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Cannabidiol efficacy independent of clobazam: Meta-analysis of four randomized controlled trials.

ABSTRACT: Objective: The efficacy of cannabidiol (CBD) with and without concomitant clobazam (CLB) was evaluated in stratified analyses of four large randomized controlled trials, two in Lennox-Gastaut syndrome, and two in Dravet syndrome.

Methods: Each trial of CBD (Epidiolex^® in the US; Epidyolex^® in the EU; 10 and 20 mg/kg/day) was evaluated by CLB use. The treatment ratio was analyzed using negative binomial regression for changes in seizure frequency and logistic regression for the 50% responder rate, where the principle analysis combined both indications and CBD doses in a stratified meta-analysis. Pharmacokinetic data were examined for an exposure/response relationship based on CLB presence/absence. Safety data were analyzed using descriptive statistics.

Results: The meta-analysis favored CBD vs. placebo regardless of CLB use. The treatment ratio (95% CI) of CBD over placebo for the average reduction in seizure frequency was 0.59 (0.52, 0.68; P < .0001) with CLB and 0.85 (0.73, 0.98; P = .0226) without CLB, and the 50% responder rate odds ratio (95% CI) was 2.51 (1.69, 3.71; P < .0001) with CLB and 2.40 (1.38, 4.16; P = .0020) without CLB. Adverse events (AEs) related to somnolence, rash, pneumonia, or aggression were more common in patients with concomitant CLB. There was a significant exposure/response relationship for CBD and its active metabolite.

Conclusions: These results indicate CBD is efficacious with and without CLB, but do not exclude the possibility of a synergistic effect associated with the combination of agents. The safety and tolerability profile of CBD without CLB show a lower rate of certain AEs than with CLB.

SUBMITTER: Devinsky O

PROVIDER: S-EPMC7689899 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Cannabidiol efficacy independent of clobazam: Meta-analysis of four randomized controlled trials.

Devinsky Orrin O Thiele Elizabeth A EA Wright Stephen S Checketts Daniel D Morrison Gilmour G Dunayevich Eduardo E Knappertz Volker V

Acta neurologica Scandinavica 20200717 6

<h4>Objective</h4>The efficacy of cannabidiol (CBD) with and without concomitant clobazam (CLB) was evaluated in stratified analyses of four large randomized controlled trials, two in Lennox-Gastaut syndrome, and two in Dravet syndrome.<h4>Methods</h4>Each trial of CBD (Epidiolex<sup>®</sup> in the US; Epidyolex<sup>®</sup> in the EU; 10 and 20 mg/kg/day) was evaluated by CLB use. The treatment ratio was analyzed using negative binomial regression for changes in seizure frequency and logistic re ...[more]

PMID: 32592183

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Project description:Several studies have shown that lisdexamfetamine (LDX) is efficacious in children and adolescents with attention-deficit/hyperactivity disorder (ADHD).Aims of this study were to systematically review the efficacy, acceptability, and tolerability of LDX in child and adolescent ADHD. Any randomized controlled trials (RCTs) of LDX versus placebo carried out in children and adolescents with ADHD were included.The searches of the SCOPUS, MEDLINE, CINAHL and Cochrane Controlled Trials Register were performed in September 2014. Additional searches in the ClinicalTrials. gov and EU Clinical Trials Register database were conducted.This review included all RCTs of LDX versus placebo which were carried out in children and adolescents up to 18 years old. Additionally, the included studies must have reported the final outcomes of: i) severity of ADHD symptoms with standardized scales, ii) rates of improvement, iii) rates of discontinuation. To be more thorough, the languages of such RCTs were not limited.The abstracts from databases were inspected and the full text versions of relevant trials were examined and extracted for important outcomes. The efficacious measurements included either the pooled mean end-point or changed scores of ADHD rating scales, and the rate of improvement. Acceptability and tolerability were measured by the pooled overall discontinuation rate and the pooled discontinuation rate due to adverse events, respectively. A random effect model technique was utilized to synthesize the mean differences (either standardized mean differences or weighted mean differences) and relative risks (RRs) with 95% confidence intervals (CIs).A total of 1,016 children and adolescents with ADHD were included. The dosage of LDX was 30 to 70 mg/day. The pooled mean change scores of LDX-treated group was significantly greater than that of the placebo (weighted mean difference [95% CI] of -15.20 [-19.95, -10.46], I (2)=94%). The pooled improvement rate of the LDX-treated group was also significantly higher than that of the placebo (RR [95% CI] of 0.34 [0.24, 0.47], I (2)=80%). The pooled overall discontinuation rate between the two groups was not significantly different (RR [95% CI] of 0.78 [0.46, 1.31], I (2)=63%). Similarly, the pooled discontinuation rate due to adverse events between the two groups showed no significant difference (RR [95% CI] of 1.99 [0.70, 5.64], I (2)=0%).The number of included studies was limited (five RCTs).According to the present review, LDX was effective and well-tolerated in the treatment of child and adolescent ADHD. Unfortunately, the acceptability of LDX was not better than the placebo. Since the number of included studies was limited, the outcome from this review should be carefully interpreted and considered as preliminary. Further studies, therefore, should be conducted to confirm these findings.Lisdexamfetamine is an efficacious stimulant for treating child and adolescent ADHD.

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Cannabidiol efficacy independent of clobazam: Meta-analysis of four randomized controlled trials.

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Cannabidiol efficacy independent of clobazam: Meta-analysis of four randomized controlled trials.

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