Clobazam: An effective add‐on therapy in refractory status epilepticus

Abstract

SUMMARYRefractory status epilepticus (RSE) is a medical emergency, with significant morbidity and mortality. The use and effectiveness of clobazam, a unique 1,5-benzodiazepine, in the management of RSE has not been reported before. Over the last 24 months, we identified 17 patients with RSE who were treated with clobazam in our hospital. Eleven of the 17 patients had prior epilepsy. Fifteen patients had focal status epilepticus. Use of clobazam was prompted by a favorable pharmacokinetic profile devoid of drug interactions. Clobazam was introduced after a median duration of 4 days and after a median of three failed antiepileptic drugs. A successful response, defined as termination of RSE within 24 h of administration, without addition or modification of concurrent AED and with successful wean of anesthetic infusions, was seen in 13 patients. Indeterminate response was seen in three patients, whereas clobazam was unsuccessful in one patient. Clobazam averted the need for anesthetic infusions in five patients. Clobazam was well tolerated, and appears to be an effective and promising option as add-on therapy in RSE. Its efficacy, particularly early in the course of SE, should be further investigated in prospective, randomized trials.

Use of Newer Anticonvulsants for the Treatment of Status Epilepticus

“…Review of the literature showed different success rates than those just described. For example, the success rate in the second study seems much lower than the success rate described in the first study . This was also evident after correcting for the definition of success because CLB was the last antiseizure medication in 16 of 17 patients (94%) in the first .…”

“…Finally, the second study excluded patients with focal RSE without impairment of awareness, absence RSE, and RSE secondary to anoxic brain damage, whereas the first study did not exclude these patients. In fact, 88% of the patients in that study had focal SE, making it difficult to compare these two cohorts and different success rates …”

“…Two studies were found on the use of CLB in SE and RSE. The first study reported their single‐center experience with CLB in 17 patients with RSE . CLB was started after a median duration of 4 days (range 1–61 days) and after a median of three AEDs.…”

“…Considering that the dose of CLB and sequence of administration were similar in the two studies, other factors such as prior history of epilepsy and use of anesthetic agents may have contributed to the difference in success rate. Fewer patients had a prior history of epilepsy in second study (42% [10/24]) compared with the trial in the first study (65% [11/17]). In addition, the number of seizure episodes treated with anesthetic agents was lower in the second study compared with the first.…”

Systematic review of clobazam use in patients with status epilepticus

“…Given its distinct 1,5‐benzodiazepine structure, CLB displays unique properties when compared to other commonly used benzodiazepines (BDZs) . Recent evidence has shown that clobazam may demonstrate therapeutic efficacy in status epilepticus (SE) . CLB's rapid and complete absorption, minimal drug interactions, low propensity for sedation, and possibility of being administered by enteral feeding tube without affecting its absorption make CLB a plausible option in the setting of SE .…”