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 .
Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin.
Phenytoin and carbamazepine are effective and inexpensive anti-epileptic drugs ( AEDs ) . As with many AEDs , a broad range of doses is used , with the final " maintenance " dose normally determined by trial and error . Although many genes could influence response to these medicines , there are obvious c and i date s. Both drugs target the alpha-subunit of the sodium channel , encoded by the SCN family of genes . Phenytoin is principally metabolized by CYP2C9 , and both are probable substrates of the drug transporter P-glycoprotein . We therefore assessed whether variation in these genes associates with the clinical use of carbamazepine and phenytoin  in cohorts of 425 and 281 patients , respectively . We report that a known functional polymorphism in CYP2C9 is highly associated with the maximum dose of phenytoin ( P = 0.0066 ) . We also show that an intronic polymorphism in the SCN1A gene shows significant association with maximum doses in regular usage of both carbamazepine and phenytoin ( P = 0.0051 and P = 0.014 , respectively ) . This polymorphism disrupts the consensus sequence of the 5 ' splice donor site of a highly conserved alternative exon ( 5N ) , and it significantly affects the proportions of the alternative transcripts in individuals with a history of epilepsy . These results provide evidence of a drug target polymorphism associated with the clinical use of AEDs and set the stage for a prospect i ve evaluation of how pharmacogenetic diagnostics can be used to improve dosing decisions in the use of phenytoin and carbamazepine . Although the case made here is compelling , our results can not be considered definitive or ready for clinical application until they are confirmed by independent replication
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 .