PHILADELPHIA — The sedative drugs diazepam (Valium) and lorazepam (Ativan) are equally effective in treating the prolonged seizures known as status epilepticus in children, according to a randomized, controlled study by a multi-institution team of researchers with the Pediatric Emergency Care Applied Research Network, including an expert from the Perelman School of Medicine at the University of Pennsylvania. Diazepam and lorazepam are given intravenously (IV) for the treatment of prolonged seizures. Previous studies in children had suggested that lorazepam was more effective in stopping convulsions or had lower rates of breathing-related side effects.
The new study, published in the April 23rd issue of JAMA, found that both medications were effective in stopping status epilepticus in more than 70 percent of cases and caused respiratory side effects in less than 20 percent of patients.
Both medications are benzodiazepines, a class of drugs primarily used for treating anxiety, but which are also effective in treating several other conditions, including seizures. Benzodiazepines are sedatives that also prevent or stop seizures by slowing down the central nervous system, making abnormal electrical activity less likely. The FDA has approved diazepam, but not lorazepam, for the treatment of prolonged seizures in children. Despite many experts advocating its use, lorazepam is not yet FDA-approved for this purpose.
“The data from this study show that both medications are equally effective and safe and may lead to expanded options for selecting drugs that are stable for use in emergency settings or resource poor environments,” said Jill M. Baren, MD, chair of the Department of Emergency Medicine at Penn and the study’s senior author. “Our results can also be used to support efforts to obtain FDA approval for lorazepam for treating children who suffer prolonged seizures.”
Baren also notes that the current study was designed to improve upon the limitations of previous studies. Earlier “off-patent” comparisons were retrospective, from single hospitals, and had small sample sizes, thus limiting generalizability. Retrospective studies, however, cannot ensure that dosing was given in a standardized manner or that patients were randomly assigned to receive one medication or the other, raising the possibility of extraneous variables contributing to the findings.
The current study was a large, double-blinded, prospective, randomized, controlled clinical trial in children presenting to emergency departments in 11 hospitals across the U.S. during generalized convulsive status epilepticus.
The study results have important implications for both pre-hospital (administered at home or in school, for example) and emergency department care. First, they support the choice of either diazepam or lorazepam as a first choice for pediatric status epilepticus. Second, because diazepam can be stored without refrigeration, it could be more convenient for use in certain pre-hospital settings such as by EMS personnel. “It may be that logistic considerations, rather than concerns about efficacy or safety, should influence the choice,” said Baren.
The new JAMA study is the largest prospective randomized trial comparing intravenous lorazepam to diazepam for the treatment of status epilepticus in children. It assessed 273 patients, aged three months to 17 years, from 11 large, geographically diverse pediatric academic hospitals in the US and Canada; 140 were randomized to diazepam and 133 to lorazepam. Prior pre-hospital care was controlled for by excluding all patients who had received a benzodiazepine in the previous seven days, allowing for an uncontaminated examination of efficacy and safety.
The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (HHSN275201100017C).
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