The clinical, economic, and humanistic burden of Dravet syndrome – A systematic literature review

Sullivan, Joseph; Deighton, Alison; Vila, Maria Candida; Szabo, Shelagh M.; Maru, B.; Gofshteyn, Jacqueline S.; James, Emma; Rico, Salvador; Zuberi, Sameer M.

doi:10.1016/j.yebeh.2022.108661

Cited by 23 publications

(34 citation statements)

References 150 publications

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“…This is particularly pertinent when considering the substantial impact that these comorbidities have on the QoL of patients with DEEs and their family caregivers [ 9 – 13 , 312 , 328 ]. Furthermore, comorbidities contribute to the heavy economic burden that DEEs impose on healthcare systems, families and society [ 329 – 332 ].…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…After the initial febrile phase, a second phase usually occurs between early childhood until late childhood/early puberty [ 6 , 14 ]. The second phase is very taxing on children and their parents, because seizures of multiple different types occur at a very high frequency.…”

Section: The Second Phase: Clinician’s Viewmentioning

confidence: 99%

“…The third phase of DS tends to occur well into adolescence [ 6 , 14 ]. This phase is characterized by relative improvements in seizure frequency and intensity, but continuation of the developmental, communication, and behavioral symptoms.…”

Section: The Third Phase: Clinician’s Viewmentioning

confidence: 99%

Two Perspectives on Dravet Syndrome: Viewpoints from the Clinician and the Caregiver

Bluvstein

Wenniger

2023

Neurol Ther

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Dravet syndrome (DS) is a severe genetic epilepsy characterized by early-life onset, seizures, and neurodevelopmental delays that have major impacts on affected children. DS is an incurable condition that requires a lifelong multidisciplinary approach involving both clinical and caregiver support. A better understanding of the multiple perspectives involved in the care of patients is necessary for supporting the diagnosis, management, and treatment of DS. Here we describe the personal experiences of a caregiver and a clinician facing the challenges of diagnosing and treating a patient throughout the three phases of DS. During the initial phase, the main goals include establishing an accurate diagnosis, coordination of care, and communication between clinicians and caregivers. After a diagnosis is established, frequent seizures and developmental delays are a major concern in the second phase, which is very taxing on children and their caregivers, so caregivers require support and resources to advocate for safe and effective care. Seizures may improve in the third phase, but developmental, communication, and behavioral symptoms persist as caregivers navigate the eventual transition from pediatric to adult care. Optimal care for patients is provided when clinicians are well educated on the syndrome and collaboration is established between members of the medical team and family.

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“…In addition to clinical research investigating therapies, evaluating the burden of illness is key to understanding the challenges and needs of patients and their caregivers, together with understanding the impact and challenges on healthcare systems and society. Systematic literature reviews (SLRs) evaluating the burden of illness in DS and TSC have recently been published [ 25 , 26 ]. However, there are no SLRs on this topic for LGS.…”

Section: Introductionmentioning

confidence: 99%

The burden of illness in Lennox–Gastaut syndrome: a systematic literature review

Strzelczyk

Zuberi

Striano

et al. 2023

Orphanet J Rare Dis

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Background Lennox–Gastaut syndrome (LGS) is a severe developmental and epileptic encephalopathy characterized by drug-resistant epilepsy with multiple seizure types starting in childhood, a typical slow spike-wave pattern on electroencephalogram, and cognitive dysfunction. Methods We performed a systematic literature review according to the PRISMA guidelines to identify, synthesize and appraise the burden of illness in LGS (including “probable” LGS). Studies were identified by searching MEDLINE, Embase and APA PsychInfo, Cochrane’s database of systematic reviews, and Epistemonikos. The outcomes were epidemiology (incidence, prevalence or mortality), direct and indirect costs, healthcare resource utilization, and patient and caregiver health-related quality of life (HRQoL). Results The search identified 22 publications evaluating the epidemiology (n = 10), direct costs and resource (n = 10) and/or HRQoL (n = 5). No studies reporting on indirect costs were identified. With no specific ICD code for LGS in many regions, several studies had to rely upon indirect methods to identify their patient populations (e.g., algorithms to search insurance claims databases to identify “probable” LGS). There was heterogeneity between studies in how LGS was defined, the size of the populations, ages of the patients and length of the follow-up period. The prevalence varied from 4.2 to 60.8 per 100,000 people across studies for probable LGS and 2.9–28 per 100,000 for a confirmed/narrow definition of LGS. LGS was associated with high mortality rates compared to the general population and epilepsy population. Healthcare resource utilization and direct costs were substantial across all studies. Mean annual direct costs per person varied from $24,048 to $80,545 across studies, and home-based care and inpatient care were significant cost drivers. Studies showed that the HRQoL of patients and caregivers was adversely affected, although only a few studies were identified. In addition, studies suggested that seizure events were associated with higher costs and worse HRQoL. The risk of bias was low or moderate in most studies. Conclusions LGS is associated with a significant burden of illness featuring resistant seizures associated with higher costs and worse HRQoL. More research is needed, especially in evaluating indirect costs and caregiver burden, where there is a notable lack of studies.

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The clinical, economic, and humanistic burden of Dravet syndrome – A systematic literature review

Cited by 23 publications

References 150 publications

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

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

Two Perspectives on Dravet Syndrome: Viewpoints from the Clinician and the Caregiver

The burden of illness in Lennox–Gastaut syndrome: a systematic literature review

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