Tonic and atonic seizures
Tonic or atonic seizures are treated with sodium valproate
(except in female patients, seeValproatebelow); lamotrigine
can be considered as adjunctive treatment if sodium
valproate is ineffective or not tolerated. If adjunctive
treatment fails, a tertiary specialist should be consulted who
may consider rufinamide p. 207 or topiramate.
Carbamazepine, gabapentin, oxcarbazepine, pregabalin,
tiagabine, and vigabatrin are not recommended in atonic or
tonic seizures.Epilepsy syndromes
Infantile spasms
Vigabatrin is the drug of choice for infantile spasms
associated with tuberous sclerosis. Corticosteroids, such as
prednisolone p. 442 or tetracosactide p. 473 , are second-line
options if vigabatrin is ineffective. In spasms of other causes,
vigabatrin, prednisolone or tetracosactide can be considered
asfirst-line options. A tertiary specialist should be consulted
before treating infantile spasms.
Dravet syndrome
Sodium valproate (except in female patients, seeValproate
below) or topiramate is the treatment of choice in Dravet
syndrome. Clobazam or stiripentol p. 210 may be considered
as adjunctive treatment. Carbamazepine, gabapentin,
lamotrigine, oxcarbazepine, phenytoin, pregabalin,
tiagabine, and vigabatrin should not be used as they may
exacerbate myoclonic seizures. A tertiary specialist should
be involved in decisions regarding treatment of Dravet
syndrome.
Lennox-Gastaut syndrome
Sodium valproate is thefirst-line drug for treating Lennox-
Gastaut syndrome (except in female patients, seeValproate
below); lamotrigine can be used as adjunctive treatment if
sodium valproate is ineffective or not tolerated. Rufinamide
and topiramate may be considered by tertiary epilepsy
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.Landau-Kleffner syndrome
Always discuss with or refer to tertiary epilepsy specialists.Neonatal seizures
Seizures can occur before delivery, but they are most
common up to 24 hours after birth. Seizures in neonates
occur as a result of biochemical disturbances, inborn errors
of metabolism, hypoxic ischaemic encephalopathy, drug
withdrawal, meningitis, stroke, cerebral haemorrhage or
malformation, or severe jaundice (kernicterus).
Seizures caused by biochemical imbalance and those in
neonates with inherited abnormal pyridoxine or biotin
metabolism should be corrected by treating the underlying
cause. Seizures caused by drug withdrawal following intra-
uterine exposure are treated with a drug withdrawal
regimen.
Phenobarbital can be used to manage neonatal seizures
where there is a risk of recurrence; phenytoin is an
alternative. Midazolam p. 223 andrectalparaldehyde p. 221
may also be useful in the management of acute neonatal
seizures. Lidocaine hydrochloride p. 826 may be used if other
treatments are unsuccessful; lidocaine hydrochloride should
not be given to neonates who have received phenytoin
infusion because of the risk of cardiac toxicity.Antiepileptic drugs
Carbamazepine and related antiepileptics
Carbamazepine is a drug of choice for simple and complex
focal seizures and is afirst-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 carbamazepinep. 196 therapy at a low dose and build this up slowly in small
increments every 3 – 7 days. Carbamazepine may exacerbate
tonic, atonic, myoclonic and absence seizures and is
therefore not recommended if these seizures are present.
Oxcarbazepine p. 204 is not recommended in tonic, atonic,
absence or myoclonic seizures due to the risk of seizure
exacerbation.
Ethosuximide
Ethosuximide is afirst-line treatment option for absence
seizures, and may be used as adjunctive treatment when
monotherapy has failed.
Gabapentin
Gabapentin p. 200 is used as adjunctive therapy for the
treatment of focal seizures with or without secondary
generalisation; it is licensed as monotherapy in children over
12 years. It is not recommended if tonic, atonic, absence or
myoclonic seizures are present.
Lamotrigine
Lamotrigine p. 202 is an antiepileptic drug recommended as
afirst-line treatment for focal seizures and primary and
secondary generalised tonic-clonic seizures. It is also
licensed as monotherapy for typical absence seizures in
children (but efficacy may not be maintained in all children).
It may be tried as an adjunctive treatment for atonic and
tonic seizures iffirst-line treatment has failed [unlicensed].
Myoclonic seizures may be exacerbated by lamotrigine and it
can cause serious rashes; 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. 203 is used for monotherapy and adjunctive
treatment of focal seizures with or without secondary
generalisation, and for adjunctive treatment of myoclonic
seizures in children 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. 195 is used as adjunctive therapy in the
treatment of partial-onset seizures with or without
secondary generalisation.Phenobarbital and primidone
Phenobarbital p. 216 is effective for tonic-clonic, focal
seizures and neonatal seizures but may cause behavioural
disturbances and hyperkinesia. It may be tried for atypical
absence, atonic, and tonic seizures. For therapeutic purposes
phenobarbital andphenobarbital sodiumshould be
considered equivalent in effect. Rebound seizures may be a
problem on withdrawal.
Primidone p. 217 is largely converted to phenobarbital and
this is probably responsible for its antiepileptic action. It is
used rarely in children. A low initial dose of primidone is
essential.
Phenytoin
Phenytoin p. 205 is licensed for tonic-clonic and focal
seizures but may exacerbate absence or myoclonic seizures
and should be avoided if theses 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-drug194 Epilepsy and other seizure disorders BNFC 2018 – 2019
Nervous system4