The Use of Clobazam, Midazolam, and Nitrazepam in Epilepsy

Summary: The benzodiazepines clobazam (CLB), midazolam (MDL), and nitrazepam (NZP) all have proven efficacy in epilepsy management, but their differences in physical properties, pharmacokinetic characteristics, side-effect profiles, and intrinsic antiepileptic activity lead to different indications for use. CLB is a 1,5-benzodiazepine that causes less sedation 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 widely used in European countries as adjunctive therapy for partial and secondarily generalized seizures. Clinical trial experience, however, indicates that more than 50% of patients develop tolerance to the antiepileptic effects of CLB. Therefore, CLB has had a relatively limited role as a routine antiepileptic drug. It has further use as an intermittent or occasional therapy, in which tolerance is of less concern. MDL is a water-soluble 1,4-benzodiazepine. It is the only drug in this class that is useful when given by i.m. injection, although MDL can also be administered rectally or by i.v. bolus or infusion. MDL has a very short elimination half-life and is used for emergency treatment of status epilepticus or acute seizures. NZP has reported efficacy in acute epilepsy, although it is not routinely used for this situation. Although there have been no controlled studies of NZP for chronic epilepsy treatment, this drug appears to be moderately effective in a wide range of seizure types. NZP is predominantly used in children with severe epilepsy intractable to conventional medications.