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 .
Psychologic and behavioral effects of antiepileptic drugs in children: a double-blind comparison between phenobarbital and valproic acid.
Traditional clinical monitoring of children with epilepsy does not appear to be sufficiently sensitive to cognitive functioning and behavioral problems . Although subtle , these changes may alter a child 's ability to perform well in school and in society . Physicians must prevent seizures without producing intolerable side effects , and ways of more appropriately assessing these side effects must be developed . In this double-blind , counter-balanced , crossover study of 21 children , the effects of phenobarbital and valproic acid on cognitive functioning and behavior were measured . There was no difference in seizure control between the drugs , and each medication was maintained in the therapeutic range for 6 months ( mean phenobarbital level , 21.2 micrograms/mL ; mean valproic acid level , 94.1 micrograms/mL ) . Children were treated with each drug for 6 months . Differences between the drugs were seen on measurements of cognitive function and behavior . On four tests of neuropsychologic function , children performed significantly less well while receiving phenobarbital ( P less than .01 ) . There was no evidence that the patients were se date d or less able to perform continuous performance tasks while receiving phenobarbital .  Parental assessment of behavior indicated significantly worse behavior with the phenobarbital regimen for three items ( P less than .01 ) and children were measurably more " hyperactive " ( P less than .05 ) . Routine clinical assessment of the patients did not reveal differences between the drugs with respect to routine laboratory measurements or side effects as assessed by history or physical examination . Although children may appear to tolerate a medication without clinical ly apparent problems , subtle but significant changes in intellectual function and behavior may be occurring . Additional , more sensitive , methods of monitoring patients while receiving these drugs is necessary
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 .