Clobazam as an adjunctive therapy in treating seizures associated with Lennox&amp;ndash;Gastaut syndrome

Leahy, Jennifer T; Chu-Shore, Catherine J.; Fisher, Janet L.

doi:10.2147/ndt.s20173

Cited by 9 publications

(3 citation statements)

References 86 publications

(186 reference statements)

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“…95 This is a major requirement to make clobazam TDM a better instrument in the prediction of response and ADRs. Unfortunately, it is not easy to study this issue in a definitive way.…”

Section: Discussionmentioning

confidence: 99%

Clobazam Therapeutic Drug Monitoring

Leon

Spina

Díaz

2013

Therapeutic Drug Monitoring

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Background Clobazam was recently approved for Lennox-Gastaut syndrome in the US. There is no published review article focused on clobazam therapeutic drug monitoring (TDM) in English. Methods More than two hundred clobazam articles identified by a PubMed search were carefully reviewed for information on clobazam pharmacokinetics. Clobazam is mainly metabolized by a cytochrome P450 (CYP) isoenzyme, CYP3A4, to its active metabolite, N-desmethylclobazam. Then, N-desmethylclobazam is mainly metabolized by CYP2C19 unless the individual has no CYP2C19 activity (poor metabolizer, PM). Results Using a mechanistic approach to reinterpret the published findings of steady-state TDM and single-dosing pharmacokinetic studies, four different serum clobazam concentration ratios were studied. The available limited steady-state TDM data suggest that the serum N-desmethylclobazam/clobazam ratio can be useful for clinicians, including identifying CYP2C19 PMs (ratio >25 in the absence of inhibitors). There are three possible concentration/dose (C/D) ratios. The clobazam C/D ratio has the potential to measure the contribution of CYP3A4 activity to the clearance of clobazam from the body. The N-desmethylclobazam C/D ratio does not appear to be a good measure of clobazam clearance and should be substituted with the total (clobazam+N-desmethylclobazam) C/D ratio. Conclusions Future clobazam TDM studies need to use trough concentrations after steady-state has been reached (>3 weeks in normal individuals and several months in CYP2C19 PMs). These future studies need to explore the potential of clobazam and total C/D ratios. Better studies on the relative potency of N-desmethylclobazam compared to the parent compound are needed to provide weighted total serum concentrations that correct for the possible lower N-desmethylclobazam pharmacodynamic activity. Standardization and more studies of C/D ratios from clobazam and other drugs can be helpful to move TDM forward.

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“…95 This is a major requirement to make clobazam TDM a better instrument in the prediction of response and ADRs. Unfortunately, it is not easy to study this issue in a definitive way.…”

Section: Discussionmentioning

confidence: 99%

Clobazam Therapeutic Drug Monitoring

Leon

Spina

Díaz

2013

Therapeutic Drug Monitoring

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“…A review study conducted in 2011 evaluated several studies on the effectiveness of CLB, 10 both prospective and retrospective studies. In pediatric patients with refractory epilepsy, six open-label prospective studies have shown that at least 54%-85% of patients experienced at least a 50% drop in seizure rates ( Table 1 ).…”

Section: The Use Of Clobazam As An Adjunct Therapy In the Treatment Omentioning

confidence: 99%

Clobazam and Its Use in Epilepsy

Pernea

Sutcliffe

2016

Pediatric Reports

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Clobazam (CLB) is an older anti-epileptic drug, with a slightly different chemical structure from that of the classic benzodiazepines currently used in the treatment of epilepsy, which confers less sedative properties in terms of negative adverse effects. It is also thought to be better tolerated than other anti-epileptic drugs, whilst maintaining a very similar level of efficacy. It has been tested extensively in over 50 studies on more than 3000 patients with epilepsy and is now approved as an adjunctive treatment of epilepsy in >100 countries. The aim of this review is to evaluate several existing studies on the effectiveness of CLB as an adjunctive therapy in the treatment of epilepsy and whether this therapy is more useful in particular types of epilepsy or seizure prevention. This is not a systematic review but a general overview of some of the most recent studies on the effectiveness of CLB as an adjunctive therapy. Additionally, the benefits of having an oral suspension of CLB will be evaluated with regards to patient groups benefiting from this formulation. The last issue addressed is that of the importance of prescribing CLB by brand, along with the benefits and risks of not doing so.

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“…Current treatments for epileptic seizures generally aim to increase inhibition or decrease hyperexcitation in the neurotransmission pathways related to seizure pathogenesis ( 11 , 12 ). However, many AEDs, such as Clobazam, do not show adequate effect in many patients ( 13 ). These AEDs could not work as an intervention to control refractory seizures by targeting different intercellular pathways ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

Comparison of various doses of oral cannabidiol for treating refractory epilepsy indications: a network meta-analysis

Wang,

Zhu,

Liu

et al. 2024

Front. Neurol.

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AimTo evaluate the comparative efficacy and safety of various doses of oral cannabidiol (CBD) in treating refractory epilepsy indications, thus providing more informative evidence for clinical decision-making.MethodsA literature search of PubMed, Embase, the Cochrane library, and Web of Science (WoS) was performed to retrieve relevant randomized controlled trials (RCTs) that compared different doses of oral CBD with placebo or each other in refractory epilepsy indications. The search was limited from the inception of each database to January 3, 2023. Relative risk [RR] with a 95% confidence interval [CI] was used to express results. STATA/SE 14 was employed for network meta-analysis.ResultsSix RCTs involving 972 patients were included in the final data analysis. Network meta-analysis showed that, CBD10 (10 mg/kg/day) (RR: 1.77, 95%CI: 1.28 to 2.44), CBD20 (20 mg/kg/day) (RR: 1.91, 95%CI: 1.49 to 2.46), CBD25 (25 mg/kg/day) (RR: 1.61, 95%CI: 0.96 to 2.70), and CBD50 (50 mg/kg/day) (RR: 1.78, 95%CI: 1.07 to 2.94) were associated with higher antiseizure efficacy although the pooled result for CBD25 was only close to significant. In addition, in terms of the risk of treatment-emergent adverse events (TEAEs), the difference between different doses is not significant. However, CBD20 ranked first in terms of antiseizure efficacy, followed by CBD50, CBD10, and CBD25. For TEAEs, CBD25 ranked first, followed by CBD10, CBD50, CBD5, and CBD20.ConclusionFor refractory indications, CBD20 may be optimal option for antiseizure efficacy; however, CBD25 may be best for TEAEs. Therefore, an appropriate dose of oral CBD should be selected based on the actual situation. Due to the limitations of eligible studies and the limited sample size, more studies are needed in the future to validate our findings.

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Clobazam as an adjunctive therapy in treating seizures associated with Lennox–Gastaut syndrome

Cited by 9 publications

References 86 publications

Clobazam Therapeutic Drug Monitoring

Clobazam Therapeutic Drug Monitoring

Clobazam and Its Use in Epilepsy

Comparison of various doses of oral cannabidiol for treating refractory epilepsy indications: a network meta-analysis

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