THE USE OF CLOBAZAM, MIDAZOLAM, AND NITRAZEPAM IN EPILEPSY

The benzodiazepines clobazam (CLB), midazolam (MDL), and nitrazepam (N ZP) all have proven efficacy in epilepsy management, but their differe nces in physical properties, pharmacokinetic characteristics, side-eff ect profiles, and intrinsic antiepileptic activity lead to different i ndications for use. CLB is a 1,5-benzodiazepine that causes less sedat ion than 1,4-benzodiazepines but offers improved antiepileptic action. It has been extensively studied in both open and controlled trials as antiepileptic therapy for a variety of seizure types. It is now widel y used in European countries as adjunctive therapy for partial and sec ondarily generalized seizures. Clinical trial experience, however, ind icates that more than 50% of patients develop tolerance to the antiepi leptic effects of CLB. Therefore, CLB has had a relatively limited rol e as a routine antiepileptic drug. It has further use as an intermitte nt or occasional therapy, in which tolerance is of less concern. MDL i s a water-soluble 1,4-benzodiazepine. It is the only drug in this clas s that is useful when given by i.m. injection, although MDL can also b e administered rectally or by i.v. bolus or infusion. MDL has a very s hort elimination half-life and is used for emergency treatment of stat us epilepticus or acute seizures. NZP has reported efficacy in acute e pilepsy, although it is not routinely used for this situation. Althoug h there have been no controlled studies of NZP for chronic epilepsy tr eatment, this drug appears to be moderately effective in a wide range of seizure types. NZP is predominantly used in children with severe ep ilepsy intractable to conventional medications.