Guidance

6 Treating childhood-onset epilepsies

6 Treating childhood-onset epilepsies

Antiseizure medications for childhood-onset epilepsy syndromes are considered off-label unless they are authorised for the specific syndrome.

6.1 Dravet syndrome

For more information on treatment in women and girls, see the section on antiseizure medications for women and girls.

Follow the Medicines and Healthcare products Regulatory Agency (MHRA) safety advice on valproate use by women and girls and antiepileptic drugs in pregnancy.

Antiseizure medicines: NICE is assessing the impact of the following MHRA drug safety updates on recommendations in this guideline:

For guidance on safe prescribing and managing withdrawal of clobazam in adults, see NICE's guideline on medicines associated with dependence or withdrawal symptoms.

Specialist involvement

6.1.1

Ensure that people with Dravet syndrome have an adult or paediatric neurologist with expertise in epilepsy involved in their care.

First-line treatment

6.1.2

Consider sodium valproate as first-line treatment for people with Dravet syndrome. Be aware that sodium valproate should be used with caution in women and girls, but it is recommended as first-line treatment for Dravet syndrome because of the severity of the syndrome and the lack of evidence for other effective first-line treatment options.

6.1.3

If sodium valproate first-line monotherapy is started or continued for Dravet syndrome in women and girls able to have children (including young girls who are likely to need treatment when they are old enough to have children):

  • discuss the potential risks and benefits of treatment, including the risks to an unborn child

  • take into account the likelihood of pregnancy and put in place a pregnancy prevention programme, if appropriate.

    Follow the MHRA safety advice on valproate use by women and girls.

6.1.4

If sodium valproate alone is unsuccessful as first-line monotherapy for Dravet syndrome, consider triple therapy with stiripentol and clobazam as first-line add-on therapy. Carefully titrate the additional drugs and review treatment frequently, including monitoring for adverse effects such as sedation.

In April 2022, these were off-label uses of clobazam as add-on therapy in children under 6 months, and stiripentol when it is started in adults over 18 years. See NICE's information on prescribing medicines.

Second-line treatment

Further treatment options

6.1.6

If triple therapy is unsuccessful for Dravet syndrome in a child aged under 2 years or second-line treatment is unsuccessful in a child aged over 2 years, consider 1 of the following add-on options under the supervision of a ketogenic diet team or a neurologist with expertise in epilepsy, as appropriate:

  • ketogenic diet

  • levetiracetam

  • topiramate.

    If the first choice is unsuccessful, consider the other add-on options.

    In April 2022, these were off-label uses of levetiracetam and topiramate. See NICE's information on prescribing medicines.

6.1.7

If all other treatment options for Dravet syndrome are unsuccessful, consider potassium bromide under the guidance of a neurologist with expertise in epilepsy.

In April 2022, potassium bromide was not licensed for use in the UK. See NICE's information on prescribing medicines.

Other treatment considerations

For a short explanation of why the committee made these recommendations and how they might affect practice, see the rationale and impact section on Dravet syndrome.

Full details of the evidence and the committee's discussion are in evidence review K: effectiveness of antiseizure therapies in the treatment of Dravet syndrome.

6.2 Lennox–Gastaut syndrome

For more information on treatment in women and girls, see the section on antiseizure medications for women and girls.

Follow the MHRA safety advice on valproate use by women and girls and antiepileptic drugs in pregnancy.

Antiseizure medicines: NICE is assessing the impact of the following MHRA drug safety updates on recommendations in this guideline:

Specialist involvement

6.2.1

Ensure that people with Lennox–Gastaut syndrome have an adult or paediatric neurologist with expertise in epilepsy involved in their care.

First-line treatment

6.2.2

Consider sodium valproate as first-line treatment for people with Lennox–Gastaut syndrome. Be aware that sodium valproate should be used with caution in women and girls, but it is recommended as first-line treatment for Lennox–Gastaut syndrome because of the severity of the syndrome and the lack of evidence for other effective first-line treatment options.

6.2.3

If sodium valproate treatment is started or continued for Lennox–Gastaut syndrome in women and girls able to have children (including young girls who are likely to need treatment when they are old enough to have children):

Second-line treatment

6.2.4

If first-line treatment is unsuccessful, consider lamotrigine as a second-line monotherapy or add-on treatment for people with Lennox–Gastaut syndrome.

In April 2022, this use of lamotrigine was off-label as monotherapy in children under 13 years and add-on therapy for children under 2 years. See NICE's information on prescribing medicines.

Third-line treatment

For guidance on safe prescribing and managing withdrawal of clobazam in adults, see NICE's guideline on medicines associated with dependence or withdrawal symptoms.

6.2.5

If second-line treatment is unsuccessful, consider the following as third-line add-on treatment options for people with Lennox–Gastaut syndrome:

Starting an add-on treatment

6.2.6

When starting an add-on treatment in people with Lennox–Gastaut syndrome, carefully titrate the additional medicine and review treatment frequently, including monitoring for adverse effects such as sedation.

Further treatment options

6.2.7

If seizures continue with third-line treatments for Lennox–Gastaut syndrome, consider a ketogenic diet as an add-on treatment under the supervision of a ketogenic diet team.

6.2.8

If all other treatment options for Lennox–Gastaut syndrome are unsuccessful, consider felbamate as add-on treatment under the supervision of a neurologist with expertise in epilepsy.

In April 2022, felbamate was not licensed for use in the UK. See NICE's information on prescribing medicines.

Other treatment considerations

6.2.9

Be aware that the following medications may exacerbate seizures in people with Lennox–Gastaut syndrome:

  • carbamazepine

  • gabapentin

  • lacosamide

  • lamotrigine

  • oxcarbazepine

  • phenobarbital

  • pregabalin

  • tiagabine

  • vigabatrin.

For a short explanation of why the committee made these recommendations and how they might affect practice, see the rationale and impact section on Lennox–Gastaut syndrome.

Full details of the evidence and the committee's discussion are in evidence review L: effectiveness of antiseizure therapies in the treatment of Lennox-Gastaut syndrome.

6.3 Infantile spasms syndrome

Specialist involvement

6.3.1

If a child under 2 years has suspected or confirmed infantile spasms, within 24 hours seek guidance from, and refer the child urgently to, a tertiary paediatric neurologist to ensure rapid assessment, including a sleep electroencephalogram (EEG), and rapid treatment to stop spasms.

Monitoring

6.3.2

Review children under 2 years with infantile spasms at least weekly during treatment and repeat sleep EEG at 2 weeks after starting treatment.

6.3.3

When infantile spasms have stopped, review children monthly and repeat sleep EEG if spasms recur or there are clinical concerns.

First-line treatment

6.3.4

Offer combination therapy with high-dose oral prednisolone and vigabatrin as first-line treatment for infantile spasms that are not due to tuberous sclerosis, unless the child is at high risk of steroid-related side effects.

In April 2022, this was an off-label use of vigabatrin in combination with prednisolone. See NICE's information on prescribing medicines.

6.3.5

Consider vigabatrin alone as first-line treatment for infantile spasms in children at high risk of steroid-related side effects.

6.3.6

Offer vigabatrin alone as first-line treatment for infantile spasms due to tuberous sclerosis. If vigabatrin is ineffective after 1 week, add high-dose oral prednisolone.

In April 2022, this was an off-label use of vigabatrin in combination with prednisolone. See NICE's information on prescribing medicines.

6.3.7

Before starting oral prednisolone for infantile spasms:

  • discuss the possible side effects of steroid treatment with parents and carers

  • test whether the child has antibodies to the varicella zoster virus

  • give the parents and carers a steroid card and information about when to seek medical help for side effects.

6.3.9

When using vigabatrin to treat infantile spasms, increase the dose as outlined in the BNF for children on vigabatrin. Discuss further dose increases with a tertiary paediatric neurologist if the spasms do not stop (clinically and on EEG).

Second-line treatment

6.3.10

If first-line treatment for infantile spasms is unsuccessful, discuss further treatment with a tertiary paediatric epilepsy specialist.

6.3.11

Consider the following as a second-line monotherapy or add-on treatment options for infantile spasms, guided by a ketogenic diet team or tertiary paediatric epilepsy specialist, as appropriate:

  • ketogenic diet

  • levetiracetam

  • nitrazepam

  • sodium valproate

  • topiramate.

    If the first choice is unsuccessful, consider the other second-line options.

    In April 2022, these were off-label uses of levetiracetam, nitrazepam and topiramate. See NICE's information on prescribing medicines.

For a short explanation of why the committee made these recommendations and how they might affect practice, see the rationale and impact section on infantile spasms syndrome.

Full details of the evidence and the committee's discussion are in evidence review P: effectiveness of antiseizure therapies for infantile spasms.

6.4 Self-limited epilepsy with centrotemporal spikes

For more information on treatment in women and girls, see the section on antiseizure medications for women and girls. Follow the MHRA safety advice on antiepileptic drugs in pregnancy.

Discussing starting treatment

6.4.1

Discuss with children and young people with self-limited epilepsy with centrotemporal spikes, and their families or carers as appropriate, whether they wish to start treatment. In particular, discuss:

  • frequency and severity of seizures

  • possible hazards of ongoing seizures (including the small risk of death)

  • possible side effects of treatment.

First-line treatment

6.4.2

Consider lamotrigine or levetiracetam as first-line treatment for self-limited epilepsy with centrotemporal spikes. If either lamotrigine or levetiracetam is unsuccessful, try the other of these options.

In April 2022, these were off-label uses of lamotrigine in children under 13 years, and levetiracetam in children under 16 years. See NICE's information on prescribing medicines.

Second-line treatment

6.4.3

If first-line treatments for self-limited epilepsy with centrotemporal spikes are unsuccessful, consider the following as second-line monotherapy treatment options:

  • carbamazepine

  • oxcarbazepine

  • zonisamide.

    If the first choice is unsuccessful, consider the other second-line monotherapy options.

    In April 2022, these were off-label uses for oxcarbazepine in children under 6 years, and zonisamide in adults and children. See NICE's information on prescribing medicines.

Third-line treatment

6.4.4

If second-line treatments tried are unsuccessful for self-limited epilepsy with centrotemporal spikes, consider sulthiame as monotherapy or add-on treatment, but only after discussion with a tertiary paediatric neurologist.

In April 2022, sulthiame was not licensed for use in the UK. See NICE's information on prescribing medicines.

Other treatment considerations

6.4.5

Be aware that carbamazepine, oxcarbazepine and lamotrigine may rarely exacerbate seizures or the development of another epilepsy syndrome, or affect cognitive performance, in a small number of children and young people with self-limited epilepsy with centrotemporal spikes.

6.4.6

If there is concern about the school performance of a child or young person having antiseizure medication, seek guidance from an epilepsy specialist and consider:

  • sleep electroencephalogram (EEG) to exclude exacerbation of epileptic activity (electrical status epilepticus during sleep) and

  • neuropsychology assessment to review academic performance.

6.4.7

If a child or young person having antiseizure medication treatment develops other seizure types, consider a sleep EEG to exclude exacerbation of epileptic activity (developmental epileptic encephalopathy with spike-wave activation in sleep).

6.4.8

Offer follow up at a frequency and with a healthcare professional appropriate to the child or young person's individual needs. Discuss discontinuing treatment if a child or young person with self-limited epilepsy with centrotemporal spikes is seizure-free for at least 2 years or at age 14 years.

For a short explanation of why the committee made these recommendations and how they might affect practice, see the rationale and impact section on self-limited epilepsy with centrotemporal spikes.

Full details of the evidence and the committee's discussion are in evidence review Q: effectiveness of antiseizure medications for self-limited epilepsy with centrotemporal spikes.

6.5 Epilepsy with myoclonic-atonic seizures (Doose syndrome)

For more information on treatment in women and girls, see the section on antiseizure medications for women and girls.

Follow the MHRA safety advice on valproate use by women and girls and antiepileptic drugs in pregnancy.

Antiseizure medicines: NICE is assessing the impact of the following MHRA drug safety updates on recommendations in this guideline:

Specialist involvement

6.5.1

Discuss the treatment and management of epilepsy with myoclonic-atonic seizures in children with a tertiary paediatric neurologist.

First-line treatment

6.5.2

Consider levetiracetam or sodium valproate as first-line treatments for epilepsy with myoclonic-atonic seizures. If either levetiracetam or sodium valproate is unsuccessful, try the other of these options.

In April 2022, this was an off-label use of levetiracetam. See NICE's information on prescribing medicines.

6.5.3

If sodium valproate is started or continued for epilepsy with myoclonic-atonic seizures in girls or women able to have children (including young girls who are likely to need treatment when they are old enough to have children):

Second-line treatment

6.5.4

If first-line treatments for epilepsy with myoclonic-atonic seizures are unsuccessful, consider a ketogenic diet as a second-line monotherapy or add-on treatment, under the supervision of a ketogenic diet team.

Third-line treatment

For guidance on safe prescribing and managing withdrawal of clobazam in adults, see NICE's guideline on medicines associated with dependence or withdrawal symptoms.

6.5.5

If second-line treatment for epilepsy with myoclonic-atonic seizures is unsuccessful, consider the following as third-line monotherapy or add-on treatment options:

  • clobazam

  • ethosuximide

  • topiramate

  • zonisamide.

    If the first choice is unsuccessful, consider the other third-line options.

    In April 2022, these were off-label uses of clobazam as monotherapy in adults and children, and add-on therapy in children under 6 months, and topiramate and zonisamide in adults and children. See NICE's information on prescribing medicines.

Other treatment considerations

6.5.6

Do not use any of the following medications because they may exacerbate seizures in people with epilepsy with myoclonic-atonic seizures:

  • carbamazepine

  • gabapentin

  • oxcarbazepine

  • phenytoin

  • pregabalin

  • vigabatrin.

Discontinuing medication

6.5.7

Consider discontinuing antiseizure medication treatment in children with epilepsy with myoclonic-atonic seizures who are seizure-free for 2 years.

For a short explanation of why the committee made these recommendations and how they might affect practice, see the rationale and impact section on epilepsy with myoclonic-atonic seizures (Doose syndrome).

Full details of the evidence and the committee's discussion are in evidence review R: effectiveness of antiseizure therapies for epilepsy with myoclonic-atonic seizures (Doose syndrome).