Abstracts

RATIONALE: Lamotrigine (LTG) is a novel antiepileptic drug (AED) with proven efficacy against refractory complex partial seizures. A slow titration of LTG over one month is recommended to decrease the incidence of adverse events, notably rash. Of particular concern is the concomitant use of LTG with valproic acid, which has lead to an increased incidence of rash. Unfortunately, this slow titration precludes its utility in critically ill patients requiring immediate intervention for cessation of refractory seizures. The intention of the use of this rapid dose escalation of LTG was to potentially spare the use of high-dose barbiturate therapy. The purpose of this report was to evaluate the tolerability of rapid LTG titration in patients with seizures refractory to traditional AEDs in a controlled intensive care unit setting.
METHODS: After human investigation committee approval, a search of our hospital database identified charts in which LTG was prescribed in the intensive care unit.
RESULTS: The median age was 60 (27-81) years with six females and three males. Admission diagnosis included: status epilepticus (3), ischemic stroke (2), aneurysmal subarachnoid hemorrhage (2), traumatic brain injury (1), and intracerebral hemorrhage (1). Only 4/9 patients had history of seizures. All patients were receiving at least one other antiepileptic drug at the time LTG was prescribed (median 3; range 1-4), primarily phenytoin (8/9), carbamazepine (5/9) and valproic acid (5/9). The initial LTG dose ranged from 25 to 100 mg/day with a median maintenance dose of 300 mg/day (range 100-500 mg/day) per gastric tube and this was achieved in 3 (1-4) days. All patients expressed clinical seizure activity and 4/9 displayed epileptiform activity on EEG prior to LTG initiation. Clinical seizure activity ceased in 8/9 patients within 1 (1-19) day of LTG initiation. Thirty-three percent of patients required supplemental doses of lorazepam (median 2.5 mg; range 1-4 mg) after LTG initiation. Only one patient required high dose barbiturate therapy to gain control of their seizures. Two patients developed a rash. Of those, the rashes were thought to be due to other agents (risperidone and ampicillin/sulbactam) and not related to LTG. Both of the suspected agents were discontinued while LTG therapy was continued with resolution of the rash. All patients were discharged to home, rehab, or nursing home on LTG with the exception of one patient who expired.
CONCLUSIONS: In this report, rapid escalation of LTG was well tolerated in these nine patients. LTG also appears to abate seizure activity quickly following initiation of this rapid dose titration. The use of LTG may indeed spare high dose barbiturate therapy for refractory seizures. Further investigation of rapid dose escalation with LTG is needed in critically ill patients as an alternative for refractory seizures. The information presented should provide clinicians with the initial experience of rapidly administering LTG to critically ill patients.
(Disclosure: Grant - Dr. Coplin support in part by NIH/NINDS NS 38905)