The effi cacy of topiramate in status epilepticus, experience from Thailand

Background: Oral topiramate is a broad-spectrum antiepileptic drug. There is limited documented data on its use in refractory convulsive and non-convulsive status epilepticus. Methods: A retrospective study of the clinical characteristics and responses of patients diagnosed as status epilepticus treated with topiramate at the Srinagarind Hospital, Khon Kaen University from 2001-2010. Results: There were 8 patients included in this study, 6 patients were convulsive status epilepticus and 2 patients were non-convulsive status epilepticus. The most common cause was stroke seen in 4 patients. Oral topiramate successfully controlled status epilepticus in 7 out of 8 patients with no serious adverse events. Of these 7 patients, status epilepticus was controlled after initial loading and re-loading of oral topiramate in 3 and 4 patients, respectively. In two patients with hepatitis, oral topiramate was successful after failure with benzodiazepine. The initial loading dose of topiramate in most cases was 400 mg with a maintenance dose of 100 mg/day. Conclusion: Oral topiramate has the potential to treat both convulsive and non-convulsive status epilepticus after failing the fi rst antiepileptic drug. Further study with larger number of patients is needed to confi rm this. Neurology Asia 2012; 17(4) : 297 – 302 Address correspondence to: Dr Somsak Tiamkao, Department of Medicine, Faculty of Medicine, Integrated Epilepsy Research Group, Khon Kaen University, Khon Kaen, 40002, Thailand Tel: 66-43-363664, Fax: 66-43-348399, Email: [email protected] INTRODUCTION Status epilepticus (SE) is a life-threatening emergency condition that requires prompt and proper management with intravenous (IV) antiepileptic drugs (AEDs). The most common fi rst-line AEDs therapy is IV benzodiazepine, either lorazepam or diazepam. If seizures persist, the second-line such as phenytoin, fosphenytoin or sodium valproate are often given. In case of refractory SE, phenobarbital, propofol, or sodium thiopental are recommended medications. Topiramate (TPM), a sulfamate-substituted monosaccharide, is an oral, broad-spectrum AEDs approved as adjunctive and monotherapy in the treatment of epilepsy. There are multiple mode of action involving blockade of voltage-dependent sodium channels, potentiation of GABAergic transmission and inhibition of excitatory pathways through an action at AMPA receptor sites. Carbonic anhydrase inhibiting properties have also been demonstrated. The pharmacokinetics of TPM are characterised by linear pharmacokinetics over the dose range 100-800mg, which, in monotherapy, is predominantly through renal excretion (renal clearance 10-20 mL/min) and can be used in patients with hepatic impairment. It has minimal protein binding and a long half-life (19-25 hours). TPM is well absorbed from the gastrointestinal tract. Oral availability is 81-95% and is not affected by food intake. A peak plasma level is usually attained in 2–3 hours. TPM has little effect on the plasma concentrations of other AEDs except phenytoin. TPM metabolism is increased when administered with carbamazepine or phenytoin. Adverse effects of TPM include ataxia, decreased concentration, confusion, dizziness, and fatigue. The appropriate dosage of TPM ranges from 50 mg and up to 1,000 mg as monotherapy or addon therapy. Privitera et al showed that an initial target dose of TPM 100 mg/day is at least as effective as therapeutic doses of carbamazepine and valproate and some studies have suggested that most patients are likely to benefi t from receiving 400 mg day or less. Higher dose TPM treatment is associated with side effects, especially CNSrelated. TPM has been reported to be effective in both refractory and non-convulsive SE which are unresponsive to standard AEDs. The use of TPM in SE was fi rst reported by Reuber in 2002. Since then, case series have been published in both adult and children. In adult patients, Bensalem and Fakhoury reported the effectiveness of TPM Neurology Asia December 2012 298 in treating SE in 3 patients, Towne et al. in 6 cases, Soler et al. in 3 cases, Stojanova et al. in 4 of 7 cases. Synowiec et al. reported success in 14 out of 35 cases, and needed no further IV anesthetic agents or additional AEDs in 3 days. In the pediatric population, Kahriman et al. reported that success in 3 children, Blumkin et al. in 2 cases, and Perry et al. in 3 cases. Akyildiz and Kumandas reported TPM use in 14 patients. Of those, 9 patients had full response, 3 patients had partial response, and 2 patients did not respond. In Asia, Xiong et al. reported the fi rst case of TPM use in a child with SE. Despite these, clinical data of oral TPM treatment in SE is still limited, particularly among the Asians. In Thailand, TPM has been commonly used in SE with hepatitis and refractory SE in the recent years, partly because IV phenobarbital has not been available in Thailand since 2009. We report here the clinical features and outcomes of 8 SE patients treated with oral TPM at Khon Kaen University Hospital (Srinagarind hospital), Thailand.