Konrad Werhahn

Adjunctive brivaracetam in adults with uncontrolled focal epilepsy: Results from a double‐blind, randomized, placebo‐controlled trial

Brivaracetam (BRV) is a novel high‐affinity synaptic vesicle protein 2A ligand in clinical development for the treatment of epilepsy. This phase III study (N01252; NCT00490035) evaluated the efficacy and safety/tolerability of BRV (20, 50, and 100 mg/day) compared with placebo (PBO) in patients aged 16–70 years with uncontrolled focal seizures with/without secondary generalization, despite treatment with one to two concomitant antiepileptic drugs at a stable and optimal dosage.

Effects of the serotonin1B/1D receptor agonist zolmitriptan on motor cortical excitability in humans

Oral administration of zolmitriptan, a novel 5-hydroxytriptamine receptor agonist, to eight healthy volunteers significantly reduced motor cortical excitability as tested by paired transcranial magnetic stimulation (TMS) at short interstimulus intervals. Zolmitriptan did not change motor thresholds to TMS or electromyographic silent period durations. We conclude that zolmitriptan acts centrally by reducing the inhibition within the motor cortex. The results suggest that the action of zolmitriptan on motor cortical excitability does not result from changes at the level of the cell membrane but from the influence on GABAergic inhibitory interneurons.

Efficacy, safety, and tolerability of lacosamide monotherapy versus controlled-release carbamazepine in patients with newly diagnosed epilepsy: a phase 3, randomised, double-blind, non-inferiority trial

BACKGROUND Further options for monotherapy are needed to treat newly diagnosed epilepsy in adults. We assessed the efficacy, safety, and tolerability of lacosamide as a first-line monotherapy option for these patients. METHODS In this phase 3, randomised, double-blind, non-inferiority trial, patients from 185 epilepsy or general neurology centres in Europe, North America, and the Asia Pacific region, aged 16 years or older and with newly diagnosed epilepsy were randomly assigned in a 1:1 ratio, via a computer-generated code, to receive lacosamide monotherapy or controlled-release carbamazepine (carbamazepine-CR) twice daily. Patients, investigators, and trial personnel were masked to treatment allocation. From starting doses of 100 mg/day lacosamide or 200 mg/day carbamazepine-CR, uptitration to the first target level of 200 mg/day and 400 mg/day, respectively, took place over 2 weeks. After a 1-week stabilisation period, patients entered a 6-month assessment period. If a seizure occurred, the dose was titrated to the next target level (400 or 600 mg/day for lacosamide and 800 or 1200 mg/day for carbamazepine-CR) over 2 weeks with a 1-week stabilisation period, and the 6-month assessment period began again. Patients who completed 6 months of treatment and remained seizure-free entered a 6-month maintenance period on the same dose. The primary efficacy outcome was the proportion of patients remaining free from seizures for 6 consecutive months after stabilisation at the last assessed dose. The predefined non-inferiority criteria were -12% absolute and -20% relative difference between treatment groups. This trial is registered with ClinicalTrials.gov, number NCT01243177. FINDINGS The trial was done between April 27, 2011, and Aug 7, 2015. 888 patients were randomly assigned treatment. 444 patients taking lacosamide and 442 taking carbamazepine-CR were included in the full analysis set (took at least one dose of study treatment), and 408 and 397, respectively, were included in the per-protocol set. In the full analysis set, 327 (74%) patients in the lacosamide group and 308 (70%) in the carbamazepine-CR group completed 6 months of treatment without seizures. The proportion of patients in the full analysis set predicted by the Kaplan-Meier method to be seizure-free at 6 months was 90% taking lacosamide and 91% taking carbamazepine-CR (absolute treatment-difference: -1·3%, 95% CI -5·5 to 2·8 relative treatment difference: -6·0%). Kaplan-Meier estimates results were similar in the per-protocol set (92% and 93%; -1·3%, -5·3 to 2·7; -5·7%). Treatment-emergent adverse events were reported in 328 (74%) patients receiving lacosamide and 332 (75%) receiving carbamazepine-CR. 32 (7%) patients taking lacosamide and 43 (10%) taking carbamazepine-CR had serious treatment-emergent adverse events, and 47 (11%) and 69 (16%), respectively, had treatment-emergent adverse events that led to withdrawal. INTERPRETATION Treatment with lacosamide met the predefined non-inferiority criteria when compared with carbamazepine-CR. Therefore, it might be useful as first-line monotherapy for adults with newly diagnosed epilepsy. FUNDING UCB Pharma.

Impact of carbamazepine, lamotrigine, and levetiracetam on vascular risk markers and lipid‐lowering agents in the elderly

To examine serologic markers of vascular risk under treatment with commonly used antiepileptic drugs (AEDs) in the elderly in a randomized setting, and to determine whether the reduced exposure to hydroxymethylglutaryl‐CoA reductase inhibitors (“statins”) caused by carbamazepine reduces the effectiveness of the drugs as lipid‐lowering agents.

Safety and tolerability of lacosamide monotherapy in the elderly: A subgroup analysis from lacosamide trials in diabetic neuropathic pain

To assess the safety profile of lacosamide monotherapy in elderly (≥65 years) subjects with diabetic neuropathic pain (DNP).