clobazam / Generic mfg. - LARVOL DELTA

Navigating classical Hodgkin lymphoma in a patient with DIAPH1 deletion syndrome: Diagnostic and therapeutic challenges in a rare immuno-genetic context (ASH 2025) - P | "He was commenced on full dose OEPA (vincristine, etoposide, prednisolone, doxorubicin) after histopathologic confirmation of cHL, and following 2 cycles his early response assessment PET showed complete metabolic response. Due to concerns about hepatic enzyme induction and mitochondrial toxicity, anti-seizure therapy was changed to levetiracetam and clobazam, as carbamazepine is a potent CYP3A4 inducer that may decrease exposure to drugs like methylprednisolone (Bartoszek et al., 1987)...This is the first report showing feasibility of full dose induction therapy for cHL with intensive supportive care in DIAPH1 deficiency. Nonetheless, ongoing careful individualised dosing, vigilant toxicity monitoring, and multidisciplinary input remain essential."

Clinical • B Cell Lymphoma • Classical Hodgkin Lymphoma • CNS Disorders • Dental Disorders • Developmental Disorders • Diffuse Large B Cell Lymphoma • Epilepsy • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Mental Retardation • Mucositis • Neutropenia • Non-Hodgkin’s Lymphoma • Ophthalmology • Stomatitis • CYP3A4

Quality of life and synergistic combinations of antiseizure medication in patients treated with cenobamate in early therapy lines for focal-onset seizures. (PubMed, Epilepsy Behav) - "Our study provides evidence that CNB in early therapy lines for focal-onset seizures is associated with an increased HrQoL. Low-dose clobazam can wok synergistically with CNB. The combination with SV2A modulators showed a positive trend."

HEOR • Journal • CNS Disorders • Epilepsy

A Study of Adverse Drug Reactions to Antiepileptic Drugs in Pediatric Epileptic Patients From North India. (PubMed, Cureus) - "The study highlights that ADRs are more common in patients on conventional drugs like valproate, either as monotherapy or polytherapy. Use of newer drugs by physicians and reporting of ADRs by patients should be encouraged for the comprehensive management of childhood epilepsy."

Adverse drug reaction • Journal • CNS Disorders • Epilepsy • Pediatrics

Impact of clobazam on seizure control and antiseizure medication reduction in refractory brain tumor related epilepsy (SNO 2025) - "Despite failing other ASMs, the majority of patients who took clobazam became seizure free. While seizure freedom is the overall goal, reducing side effects is equally important for quality of life. After initiating clobazam, number and dosages of concurrent ASMs may also be reduced while maintaining seizure freedom or a reduced seizure frequency."

Brain Cancer • CNS Disorders • Epilepsy • Glioma • Oncology • Solid Tumor

Impact of clobazam on seizure control and antiseizure medication reduction in refractory brain tumor related epilepsy (SNO 2025) - "Despite failing other ASMs, the majority of patients who took clobazam became seizure free. While seizure freedom is the overall goal, reducing side effects is equally important for quality of life. After initiating clobazam, number and dosages of concurrent ASMs may also be reduced while maintaining seizure freedom or a reduced seizure frequency."

Brain Cancer • CNS Disorders • Epilepsy • Glioma • Oncology • Solid Tumor

Physiologically Based Pharmacokinetic Modeling of Clobazam and Stiripentol Co-Therapy in Dravet Syndrome. (PubMed, J Pers Med) - "Extrapolation to pediatric patients under two years of age predicted CLB, N-CLB, and STP exposures that were comparable to older children and remained within their reported efficacy and safety margins, suggesting no major ontogeny-related effect on exposure. The PBPK model supports the safe extrapolation of CLB and STP co-administration to pediatric Dravet syndrome patients as young as six months."

Journal • PK/PD data • CNS Disorders • Epilepsy • Pediatrics • CYP2C19

Stiripentol Use in Lennox-Gastaut Syndrome: Results from a Phase 2 Clinical Trial (AES 2025) - "They received an average of 3 ASMs, most commonly valproate (n=10) and clobazam (n=8). Despite the small sample size, stiripentol appeared to reduce seizure burden in LGS patients. These promising results support further investigation in a larger, controlled trial."

Clinical • Late-breaking abstract • P2 data • Absence Seizure Disorder • CNS Disorders • Epilepsy • Gastroenterology • Gastrointestinal Disorder

Long-Term Use of Cannabidiol (Epidiolex) in Patients with Refractory Epilepsy - The UM Experience (AES 2025) - "The most frequently used prior ASM was clobazam (70%). Purified Pharmaceutical cannabidiol (CBD) provides modest seizure control in refractory epilepsy of multiple types. While adverse events were common, they led to discontinuation in only a quarter of patients. These real-world findings can provide valuable insights into its potential use in other epilepsy types beyond its current FDA-labeled indications."

Clinical • Late-breaking abstract • Anesthesia • CNS Disorders • Epilepsy • Psychiatry

Cenobamate in real world : a single center study (AES 2025) - "68 patients had a proactive decrease in one or several concomitant ASM dosage, mainly lacosamide (N=25), perampanel (N=14), clobazam (N=12). 51 patients needed a further decrease in other ASM dosage (mainly brivaracetam and lacosamide), and 52 patients could stop at least one concomitant ASM (mainly lacosamide and perampanel)... Efficacy of CNB is confirmed in this real world series of patients. After one year of follow up, the efficacy is maintained with 52% of the patients being either seizure free or responders. Side effects are common and in line with those found in regulatory studies."

Clinical • Real-world • Real-world evidence • Ataxia • CNS Disorders • Epilepsy • Movement Disorders

Corpus Callosotomy for Treatment of Infantile Epileptic Spasms Syndrome: The UCLA Experience (AES 2025) - "Median number of prior anti-seizure medications was 8 (IQR 7 – 10), and all subjects failed to respond to a trial of standard first-line therapy (prednisolone, ACTH, vigabatrin, or a combination thereof)...Patient 2 achieved seizure-freedom (now >1 yr) in response to cannabidiol and clobazam, prior to proposed surgical resection...After relapse with tonic seizures and epileptic spasms, both patients have since responded to cenobamate and remain seizure-free > 1yr... This study suggests that corpus callosotomy may aid in treatment of children with IESS, though the response rate in this series is lower than prior reports (Baba et al, 2018). Nevertheless, CC appears to be helpful in a substantial minority of patients, and CC should perhaps be considered much earlier in the course of epilepsy. Further study is clearly warranted to identify best candidates for CC in the setting of IESS."

CNS Disorders • Epilepsy

Longitudinal Patterns of Obstetrical and Neurological Care for Canadian Women with Epilepsy (1997-2023): Insights from the North American Anti-epileptic Drug Pregnancy Registry (NAAPR) (AES 2025) - "The top three anti-seizure medications at the time of last menstrual period were lamotrogine (25.1%), carbamazepine (23%), and levetiracetam (21.1%) with average reported total daily dose of 309.8 mg (SD = 165.8, range 50-1500), 761.5 mg (SD = 492,4, range 100-3600), and 1651.4 mg (SD = 1005.3, range 125-4000) respectively. Lesser used drugs were topiramate (6.8%), valproic acid (6.1%), and clobazam (0.9%) with an average total daily dose of 250.9 mg (SD = 136.8, range = 25-500), 855.8 mg (SD = 136.8, range = 25-500), and 42.5 mg (SD = 33.0, 10-80) respectively... This study provides one of the largest, multi-decade Canadian-specific data on PPWE to fill a critical gap in current research. Findings of this study can provide insight into important Canadian-specific differences compared to other population-based pregnancy registries."

Clinical • CNS Disorders • Epilepsy • Obstetrics

Real-World Utilization of Stiripentol in Children Aged 3 Years and Younger: A US Perspective (AES 2025) - "At STP initiation, 77% of patients/caregivers reported use of clobazam. Thirty percent of patients had been on cannabidiol (21%) or fenfluramine (9%) prior to starting STP (Table 2)... This analysis represents the 1st, US-led real-world perspective of STP use in patients <3 since the label expansion in 2022. This cohort was dosed near the recommended STP maintenance dose (50mg/kg/day) which aligns with the original RCT. Less than 10% of patients reported somnolence or decreased weight/appetite as an adverse event suggesting increased tolerability."

Clinical • Real-world • Real-world evidence • CNS Disorders • Epilepsy

Allosteric inhibition of phosphodiesterase 4B as a broad-spectrum therapeutic strategy for refractory epilepsy (AES 2025) - "Standardized doses (50 mM) of SN-2000, standard-of-care ASMs (valproic acid [VPA], carbamazepine [CBZ], levetiracetam (LEV), lamotrigine [LTG], VPA + clobazam [CLO]) or vehicle were added to zebrafish media, and seizure-like locomotor activity was quantified using established automated behavioral tracking methods.2Maximal Electroshock (MES) seizure stimulation was performed on C57BL6/129 (WT) mice following oral gavage of SN-2000 40, 60, or 80 mg/kg, VPA 250 mg/kg or vehicle. These findings support PDE4B inhibition as a disease-relevant mechanism in epilepsy and highlight SN-2000 as a promising broad-spectrum anti-seizure therapeutic candidate. SN-2000 demonstrates potential pro-cognitive and behavioral benefits beyond those of available ASMs.1Kinch et al. AES 2024; 2.3492Ibhazehiebo et al., Brain."

CNS Disorders • Epilepsy • Mood Disorders • Psychiatry

A Rare Case of Adult-Onset Lennox-Gastaut Syndrome and possible association with Retinitis Pigmentosa (AES 2025) - "After a month, she was readmitted for breakthrough seizures which progressed to status epilepticus and her epilepsy became intractable, necessitating her to be on multiple antiseizure medications including phenytoin, clobazam, rufinamide, valproic acid, levetiracetam, and topiramate. This is an unusual case of late onset LGS that manifested in adulthood and rapidly became medically intractable. It was associated with simultaneous development of ophthalmologic findings suggestive of retinitis pigmentosa. Adult onset LGS has only been described in 3 cases in the literature."

Clinical • CNS Disorders • Developmental Disorders • Epilepsy • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

Efficacy and Tolerability of RAP-219, a Potential First-in-Class Negative Allosteric Modulator of γ8 Transmembrane AMPA Receptor Associated Protein: Impact on RNS Long Episodes and Focal Seizures (AES 2025) - "Use of perampanel was exclusionary...The most common ASMs were lamotrigine, cenobamate, levetiracetam, zonisamide, and clobazam... The baseline characteristics of the patients enrolled in this innovative POC study testing the electrographic and clinical effect of RAP-219 in RNS patients with FOS are similar to those reported in contemporary Phase 2 and 3 studies. Efficacy, safety, and tolerability of RAP-219 (to be reported) as evaluated during the 8-week, open-label treatment trial are expected to be highly relevant to patients with drug-resistant FOS."

Clinical • Late-breaking abstract • CNS Disorders • Epilepsy

Multi-Night Analysis on the Effect of Epilepsy Medication on Sleep Spindles in Intracranial EEG (AES 2025) - "Each patient took between 1-4 anti-epilepsy medications, which included Lamotrigine, Topiramate, Cenobamate, Clobazam, Oxcarbazepine, Briviact, Carbamazepine, Lacosamide, and Zonisamide. This preliminary analysis into muti-medication effects on sleep spindles during a multi-night EMU stay with intracranial EEG, suggests that there could be a relationship between anti-epilepsy medication dosages and sleep spindle rates. If confirmed in a larger cohort, the observed increase in sleep spindle rate with higher medication doses might suggest a positive effect of medication on sleep. This could be an indirect consequence of the decrease in epileptiform activity, which might permit the augmentation of sleep spindles even outside the seizure onset zone."

CNS Disorders • Epilepsy

Cannabidiol Inhibits Phenytoin Clearance and Can Result in Clinical Changes (AES 2025) - "A CBD interaction has been well documented for patients taking clobazam (CLB) but not for PHT...On presentation, he was taking levetiracetam, clonazepam, and PHT (which mom reported minimized the frequency and severity of his tonic-clonic seizures)...Epidiolex (CBD) was initiated according to the standard titration... These two cases show CBD inhibition of PHT metabolism can lead to significant increases in levels and meaningful clinical changes (in one case sz control and in the other drug toxicity). In case 1, clinical benefit may also relate to the increase in CLB metabolite and direct effect of CBD. However, the recurrence of seizures on lowering the PHT dose and the resumption of improved control once PHT was restored suggests the elevated PHT was most significant."

Clinical • Late-breaking abstract • Ataxia • CNS Disorders • Epilepsy • Movement Disorders • Ophthalmology • CYP2C19

Extending Epilepsy and Pregnancy Registers: A Pilot in The UK Epilepsy and Pregnancy Register to Include Routine Longitudinal Child Follow Up (AES 2025) - "These numbers included rarer ASM exposures such as clobazam, cenobamate, zonisamide, lacosamide and brivaracetam. A dual model of both surveillance and enhanced investigations offers the opportunity to routinely collect screening level child health and neurodevelopmental outcome data across large geographical regions, alongside more enhanced researcher-led data collection for subpopulations. Implementing longitudinal routine child health and neurodevelopmental investigations into already established initiatives such as Epilepsy and Pregnancy Registers will improve available data regarding the safe use of ASMs in women of reproductive age."

Clinical • CNS Disorders • Epilepsy

Epilepsy and Neurodevelopmental Disorders Associated with ASH1L mutations: A Natural History Study of Genotype-Phenotype Correlation (AES 2025) - "Seizures responded to broad spectrum anti-seizure medications (ASMs), mostly with mono- or dual therapy, including Ethosuximide, Valproate, Lamotrigine, Levetiracetam, Clobazam. Our study has demonstrated a higher prevalence and worse phenotypic severity of epilepsy, in female patients with ASH1L mutations, which may implicate sex-specific epigenetic mechanisms of ASH1L in epileptogenesis."

Late-breaking abstract • Neurodevelopmental • Absence Seizure Disorder • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Epilepsy • Genetic Disorders • Mental Retardation • Psychiatry • Tic Disorders • Tourette Syndrome • ASH1L

Practical Consensus Recommendations for Polytherapy Involving Stiripentol in Dravet Syndrome: A Nominal Group Approach (AES 2025) - "The therapeutic arsenal includes non-specific first-line treatments (valproate and clobazam), specific therapies including stiripentol (STP), cannabidiol (CBD) fenfluramine (FFA), and other ASMs such as bromide, topiramate and levetiracetam. This expert consensus, developed through a nominal group technique and supported by an independent vote from international clinicians, provides a framework for all physicians managing DS to evaluate and refine their polytherapy practices with the goal of improving patient care."

CNS Disorders • Epilepsy

Need for Reintroduction of Stiripentol After Weaning in Patients with Dravet Syndrome: A Multicenter Case Series (AES 2025) - "We aimed to evaluate polypharmacy management in DS individuals treated with stiripentol (STP), an approved adjunctive therapy to clobazam (CLB) in the US, and to CLB and valproate (VPA) in Europe. Ten patients with DS from six centres who underwent STP weaning followed by reinstitution of STP were retrospectively ascertained, and descriptive analysis performed. STP was introduced in all patients for seizure control despite multiple prior ASM attempts (median 3 [range 1-7, n=9], most commonly VPA [88.9% patients], topiramate [55.6%], CLB [44.4%])...STP was tapered or discontinued after a median treatment duration of 102 months (range 17-203) for (i) AEs with add-on fenfluramine (FFA) (unsteadiness, tiredness and weight loss, myoclonic seizure cluster and moderate anorexia, severe psychiatric disorder, n=3), (ii) FFA clinical trials or dose increase (n=4), (iii) attempts to simplify polytherapy after seizure reduction with add-on FFA (n=2), cannabidiol (n=2) or ketogenic..."

Clinical • Late-breaking abstract • Absence Seizure Disorder • Anorexia • CNS Disorders • Constipation • Epilepsy • Gastroenterology • Gastrointestinal Disorder • Mental Retardation • Movement Disorders • Psychiatry

Practical Consensus Recommendations for Rational Polytherapy Involving Stiripentol in Dravet Syndrome: Preliminary results of a US Cohort (AES 2025) - "Consensus recommendations1 highlight valproic acid as 1st line treatment, stiripentol (STP), fenfluramine (FFA), and/ or clobazam (CLB) as 1st or 2nd line and other ASMs including cannabidiol (CBD), levetiracetam (LEV) and topiramate (TPM) as 3rd and 4th line. The preliminary results of the expert consensus on DS treatment, developed through a nominal group and validated by independent voting among US clinicians, provide a practical framework for US providers managing DS to help guide polytherapy decisions. The initial results reinforce the infrequent use of DS-specific ASMs highlighted in previous reviews.2 While there was a strong consensus supporting STP's efficacy when added to an existing ASMs, the data revealed limited provider confidence in the management of these DS-specific ASMs, including STP, underscoring the need for targeted education."

Late-breaking abstract • CNS Disorders • Epilepsy

Vagus Nerve Stimulator Placement in a 7-Month-Old with GABRB3 Pathogenic Variant: A Case Report (AES 2025) - "Despite trials of multiple anti-seizure medications (Levetiracetam, Phenobarbital, Felbamate, Clobazam, and Lacosamide) and initiation of the ketogenic diet, seizures persisted ( >20/day) and were accompanied by developmental regression. This case illustrates the potential efficacy and tolerability of VNS in an infant under one year of age with drug-resistant epilepsy due to a GABRB3 pathogenic variant. The patient eventually became seizure free after VNS modification to rapid cycling and weaning all seizure medication. Although data remains sparse for this population, both the age and genetic variant, our findings support the consideration of VNS as an early intervention in infants under 1 year of age with medically refractory epilepsy."

Case report • Clinical • CNS Disorders • Epilepsy

Utilization and Prescribing Patterns of Stiripentol for Dravet Syndrome: Preliminary Results of an International Physician Survey (AES 2025) - "Rationale: Stiripentol (STP) is approved for the treatment of seizures associated with Dravet Syndrome (DS) in patients taking clobazam who are 6 months of age and older...64.3% co-prescribed sodium valproate. Half prescribed STP in conjunction with fenfluramine (FFA), 75.0% with cannabidiol (CBD) with most (85.7%) adjusting the FFA dose when used in combination.When initiating therapy, providers prioritized seizure frequency (53.6%), seizure length (35.7%), and seizure character (10.7%)... Preliminary findings from this survey highlight a modest uptick in STP utilization in DS across experienced pediatric epilepsy specialists. While most providers reported experiencing clinical benefit, adverse effects, and insurance-related barriers were common. These findings suggest STP is utilized but variably implemented in practice, with opportunities to refine dosing strategies and address systemic barriers to optimize outcomes for patients with DS."

Late-breaking abstract • Anesthesia • CNS Disorders • Epilepsy

Real World Utilization of Stiripentol (STP) by United States (US) Prescribers: A 3-Year Analysis Update (AES 2025) - "Despite rational polytherapy recommendations and availability of DS-approved antiseizure medications (ASMs), stiripentol (STP), cannabidiol (CBD), and fenfluramine (FFA), integration into treatment regimens remains limited1...At STP initiation, 71% were taking clobazam (CLB), 33% CBD, and 21% on FFA (previously 75%, 37%, 24%)...Levetiracetam (16%) and valproic acid (15%) were the most common non-DS approved ASMs... This 3-year analysis shows STP dosing remained consistent and below the FDA-approved dose of 50 mg/kg/day, with higher doses in younger patients. Doses of STP increased with longer treatment duration, reflecting titration to maintenance dosing, which is critical for tolerability and reduced premature discontinuations. While maintenance doses in younger patients were consistent with approved dosing, patients ≥ 6 years received lower average STP doses even after 8+ months on therapy."

Clinical • Late-breaking abstract • Real-world • Real-world evidence • CNS Disorders • Epilepsy