Function and clinical meaningfulness of treatments for mild Alzheimer's disease.

INTRODUCTION: Effectiveness of Alzheimer's disease (AD) treatments is commonly evaluated with coprimary outcomes; cognition with function to ensure clinical meaningfulness of a cognitive effect. METHODS: We reviewed the literature for functional outcomes in mild AD or mild cognitive impairment (MCI) patients (distinct from combined mild-moderate/severe AD) treated with approved AD drugs. Cognitive and functional treatment differences in mild AD patients in solanezumab EXPEDITION/EXPEDITION2 studies were compared across time. RESULTS: Seven publications provided MCI/mild AD functional outcomes, one of which reported a significant functional treatment effect. Secondary analyses of EXPEDITION studies suggested a smaller functional effect of solanezumab relative to cognition. An increasing effect of solanezumab over 18 months was shown for cognition and function. DISCUSSION: Function as the sole measure to demonstrate clinical meaningfulness of cognitive effects in mild AD may have limitations. For disease-modifying treatments, point differences on cognitive and functional scales should be qualified with duration of treatment.

Seizure risk in patients with attention-deficit-hyperactivity disorder treated with atomoxetine.

The comorbidity of seizures, epilepsy, and attention-deficit-hyperactivity disorder (ADHD) prompted the examination of whether atomoxetine use for ADHD is associated with an increased risk of seizures. Seizures and seizure-related symptoms were reviewed from two independent Eli Lilly and Company databases: the atomoxetine clinical trials database and the atomoxetine postmarketing spontaneous adverse event database. Review of clinical trial data indicated that the crude incidence rates of seizure adverse events were between 0.1 and 0.2%, and were not significantly different between atomoxetine, placebo, and methylphenidate. Only 2% of the postmarketing spontaneous reports of seizure events were classified as having no clear contributing or confounding factors, and the reporting rate (8 per 100 000 patients exposed) was within the expected range of population-based incidence. Although children with ADHD are increasingly recognized as being at an elevated risk for seizures, treatment of ADHD symptoms with atomoxetine does not appear to elevate this risk further. The shared vulnerability between ADHD and seizure activity should be taken into account when making treatment decisions for populations of children with epilepsy and children with ADHD.