International SCN8A Alliance Logo

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.

Play Video

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.

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

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

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

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.