In Refractory Status Epilepticus, Lacosamide May Be a Good Option

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Second-line therapy with lacosamide is not indicated in patients with renal failure.
Second-line therapy with lacosamide is not indicated in patients with renal failure.

Lacosamide was found to have similar efficacy and safety to sodium valproate for lorazepam-resistant status epilepticus (SE) in a small, randomized trial published in Epilepsia.

"Status epilepticus is a life threatening emergency, and about one-third of patients do not respond to benzodiazepines, more so if there is structural brain lesion or central nervous system infections," study investigator Jayantee Kalita, MD, told Neurology Advisor.  

"Lacosamide has been shown to be effective in small case series; therefore, its efficacy and safety compared to conventional second line antiepileptic drugs [are] important."

SE is considered a neurological emergency requiring management in the intensive care unit to monitor for respiratory and cardiovascular depression from antiepileptic drugs (AEDs). However, not all patients with SE respond to first-line treatments. There is a need to identify second-line AEDs for SE that are effective and minimize respiratory and cardiovascular depression. Although intravenous lacosamide is available, there is limited research and no randomized control trials to assess its safety and efficacy as a second-line option in SE.

Usha K. Misra, MD, head of neurology at Sanjay Gandhi Postgraduate Institutes of Medical Science in Lucknow, India, and colleagues conducted a randomized, open-label trial to evaluate the efficacy and safety of lacosamide compared with sodium valproate in patients with lorazepam-resistant SE. Patients were considered to have SE if they had continuous convulsions for more than 5 minutes, 2 or more convulsive seizures without full recovery, or subtle convulsive movements with coma and evidence of seizure on electroencephalography. Exclusion criteria included renal and hepatic failure.

Patients were randomly assigned to receive lacosamide (400 mg at 60 mg/min) or sodium valproate (30 mg/kg at 100 mg/min) after failing to respond to 2 doses of intravenous lorazepam (4 mg) at 10-minute intervals. Participants who did not respond to the second-line treatment after 10 minutes could be treated with an additional agent at the physician's discretion. Participants' vitals were monitored closely and given supportive treatments as needed.

The investigators identified 66 patients resistant to lorazepam with a mean duration of SE of 2 hours. Etiology of SE included central nervous system infection, stroke, metabolic disorders, and drugs, with 51.5% of patients demonstrating abnormalities on cranial imaging.

There were no differences between the lacosamide and sodium valproate groups for the primary outcome of seizure cessation for 1 hour (63.6% vs 69.7%; P =.79). Likewise, there were no statistically significant differences between the groups for 24-hour seizure control (45.5% vs 60.6%; P =.20) or death (30.3% vs 36.4%; P =.60).

Adverse effects in the lacosamide group included prolonged sedation, bradycardia, hypotension, and liver disfunction in the sodium valproate group. However, there were no significant differences between the groups for composite adverse effects (P =.49). Both groups had 16 patients who required mechanical ventilation.

"This study for the first time demonstrated comparable efficacy and safety of sodium valproate and lacosamide, although seizure freedom at 24 hours was better with sodium valproate," Dr Kalita said. "Lacosamide should be avoided in severe renal failure, and sodium valproate in liver failure," she concluded.

Reference

Misra UK, Dubey D, Kalita J. A randomized controlled trial of lacosamide versus sodium valproate in status epilepticus [published February 18, 2017]. Epilepsia. doi: 10.1111/epi.13706
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