ABSTRACT. Objectives. Atomoxetine seems to be as effective for treating attention-deficit/hyperactivity disorder (ADHD) when the daily dose is administered once in the morning as when the dose is divided and administered in the morning and evening. In the present study, the efficacy of atomoxetine administered once daily among children with ADHD was assessed throughout the day, including the evening and early morning. Another goal was to determine how early in treatment it was possible to discern a specific effect of the drug on ADHD symptoms.Methods. This study was a randomized, multicenter, double-blind, placebo-controlled trial conducted at 12 outpatient sites in the United States. A total of 197 children, 6 to 12 years of age, who had been diagnosed as having ADHD, on the basis of the Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria, were randomized to receive 8 weeks of treatment with atomoxetine or placebo, dosed once daily in the mornings. ADHD symptoms were assessed with parent and investigator rating scales. The primary outcome measure was the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored total score. Daily parent assessments of children's home behaviors in the evening and early morning were recorded with an electronic data entry system. This instrument measures 11 specific morning or evening activities, including getting up and out of bed, doing or completing homework, and sitting through dinner.Results. Seventy-one percent of the children enrolled were male, 69% met criteria for the combined subtype (both inattentive and hyperactive/impulsive symptoms), and the most common psychiatric comorbidity was oppositional defiant disorder (35%). Once-daily atomoxetine (final mean daily dose of 1.3 mg/kg) was significantly more effective than placebo in treating core symptoms of ADHD. Mean reductions in the AttentionDeficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored total score were significantly greater for patients randomized to atomoxetine, beginning at the first visit after the initiation of treatment and continuing at all subsequent visits. Both inattentive and hyperactive/impulsive symptom clusters were significantly reduced with atomoxetine, compared with placebo. With continued treatment and dose titrations, core symptoms of ADHD continued to decrease throughout the 8-week study. Mean reductions in the daily parent assessment total scores for patients randomized to atomoxetine were superior during the first week, beginning with the first day of dosing, and were also superior at endpoint. Efficacy outcomes for the evening hours for atomoxetine-treated patients were superior to those for placebo-treated patients, as assessed with 2 different assessment scales. Decreases in the daily parent assessment morning subscores at endpoint showed a significant reduction in symptoms that lasted into the mornings. Rates of discontinuations attributable to adverse events were <5% for...

Patients receiving twice-daily atomoxetine had shorter sleep-onset latencies, relative to thrice-daily methylphenidate, based on objective actigraphy and polysomnography data. Although both medications decreased nighttime awakenings, the decrease was greater for methylphenidate.

ATX monotherapy effectively improved symptoms of ADHD and comorbid social anxiety disorder in adults and was well tolerated.

Background: Alzheimer’s disease (AD), the most common form of dementia, is a progressive neurodegenerative disorder with interrelated molecular, physiological, anatomical, biomarker, and cognitive dimensions. Methods: This article reviews the biological changes (genetic, molecular, and cellular) underlying AD and their correlation with the clinical syndrome. Results: Dementia associated with AD is related to the aberrant production, processing, and clearance of beta-amyloid and tau. Beta-amyloid deposition in brain follows a distinct spatial progression starting in the basal neocortex, spreading throughout the hippocampus, and eventually spreading to the rest of the cortex. The spread of tau pathology through neural networks leads to a distinct and consistent spatial progression of neurofibrillary tangles, beginning in the transentorhinal and hippocampal region and spreading superolaterally to the primary areas of the neocortex. Synaptic dysfunction and cell death is shown by progressive loss of cerebral metabolic rate for glucose and progressive brain atrophy. Decreases in synapse number in the dentate gyrus of the hippocampus correlate with declining cognitive function. Amyloid changes are detectable in cerebrospinal fluid and with amyloid imaging up to 20 years prior to the onset of symptoms. Structural atrophy may be detectable via magnetic resonance imaging up to 10 years before clinical signs appear. Conclusion: This review highlights the progression of biological changes underlying AD and their association with the clinical syndrome. Many changes occur before overt symptoms are evident and biomarkers provide a means to detect AD pathology even in patients without symptoms.

This randomized, double-blind, placebo-controlled, 6-month trial examined the efficacy and safety of once-daily morning-dosed atomoxetine in adult patients with attention-deficit/hyperactivity disorder (ADHD) and the efficacy of atomoxetine in ameliorating symptoms through the evening hours. Patients received once-daily atomoxetine (n = 250) or placebo (n = 251) in the morning for approximately 6 months. The efficacy measures included the Adult ADHD Investigator Symptom Rating Scale (AISRS), Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version, Clinical Global Impressions-ADHD-Severity of Illness, and Adult ADHD Quality of Life Scale. Overall, 94 patients randomized to atomoxetine and 112 patients randomized to placebo completed the study. On the AISRS total score, Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version evening index total score, Clinical Global Impressions-ADHD-Severity of Illness score, and Adult ADHD Quality of Life Scale total score, atomoxetine was statistically superior to placebo at the 10-week and 6-month time points. From the visitwise analysis, the mean (SD) AISRS total scores for atomoxetine decreased from 38.2 (7.5) at baseline to 21.4 (12.3) at the 6-month end point compared with 38.6 (7.0) to 25.8 (13.2) for placebo (P = 0.035). Nausea, dry mouth, fatigue, decreased appetite, urinary hesitation, and erectile dysfunction were the treatment-emergent adverse events reported significantly more often with atomoxetine. Discontinuations due to adverse events were 17.2% and 5.6% for atomoxetine and placebo, respectively (P < 0.001). Once-daily morning-dosed atomoxetine is efficacious for treating ADHD in adults when measured 10 weeks and 6 months after initiating treatment. Atomoxetine demonstrated significant efficacy that continued into the evening. Adverse events were similar to previous trials.