Epilepsies in children, young people and adults

Offer sodium valproate as first-line monotherapy for generalised tonic-clonic seizures in:

• boys and men

• girls aged under 10 years and who are unlikely to need treatment when they are old enough to have children

• women who are unable to have children.

Offer lamotrigine or levetiracetam as first-line monotherapy for generalised tonic-clonic seizures 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). If the first choice is unsuccessful, offer the other of these options.

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

If first-line monotherapy with sodium valproate is unsuccessful for generalised tonic-clonic seizures, offer lamotrigine or levetiracetam as second-line monotherapy treatment. If the first choice 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 adults and children. See NICE's information on prescribing medicines.

Do not offer sodium valproate monotherapy for generalised tonic-clonic seizures 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), unless:

• other treatment options are unsuccessful

• the risks and benefits have been fully discussed, including the risks to an unborn child

• the likelihood of pregnancy has been taken into account and a pregnancy prevention programme put in place, if appropriate.
  
  Follow the MHRA safety advice on valproate use by women and girls.

If monotherapy is unsuccessful in people with generalised tonic-clonic seizures, consider 1 of the following first-line add-on treatment options:

• clobazam

• lamotrigine

• levetiracetam

• perampanel

• sodium valproate, except in women and girls able to have children

• topiramate.
  
  If the first choice is unsuccessful, consider the other first-line add-on options.
  
  In April 2022, these were off-label uses of clobazam as add-on therapy in children under 6 months, lamotrigine in children under 2 years, levetiracetam in children under 12 years, perampanel in children under 7 years, and topiramate in children under 2 years. See NICE's information on prescribing medicines.

If first-line add-on treatments tried are unsuccessful in people with generalised tonic-clonic seizures, consider 1 of the following second-line add-on treatment options:

• brivaracetam

• lacosamide

• phenobarbital

• primidone

• zonisamide.
  
  If the first choice is unsuccessful, consider the other second-line add-on options.
  
  In April 2022, these were off-label uses of brivaracetam in adults and children, lacosamide in children under 4 years, and zonisamide in adults and children. See NICE's information on prescribing medicines.

Do not offer sodium valproate as an add-on treatment for generalised tonic-clonic seizures 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), unless:

• other treatment options are unsuccessful

• the risks and benefits have been fully discussed, including the risks to an unborn child

• the likelihood of pregnancy has been taken into account and a pregnancy prevention programme put in place, if appropriate.
  
  Follow the MHRA safety advice on valproate use by women and girls.

Be aware that the following antiseizure medications may exacerbate seizures in people with absence or myoclonic seizures, including in juvenile myoclonic epilepsy:

• carbamazepine

• gabapentin

• lamotrigine (for myoclonic seizures)

• oxcarbazepine

• phenytoin

• pregabalin

• tiagabine

• vigabatrin.

Consider lamotrigine or levetiracetam as first-line monotherapy for people with focal seizures. If the first choice is unsuccessful, consider the other of these options.

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

If first-line monotherapies are unsuccessful in people with focal seizures, consider 1 of the following second-line monotherapy 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 of oxcarbazepine in children under 6 years, and zonisamide in children. See NICE's information on prescribing medicines.

If second-line monotherapies tried are unsuccessful in people with focal seizures, consider lacosamide as third-line monotherapy.

In April 2022, this was an off-label use of lacosamide in children under 4 years. See NICE's information on prescribing medicines.

If monotherapy is unsuccessful in people with focal seizures, consider 1 of the following first-line add-on treatment options:

• carbamazepine

• lacosamide

• lamotrigine

• levetiracetam

• oxcarbazepine

• topiramate

• zonisamide.
  
  If the first choice is unsuccessful, consider the other first-line add-on options.
  
  In April 2022, these were off-label uses of lacosamide in children under 4 years, lamotrigine in children under 2 years, levetiracetam in children under 4 years, oxcarbazepine in children under 6 years, topiramate in children under 2 years, and zonisamide in children under 6 years. See NICE's information on prescribing medicines.

If first-line add-on treatments tried are unsuccessful in people with focal seizures, consider 1 of the following second-line add-on treatment options:

• brivaracetam

• cenobamate (in line with NICE's technology appraisal guidance on cenobamate for treating focal onset seizures in epilepsy)

• eslicarbazepine acetate

• perampanel

• pregabalin

• sodium valproate, except in women and girls able to have children.
  
  If the first choice is unsuccessful, consider the other second-line add-on options.
  
  In April 2022, these were off-label uses of brivaracetam in children under 4 years, eslicarbazepine acetate in children under 6 years, perampanel in children under 4 years, and pregabalin in children. See NICE's information on prescribing medicines.

If second-line add-on treatments tried are unsuccessful in people with focal seizures, consider 1 of the following third-line add-on treatment options:

• phenobarbital

• phenytoin

• tiagabine

• vigabatrin.
  
  If the first choice is unsuccessful, consider the other third-line add-on options.
  
  In April 2022, this was an off-label use of tiagabine in children under 12 years. See NICE's information on prescribing medicines.

Do not offer sodium valproate as an add-on treatment for focal seizures 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), unless:

• other treatment options are unsuccessful

• the risks and benefits have been fully discussed, including the risks to an unborn child

• the likelihood of pregnancy has been taken into account and a pregnancy prevention programme put in place, if appropriate.
  
  Follow the MHRA safety advice on valproate use by women and girls.

Offer ethosuximide as first-line treatment for absence seizures.

If first-line treatment is unsuccessful, offer sodium valproate as second-line monotherapy or add-on treatment for absence seizures in:

• boys of all ages

• girls aged under 10 years and who are unlikely to need treatment when they are old enough to have children

• women who are unable to have children.

If second-line treatment is unsuccessful for absence seizures, consider lamotrigine or levetiracetam as a third-line monotherapy or add-on treatment options. If the first choice is unsuccessful, consider the other of these options.

In April 2022, these were off-label uses of lamotrigine in children under 2 years and levetiracetam in adults and children. See NICE's information on prescribing medicines.

Be aware that the following antiseizure medications may exacerbate seizures in people with absence seizures:

• carbamazepine

• gabapentin

• oxcarbazepine

• phenobarbital

• phenytoin

• pregabalin

• tiagabine

• vigabatrin.

Consider sodium valproate as first-line treatment for absence seizures with other seizure types (or at risk of these) in:

• boys and men

• girls aged under 10 years and who are unlikely to need treatment when they are old enough to have children

• women who are unable to have children.

Consider lamotrigine or levetiracetam as first-line treatment options 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) with absence seizures and other seizure types (or at risk of these). If the first choice is unsuccessful, consider the other of these options.

In April 2022, these were off-label uses of levetiracetam as monotherapy for adults and children, and as an add-on therapy for children under 12 years. See NICE's information on prescribing medicines.

Do not offer sodium valproate for absence seizures with other seizure types (or at risk of these) 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), unless:

• other treatment options are unsuccessful

• the risks and benefits have been fully discussed, including the risks to an unborn child

• the likelihood of pregnancy has been taken into account and a pregnancy prevention programme put in place, if appropriate.
  
  Follow the MHRA safety advice on valproate use by women and girls.

If first-line treatments tried are unsuccessful for absence seizures and other seizure types (or at risk of these), consider:

• lamotrigine or levetiracetam as a second-line monotherapy or add-on treatment options or

• ethosuximide as a second-line add-on treatment.
  
  If the first choice is unsuccessful, consider the other second-line options.
  
  In April 2022, these were off-label uses of lamotrigine in children under 2 years, and levetiracetam in adults and children. See NICE's information on prescribing medicines.

Be aware that the following antiseizure medications may exacerbate seizures in people with absence seizures and other seizure types (or at risk of these):

• carbamazepine

• gabapentin

• oxcarbazepine

• phenobarbital

• phenytoin

• pregabalin

• tiagabine

• vigabatrin.

If a child under 4 years has myoclonic seizures, either seek guidance on treatment from or refer to a tertiary paediatric neurologist.

Offer sodium valproate as first-line treatment for myoclonic seizures in:

• boys and men

• girls aged under 10 years and who are unlikely to need treatment when they are old enough to have children

• women who are unable to have children.

Offer levetiracetam as first-line treatment for myoclonic seizures 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).

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

If sodium valproate is unsuccessful as first-line treatment for myoclonic seizures, offer levetiracetam as a second-line monotherapy or add-on treatment.

In April 2022, these were off-label uses of levetiracetam as monotherapy for adults and children, and as an add-on therapy for children under 12 years. See NICE's information on prescribing medicines.

If levetiracetam is unsuccessful for myoclonic seizures, consider 1 of the following as monotherapy or add-on treatment options:

• brivaracetam

• clobazam

• clonazepam

• lamotrigine

• phenobarbital

• piracetam

• topiramate

• zonisamide.
  
  If the first choice is unsuccessful, consider any other of these options.
  
  In April 2022, these were off-label uses for brivaracetam in adults and children, clobazam as monotherapy in adults and children, clobazam as add-on therapy in children under 6 months, clonazepam solution in children, lamotrigine as monotherapy for children under 13 years and add-on therapy for children under 2 years, piracetam in children, topiramate in adults and children, and zonisamide in adults and children. See NICE's information on prescribing medicines.

Do not offer sodium valproate for myoclonic seizures 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), unless:

• other treatment options are unsuccessful

• the risks and benefits have been fully discussed, including the risks to an unborn child

• the likelihood of pregnancy has been taken into account and a pregnancy prevention programme put in place, if appropriate.
  
  Follow the MHRA safety advice on valproate use by women and girls.

Be aware that lamotrigine can occasionally exacerbate myoclonic seizures.

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

• carbamazepine

• gabapentin

• oxcarbazepine

• phenytoin

• pregabalin

• tiagabine

• vigabatrin.

Ensure that people with a diagnosis of tonic or atonic seizures are assessed by a neurologist with expertise in epilepsy to:

• diagnose the syndrome if possible and

• advise on investigation and treatment.

Offer sodium valproate as first-line treatment for tonic or atonic seizures in:

• boys and men

• girls aged under 10 years and who are unlikely to need treatment when they are old enough to have children

• women who are unable to have children.

Consider lamotrigine as first-line treatment for tonic or atonic seizures 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).

In April 2022, this was an off-label use of lamotrigine in children under 13 years. See NICE's information on prescribing medicines.

If sodium valproate is unsuccessful as first-line treatment for tonic or atonic seizures, consider lamotrigine as a second-line monotherapy or add-on treatment.

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

If lamotrigine is unsuccessful for treating tonic or atonic seizures, consider 1 of the following as monotherapy or add-on treatment options:

• clobazam

• rufinamide

• topiramate.
  
  If the first choice is unsuccessful, consider any other of these options.
  
  In April 2022, these were off-label uses for clobazam as monotherapy in adults and children, clobazam as add-on therapy in children under 6 months, rufinamide, and topiramate as monotherapy in children under 6 years, and topiramate as add-on therapy in children under 2 years. See NICE's information on prescribing medicines.

Do not offer sodium valproate for tonic or atonic seizures 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), unless:

• other treatment options are unsuccessful

• the risks and benefits have been fully discussed, including the risks to an unborn child

• the likelihood of pregnancy has been taken into account and a pregnancy prevention programme put in place, if appropriate.
  
  Follow the MHRA safety advice on valproate use by women and girls.

If third-line treatment is unsuccessful for tonic or atonic seizures in children, consider a ketogenic diet as an add-on treatment under the supervision of a ketogenic diet team.

If all other treatment options for tonic or atonic seizures are unsuccessful, consider felbamate as an 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.

Be aware that the following antiseizure medications may exacerbate seizures in people with tonic or atonic seizures:

• carbamazepine

• gabapentin

• oxcarbazepine

• pregabalin

• tiagabine

• vigabatrin.

Offer sodium valproate as first-line treatment for idiopathic generalised epilepsies in:

• boys and men

• girls aged under 10 years and who are unlikely to need treatment when they are old enough to have children

• women who are unable to have children.

Offer lamotrigine or levetiracetam as first-line treatment for idiopathic generalised epilepsies 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). If the first choice is unsuccessful, offer the other of these options.

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

If first-line treatments are unsuccessful for idiopathic generalised epilepsies, consider lamotrigine or levetiracetam as a second-line monotherapy or add-on treatment options. If the first choice is unsuccessful, consider the other of these options.

In April 2022, these were off-label uses of lamotrigine as monotherapy in children under 13 years and add-on therapy for children under 2 years, and levetiracetam as monotherapy in adults and children and add-on therapy for children under 12 years. See NICE's information on prescribing medicines.

If second-line treatments tried are unsuccessful for idiopathic generalised epilepsies, consider perampanel or topiramate as third-line add-on treatment options. If the first choice is unsuccessful, consider the other of these options.

In April 2022, this was an off-label use of perampanel for children under 7 years. See NICE's information on prescribing medicines.

Do not offer sodium valproate for idiopathic generalised epilepsies 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), unless:

• other treatment options are unsuccessful

• the risks and benefits have been fully discussed, including the risks to an unborn child

• the likelihood of pregnancy has been taken into account and a pregnancy prevention programme put in place, if appropriate.
  
  Follow the MHRA safety advice on valproate use by women and girls.