Simona Lattanzi1, Francesco Brigo2,3, Eugen Trinka4,5,6, Gaetano Zaccara7, Pasquale Striano8, Cinzia Del Giovane9, Mauro Silvestrini10. 1. Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Via Conca71, 60020, Ancona, Italy. alfierelattanzisimona@gmail.com. 2. Department of Neuroscience, Biomedicine and Movement Science, University of Verona, Verona, Italy. 3. Division of Neurology, "Franz Tappeiner" Hospital, Merano, BZ, Italy. 4. Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria. 5. Center for Cognitive Neuroscience, Salzburg, Austria. 6. Public Health, Health Services Research and HTA, University for Health Sciences, Medical Informatics and Technology, Hall i. T, Austria. 7. Health Agency of Tuscany, Florence, Italy. 8. Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology Genetics, Maternal and Child Health, "G. Gaslini" Institute, University of Genoa, Genoa, Italy. 9. Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland. 10. Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Via Conca71, 60020, Ancona, Italy.
Abstract
BACKGROUND: Dravet syndrome (DS) is one of the most severe forms of drug-resistant epilepsy and available interventions fail to control seizures in most patients. Cannabidiol (CBD) is the first in a new class of antiepileptic drugs with a distinctive chemical structure and mechanism of action. OBJECTIVE: The aim of this systematic review was to evaluate the efficacy and safety of CBD as adjunctive treatment for seizures in patients with DS using meta-analytical techniques. METHODS: We searched for randomized, placebo-controlled, single- or double-blinded trials. Main outcomes included ≥ 50% reduction in baseline convulsive seizure frequency and the incidence of treatment withdrawal and adverse events (AEs). Risk ratios (RRs) with 95% confidence intervals (95% CIs) were estimated through the inverse variance method. RESULTS: Three trials were included involving 359 participants, 228 for CBD and 131 for placebo groups. In all trials, the active treatment was a plant-derived pharmaceutical formulation of purified CBD oral solution. The pooled RR for 50% response during the treatment was 1.69 (95% CI 1.21-2.36; p = 0.002). Across the trials, treatment was discontinued in 20 (9.0%) and 3 (2.3%) cases in the add-on CBD and placebo groups, respectively; the RR for CBD withdrawal was 3.12 (95% CI 1.07-9.10; p = 0.037). The RR to develop any AE during add-on CBD treatment was 1.06 (95% CI 0.87-1.28; p = 0.561). AEs significantly associated with adjunctive CBD were somnolence, decreased appetite, diarrhea, and increased serum aminotransferases. CONCLUSIONS: Adjunctive CBD resulted in a greater reduction in convulsive seizure frequency than placebo and a higher rate of AEs in patients with DS presenting with seizures uncontrolled by concomitant antiepileptic therapy.
BACKGROUND:Dravet syndrome (DS) is one of the most severe forms of drug-resistant epilepsy and available interventions fail to control seizures in most patients. Cannabidiol (CBD) is the first in a new class of antiepileptic drugs with a distinctive chemical structure and mechanism of action. OBJECTIVE: The aim of this systematic review was to evaluate the efficacy and safety of CBD as adjunctive treatment for seizures in patients with DS using meta-analytical techniques. METHODS: We searched for randomized, placebo-controlled, single- or double-blinded trials. Main outcomes included ≥ 50% reduction in baseline convulsive seizure frequency and the incidence of treatment withdrawal and adverse events (AEs). Risk ratios (RRs) with 95% confidence intervals (95% CIs) were estimated through the inverse variance method. RESULTS: Three trials were included involving 359 participants, 228 for CBD and 131 for placebo groups. In all trials, the active treatment was a plant-derived pharmaceutical formulation of purified CBD oral solution. The pooled RR for 50% response during the treatment was 1.69 (95% CI 1.21-2.36; p = 0.002). Across the trials, treatment was discontinued in 20 (9.0%) and 3 (2.3%) cases in the add-on CBD and placebo groups, respectively; the RR for CBD withdrawal was 3.12 (95% CI 1.07-9.10; p = 0.037). The RR to develop any AE during add-on CBD treatment was 1.06 (95% CI 0.87-1.28; p = 0.561). AEs significantly associated with adjunctive CBD were somnolence, decreased appetite, diarrhea, and increased serum aminotransferases. CONCLUSIONS: Adjunctive CBD resulted in a greater reduction in convulsive seizure frequency than placebo and a higher rate of AEs in patients with DS presenting with seizures uncontrolled by concomitant antiepileptic therapy.
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