risk of seizure recurrence on drug withdrawal. In patients

receiving several antiepileptic drugs, only one drug should

be withdrawn at a time.

Driving

If a driver has a seizure (of any type) they must stop driving

immediately and inform the Driver and Vehicle Licensing

Agency (DVLA)

Patients who have had a first unprovoked epileptic seizure

or a single isolated seizure must not drive for 6 months;

driving may then be resumed, provided the patient has been

assessed by a specialist as fit to drive and investigations do

not suggest a risk of further seizures.

Patients with established epilepsy may drive a motor

vehicle provided they are not a danger to the public and are

compliant with treatment and follow up. To continue

driving, these patients must be seizure-free for at least one

year (or have a pattern of seizures established for one year

where there is no influence on their level of consciousness or

the ability to act); also, they must not have a history of

unprovoked seizures.

Note: additional criteria apply for drivers of large goods or

passenger carrying vehicles—consult DVLA guidance.

Patients who have had a seizure while asleep are not

permitted to drive for one year from the date of each seizure,

unless:

. a history or pattern of sleep seizures occurring only ever

while asleep has been established over the course of at

least one year from the date of the first sleep seizure; or

. an established pattern of purely asleep seizures can be

demonstrated over the course of three years if the patient

has previously had seizures whilst awake (or awake and

asleep).

The DVLA recommends that patients should not drive

during medication changes or withdrawal of antiepileptic

drugs, and for 6 months after their last dose. If a seizure

occurs due to a prescribed change or withdrawal of epilepsy

treatment, the patient will have their driving license revoked

for 1 year; relicensing may be considered earlier if treatment

has been reinstated for 6 months and no further seizures

have occurred.

Pregnancy

Women of child-bearing potential should discuss with a

specialist the impact of both epilepsy, and its treatment, on

the outcome of pregnancy.

There is an increased risk of teratogenicity associated with

the use of antiepileptic drugs (especially if used during the

first trimester and particularly if the patient takes two or

more antiepileptic drugs). Valproate is associated with the

highest risk of serious developmental disorders (up to

30–40% risk) and congenital malformations (approx. 10%

risk). Valproate must not be used in females of childbearing

potential unless the conditions of the Pregnancy Prevention

Programme are met and alternative treatments are

ineffective or not tolerated; during pregnancy, it must not be

used for epilepsy, unless it is the only possible treatment.

There is also an increased risk of teratogenicity with

phenytoin, primidone, phenobarbital, lamotrigine, and

carbamazepine. Topiramate carries an increased risk of

congenital malformations (including cleft palate,

hypospadias, and anomalies involving various body systems)

if taken in the first trimester of pregnancy. There is not

enough evidence to establish the risk of teratogenicity with

other antiepileptic drugs.

Prescribers should also consider carefully the choice of

antiepileptic therapy in pre-pubescent girls who may later

become pregnant. Women of child-bearing potential who

take antiepileptic drugs should be given advice about the

need for an effective contraception method to avoid

unplanned pregnancy—for further information, see

Conception and contraception in the individual drug

monographs. Some antiepileptic drugs can reduce the

efficacy of hormonal contraceptives, and the efficacy of some

antiepileptics may be affected by hormonal contraceptives.

Women who want to become pregnant should be referred

to a specialist for advice in advance of conception. For some

women, the severity of seizure or the seizure type may not

pose a serious threat, and drug withdrawal may be

considered; therapy may be resumed after the first trimester.

If treatment with antiepileptic drugs must continue

throughout pregnancy, then monotherapy is preferable at

the lowest effective dose.

Once an unplanned pregnancy is discovered it is usually

too late for changes to be made to the treatment regimen;

the risk of harm to the mother and fetus from convulsive

seizures outweighs the risk of continued therapy. The

likelihood of a woman who is taking antiepileptic drugs

having a baby with no malformations is at least 90%, and it is

important that women do not stop taking essential

treatment because of concern over harm to the fetus. To

reduce the risk of neural tube defects, folate

supplementation is advised before conception and

throughout the first trimester. In the case of sodium

valproate p. 327 and valproic acid p. 354 an urgent

consultation is required to reconsider the benefits and risks

of valproate therapy.

The concentration of antiepileptic drugs in the plasma can

change during pregnancy. Doses of phenytoin,

carbamazepine, and lamotrigine should be adjusted on the

basis of plasma-drug concentration monitoring; the dose of

other antiepileptic drugs should be monitored carefully

during pregnancy and after birth, and adjustments made on

a clinical basis. Plasma-drug concentration monitoring

during pregnancy is also useful to check compliance.

Additionally, in patients taking topiramate or levetiracetam,

it is recommended that fetal growth should be monitored.

Women who have seizures in the second half of pregnancy

should be assessed for eclampsia before any change is made

to antiepileptic treatment. Status epilepticus should be

treated according to the standard protocol.

Routine injection of vitamin K at birth minimises the risk

of neonatal haemorrhage associated with antiepileptics.

Withdrawal effects in the newborn may occur with some

antiepileptic drugs, in particular benzodiazepines and

phenobarbital.

Epilepsy and Pregnancy Register

All pregnant women with epilepsy, whether taking

medication or not, should be encouraged to notify the UK

Epilepsy and Pregnancy Register (Tel: 0800 389 1248).

Breast-feeding

Women taking antiepileptic monotherapy should generally

be encouraged to breast-feed; if a woman is on combination

therapy or if there are other risk factors, such as premature

birth, specialist advice should be sought.

All infants should be monitored for sedation, feeding

difficulties, adequate weight gain, and developmental

milestones. Infants should also be monitored for adverse

effects associated with the antiepileptic drug particularly

with newer antiepileptics, if the antiepileptic is readily

transferred into breast-milk causing high infant serum-drug

concentrations (e.g. ethosuximide, lamotrigine, primidone,

and zonisamide), or if slower metabolism in the infant

causes drugs to accumulate (e.g. phenobarbital and

lamotrigine). Serum-drug concentration monitoring should

be undertaken in breast-fed infants if suspected adverse

reactions develop; if toxicity develops it may be necessary to

introduce formula feeds to limit the infant’s drug exposure,

or to wean the infant off breast-milk altogether.

Primidone, phenobarbital, and the benzodiazepines are

associated with an established risk of drowsiness in breastfed babies and caution is required.

Withdrawal effects may occur in infants if a mother

suddenly stops breast-feeding, particularly if she is taking

phenobarbital, primidone, or lamotrigine.

BNF 78 Epilepsy and other seizure disorders 307

Nervous system

4

Focal seizures with or without secondary

generalisation

Carbamazepine p. 311 and lamotrigine p. 318 are first-line

options for treating newly diagnosed focal seizures;

oxcarbazepine p. 321, sodium valproate p. 327 and

levetiracetam p. 320 may be used if carbamazepine or

lamotrigine are unsuitable or not tolerated. If monotherapy

is unsuccessful with two of these first-line antiepileptic

drugs, adjunctive treatment may be considered. Options for

adjunctive treatment include carbamazepine, clobazam

p. 336, gabapentin p. 315, lamotrigine, levetiracetam,

oxcarbazepine, sodium valproate, or topiramate p. 331. If

adjunctive treatment is ineffective or not tolerated, a tertiary

epilepsy specialist should be consulted who may consider

eslicarbazepine acetate p. 313, lacosamide p. 317,

phenobarbital p. 335, phenytoin p. 323, pregabalin p. 324,

tiagabine p. 331, vigabatrin p. 333 and zonisamide p. 334.

Generalised seizures

Tonic-clonic seizures

Sodium valproate is the first-line treatment for newly

diagnosed generalised tonic-clonic seizures (except in

female patients who are premenopausal, see Valproate

below). Lamotrigine is the alternative choice if sodium

valproate is not suitable, but may exacerbate myoclonic

seizures. In those with established epilepsy with generalised

tonic-clonic seizures only, lamotrigine or sodium valproate

may be prescribed as the first-line treatment.

Carbamazepine and oxcarbazepine may also be considered in

newly diagnosed and established tonic-clonic seizures, but

may exacerbate myoclonic and absence seizures. Clobazam,

lamotrigine, levetiracetam, sodium valproate or topiramate

may be used as adjunctive treatment if monotherapy is

ineffective or not tolerated.

Absence seizures

Ethosuximide p. 314, or sodium valproate (except in female

patients who are premenopausal, see Valproate below), are

the drugs of choice in absence seizures and syndromes;

lamotrigine is a suitable alternative when ethosuximide and

sodium valproate are unsuitable, ineffective or not tolerated.

Sodium valproate should be used as the first choice if there is

a high risk of generalised tonic-clonic seizures. A

combination of any two of these drugs may be used if

monotherapy is ineffective. Clobazam, clonazepam p. 337,

levetiracetam, topiramate or zonisamide may be considered

by a tertiary epilepsy specialist if adjunctive treatment fails.

Carbamazepine, gabapentin, oxcarbazepine, phenytoin,

pregabalin, tiagabine and vigabatrin are not recommended

in absence seizures or syndromes.

Myoclonic seizures

Myoclonic seizures (myoclonic jerks) occur in a variety of

syndromes, and response to treatment varies considerably.

Sodium valproate is the drug of choice in newly diagnosed

myoclonic seizures (except in female patients who are

premenopausal, see Valproate below); topiramate and

levetiracetam are alternative options if sodium valproate is

unsuitable but consideration should be given to the less

favourable side-effect profile of topiramate. A combination

of two of these drugs may be used if monotherapy is

ineffective or not tolerated. If adjunctive treatment fails, a

tertiary epilepsy specialist should be consulted and may

consider clobazam, clonazepam, zonisamide or piracetam

p. 406. Carbamazepine, gabapentin, oxcarbazepine,

phenytoin, pregabalin, tiagabine and vigabatrin are not

recommended for the treatment of myoclonic seizures.

Sodium valproate and levetiracetam are effective in

treating the generalised tonic-clonic seizures that coexist

with myoclonic seizures in idiopathic generalised epilepsy.

Atonic and tonic seizures

Atonic and tonic seizures are usually seen in childhood, in

specific epilepsy syndromes, or associated with cerebral

damage or mental retardation. They may respond poorly to

the traditional drugs. Sodium valproate is the drug of choice

(except in female patients who are premenopausal, see

Valproate below); lamotrigine can be added as adjunctive

treatment. If adjunctive treatment is ineffective or not

tolerated, a tertiary epilepsy specialist should be consulted,

and may consider rufinamide p. 326 or topiramate.

Carbamazepine, gabapentin, oxcarbazepine, pregabalin,

tiagabine or vigabatrin are not recommended in atonic and

tonic seizures.

Epilepsy syndromes

Some drugs are licensed for use in particular epilepsy

syndromes. The epilepsy syndromes are specific types of

epilepsy that are characterised according to a number of

features including seizure type, age of onset, and EEG

characteristics. For more information on epilepsy syndromes

in children see BNF for children.

Dravet syndrome

A tertiary specialist should be involved in decisions

regarding treatment of Dravet syndrome. Sodium valproate

(except in pregnancy or females of childbearing potential,

see Valproate below) or topiramate are first-line treatment

options in children with Dravet syndrome. Clobazam or

stiripentol p. 330 may be considered as adjunctive treatment

in children and adults if first-line treatments are ineffective

or not tolerated. Carbamazepine, gabapentin, lamotrigine,

oxcarbazepine, phenytoin, pregabalin, tiagabine, and

vigabatrin should not be used as they may exacerbate

myoclonic seizures.

Lennox-Gastaut syndrome

A tertiary specialist should be involved in decisions

regarding treatment of Lennox-Gastaut syndrome. Sodium

valproate is the first-line drug for treating children with

Lennox-Gastaut syndrome (except in pregnancy or females

of childbearing potential, see Valproate below); lamotrigine

can be used as adjunctive treatment in children and adults if

sodium valproate is unsuitable, ineffective or not tolerated.

If adjunctive treatment is ineffective or not tolerated,

rufinamide and topiramate may be considered by tertiary

specialists. Carbamazepine, gabapentin, oxcarbazepine,

pregabalin, tiagabine, and vigabatrin should not be used.

Felbamate [unlicensed] may be used in tertiary specialist

centres when all other treatment options have failed.

Antiepileptic drugs

Carbamazepine and related antiepileptics

Carbamazepine is a drug of choice for simple and complex

focal seizures and is a first-line treatment option for

generalised tonic-clonic seizures. It can be used as

adjunctive treatment for focal seizures when monotherapy

has been ineffective. It is essential to initiate carbamazepine

therapy at a low dose and build this up slowly.

Carbamazepine may exacerbate tonic, atonic, myoclonic and

absence seizures and is therefore not recommended if these

seizures are present.

Oxcarbazepine is licensed as monotherapy or adjunctive

therapy for the treatment of focal seizures with or without

secondary generalised tonic-clonic seizures. It can also be

considered for the treatment of primary generalised tonicclonic seizures [unlicensed]. Oxcarbazepine is not

recommended in tonic, atonic, absence or myoclonic

seizures due to the risk of seizure exacerbation.

Eslicarbazepine acetate p. 313 is licensed for adjunctive

treatment in adults with focal seizures with or without

secondary generalisation.

308 Epilepsy and other seizure disorders BNF 78

Nervous system

4

Ethosuximide

Ethosuximide p. 314 is a first-line treatment option for

absence seizures. It may also be prescribed as adjunctive

treatment for absence seizures when monotherapy is

ineffective. Ethosuximide is also licensed for myoclonic

seizures.

Gabapentin and pregabalin

Gabapentin p. 315 and pregabalin p. 324 are used for the

treatment of focal seizures with or without secondary

generalisation. They are not recommended if tonic, atonic,

absence or myoclonic seizures are present. Both are also

licensed for the treatment of neuropathic pain. Pregabalin is

licensed for the treatment of generalised anxiety disorder.

Lamotrigine

Lamotrigine p. 318 is an antiepileptic drug recommended as

a first-line treatment for focal seizures and primary and

secondary generalised tonic-clonic seizures. It is also

licensed for typical absence seizures in children (but efficacy

may not be maintained in all children) and is an unlicensed

treatment option in adults if first-line treatments have been

unsuccessful. Lamotrigine can also be used as adjunctive

treatment in atonic or tonic seizures if first-line treatment

has failed [unlicensed]. Myoclonic seizures may be

exacerbated by lamotrigine and it can cause serious rashes

especially in children; dose recommendations should be

adhered to closely.

Lamotrigine is used either as sole treatment or as an

adjunct to treatment with other antiepileptic drugs.

Valproate increases plasma-lamotrigine concentration,

whereas the enzyme-inducing antiepileptics reduce it; care

is therefore required in choosing the appropriate initial dose

and subsequent titration. When the potential for interaction

is not known, treatment should be initiated with lower

doses, such as those used with valproate.

Levetiracetam and brivaracetam

Levetiracetam p. 320 is used for monotherapy and adjunctive

treatment of focal seizures with or without secondary

generalisation, and for adjunctive treatment of myoclonic

seizures in patients with juvenile myoclonic epilepsy and

primary generalised tonic-clonic seizures. Levetiracetam

may be prescribed alone and in combination for the

treatment of myoclonic seizures, and under specialist

supervision for absence seizures [both unlicensed].

Brivaracetam p. 310 is used as adjunctive therapy in the

treatment of partial-onset seizures with or without

secondary generalisation.

Phenobarbital and primidone

Phenobarbital p. 335 is effective for tonic-clonic and focal

seizures but may be sedative in adults. It may be tried for

atypical absence, atonic, and tonic seizures. Rebound

seizures may be a problem on withdrawal.

Primidone p. 336 is largely converted to phenobarbital and

this is probably responsible for its antiepileptic action. A low

initial dose of primidone is essential.

Phenytoin

Phenytoin p. 323 is licensed for tonic-clonic and focal

seizures but may exacerbate absence or myoclonic seizures

and should be avoided if these seizures are present. It has a

narrow therapeutic index and the relationship between dose

and plasma-drug concentration is non-linear; small dosage

increases in some patients may produce large increases in

plasma concentration with acute toxic side-effects.

Similarly, a few missed doses or a small change in drug

absorption may result in a marked change in plasma-drug

concentration. Monitoring of plasma-drug concentration

improves dosage adjustment.

When only parenteral administration is possible,

fosphenytoin sodium p. 314, a pro-drug of phenytoin, may

be convenient to give. Unlike phenytoin (which should only

be given intravenously), fosphenytoin sodium may also be

given by intramuscular injection.

Rufinamide

Rufinamide p. 326 is licensed for the adjunctive treatment of

seizures in Lennox-Gastaut syndrome. It may be considered

by a tertiary specialist for the treatment of refractory tonic or

atonic seizures [unlicensed].

Topiramate

Topiramate p. 331 can be given alone or as adjunctive

treatment in generalised tonic-clonic seizures or focal

seizures with or without secondary generalisation. It can be

used as adjunctive treatment for seizures associated with

Lennox-Gastaut syndrome and for absence, tonic and atonic

seizures under specialist supervision [unlicensed]. It can also

be considered as an option in myoclonic seizures

[unlicensed]. Female patients should be fully informed of the

risks related to the use of topiramate during pregnancy and

the need to use effective contraception—for further

information, see Conception and contraception and Pregnancy

in the topiramate drug monograph.

Valproate

Sodium valproate p. 327 is effective in controlling tonicclonic seizures, particularly in primary generalised epilepsy.

It is a drug of choice in primary generalised tonic-clonic

seizures, focal seizures, generalised absences and myoclonic

seizures, and can be tried in atypical absence seizures. It is

recommended as a first-line option in atonic and tonic

seizures. Sodium valproate has widespread metabolic effects

and monitoring of liver function tests and full blood count is

essential. Because of its high teratogenic potential, valproate

must not be used in females of childbearing potential unless

the conditions of the Pregnancy Prevention Programme are

met and alternative treatments are ineffective or not

tolerated. During pregnancy, it must not be used for epilepsy

unless it is the only possible treatment. For further

information see Important safety information, Conception and

contraception, and Pregnancy in the sodium valproate and

valproic acid p. 354 drug monographs.

Valproic acid (as semisodium valproate) is licensed for

acute mania associated with bipolar disorder.

Zonisamide

Zonisamide p. 334 can be used alone for the treatment of

focal seizures with or without secondary generalisation in

adults with newly diagnosed epilepsy, and as adjunctive

treatment for refractory focal seizures with or without

secondary generalisation in adults and children aged 6 years

and above. It can also be used under the supervision of a

specialist for refractory absence and myoclonic seizures

[unlicensed indications].

Benzodiazepines

Clobazam p. 336 may be used as adjunctive therapy in the

treatment of generalised tonic-clonic and refractory focal

seizures. It may be prescribed under the care of a specialist

for refractory absence and myoclonic seizures. Clonazepam

p. 337 may be prescribed by a specialist for refractory

absence and myoclonic seizures, but its sedative side-effects

may be prominent.

Other drugs

Acetazolamide p. 1181, a carbonic anhydrase inhibitor, has a

specific role in treating epilepsy associated with

menstruation. Piracetam p. 406 is used as adjunctive

treatment for cortical myoclonus.

Status epilepticus

Convulsive status epilepticus

Immediate measures to manage status epilepticus include

positioning the patient to avoid injury, supporting

respiration including the provision of oxygen, maintaining

blood pressure, and the correction of any hypoglycaemia.

Parenteral thiamine p. 1080 should be considered if alcohol

BNF 78 Epilepsy and other seizure disorders 309

Nervous system

4

abuse is suspected; pyridoxine hydrochloride p. 1080 should

be given if the status epilepticus is caused by pyridoxine

hydrochloride deficiency.

Seizures lasting longer than 5 minutes should be treated

urgently with intravenous lorazepam p. 339 (repeated once

after 10 minutes if seizures recur or fail to respond).

Intravenous diazepam p. 343 is effective but it carries a high

risk of thrombophlebitis (reduced by using an emulsion

formulation). Absorption of diazepam from intramuscular

injection or from suppositories is too slow for treatment of

status epilepticus. Patients should be monitored for

respiratory depression and hypotension.

Where facilities for resuscitation are not immediately

available, diazepam p. 343 can be administered as a rectal

solution or midazolam p. 340 oromucosal solution can be

given into the buccal cavity.

Important

If, after initial treatment with benzodiazepines, seizures

recur or fail to respond 25 minutes after onset, phenytoin

sodium, fosphenytoin sodium p. 314, or phenobarbital

sodium should be used; contact intensive care unit if

seizures continue. If these measures fail to control seizures

45 minutes after onset, anaesthesia with thiopental sodium

p. 338, midazolam, or a non-barbiturate anaesthetic such as

propofol p. 1330 [unlicensed indication], should be

instituted with full intensive care support.

Phenytoin sodium can be given by slow intravenous

injection, followed by the maintenance dosage if

appropriate.

Alternatively, fosphenytoin sodium (a pro-drug of

phenytoin), can be given more rapidly and when given

intravenously causes fewer injection-site reactions than

phenytoin sodium. Although it can also be given

intramuscularly, absorption is too slow by this route for

treatment of status epilepticus. Doses of fosphenytoin

sodium should be expressed in terms of phenytoin sodium.

Non-convulsive status epilepticus

The urgency to treat non-convulsive status epilepticus

depends on the severity of the patient’s condition. If there is

incomplete loss of awareness, usual oral antiepileptic

therapy should be continued or restarted. Patients who fail

to respond to oral antiepileptic therapy or have complete

lack of awareness can be treated in the same way as for

convulsive status epilepticus, although anaesthesia is rarely

needed.

Febrile convulsions

Brief febrile convulsions need no specific treatment;

antipyretic medication (e.g. paracetamol p. 444), is

commonly used to reduce fever and prevent further

convulsions but evidence to support this practice is lacking.

Prolonged febrile convulsions (those lasting 5 minutes or

longer), or recurrent febrile convulsions without recovery must

be treated actively (as for convulsive status epilepticus).

Long-term anticonvulsant prophylaxis for febrile

convulsions is rarely indicated.

Other drugs used for Epilepsy and other seizure

disorders Magnesium sulfate, p. 1051

ANTIEPILEPTICS

Brivaracetam 19-Jul-2018

l INDICATIONS AND DOSE

Adjunctive therapy of focal seizures with or without

secondary generalisation

▶ BY MOUTH, OR BY INTRAVENOUS INJECTION, OR BY

INTRAVENOUS INFUSION

▶ Adult: Initially 25–50 mg twice daily, adjusted

according to response; usual maintenance 25–100 mg

twice daily (max. per dose 100 mg twice daily)

l INTERACTIONS → Appendix 1: antiepileptics

l SIDE-EFFECTS

▶ Common or very common Anxiety . appetite decreased . constipation . cough . depression . dizziness . drowsiness . fatigue . increased risk of infection . insomnia . irritability . nausea . vertigo . vomiting

▶ Uncommon Aggression . psychotic disorder

l PREGNANCY Manufacturer advises avoid unless potential

benefit outweighs risk—limited information available. See

also Pregnancy in Epilepsy p. 305.