Objective: To examine clinical response and symptomatic remission in two studies of lisdexamfetamine dimesylate (LDX) in children with attention-deficit/hyperactivity disorder (ADHD).

Methods: In a 4-week, placebo-controlled, double-blind trial, children 6–12 years of age with ADHD received LDX (30–70 mg/day) or placebo. In an open-label trial, children from previous studies were titrated to optimal dose over 4 weeks and maintained up to 1 year. Primary and secondary efficacy assessments were the ADHD Rating Scale IV (ADHD-RS-IV) and Clinical Global Impressions-Improvement (CGI-I) scale, respectively. Clinical response was defined as ≥30% reduction in ADHD-RS-IV total score with a CGI-I rating of 1 or 2; symptomatic remission was defined by ADHD-RS-IV total score ≤18.

Results: In the 4-week study (N=285), at any postdose assessment, 79.3% achieved response (median 13 days) and 67.1% achieved remission (median 22 days) with LDX versus 29.2% and 23.6% with placebo. In the long-term study (N=251), at any postdose assessment, 96.0% responded and 62.7% maintained response; 88.8% achieved remission and 46.4% maintained remission.

Conclusion: Most children treated with LDX achieved clinical response and symptomatic remission at one time point; once achieved, almost half maintained remission.

Objectives: Alterations in serotonin impact bone metabolism in animal models, and selective serotonin reuptake inhibitors (SSRIs) have been associated with increased fracture risk in older adults. SSRIs are commonly used in anorexia nervosa (AN), a condition that predisposes to low bone mineral density (BMD). Our objective was to determine whether SSRI use is associated with low BMD in AN.

Methods: We examined Z-scores for spine, hip, and whole body (WB) BMD, spine bone mineral apparent density, and WB bone mineral content/height (BMC/Ht) in females 12–21 years of age with AN who had never been on SSRIs, had been on SSRIs for <6 months (<6M), or had been on SSRIs for >6 months (>6M).

Results: Subjects on SSRIs for >6M had lower spine, femoral-neck, and WBBMD Z-scores than those on SSRIs for <6M. Hip BMD and WBBMC/Ht Z-scores were lowest in subjects on SSRIs for >6M. Duration of SSRI use, duration since AN diagnosis and duration of amenorrhea inversely predicted BMD, whereas BMI was a positive predictor. In a regression model, duration of SSRI use remained an independent negative predictor of BMD.

Discussion: Duration of SSRI use >6M is associated with low BMD in AN.

Conclusion: It may be necessary to monitor BMD more rigorously when duration of SSRI use exceeds 6M.

Objective: The aim of this study was to investigate the influence of cerebrospinal fluid (CSF), amyloid β42(Aβ42), phosphorylated tau181 (p-tau), and total tau (t-tau) on cognitive functioning.

Methods: We analyzed the ability of the CSF biomarkers Aβ42, p-tau, and t-tau to predict the results on the Cambridge Cognitive Examination–Revised (CAMCOG-R), a cognitive screening test that assesses multiple cognitive domains, in 65 memory clinic patients (73.1±8.2 years) (n=30 probable Alzheimer's disease [AD], n=7 possible AD, n=12 non-AD dementia, n=16 mild cognitive impairment).

Results: We found no correlations between CSF biomarkers and CAMCOG-R performance in the whole group, nor in subgroups based on aberrant biomarker concentrations.

Discussion: Changed concentrations of CSF amyloid β42, p-tau, and t-tau cannot be directly linked to cognitive function in our sample of patients with cognitive impairment. Possibly, compensatory mechanisms such as cognitive reserve determine cognitive performance, rather than the absolute amount of damage caused by Aβ deposition and tangle formation. In addition, abnormal CSF biomarker concentrations may not be a direct reflection of the amount of neuronal damage, but merely serve as an indicator of AD pathology.

Conclusion: While CSF biomarkers are valuable in establishing AD pathology, they cannot be used to predict severity of cognitive impairment.

Background: Investigate the safety and tolerability of rivastigmine capsules and transdermal patch in patients with moderate Alzheimer's disease receiving concomitant memantine.

Methods: Safety data from two prospective, open-label, multicenter trials were analyzed. Study US32: patients received rivastigmine capsules (3–12 mg/day) plus memantine (20 mg/day). Study US38: patients switched from donepezil to rivastigmine patches (4.6 mg/24 hours) immediately or following 7 days' withdrawal; ∼50% received concomitant memantine (20 mg/day).

Results: The rivastigmine patch demonstrated more favorable tolerability than rivastigmine capsules, being associated with fewer adverse events (AEs) (73% versus 83%), serious AEs (10% versus 23%) and gastrointestinal symptoms (4% versus 26% for nausea; 4% versus 11% for vomiting). Application site reactions occurred in 17% of patients.

Conclusion: Concomitant memantine treatment with rivastigmine patch and capsule is generally well tolerated. The favorable tolerability and safety profile of rivastigmine transdermal patch is not further improved with concomitant memantine. Recommendations to minimize application site reactions are provided.