Benzodiazepines Used in the Treatment of Epilepsy
Eugen Trinka
Paracelsus Medical University Salzburg, Salzburg, Austria
Search for more papers by this authorEugen Trinka
Paracelsus Medical University Salzburg, Salzburg, Austria
Search for more papers by this authorSimon Shorvon MA MB BChir MD FRCP
Professor in Clinical Neurology and Consultant Neurologist
UCL Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, London, UK
Search for more papers by this authorEmilio Perucca MD PhD FRCP(Edin)
Professor of Medical Pharmacology and Director, Clinical Trial Center
Clinical Pharmacology Unit, Department of Internal Medicine and Therapeutics University of Pavia, C. Mondino National Neurological Institute Pavia, Italy
Search for more papers by this authorJerome Engel Jr. MD PhD
Jonathan Sinay Distinguished Professor of Neurology and Director UCLA Seizure Disorder Center
Neurobiology, and Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at University of California, Los Angeles, USA
Search for more papers by this authorSummary
Benzodiazepines have been used in the treatment of epilepsy since the early 1970s. The use of benzodiazepines in chronic epilepsy treatment has been limited by concerns for tolerance, and behavioural or sedative effects, which has relegated benzodiazepines, with the exception of clobazam, to second-line and add-on antiepileptic drugs (AEDs). This chapter summarizes the main pharmacokinetic parameters of clobazam, clonazepam, clorazepate, diazepam, lorazepam, midazolam and nitrazepam. As enzyme-inducing AEDs such as carbamazepine, phenytoin and barbiturates stimulate the activity of cytochrome P450 (CYP) enzymes and glucuronyl transferase an increase in the clearance of clobazam, clonazepam, diazepam, lorazepam, midazolam and nitrazepam should be anticipated in patients co-medicated with strong enzyme inducers. Benzodiazepines in general have no major influence on the pharmacokinetics of concomitantly administered AEDs. The vast majority of adverse effects involve the CNS and they are generally dose-dependent. Diazepam is widely available throughout the world than either lorazepam or midazolam.
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