hypospadias, and anomalies involving various body systems)
if taken in thefirst 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. Young 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 contraceptionin 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.
Young 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 thefirst 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 thefirst trimester. In the case of sodium
valproate p. 208 and valproic acid p. 213 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, and can take several days to diminish.
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
Young 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 breast-
fed 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.Focal seizures with or without secondary
generalisation
Carbamazepine p. 196 and lamotrigine p. 202 are the drugs
of choice for focal seizures; levetiracetam p. 203 ,
oxcarbazepine p. 204 and sodium valproate p. 208 can be
considered if these are unsuitable. These drugs may also be
used as adjunctive treatment. Other adjunctive options
include clobazam p. 218 , gabapentin p. 200 , and topiramate
p. 212. If adjunctive treatment is ineffective or not tolerated,
a tertiary specialist should be consulted who may consider
eslicarbazepine acetate, lacosamide p. 201 , phenobarbital
p. 216 , phenytoin p. 205 , pregabalin [unlicensed], tiagabine
p. 211 , vigabatrin p. 214 , and zonisamide p. 215.Generalised seizures
Tonic-clonic seizures
The drug of choice for newly diagnosed tonic-clonic seizures
in children is sodium valproate (except in female patients,
seeValproatebelow), or lamotrigine where sodium valproate
is unsuitable (but may exacerbate myoclonic seizures). In
children with established epilepsy with generalised tonic-
clonic seizures only, lamotrigine may be prescribed as the
first-line choice. Carbamazepine or oxcarbazepine can also
be considered but may exacerbate myoclonic or 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. 198 and sodium valproate (except in female
patients, seeValproatebelow) are the drugs of choice for
absence seizures and syndromes; lamotrigine can be used if
these are unsuitable, ineffective or not tolerated. Sodium
valproate should be used as thefirst 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. Second-line therapy includes clobazam,
clonazepam p. 219 , levetiracetam, topiramate or zonisamide
which may be considered by a tertiary 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 (except in female
patients, seeValproatebelow); consider levetiracetam or
topiramate if sodium valproate is unsuitable (but consider
the less favourable side-effect profile of topiramate). A
combination of two of these drugs may be used if
monotherapy is ineffective or poorly tolerated. Second-line
therapy includes clobazam, clonazepam, piracetam or
zonisamide which should be prescribed under the
supervision of a tertiary specialist. Carbamazepine,
gabapentin, oxcarbazepine, phenytoin, pregabalin,
tiagabine, and vigabatrin are not recommended for the
treatment of myoclonic seizures.BNFC 2018 – 2019 Epilepsy and other seizure disorders 193
Nervous system4