Quality of Life in Childhood Epilepsy in pediatric patients enrolled in a prospective, open‐label clinical study with cannabidiol

Rosenberg, Evan C.; Louik, Jay; Conway, Erin; Devinsky, Orrin; Friedman, Daniel J.

doi:10.1111/epi.13815

Cited by 95 publications

(84 citation statements)

References 14 publications

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“…This retention rate compares favorably to other AED trials in TREs (63%‐72%) . This is possibly due to maintenance of long‐term efficacy and/or adverse events that were generally mild; improvements in quality of life and seizure severity also have been reported with CBD, likely resulting in better retention. Withdrawals were spread relatively consistently through the study follow‐up period, and the LOCF sensitivity analysis demonstrated consistent reductions in seizure frequency when data from withdrawn patients were carried through the 96‐week visit window.…”

Section: Discussionmentioning

confidence: 48%

“…This retention rate compares favorably to other AED trials in TREs (63%-72%). 9,10 This is possibly due to maintenance of long-term efficacy and/or adverse events that were generally mild; improvements in quality of life 11,12 and seizure F I G U R E 2 Percentage reduction from baseline in convulsive and total* seizures for (A) efficacy analysis set and (B) LOCF analysis. *Total seizures included convulsive seizures (ie, clonic, tonic, tonic-clonic, atonic, focal secondary generalized) and nonconvulsive seizures (ie, myoclonic, absence, myoclonic-absence, focal with and without impaired consciousness).…”

Section: Discussionmentioning

confidence: 99%

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Long‐term safety and treatment effects of cannabidiol in children and adults with treatment‐resistant epilepsies: Expanded access program results

et al. 2018

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SummaryObjectiveSince 2014, cannabidiol (CBD) has been administered to patients with treatment‐resistant epilepsies (TREs) in an ongoing expanded‐access program (EAP). We report interim results on the safety and efficacy of CBD in EAP patients treated through December 2016.MethodsTwenty‐five US‐based EAP sites enrolling patients with TRE taking stable doses of antiepileptic drugs (AEDs) at baseline were included. During the 4‐week baseline period, parents/caregivers kept diaries of all countable seizure types. Patients received oral CBD starting at 2‐10 mg/kg/d, titrated to a maximum dose of 25‐50 mg/kg/d. Patient visits were every 2‐4 weeks through 16 weeks and every 2‐12 weeks thereafter. Efficacy endpoints included the percentage change from baseline in median monthly convulsive and total seizure frequency, and percentage of patients with ≥50%, ≥75%, and 100% reductions in seizures vs baseline. Data were analyzed descriptively for the efficacy analysis set and using the last‐observation‐carried‐forward method to account for missing data. Adverse events (AEs) were documented at each visit.ResultsOf 607 patients in the safety dataset, 146 (24%) withdrew; the most common reasons were lack of efficacy (89 [15%]) and AEs (32 [5%]). Mean age was 13 years (range, 0.4‐62). Median number of concomitant AEDs was 3 (range, 0‐10). Median CBD dose was 25 mg/kg/d; median treatment duration was 48 weeks. Add‐on CBD reduced median monthly convulsive seizures by 51% and total seizures by 48% at 12 weeks; reductions were similar through 96 weeks. Proportion of patients with ≥50%, ≥75%, and 100% reductions in convulsive seizures were 52%, 31%, and 11%, respectively, at 12 weeks, with similar rates through 96 weeks. CBD was generally well tolerated; most common AEs were diarrhea (29%) and somnolence (22%).SignificanceResults from this ongoing EAP support previous observational and clinical trial data showing that add‐on CBD may be an efficacious long‐term treatment option for TRE.

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Section: Discussionmentioning

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Long‐term safety and treatment effects of cannabidiol in children and adults with treatment‐resistant epilepsies: Expanded access program results

et al. 2018

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“…Significant improvements were observed compared to placebo as an add‐on therapy. Within the other 3 clinical trials of prospective open‐label design ( n = 203), CBD was administered at an average dosing of 42 mg/kg/d and significant improvements in quality of life and seizure frequency compared to baseline were observed . 3 case series and 1 case report (total n = 16) reported beneficial effects of CBD on seizure frequency, duration and severity with an average administered dose of 21 mg/kg/d …”

Section: Resultsmentioning

confidence: 99%

“…18 In the remaining 8 clinical trials of various Epilepsy was the most frequently studied medical condition, with all 11 studies describing beneficial effects of CBD in reducing the severity or frequency of seizures. 12,13,16,24,[26][27][28][33][34][35][36] Within the 4 conducted RCTs (n = 531), an average dosing of 15 mg/kg/d was used where CBD was administered successfully as an add-on therapy to usual anti-epileptic drugs. 12,13,16,24 Significant improvements were observed reported beneficial effects of CBD on seizure frequency, duration and severity with an average administered dose of 21 mg/kg/d.…”

Section: Resultsmentioning

confidence: 99%

A systematic review of cannabidiol dosing in clinical populations

Millar

Stone

Bellman

et al. 2019

Brit J Clinical Pharma

172

148

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Aims Cannabidiol (CBD) is a cannabis‐derived medicinal product with potential application in a wide‐variety of contexts; however, its effective dose in different disease states remains unclear. This review aimed to investigate what doses have been applied in clinical populations, in order to understand the active range of CBD in a variety of medical contexts. Methods Publications involving administration of CBD alone were collected by searching PubMed, EMBASE and ClinicalTrials.gov . Results A total of 1038 articles were retrieved, of which 35 studies met inclusion criteria covering 13 medical contexts. Twenty‐three studies reported a significant improvement in primary outcomes (e.g. psychotic symptoms, anxiety, seizures), with doses ranging between <1 and 50 mg/kg/d. Plasma concentrations were not provided in any publication. CBD was reported as well tolerated and epilepsy was the most frequently studied medical condition, with all 11 studies demonstrating positive effects of CBD on reducing seizure frequency or severity (average 15 mg/kg/d within randomised controlled trials). There was no signal of positive activity of CBD in small randomised controlled trials (range n = 6–62) assessing diabetes, Crohn's disease, ocular hypertension, fatty liver disease or chronic pain. However, low doses (average 2.4 mg/kg/d) were used in these studies. Conclusion This review highlights that CBD has a potential wide range of activity in several pathologies. Pharmacokinetic studies as well as conclusive phase III trials to elucidate effective plasma concentrations within medical contexts are severely lacking and highly encouraged.

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“…In parallel, several open-label state expanded access programs (EAPs) have been initiated in order to study this formulation of CBD for the management of TRE in patients with other seizure etiologies, e.g., focal onset seizures or those with tuberous sclerosis complex (TSC) [10][11][12]. In the EAPs, in addition to improved seizure frequency (SF), improved quality of life has been reported in patients taking CBD [13]. However, the effects of CBD on seizure severity and adverse events profiles (AEPs) have not been examined to date.…”

Section: Introductionmentioning

confidence: 99%

Cannabidiol improves frequency and severity of seizures and reduces adverse events in an open-label add-on prospective study

Szaflarski

Bebin

Cutter

et al. 2018

Epilepsy & Behavior

121

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The objective of this study was to characterize the changes in adverse events, seizure severity, and frequency in response to a pharmaceutical formulation of highly purified cannabidiol (CBD; Epidiolex®) in a large, prospective, single-center, open-label study. We initiated CBD in 72 children and 60 adults with treatment-resistant epilepsy (TRE) at 5 mg/kg/day and titrated it up to a maximum dosage of 50 mg/kg/day. At each visit, we monitored treatment adverse events with the adverse events profile (AEP), seizure severity using the Chalfont Seizure Severity Scale (CSSS), and seizure frequency (SF) using seizure calendars. We analyzed data for the enrollment and visits at 12, 24, and 48 weeks. We recorded AEP, CSSS, and SF at each follow-up visit for the weeks preceding the visit (seizures were averaged over 2-week periods). Of the 139 study participants in this ongoing study, at the time of analysis, 132 had 12-week, 88 had 24-week, and 61 had 48-week data. Study retention was 77% at one year. There were no significant differences between participants who contributed all 4 data points and those who contributed 2 or 3 data points in baseline demographic and AEP/SF/CSSS measures. For all participants, AEP decreased between CBD initiation and the 12-week visit (40.8 vs. 33.2; p < 0.0001) with stable AEP scores thereafter (all p ≥ 0.14). Chalfont Seizure Severity Scale scores were 80.7 at baseline, decreasing to 39.2 at 12 weeks (p < 0.0001) and stable CSSS thereafter (all p ≥ 0.19). Bi-weekly SF decreased from a mean of 144.4 at entry to 52.2 at 12 weeks (p = 0.01) and remained stable thereafter (all p ≥ 0.65). Analyses of the pediatric and adult subgroups revealed similar patterns. Most patients were treated with dosages of CBD between 20 and 30 mg/kg/day. For the first time, this prospective, open-label safety study of CBD in TRE provides evidence for significant improvements in AEP, CSSS, and SF at 12 weeks that are sustained over the 48-week duration of treatment.

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Quality of Life in Childhood Epilepsy in pediatric patients enrolled in a prospective, open‐label clinical study with cannabidiol

Cited by 95 publications

References 14 publications

Long‐term safety and treatment effects of cannabidiol in children and adults with treatment‐resistant epilepsies: Expanded access program results

Long‐term safety and treatment effects of cannabidiol in children and adults with treatment‐resistant epilepsies: Expanded access program results

A systematic review of cannabidiol dosing in clinical populations

Cannabidiol improves frequency and severity of seizures and reduces adverse events in an open-label add-on prospective study

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