Lorazepam vs. Diazepam for Pediatric Status Epilepticus

In pediatric patients indicated for status epilepticus, benzodiazepines are considered first line therapy. Lorazepam is not FDA approved for this indication, but studies show it may be more effective and safe.

A double-blind, randomized clinical trial was conducted from March 1, 2008 to March 14, 2012 using 273 patients aged 3 months to younger than 18 years. Patients included in the trial had generalized tonic-clonic status epilepticus, which is defined as, 3 or more convulsions within the preceding hours and currently experiencing a convulsion, 2 of more convulsions in succession with no recovery of consciousness and currently experiencing a convulsion, or a current single convulsion with a duration of least 5 minutes.

140 were given 0.2 mg/kg diazepam IV and 133 were given 0.1 mg/kg lorazepam IV. In the diazepam group, 72.1% of patients had cessation of the status epilepticus and in the lorazepam group, 72.9% of patients had cessation of the status of epilepticus. Sedation was seen in 50% of patients taking diazepam and 66.9% of patients taking lorazepam.

It was determined that between the 2 medications, there were no significant differences in primary efficacy and safety outcomes. This does not support the theory that lorazepam is the superior treatment. This is interesting because the study showed that the medications have fairly equal efficacy, but lorazepam has an increase risk of producing sedation. Pharmacists should be aware of this when recommending medications for pediatric patients.

JAMA. 2014;311(16):1652-1660.

Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study

A study investigated the use of benzodiazepines the risk of it causing dementia or rapid cognitive decline. Benzodiazepines are used among 9-12% of older adults in the United States to treat anxiety and insomnia. Drugs that fall into this class are not recommended for long term use in older adults due to the associated increased risk of falls and delirium. Single dose studies found that benzodiazepines impair memory and attention span, but its effect in long term use is still uncertain. One problem with determining if long term benzodiazepine use increases the risk of dementia is that dementia is often preceded by anxiety and insomnia: symptoms often treated with benzodiazepines. Two out of three known studies that considered early dementia symptoms and potential for reverse causation reported an increased risk of dementia with benzodiazepine use.

The investigators hypothesized that cumulative, heavier benzodiazepine exposure over a long period of time was the most likely mechanism to cause an increased risk of dementia. The study was conducted within an integrated healthcare delivery system in the North West US. There were 3434 randomly selected participants in the study aged 65 or older who did not have dementia at the start of the study. Every two years, the cognitive abilities screening instrument (CASI) was administered to test for dementia. It was also used to assess cognitive trajectory. Computerized pharmacy data was use to define benzodiazepine exposure associated with risk of dementia. This consisted of the total standardized daily doses (TSDDs) over a 10 year period. The date of onset dementia was made the midpoint between the visit triggering the dementia evaluation and the visit before that.

While the study found a slightly higher risk of dementia associated with the lowest use of benzodiazepine, it did not find an increased risk in those using the highest level. Therefore, the findings do not support the theory that cumulative use of benzodiazepines at levels used in our population has a causal relationship to increased risk of cognitive decline or dementia. However, the study did not investigate acute adverse cognitive effects that can occur upon starting benzodiazepine treatment in older adults. Healthcare providers should still avoid benzodiazepine use in older adults to prevent other important adverse effects. Considering that other studies did report a causal relationship, it seems that this is a topic that still requires more investigation.

Gray GL, Dublin S, Yu O, et al. Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study. BMJ. 2016;352:90.