Effect of Cannabidiol on Interictal Epileptiform Activity and Sleep Architecture in Children with Intractable Epilepsy: A Prospective Open-Label Study

Klotz, Kerstin Alexandra; Grob, Daniel; Schönberger, Jan; Nakamura, Lea; Metternich, Birgitta; Schulze‐Bonhage, Andreas; Jacobs, Julia

doi:10.1007/s40263-021-00867-0

Cited by 18 publications

(13 citation statements)

References 33 publications

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“…Positive effects on neuro-cognition were observed in six (20%) patients treated with CBD. There is growing evidence for the improvement of neurocognition and sleep architecture after treatment with CBD [10,15,[19][20][21]. Due to the nature of real-world study data with a small population and the nature of LGS, which is usually accompanied by intellectual disabilities, the neuro-cognitive improvements in our study could not be objectively evaluated using a neuropsychiatric assessment tool, and the main resources for the cognitive and behavioral improvements were caregivers' subjective documentation.…”

Section: Discussionmentioning

confidence: 99%

Cannabidiol Treatment for Lennox-Gastaut Syndrome at a Single Tertiary Center in South Korea

et al. 2023

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This study evaluated the efficacy and tolerability of cannabidiol (CBD) as an add-on therapy for childhood-onset Lennox-Gastaut syndrome (LGS). Methods: This retrospective study enrolled patients who visited the Department of Pediatric Neurology at Asan Medical Center from March 2019 to February 2022 and were treated with CBD. Electronic medical records and clinically relevant factors (including the type of epilepsy and seizures, etiology, and the number of concomitantly used anti-epileptic drugs) were reviewed. The outcome was clinical response to CBD (≥50% or <50% seizure reduction at 1, 3, and 6 months after CBD introduction and the last follow-up visit). Relevant adverse events were monitored. Results: Thirty patients were included. The median age of epilepsy onset was 5.5 years (interquartile range [IQR], 3.3 to 25.3), with a median treatment duration of CBD of 6 months (IQR, 3.3 to 7.0). Sixteen patients (53.3%) showed ≥50% seizure reduction at the last follow-up. In a univariate analysis, patients whose epilepsy commenced after 3 years of age were more likely to respond to CBD (odds ratio, 10.11; 95% confidence interval, 1.05 to 97.00; P=0.04). Adverse events were observed in 11 patients (36.6%); the most common adverse event was somnolence. Conclusion: CBD could be a treatment option for children and young adults with drug-resistant LGS with a tolerable safety profile. Age at epilepsy onset (>3 years) was associated with a favorable response to CBD treatment. Further prospective studies with larger populations are needed to evaluate the tolerability and efficacy of CBD in patients with drug-resistant epilepsy of various etiologies.

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Section: Discussionmentioning

confidence: 99%

Cannabidiol Treatment for Lennox-Gastaut Syndrome at a Single Tertiary Center in South Korea

et al. 2023

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“…In-line with this, a recent meta-analysis of CBD trials across multiple therapy areas noted that CBD was only associated with somnolence and sedation in childhood epilepsy trials, most likely owing to interactions with other ASMs such as CLB and VPA [ 94 ]. A small study in children with DRE ( n = 35, including DS, LGS and other genetic epilepsy syndromes) found that of 13 patients with abnormal sleep architecture at baseline, sleep improved in 11 (84.6%) patients [ 95 ].…”

Section: Asms Used In the Treatment Of More Than One Of The Syndromes...mentioning

confidence: 99%

Psychobehavioural and Cognitive Adverse Events of Anti-Seizure Medications for the Treatment of Developmental and Epileptic Encephalopathies

Strzelczyk

Schubert‐Bast

2022

CNS Drugs

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The developmental and epileptic encephalopathies encompass a group of rare syndromes characterised by severe drug-resistant epilepsy with onset in childhood and significant neurodevelopmental comorbidities. The latter include intellectual disability, developmental delay, behavioural problems including attention-deficit hyperactivity disorder and autism spectrum disorder, psychiatric problems including anxiety and depression, speech impairment and sleep problems. Classical examples of developmental and epileptic encephalopathies include Dravet syndrome, Lennox–Gastaut syndrome and tuberous sclerosis complex. The mainstay of treatment is with multiple anti-seizure medications (ASMs); however, the ASMs themselves can be associated with psychobehavioural adverse events, and effects (negative or positive) on cognition and sleep. We have performed a targeted literature review of ASMs commonly used in the treatment of developmental and epileptic encephalopathies to discuss the latest evidence on their effects on behaviour, mood, cognition, sedation and sleep. The ASMs include valproate (VPA), clobazam, topiramate (TPM), cannabidiol (CBD), fenfluramine (FFA), levetiracetam (LEV), brivaracetam (BRV), zonisamide (ZNS), perampanel (PER), ethosuximide, stiripentol, lamotrigine (LTG), rufinamide, vigabatrin, lacosamide (LCM) and everolimus. Bromide, felbamate and other sodium channel ASMs are discussed briefly. Overall, the current evidence suggest that LEV, PER and to a lesser extent BRV are associated with psychobehavioural adverse events including aggressiveness and irritability; TPM and to a lesser extent ZNS are associated with language impairment and cognitive dulling/memory problems. Patients with a history of behavioural and psychiatric comorbidities may be more at risk of developing psychobehavioural adverse events. Topiramate and ZNS may be associated with negative effects in some aspects of cognition; CBD, FFA, LEV, BRV and LTG may have some positive effects, while the remaining ASMs do not appear to have a detrimental effect. All the ASMs are associated with sedation to a certain extent, which is pronounced during uptitration. Cannabidiol, PER and pregabalin may be associated with improvements in sleep, LTG is associated with insomnia, while VPA, TPM, LEV, ZNS and LCM do not appear to have detrimental effects. There was variability in the extent of evidence for each ASM: for many first-generation and some second-generation ASMs, there is scant documented evidence; however, their extensive use suggests favourable tolerability and safety (e.g. VPA); second-generation and some third-generation ASMs tend to have the most robust evidence documented over several years of use (TPM, LEV, PER, ZNS, BRV), while evidence is still being generated for newer ASMs such as CBD and FFA. Finally, we discuss how a variety of factors can affect mood, behaviour and cognition, and untangling the associations between the effects of the underlying syndrome and those of the ASMs can be challenging. In particular, there is enormous h...

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“…They suggest the utility of CBD in reducing IEDs and improving sleep microstructure. Further studies are needed; however, the improvement of behaviour associated with CBD treatment may be due to the reduction in IEDs [35]. This has further implications for studying CBD's effects on cognition.…”

Section: Other Clinical Studiesmentioning

confidence: 99%

Use of cannabidiol in the treatment of epilepsy

Zawadzka

Mazurkiewicz-Bełdzińska

2022

Neurol Neurochir Pol.

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Introduction.Cannabis sativa has been cultivated for human use for about 5,000 years, and has likewise been used in the treatment of epilepsy for thousands of years.State of the art. Cannabidiol (CBD), which was isolated from cannabis sativa in 1940, has an anti-seizure effect and no psychoactive activity. Its effectiveness in reducing various types of seizures has been proven in animal seizure and epilepsy models. Recent randomised, placebo-controlled trials have confirmed its effectiveness in patients with drug-resistant epilepsy.Clinical implications. The aim of this position paper was to present the specific mechanism of CBD's anti-seizure action and current indications for CBD's use in epilepsy. The only cannabis-derived drug that has successfully passed clinical trials and has obtained United States Food and Drug Administration and European Medicines Agency approval for epilepsy is Epidiolex®. This paper presents the outcomes of the completed clinical trials with the use of this drug.Future directions. CBD may be an effective drug in drug-resistant epilepsy, particularly in Dravet Syndrome, Lennox-Gastaut Syndrome and seizures associated with tuberous sclerosis complex. Additional randomised, placebo-controlled studies with CBD are needed.

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Effect of Cannabidiol on Interictal Epileptiform Activity and Sleep Architecture in Children with Intractable Epilepsy: A Prospective Open-Label Study

Cited by 18 publications

References 33 publications

Cannabidiol Treatment for Lennox-Gastaut Syndrome at a Single Tertiary Center in South Korea

Cannabidiol Treatment for Lennox-Gastaut Syndrome at a Single Tertiary Center in South Korea

Psychobehavioural and Cognitive Adverse Events of Anti-Seizure Medications for the Treatment of Developmental and Epileptic Encephalopathies

Use of cannabidiol in the treatment of epilepsy

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