Although the primary efficacy analysis was negative, time-to-exit analyses that included time-to-first-seizure as a covariate, between-group differences in seizure-free rates, and longer time-to-first-seizure with higher serum concentration provide evidence that topiramate is effective as monotherapy in patients with localization-related epilepsy.

No abstract

This article examines the headaches that can develop with deep brain stimulation. We identified 15 (23.4%) of 64 patients who developed chronic headaches following implantation of deep brain stimulation electrodes for relief of chronic pain syndromes. Electrodes were implanted in the periaqueductal gray, sensory thalamus, and internal capsule. None of these 15 patients reported similar headaches prior to the implantation. Although 5 patients were intermittent headache sufferers prior to implantation, they reported post-implantation headaches to be completely different in nature. Our experience suggests that headache syndromes may arise due to disturbance of serotonergic neurotransmission within deep brain structures.

BackgroundDonepezil 23 mg/d, recently approved in the United States for treatment of moderate to severe Alzheimer's disease (AD), was developed to address the need for an additional treatment option for patients with advanced AD. This report, based on a pivotal phase 3 study, presents a detailed analysis of the safety and tolerability of increasing donepezil to 23 mg/d compared with continuing 10 mg/d.MethodSafety analyses comprised examination of the incidence, severity, and timing of treatment-emergent adverse events (AEs) and their relationship to treatment initiation; changes in weight, electrocardiogram, vital signs, and laboratory parameters; and the incidence of premature study discontinuation. The analysis population (n = 1434) included all randomized patients who took at least 1 dose of study drug and had a postbaseline safety assessment. To further examine the effect of transition from a lower to a higher donepezil dose, a pooled analysis of safety data from 2 phase 3 trials of donepezil 5 mg/d and 10 mg/d was also performed.ResultsThe safety population comprised 1434 patients: donepezil 23 mg/d (n = 963); donepezil 10 mg/d (n = 471); completion rates were 71.1% and 84.7%, respectively. The most common AEs were nausea, vomiting, and diarrhea (donepezil 23 mg/d: 11.8%, 9.2%, 8.3%; donepezil 10 mg/d: 3.4%, 2.5%, 5.3%, respectively). AEs that contributed most to early discontinuations were vomiting (2.9% of patients in the 23 mg/d group and 0.4% in the 10 mg/d group), nausea (1.9% and 0.4%), diarrhea (1.7% and 0.4%), and dizziness (1.1% and 0.0%). The percentages of patients with AEs in the 23 mg/d group, as well as the timing, type, and severity of these AEs, were similar to those seen in previous donepezil trials with titration from 5 to 10 mg/d. Serious AEs were uncommon (23 mg/d, 8.3%; 10 mg/d, 9.6%).DiscussionThe 23 mg/d dose of donepezil was associated with typical cholinergic AEs, particularly gastrointestinal-related AEs, similar to those observed in studies with a dose increase from 5 to 10 mg/d.ConclusionThe good safety and predictable tolerability profile for donepezil 23 mg/d supports its favorable risk/benefit ratio in patients with moderate to severe AD.Trial RegistrationNCT00478205