Demarest ST, Olson HE, Moss A, Pestana-Knight E, Zhang X, Parikh S, Swanson LC, Riley KD, Bazin GA, Angione K, Niestroj LM, Lal D, Juarez-Colunga E, Benke TA. CDKL5 deficiency disorder: Relationship between genotype, epilepsy, cortical visual impairment, and development. Epilepsia. 2019 Aug;60(8):1733-1742. doi: 10.1111/epi.16285. Epub 2019 Jul 16.
Erdoğan M, Gümüş H, Öztop DB, Balta B, Bayram KK, Dündar M (2022), Investigation of CDKL5 Gene Mutations in Autistic Patients Accompanied with Intractable Seizures, Autistic Disorder and Seizure in Infancy and Early Childhood, Cumhuriyet Medical Journal, June 2022, 44 ( 2): 165-171.
20. Devinsky O, Verducci C, Thiele EA, Laux LC, Patel AD, Filloux F, Szaflarski JP, Wilfong A, Clark GD, Park YD, Seltzer LE, Bebin EM, Flamini R, Wechsler RT, Friedman D. Open-label use of highly purified CBD (Epidiolex®) in patients with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes. Epilepsy Behav. 2018 Sep;86:131-137. doi:10.1016/j.yebeh.2018.05.013. Epub 2018 Jul 11.
Canpolat M, Per H, Yıkılmaz A, Gümüş H, Özcan A, Poyrazoğlu H, Coşkun A, Kumandaş S. Sturge-Weber sendromu; klinik ve radyolojik değerlendirme. Gaziantep Tıp Dergisi. 2013; 19(1): 30 - 34.
Per H, Canpolat M. Malignant epileptic syndromes in infancy. Erciyes Tıp Dergisi. 2013; 35(4): 189 -197.
chromeextension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.epidiolex.com/sites/default/files/pdfs/1020/EPX-03633-1020_EPIDIOLEX_(cannabidiol)_USPI_v8.0.pdf, Reference ID: 4690296, Revised: 04/2020
chromeextension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.ema.europa.eu/en/documents/overview/epidyolex-epar-medicine-overview_en.pdf, Epidyolex (cannabidiol) EMA/191061/2021.
