First North American Regional Epilepsy Congress: Valproate Safe for Status Epilepticus and Serial Attacks
Speaker: Ketil B. Olsen, MD, Professor of Neurology, Department of Neurology, Division of Clinical Neuroscience, Rikshospitalet-Radiumhospitalet, University of Oslo, Oslo, Norway
IV valproate (Depakene, Abbott), a well-known agent that inhibits GABA transaminase, was effective and safe for patients with status epilepticus and serial attacks that were resistant to benzodiazepine therapy.
Recently, IV valproate was approved in Norway for the treatment of benzodiazepine-resistant status epilepticus. To assess the value of this approach after the drug’s approval, a prospective study was conducted on the effect of IV valproate in status epilepticus and serial attacks from patients in six Norwegian hospitals.
The investigators obtained data from the first 41 adult patients, 29 with status epilepticus and 12 with serial attacks. These patients had been treated with IV valproate after unsuccessful benzodiazepine therapy. The standard valproate protocol suggested a loading dose of 25 mg/kg over 30 minutes, followed by a continuous infusion of 100 mg/hour for 24 hours.
Of the 41 patients in the study, 19 had generalized tonic-clonic seizures, 16 had complex-partial seizures, and six had mixed or other types of seizures as their primary seizure types. The median valproate bolus dose was 1,800 mg (range, 700-2,500 mg). The median time to treatment of the status epilepticus or serial attacks for all patients was three hours. For patients with complex-partial status epilepticus or serial attacks, the median time to the start of IV valproate therapy was four hours.
Valproate was effective in 31 of the 41 patients (76%) to the degree that they did not need anesthesia—either barbiturates or propofol (Diprivan, AstraZeneca). Of the 10 patients who did need anesthesia, five faced a significant delay, between 20 and 72 hours, before starting treatment.
Generally, IV valproate was well tolerated. Only one patient experienced moderate hypotension during infusion of the bolus dose. No other side effects were reported.
Topiramate for Seizures Previously Treated with Valproic Acid
Speaker: Barbara Schauble, MD, Clinical Neurophysiolo-gist, Department of Neurology, Medical and Scientific Affairs, Janssen-Cilag, Neuss, Germany
Therapy was associated with a substantial seizure reduction, a high seizure-free rate, and few side effects in patients with epilepsy who had not previously responded to valproic acid.
In a multicenter, open-label, non-interventional study, 147 patients older than 12 years of age were prospectively followed for 20 weeks. These patients had been unsuccessfully treated with valproic acid and were switched to topiramate because of a lack of efficacy or tolerability. The median duration of epilepsy was nine years. A 12-week retrospective seizure frequency was used as a baseline, with 77% of the patients having a mean of 32 seizures during the 12-week baseline period.
The most frequent seizure types at baseline were (1) generalized tonic-clonic (52%), (2) complex-partial (23%), (3) simple-partial (12%), and (4) absence (10%). The primary reason for the switch to topiramate was a lack of efficacy (54%) or side effects (81%). Adverse effects included weight gain (37%), tremors (29%), fatigue (21%), and cognitive changes (10%).
At the endpoint of the study, 70% of patients received topi-ramate as monotherapy at a median dose of 125 mg/day, and 77% of these continued with topiramate treatment. The mean frequency of seizures decreased significantly, from 32 seizures per month at baseline to three seizures per month during the maintenance period.
The responder rate, as measured by a reduction in seizure frequency of 50% or more, was 75% in the maintenance period; 51% of these patients remained seizure-free.
Sixteen percent of the patients discontinued topiramate: 8% because of adverse events and 3% because of insufficient efficacy. Overall, 83% of physicians assessed the tolerability and 79% assessed the efficacy of topiramate as “very good” or “excellent.”
Adjunctive Lamotrigine for Tonic-Clonic Seizures in Patients with Absence Seizures
Speaker: Mutaz Tabbaa, MD, Neurologist, Bay Neurological Institute, Panama City, Florida
Adjunctive therapy with canadian lamotrigine (Medication Lamictal, Glaxo-SmithKline) was successful in controlling primary generalized tonic-clonic (PGTC) seizures and was well tolerated in patients with a history of absence seizures.
Originally, the efficacy and tolerability of lamotrigine was demonstrated in a randomized, blinded, placebo-controlled study of patients two years of age or older with PGTC seizures. That trial was the basis of the recent FDA approval of PGTCs.
A subanalysis of the data was performed. The study consisted of three phases:
- a baseline assessment
- an escalation phase, during which the drug was titrated to a target dose of 2.7 to 12 mg/kg per day in patients 2 to 12 years of age or to a target dose of 150 to 400 mg/ day in patients over 12 years of age
- a maintenance phase, during which doses of drug and concomitant antiepileptic agents were maintained for 12 weeks.
The investigators evaluated 38 patients with a history of absence seizures; 18 patients received lamotrigine, and 20 received placebo. During the entire treatment period, the median percent decrease from baseline in PGTC seizures was 64% with lamotrigine and 30% with placebo. These rates were comparable to the efficacy findings in the overall study population.
The median change in absence seizures from baseline during the treatment period was a 26% decrease with a 100% increase with placebo.