There is no evidence for a difference in antiepileptic efficacy between phenobarbital and any other compared AED , yet no evidence for absolute efficacy .
No convincing evidence exists for an excess of behavioural adverse effects , over other AEDs , attributable to phenobarbital .
Masked studies of phenobarbital in childhood epilepsy have shown no significant differences in behavioural or cognitive adverse effects compared to other AEDs .
This is in contrast to the excess of such adverse effects reported in studies open to observer bias .
However , the one finding of reduction in cognitive ability associated with phenobarbital treatment for febrile convulsions remains a concern .
INTRODUCTION : Against a background of concern about the safety of new pharmaceutical products , there has been renewed interest in one of the oldest antiepileptic drugs ( AEDs ) , phenobarbital .
Although still in widespread use in developing countries , its popularity has slipped in Western countries over the past century , partly because of controversy about its adverse effect profile .
This critical review examines the evidence supporting its effectiveness and its associated behavioural adverse effects for febrile convulsions and childhood epilepsy .
Effect of phenobarbital on seizure frequency and mortality in childhood cerebral malaria: a randomised, controlled intervention study
BACKGROUND Seizures commonly complicate cerebral malaria and are associated with an increased risk of death and neurological sequelae . We undertook a r and omised study to assess the efficacy of intramuscular phenobarbital in preventing seizures in childhood cerebral malaria . METHODS Children with cerebral malaria admitted to one hospital in Kilifi , Kenya , were r and omly assigned a single intramuscular dose of phenobarbital ( 20 mg/kg ) or identical placebo .  Clinical tolerance was assessed at the start of the trial , with particular reference to respiratory depression and hypotension . Seizures were timed and recorded , and treated in a st and ard way . Plasma phenobarbital concentrations were measured . Analyses were by intention to treat . FINDINGS 440 children with cerebral malaria were admitted to the hospital ; 100 were not recruited to the study . Of the remaining 340 , 170 received phenobarbital  and 170 placebo . The drug was adequately absorbed and well tolerated . Seizure frequency was significantly lower in the phenobarbital group than in the placebo group ( 18 [ 11 % ] vs 46 [ 27 % ] children had three or more seizures of any duration ; odds ratio 0.32 [ 95 % CI 0.18 - 0.58 ] ) but mortality was doubled ( 30 [ 18 % ] vs 14 [ 8 % ] deaths ; 2.39 [ 1.28 - 4.64 ] ) . The frequency of respiratory arrest was higher in the phenobarbital group than in the placebo group , and mortality was greatly increased in children who received phenobarbital plus three or more doses of diazepam ( odds ratio 31.7 [ 1.2 - 814 ] ) . INTERPRETATION In children with cerebral malaria , phenobarbital 20 mg/kg provides highly effective seizure prophylaxis but is associated with an unacceptable increase in mortality . Use of this dose can not , therefore , be recommended
There is no evidence for a difference in antiepileptic efficacy between phenobarbital and any other compared AED , yet no evidence for absolute efficacy .
No convincing evidence exists for an excess of behavioural adverse effects , over other AEDs , attributable to phenobarbital .
Masked studies of phenobarbital in childhood epilepsy have shown no significant differences in behavioural or cognitive adverse effects compared to other AEDs .
This is in contrast to the excess of such adverse effects reported in studies open to observer bias .
However , the one finding of reduction in cognitive ability associated with phenobarbital treatment for febrile convulsions remains a concern .
INTRODUCTION : Against a background of concern about the safety of new pharmaceutical products , there has been renewed interest in one of the oldest antiepileptic drugs ( AEDs ) , phenobarbital .
Although still in widespread use in developing countries , its popularity has slipped in Western countries over the past century , partly because of controversy about its adverse effect profile .
This critical review examines the evidence supporting its effectiveness and its associated behavioural adverse effects for febrile convulsions and childhood epilepsy .