Enteral topiramate treatment in refractory status epilepticus

Refractory status epilepticus (RSE) is defined as persistent seizure activity despite first- and second-line antiepileptic medications (ASMs). Although benzodiazepines and a range of iv ASMs are available, mortality is 3-4 times higher than in those without RSE. Topiramate (TPM), a broad-spectrum ASM, may have neuroprotective, anti-inflammatory, and mitigating effects on neuronal injury. We aimed to investigate the efficacy of TPM and mortality in RSE.

This retrospective, multicentre study was conducted on RSE ≥ 18 years of age in six different universities and state hospitals in Ankara and Istanbul, Turkey. Demographic data, seizure classification and etiology were analyzed. TPM was loaded and a maintenance dose was scheduled. The outcomes, prognoses, comorbidities were analysed. The effectiveness of TPM and mortality rates of the patients were also analyzed.

The study includes 60 patients with a mean age of 51.6 (±20, 20-84) years, 46.7 % were women. The patients were classified as having convulsive SE or nonconvulsive SE. TPM was performed as median third order ASM. The loading dose varied between 200 and 500 mg bid. The dose was subsequently reduced and maintained at 100-200 mg/day. There were 6 patients in whom TPM could not be continued due to adverse effects. TPM was considered successful in 22 patients, possibly successful in 23 patients and unsuccessful in 15 patients. Thirty-three patients were discharged from hospital, 8 were transferred to a rehabilitation center, 4 were transferred to a palliative care center and 13 died. There was no effect of age, gender, whether intubation was performed or not, etiologic classification, SE type (convulsive or nonconvulsive), duration of TPM administration, TPM loading dose on TPM success. Patients with RSE who were successfully treated with TPM had shorter hospital stays. The mortality predicting variables were determined as older age, not having epilepsy, failure to terminate RSE and acute symptomatic etiology.

This observational, multicenter study indicates that enteral TPM therapy is well tolerated, has a favorable safety profile, and is effective in patients with RSE. This is the first study in the literature to end SE with both high and low dose oral TPM treatment.