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Treatment

Phenobarbitone remains in Europe and overseas the drug of choice in the treatment of
neonates60,61. The initial dose is 20 mg/kg in unventilated babies and 30 mg/kg in those who
are ventilator-dependent (Table 3), aiming to achieve a serum level of 90180 μmol/L.
Phenobarbitone achieves clinical control in only 3040% of cases34; some claim better clinical
control with doses of up to 40 mg/kg and serum levels above 180 μmol/L35. There is, however,
evidence that phenobarbitone increases the electroclinical dissociation: while the number of
electroclinical seizures decreases, the number of electrographic seizures increases36,37. It has
been suggested that this is due to a time difference of the GABA switch which is earlier in
thalamic compared to neocortical neurons38.

Phenytoin and clonazepam are used as second-line AEDs. Phenytoin can cause significant
myocardial depression and should be avoided in babies requiring inotropic support.
Clonazepam may achieve better EEG control. Midazolam39,63 has a shorter half-life than
clonazepam and does not accumulate, and it avoids the side effect of increased oropharyngeal
secretions. Others have reported success with lignocaine40,63,64: between 70% and 92% of
newborns responded to lignocaine as second-line AED41-43. However, all these studies were
uncontrolled, apart from one with small numbers42. Lignocaine has a narrow therapeutic range
and can induce seizures in high doses. There is little experience with carbamazepine, vigabatrin
and lamotrigine in the neonatal period. Consider a trial of pyridoxine, pyridoxal-5-phosphate
and folinic acid.

A Cochrane report has reviewed the treatment of neonatal seizures44. Only two randomised
controlled studies were identified using adequate methodology34,42, both indicating that current
first-line treatment was only effective in about 4050% of babies. A recent WHO review on
neonatal seizures came to a similar conclusion45. This situation has led to high usage of off-
label drugs in this vulnerable age group46, which is associated with a high risk of adverse
events65. Only recently newer AEDs have been developed and evaluated specifically for the
use in the neonatal period65. For reviews on AED treatment of neonatal seizures see van Rooij
et al and Pressler and Mangum64,66.

Table 3. Antiepileptic drug dose in the newborn.

Drug Initial dose Route Maintenance Route Therapeutic
level
Phenobarbitone 2040 mg/kg iv 35 mg/kg iv/im/o 90180 mol/L
Phenytoin 1520 mg/kg iv/20 min 35 mg/kg iv/o 4080 mol/L
Lorazepam 0.050.1mg/kg iv every 812 hrs iv
Diazepam 0.20.5 mg/kg iv every 68 hrs iv 30100 mg/L
Clonazepam 0.1 mg/kg iv/30 min
Midazolam 0.10.2 mg/kg iv 0.10.3 mg/kg/h iv 36 mg/l
Lignocaine 2 mg/kg iv 16 mg/kg/h iv 275350 mol/L
Valproate 1020 mg/kg iv/o 20 mg/kg o
Paraldehyde 0.10.2ml/kg pr
Pyridoxine (B6) 50100mg iv 100 mg every 10
min (up to 500 mg)