SEATTLE—Levetiracetam has similar efficacy and tolerability to long-acting valproate (VPA-ER) and long-acting carbamazepine (CBZ-CR) among patients with newly diagnosed partial or generalized epilepsy, according to results of an open-label, parallel-group study presented by Bernhard Pohlmann-Eden, MD, and colleagues.
A total of 1,688 patients 16 or older from 269 centers in Europe and Australia were randomized first to “best recommended treatment” (either VPA-ER or CBZ-CR) and then to levetiracetam (n = 841; median dosage, 986.6 mg/day), VPA-ER (n = 347; median dosage, 986.5 mg/day), or CBZ-CR (n = 500; median dosage, 588.5 mg/day), for 52 weeks.
Inclusion criteria were newly diagnosed epilepsy (within the past year), at least two unprovoked seizures in the past two years, and at least one seizure in the past six months. Patients were not eligible if they had been treated previously with levetiracetam, valproate, or carbamazepine. Extended-release levetiracetam was not available at the time of the study but is now FDA approved.
“The primary outcome measure—time to withdrawal—which assesses both efficacy and tolerability, was similar for all three drugs. There was no difference in the seizure freedom rates at six months or 12 months,” said Dr. Pohlmann-Eden, a neurologist at Dalhousie University in Halifax, Nova Scotia.
The frequency of treatment-emergent adverse events was 45.6% for levetiracetam, 45.9% for VPA-ER, and 52.3% for CBZ-CR. Headache and fatigue were two of the most common side effects for all three drugs. Total discontinuation rates were similar between levetiracetam (24%) and both standard antiepileptic drugs (26.1%). However, the time to first seizure was significantly longer for VPA-ER and CBZ-CR than for levetiracetam (hazard ratio, 1.20).
Dr. Pohlmann-Eden concluded that “levetiracetam is at least as effective as standard antiepileptic drugs and slightly better for adverse events, with no significant difference for seizure freedom. In addition, it appears that levetiracetam is effective in generalized as well as partial epilepsy.”
Lacosamide Is Well Tolerated as Adjunctive Therapy
Lacosamide is well tolerated in patients with partial-onset seizures when combined with up to three concomitant antiepileptic drugs, reported Victor Biton, MD, Director of the Arkansas Epilepsy Program in Little Rock, and colleagues. The researchers presented findings from three similarly designed trials of lacosamide.
The pooled safety analysis included 1,308 subjects (944 on lacosamide, 364 on placebo) from a 21-week phase II study, a 21-week phase III study, and an 18-week phase III study. The most frequent adverse events occurring with lacosamide versus placebo were dizziness (31% vs 8%), headache (13% vs 9%), nausea (11% vs 4%), and diplopia (11% vs 2%).
The investigators observed a small, dose-related increase in the PR interval on ECG, which was not associated with second- or third-degree AV block. The percentage of patients discontinuing treatment due to an adverse event was 17% with lacosamide and 5% with placebo.
“Side effects mostly occurred in the titration phase,” said Dr. Biton. “We start with lacosamide 50 mg by mouth twice daily and increase by 100 mg/week to the maintenance phase of 200 to 400 mg/day.”
Although the recent FDA approval classifies lacosamide as a “controlled substance,” Dr. Biton said he “did not notice a euphoric factor.” Lacosamide does not induce physical dependency, and a withdrawal effect has not been documented.
“Lacosamide is effective, well tolerated, and will be available in an IV form,” concluded Dr. Biton.
Investigational Device Reduces Disabling Seizures
The RNS System, an investigational device, was safe and reduced disabling seizures when used as adjunctive therapy in adults with medically intractable partial-onset seizures participating in a two-year, multicenter feasibility study, reported Martha Morrell, MD, and colleagues.
Dr. Morrell, who is Chief Medical Officer of Neuropace, Inc (Mountain View, California), the manufacturer of the device, explained that the RNS System includes a cranially implanted, battery-powered responsive neurostimulator that detects the onset of electric seizures and responds with an electric stimulus to abort the seizure. The stimulator is connected to two leads (depth and/or subdural), each with four electrode contacts. A programmer sets detection and stimulation parameters, and EEG data are transmitted to a secure Web-based file. Dr. Morrell is also Clinical Professor of Neurology at Stanford University in Palo Alto, California.
The feasibility investigation was designed to demonstrate safety and provide preliminary evidence for efficacy. The study enrolled 65 subjects (ages 18 to 57; 52% female) who had four or more disabling simple partial, complex partial, or secondarily generalized tonic clonic seizures per month in one or two localized epileptogenic zones; participants had been treated unsuccessfully with two or more antiepileptic drugs. The mean age at seizure onset was 14 years, 28% had prior vagus nerve stimulation, and 82% had intracranial monitoring. Thirty-seven percent had had unsuccessful epilepsy surgery.