SCN8A medication choices must be based on phenotype and function and decisions about adding/weaning medications must balance seizure control and optimize quality of life. Below are findings from the consensus about optimal first line treatments, managing multiple medications, guidance on other non-seizure treatments as well as supplemental information for reference.
Finding the Right SCN8A Treatments
Get the latest consensus on treating SCN8A-related disorders. Delve into the consensus-driven insights on first-line treatments, cautionary medications, and the nuanced approach tailored to individual phenotypes. Listen as Dr. Mark P. Fitzgerald, a leading figure in neurogenetics, explains some of the essential highlights from the consensus, including groundbreaking treatment recommendations, honed by global experts, that promise to reshape care for those affected by SCN8A-related epilepsies.
Optimal First-Line Seizure Meds by Phenotype & Function
Optimal Treatments
There was moderate to strong consensus for each treatment item listed below. There are 4 treatment options that caregivers were not provided and therefore only clinician consensus is reported. There was 100% consensus on 3 items, SeL(F)IE first line treatments, sodium channel blockers for GOF variants in SCN8A, and seizure freedom among SCN8A LOF variants.
Legend:
The purple bar represents the consensus level among caregivers.
The orange bar represents the consensus level among clinicians.
Moderate Consensus: The first dashed line represents that at least 80% of respondents fully or partially agree, and fewer than 10% disagree.
Strong Consensus: The second dashed line represents when 80% or more of respondents fully agree.
Severe DEE: the optimal first line treatments are either oxcarbazepine or carbamazepine.
Severe DEE: the optimal first line treatments are either oxcarbazepine or carbamazepine.
SeL(F)IE: the optimal first line treatments are either oxcarbazepine or carbamazepine.
SeL(F)IE: the optimal first line treatments are either oxcarbazepine or carbamazepine.
Mild/Mod DEE: the optimal first line treatments are either oxcarbazepine or carbamazepine.
Mild/Mod DEE: the optimal first line treatments are either oxcarbazepine or carbamazepine.
Medications with sodium channel blocking mechanisms of action are preferred first-line therapies for people with GOF variants in SCN8A.
Medications with sodium channel blocking mechanisms of action are preferred first-line therapies for people with GOF variants in SCN8A.
If SCN8A GOF demonstrates benefit from increase dose of sodium channel drugs, increase it over the recommended maximum range if the medication is otherwise tolerated.
If SCN8A GOF demonstrates benefit from increase dose of sodium channel drugs, increase it over the recommended maximum range if the medication is otherwise tolerated.
Seizure freedom is more likely in person with SCN8A LOF.
Seizure freedom is more likely in person with SCN8A LOF.
SCN8A LOF patients should be cautious of sodium channel blockers.
SCN8A LOF patients should be cautious of sodium channel blockers.
NDD with Generalized Epilepsy: the optimal first-line treatments are either valproate, ethosuximide, or lamotrigine.
NDD with Generalized Epilepsy: the optimal first-line treatments are either valproate, ethosuximide, or lamotrigine.
Supplemental Data on Medications
These charts show how well current treatments work among different SCN8A populations. The first graph shows how the same treatments affect gain of function and loss of function variants differently. Below shows current and weaned medications on the right and physician assessment on the best and worst medications.
Legend:
Purple = Seizure Free Blue = Seizure Reduction Yellow = No Effect Orange = Worsening
From top to bottom: KD = ketogenic diet; CLZ = clonazepam; VGB = vigabatrin; PB = phenobarbital; CLB = clobazam; ESM = ethosuximide; VPA = valproate; TPM = topiramate; LEV = levetiracetam; PHT = phenytoin; CBZ = carbamazepine; LTG = lamotrigine; OXC= oxcarbazepine; ZNS = zonisamide; LCM = lacosamide.
Source: Johannesen KM, et al. Genotype-phenotype correlations in SCN8A-related disorders, Brain, 2022;145(9):2991-3009. doi:10.1093/brain/awab321
From top to bottom: KD = ketogenic diet; CLZ = clonazepam; VGB = vigabatrin; PB = phenobarbital; CLB = clobazam; ESM = ethosuximide; VPA = valproate; TPM = topiramate; LEV = levetiracetam; PHT = phenytoin; CBZ = carbamazepine; LTG = lamotrigine; OXC= oxcarbazepine; ZNS = zonisamide; LCM = lacosamide.
Source: Johannesen KM, et al. Genotype-phenotype correlations in SCN8A-related disorders, Brain, 2022;145(9):2991-3009. doi:10.1093/brain/awab321
The chart below is from the International SCN8A Alliance and shares data on 15 medications used in the treatment of SCN8A across all phenotypes and variants. The gray bar represents the caregiver reported current medication and the red bar represents weaned medications.
From top to bottom: Oxcarbazepine, Carbamazepine, Lacosamide, Phenytoin, Lamotrigine, Zonisamide, Valproic acid, Topiramate, Clobazam, Clonazepam, Phenobarbital, Vigabatrin, Levetiracetam, Prednisone, Epidiolex,
The chart below is from the International SCN8A Alliance and shares data on 15 medications used in the treatment of SCN8A across all phenotypes and variants. The light blue bar represents the caregiver reported best medication and the dark blue bar represents the caregiver reported worst medications.
From top to bottom: Oxcarbazepine, Carbamazepine, Lacosamide, Phenytoin, Lamotrigine, Zonisamide, Valproic acid, Topiramate, Clobazam, Clonazepam, Phenobarbital, Vigabatrin, Levetiracetam, Prednisone, Epidiolex,
Consensus on Rescue Medications for GOF variants
Managing Multiple Medications
Maximum number of ASMs that should be used concurrently: 3 to 4 (may vary with phenotype)
Seizure type(s) has a high impact on choice of any ASM
Factors to consider ADDING another medication for person who are not seizure free:
- Prolonged seizures of SE
- Frequent convulsive seizures
- New SCN8A-specific therapy approved
Factors to consider when determining which medications to REMOVE when modifying therapies:
Most important:
- Efficacy of current medications
- Side effects of current medications
Other factors:
- Duplicative of mechanism of action
- Impact of current medication on developmental progress
- Caregiver concerns
Other non-ASM Treatments
-
Infantile SpasmsClinicians should be aware of the high potential for infantile spasms in the severe phenotype, being aware of distinctive signs and follow well established protocols for Infantile Spasms.
-
Keto DietMild consensus on efficacy of the Keto diet - 70%.
-
VNSNo consensus.
-
CBDNo consensus.
-
Resective SurgeryHigh consensus on the lack of role of resective surgery for SCN8A = 90%.
Referrals
There was moderate to strong consensus for each treatment item listed below. There are 4 treatment options that caregivers were not provided and therefore only clinician consensus is reported. There was 100% consensus on 3 items, SeL(F)IE first line treatments, sodium channel blockers for GOF variants in SCN8A, and seizure freedom among SCN8A LOF variants.
Legend:
The purple bar represents the consensus level among caregivers.
The orange bar represents the consensus level among clinicians.
Moderate Consensus: The first dashed line represents that at least 80% of respondents fully or partially agree, and fewer than 10% disagree.
Strong Consensus: The second dashed line represents when 80% or more of respondents fully agree.
Need for seizure emergency plan and rescue medications
Need for seizure emergency plan and rescue medications
Potential for drug-resistant epilepsy balancing seizure control and quality of life
Potential for drug-resistant epilepsy balancing seizure control and quality of life
Wide spectrum of severity
Wide spectrum of severity
Varying prognosis within and across phenotypes
Varying prognosis within and across phenotypes
Risk of sudden unexpected death in epilepsy (SUDEP)
Risk of sudden unexpected death in epilepsy (SUDEP)
Expected presence and evolution of comorbidities.
Expected presence and evolution of comorbidities.
Understanding seizure types and possible triggers.
Understanding seizure types and possible triggers.
Risks and benefits of recommended treatments
Risks and benefits of recommended treatments
Prognosis, as requested
Prognosis, as requested
Transition
During the transition of care from pediatric to adult providers, providing a transition document is very important (Clinicians & Caregivers consensus: Strong). In an open-ended question, clinicians noted several factors critical to transition of care: finding the right provider with knowledge of DEEs, and SCN8A-related disorders more specifically; good communication between the pediatric and adult neurologist; and providing proper support for families. The most significant barrier to transition, noted by 18 clinicians, was that many adult providers are not comfortable or familiar with DEEs and SCN8A-related disorders.
⯆ Keep Exploring ⯆
IMPORTANT: While this consensus data provides new and valuable insights about best practices in the diagnosis and treatment of SCN8A, this is not medical advice. It can inform clinicians and caregivers alike in developing optimal treatment plans for each individual.
Disclaimer for Consensus and Individual Variation
This consensus process was carried out by a panel of expert clinicians who actively treat patients with SCN8A-related disorders. Guidelines determined from a consensus differ from those determined from a population-based study*. The extent of consensus reached is restricted by the number of patients seen by each clinician and the portion of the disease spectrum these patients represent.
Consensus guidelines serve as a recommended starting point for clinicians to treat patients based on the best evidence available. If an affected individual does not fit the expected profile, it is important to reassess your treatment plan and revise accordingly. Reassessment of the consensus guidelines will occur as new data become available and the number of patients seen by clinicians increases.
Guidelines based on future consensus processes will therefore reflect advancements in clinical care.
*Population-based studies reveal general trends for large subsets of the population. It is important to remember that each individual is unique and may not necessarily follow these trends regarding developmental progression, seizure remission, or effective treatment.