Standard of Care and Dravet Syndrome–Specific ASMs: Mechanisms and Risk Management

EP: 1.Symptoms and Disease Progression in Pediatric Patients With Dravet Syndrome

EP: 2.Role of SCN1A Genetic Testing in Diagnosis of Dravet Syndrome

EP: 3.Risk Factors and Risk Mitigation Strategies of SUPED for Patients With Dravet Syndrome

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EP: 4.Standard of Care and Dravet Syndrome–Specific ASMs: Mechanisms and Risk Management

Evolution of Treatment Standards

The treatment landscape for Dravet syndrome has undergone a dramatic paradigm shift over the past decade. Historically, clinicians relied on valproate and clobazam as primary therapies, with limited options that merely avoided worsening symptoms rather than providing targeted treatment. This changed significantly with the FDA approvals of cannabidiol (2018) and fenfluramine (2020), marking the first medications specifically studied and approved for Dravet syndrome. An international consensus group recognized this advancement and revised treatment guidelines, elevating these newer therapies from traditional "last resort" positioning to first- and second-tier recommendations alongside established medications. This represents a fundamental change requiring clinicians to become comfortable using these targeted therapies early in treatment rather than exhausting conventional antiseizure medications first.

Novel Mechanisms and Drug Differentiation

The newer Dravet syndrome–specific medications offer distinct advantages through their unique mechanisms of action, none of which overlap with traditional antiseizure medications or each other. Fenfluramine functions as a broad-spectrum serotonergic agent affecting multiple serotonin receptors, though likely possessing additional unknown mechanisms since other serotonergic drugs such as selective serotonin reuptake inhibitors lack antiseizure properties. Stiripentol works through multiple pathways including γ-aminobutyric acid. modulation and other brain receptors, potentially involving 6 to 7 different mechanisms. This mechanistic diversity provides genuine therapeutic options rather than repeated attempts with similar sodium channel-blocking drugs, offering synergistic potential when combined and representing truly novel approaches to seizure control in this population.

Clinical Implementation and Support Systems

Current treatment guidelines position valproate and clobazam as first-line therapy, with stiripentol and fenfluramine as second-line options, followed by cannabidiol in third-line positioning. Despite REMS requirements for some medications necessitating cardiac monitoring, clinicians emphasize that these safety measures shouldn't deter appropriate drug selection. Specialty pharmacy programs have evolved significantly, now providing superior service compared with traditional pharmacies, with automatic refills, home delivery, and coordinated monitoring services, including portable echocardiograms for REMS compliance, substantially improving family experience and medication adherence.