Cognitive and behavioral effects of cannabidiol in patients with treatment-resistant epilepsy

Metternich, Birgitta; Wagner, Kathrin; Geiger, Maximilian J.; Hirsch, M.; Schulze‐Bonhage, Andreas; Klotz, Kerstin Alexandra

doi:10.1016/j.yebeh.2020.107558

Cited by 24 publications

(17 citation statements)

References 45 publications

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“…This appears to be a plausible explanation for the global impression of a positive behavioral change reported in the extended-use trials on CBD and should be addressed by formalized and standardized neurocognitive assessments in the future. Indeed, a very recent publication in patients with epilepsy could show that functions of selective attention and caregiver-rated behavior significantly improved, however, without being correlated with CBD dose [51].…”

Section: Cognitive and Behavioral Effects Of Cbdmentioning

confidence: 99%

Cannabidiol in the Treatment of Epilepsy

2021

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Anecdotal reports addressing the successful seizure treatment of severe epilepsies with cannabidiol (CBD) have increased both public interest and academic research. Placebo-controlled, randomized, controlled trials proved the efficacy of pharmaceutical-grade CBD in epilepsy treatment, thus leading to pharmaceutical-grade CBD approval by the US Food and Drug Administration and the European Medicines Agency for the treatment of seizures in Dravet syndrome and Lennox–Gastaut syndrome as well as for tuberous complex syndrome by the Food and Drug Administration only. However, the CBD market is confusing because an array of products of different origins, purity, and concentration is available. Additionally, the results from the pivotal studies with plant-derived, pharmaceutical-grade CBD cannot simply be transferred to other epilepsy types or CBD of any origin. Because of the high demands and expectations that patients with epilepsy and their caregivers have regarding CBD, information outlining the proven facts and potential risks is essential. The aim of this article is to thoroughly review available research data and practical recommendations to provide the treating physician with the necessary information for counseling patients with epilepsy.

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Section: Cognitive and Behavioral Effects Of Cbdmentioning

confidence: 99%

Cannabidiol in the Treatment of Epilepsy

2021

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“…A few studies reported some improvement of language and motor skills, alertness, and sleep, but these were based on parental observations rather than standardized tests [27]. In a previous study in children and adults, we showed a slight improvement of selective attention but stable results in other investigated cognitive domains [28]. No studies have provided data to investigate the relationship between IEDs, sleep, and cognitive function during cannabidiol therapy.…”

Section: Discussionmentioning

confidence: 80%

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

et al. 2021

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Background Cannabidiol has been shown to be effective in seizure reduction in patients with Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis. However, very little is known about its potential to reduce interictal epileptiform activity and improve sleep architecture. Objective The objective of this prospective study was to evaluate the influence of cannabidiol therapy on the frequency of interictal epileptiform discharges (IEDs) and sleep microstructure in a cohort of children with drug-resistant epilepsy. Methods Children with drug-resistant epilepsy were prospectively followed from November 2019 to January 2021 during an open-label trial of cannabidiol at a dose of 20 mg/kg/day (to a maximum of 50 mg/kg/day) and stable concomitant medication. Electroencephalograms were recorded at baseline (T0) and after 3 months (T1). Two independent raters, blinded to clinical outcome, evaluated 5-min segments of sleep stage 2 or low-noise awake state. IEDs were visually identified and rates per minute calculated. Sleep microstructure was considered improved if sleep structures were seen at T1 that were not present at T0. IED rates at T0 and T1 were compared and correlated with seizure outcome, cannabidiol dose, initial IED rate, and disease duration. Results In total, 35 children (mean ± standard deviation age 10.1 ± 0.86) were included. The IED rate at T1 was significantly lower than at T0 (19.6 ± 19.5 vs. 36.8 ± 27.2, respectively; p < 0.0001). We found a moderate correlation between IED reduction and percentage of seizure reduction compared with baseline (Pearson's r = 0.39; p = 0.02), a moderate negative correlation between IED reduction and IED rate at T0 (r = − 0.34; p = 0.04), and a trend towards a moderate negative correlation between IED reduction and disease duration (r = − 0.32; p = 0.06). Sleep was recorded in 23 patients. Sleep microstructure was initially abnormal in 56.5% of sleep recordings and improved in 84.6% of those cases. Conclusion Our results strongly suggest the utility of cannabidiol in reducing IEDs and improving sleep microstructure in children with drug-resistant epilepsy. Larger controlled studies are needed to evaluate the clinical relevance of this effect in different epilepsy types.

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“…Additionally, it is noteworthy that it is currently difficult to choose an ASM based on the seizure type, although ethosuximide is better suited for absence seizures. Second, evidence around improvements in cognitive dysfunction and in quality of life is still generally lacking, although there are the beginnings of evidence that FFA and CBD have the potential for improvements in these highly relevant treatment goals [115][116][117]. In addition, while it is known that the burden of illness and healthcare costs of DS are high [118][119][120][121][122][123], there is a lack of published evaluations regarding the cost effectiveness of the ASMs used to treat patients with DS.…”

Section: Discussionmentioning

confidence: 99%

A Practical Guide to the Treatment of Dravet Syndrome with Anti-Seizure Medication

Strzelczyk

Schubert‐Bast

2022

CNS Drugs

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Dravet syndrome is a severe developmental and epileptic encephalopathy characterised by refractory seizures and cognitive dysfunction. The treatment is challenging, not least because the seizures are highly drug resistant, requiring multiple anti-seizure medications (ASMs), while some ASMs can exacerbate seizures. Initial treatments include the broad-spectrum ASMs valproate (VPA), and clobazam (CLB) in some regions; however, they are generally insufficient to control seizures. With this in mind, three adjunct ASMs have been approved specifically for the treatment of seizures in patients with Dravet syndrome: stiripentol (STP) in 2007 in the European Union and 2018 in the USA, cannabidiol (CBD) in 2018/2019 (in combination with CLB in the European Union) and fenfluramine (FFA) in 2020. These "add-on" therapies (mostly to VPA/ CLB) are used as escalation therapies, with the choice dependent on availability in different countries, patient characteristics and caregiver preferences. Topiramate is also frequently used, with evidence of efficacy in Dravet syndrome, and there is anecdotal evidence of efficacy with bromide, which is frequently used in Germany and Japan. With a growing treatment landscape for Dravet syndrome, there can be practical challenges for clinicians, particularly with issues associated with polypharmacy. This practical guide provides an overview of these main ASMs including their indications/contraindications, mechanism of action, efficacy, safety and tolerability profile, dosage requirements, and laboratory and clinical parameters to be evaluated. Standard laboratory and clinical parameters include blood counts, liver function tests, serum concentrations of ASMs, monitoring the growth of children, as well as weight loss and acceleration of behavioural problems. Regular cardiac monitoring is also important with FFA as it has previously been associated with cases of cardiac valve disease when used in adults at high doses (up to 120 mg/day) in combination with phentermine as a therapy for obesity. Importantly, no signs of heart valve disease have been documented to date at the low doses used in patients with developmental and epileptic encephalopathies. In addition, potential drug-drug interactions and their consequences are a key consideration in everyday practice. Interactions that potentially require dosage adjustments to alleviate adverse events include the following: STP + CLB resulting in increased plasma concentrations of CLB and its active metabolite norclobazam may increase somnolence, and an interaction with STP and VPA may increase gastrointestinal adverse events. Cannabidiol has a bi-directional interaction with CLB producing an increase in plasma concentrations of 7-OH-CBD and norclobazam resulting in the potential for increased somnolence and sedation. In addition, CBD is associated with elevations of liver transaminases particularly in patients taking concomitant VPA. The interaction between FFA and STP requires a dose reduction of FFA. Furthermore,

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Cognitive and behavioral effects of cannabidiol in patients with treatment-resistant epilepsy

Cited by 24 publications

References 45 publications

Cannabidiol in the Treatment of Epilepsy

Cannabidiol in the Treatment of Epilepsy

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

A Practical Guide to the Treatment of Dravet Syndrome with Anti-Seizure Medication

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