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Objectives: To examine the efficacy and tolerability of atomoxetine (ATX) in improving cognitive performance of patients with Alzheimer dementia., Design: A randomized, double-blind, placebo (PLA)-controlled, parallel-groups study, starting with a 5-33-day screening and evaluation period, followed by a 6-month treatment period., Setting: Eight independent or academic outpatient clinics in the United States., Participants: Male or female patients, aged 55 years and older, with mild-to-moderate Alzheimer disease (Mini-Mental State Examination score between 10 and 26) at baseline., Intervention: ATX (25-80 mg/day) or PLA for up to 6 months, added to ongoing cholinesterase-inhibitor therapy., Measurements: Alzheimer Disease Assessment Scale-Cognitive Portion (ADAS-Cog, primary measure), Clinician's Interview-Based Impression of Change score at end point, Neuropsychiatric Inventory, and Alzheimer's Disease Cooperative Study Inventory-Activities of Daily Living Inventory total score, safety measures (secondary measures)., Results: Patients' (N = 92) scores on assessments of cognitive function, global clinical impression, and neuropsychiatric symptoms were not significantly different between treatment groups. Neither group showed significant changes from baseline on the primary measure of efficacy, the ADAS-Cog. The ATX group showed a significantly greater increase of heart rate, and the mean increase in diastolic blood pressure and decrease in weight differed significantly from the decrease in pressure and weight increase in the PLA group. No other clinically meaningful safety results were obtained., Conclusions: Addition of ATX to ongoing cholinesterase-inhibitor therapy was generally well tolerated but did not significantly improve cognitive function.

Objective: The authors compared efficacy of olanzapine versus placebo and risperidone as measured by the Neuropsychiatric Inventory and Clinical Global Impression-Severity of Psychosis scale in patients with dementia-related psychosis., Methods: Patients with moderate-to-severe psychotic symptoms associated with dementia were recruited from outpatient or residential settings and randomly assigned to 10-week, double-blind, flexible-dose treatment with olanzapine (N=204; 2.5 mg-10 mg/day; mean: 5.2 mg/day), risperidone (N=196; 0.5 mg-2 mg/day; mean: 1.0 mg/day) or placebo (N=94)., Results: Most measures of neuropsychiatric functioning improved in all treatment groups, including the placebo group, and no significant treatment differences occurred. Overall discontinuation was lowest in the placebo group, and the olanzapine group had a significantly higher incidence of discontinuation due to adverse events (16.2%) relative to placebo (3.2%) and risperidone (8.7%) groups. Treatment-emergent extrapyramidal symptoms were more numerous for risperidone- than placebo- or olanzapine-treated patients. Abnormally high prolactin levels occurred in 78.0% of risperidone patients, compared with 16.7% for olanzapine and 5.0% for placebo. The incidence of weight gain greater than 7% from baseline was higher in the olanzapine group relative to risperidone, but neither active-treatment group showed a statistical difference from placebo (1.1%). No other statistically significant and clinically relevant differences were seen for any other vital sign, electrocardiographic measure, or laboratory hematology and chemistry, including glucose, except for cholesterol, which decreased from baseline to endpoint in both active-treatment groups., Conclusions: Patients' neuropsychiatric functioning improved with olanzapine, risperidone, and placebo treatment. There was a substantial response in the placebo group, and no significant differences emerged among treatments.

Objectives: Psychotic symptoms and behavioral disturbances are a concern in the care of elderly patients with Alzheimer's dementia (AD). This study was conducted to compare the efficacy of olanzapine versus placebo in patients with psychotic symptoms associated with AD in long-term or continuing-care settings., Methods: Patients (n = 652) with AD and delusions or hallucinations were randomly assigned to 10 weeks of double-blind treatment with placebo or fixed-dose olanzapine (1.0, 2.5, 5.0, 7.5 mg/day)., Results: Mean age was 76.6+/-10.4 years. Repeated-measures analysis showed significant improvement from baseline in NPI/NH Psychosis Total scores (sum of Delusions, Hallucinations items-primary efficacy measure) in all five treatment groups (p<0.001), but no pairwise treatment differences were seen at the 10-week endpoint. However, under LOCF analysis, improvement in the 7.5 mg olanzapine group (-6.2 +/- 4.9) was significantly greater than with placebo (-5.0 +/- 6.1, p = 0.008), while endpoint CGI-C scores showed the greatest improvement in the Olz 2.5 olanzapine group (2.8 +/- 1.4, p = 0.030) relative to placebo (3.2 +/- 1.4). There were significant overall treatment-group differences in increased weight, anorexia, and urinary incontinence, with olanzapine showing numerically higher incidences. However, neither the incidence of any other individual events, including extrapyramidal symptoms, nor of total adverse events occurred with significantly higher frequency in any olanzapine group relative to placebo. No clinically relevant significant changes were seen across groups in cognition or any other vital sign or laboratory measure, including glucose, triglyceride, and cholesterol., Conclusions: While 1.0 mg olanzapine did not show significant differences from placebo, the 2.5 mg dose was a reasonable starting dose. Olanzapine at 7.5 mg/day significantly decreased psychosis and overall behavioral disturbances (NPI/NH, BPRS) and was well tolerated., (Copyright 2004 John Wiley & Sons, Ltd.)

Background: Psychotic symptoms and behavioral disturbances are a leading cause of institutionalization in elderly patients with Alzheimer's disease (AD)., Objectives: Elderly nursing home patients (n=105) with possible or probable AD were entered into a multicenter study to determine the long-term efficacy and safety of olanzapine in treatment of psychotic symptoms and behavioral disturbances due to AD., Methods: Following a double-blind, 6-week exposure to fixed-dose olanzapine (5, 10, or 15 mg/d), patients entered an additional 18-week, open-label, flexible-dose treatment. Baseline was defined from the start of the extension phase., Results: Patients improved significantly on the primary efficacy measure, defined a priori, which consisted of the sum of the Agitation/Aggression, Delusions, and Hallucinations items ('Core':) of the NPI/NH. Olanzapine also significantly improved scores for the NPI/NH total and the Core item-associated Occupational Disruptiveness of the NPI/NH, as well as the BPRS total and CGI Severity-of-Alzheimer's scores. Barnes Akathasia scores improved significantly from baseline, while Simpson-Angus and AIMS scores were not significantly changed. Treatment-emergent symptoms included somnolence, accidental injury, and rash. No significant changes were seen in ECGs, including QT(c) interval, nor in weight or vital signs, including orthostasis., Conclusions: Low-dose olanzapine appears to be effective and well tolerated for treatment of behavioral disturbances and psychotic symptoms due to AD in elderly patients., (Copyright 2001 John Wiley & Sons, Ltd.)

Background: Elderly patients with Alzheimer's disease (AD) commonly exhibit psychotic symptoms, prompting clinicians to administer antipsychotics. This article compares the effects of olanzapine and placebo in the emergence of hallucinations or delusions in AD patients with symptoms of agitation/aggression but little or no psychotic symptomatology at baseline., Method: A multicenter, double-blind, placebo-controlled study was conducted in nursing home patients with AD according to DSM-IV criteria and symptoms of agitation/aggression and/or psychosis. Patients (N = 206) were randomly assigned to receive either placebo or fixed-dose olanzapine (5, 10, or 15 mg/day) for up to 6 weeks. This article analyzes data from a subgroup of patients (N = 165) with no or minimal delusions and/or hallucinations at baseline as measured by the Neuropsychiatric Inventory-Nursing Home Version (NPI/NH). Three subsets of patients were identified on the basis of their symptoms at baseline: those with no clinically significant hallucinations, those with no clinically significant delusions, and those with no clinically significant delusions or hallucinations., Results: Of the patients without hallucinations or delusions at baseline (N = 75), the placebo-treated patients showed significantly greater development of these symptoms compared with olanzapine-treated patients overall (NPI/NH hallucinations + delusions mean change score, +2.73 vs. +0.27, p = .006). Similarly, of the patients without baseline hallucinations (N = 153), the placebo-treated patients showed greater hallucinations score increases than did olanzapine-treated patients overall (+1.25 vs. +0.33, p = .026), whereas patients without baseline delusions (N = 87) showed no significant treatment effects. Olanzapine had a favorable safety profile in each patient subset., Conclusion: These results suggest that, overall, olanzapine effectively attenuated emergence of psychosis in a short-term trial of patients with Alzheimer's disease.

Background: Patients with Alzheimer disease (AD) commonly exhibit psychosis and behavioral disturbances that impair patient functioning, create caregiver distress, and lead to institutionalization. This study was conducted to assess the efficacy and safety of olanzapine in treating psychosis and/or agitation/aggression in patients with AD., Methods: A multicenter, double-blind, placebo-controlled, 6-week study was conducted in 206 elderly US nursing home residents with AD who exhibited psychotic and/or behavioral symptoms. Patients were randomly assigned to placebo or a fixed dose of 5, 10, or 15 mg/d of olanzapine. The primary efficacy measure was the sum of the Agitation/Aggression, Hallucinations, and Delusions items (Core Total) of the Neuropsychiatric Inventory-Nursing Home version., Results: Low-dose olanzapine (5 and 10 mg/d) produced significant improvement compared with placebo on the Core Total (-7.6 vs -3.7 [P<.001] and -6.1 vs -3. 7 [P =.006], respectively). Core Total improvement with olanzapine, 15 mg/d, was not significantly greater than placebo. The Occupational Disruptiveness score, reflecting the impact of patients' psychosis and behavioral disturbances on the caregiver, was significantly reduced in the 5-mg/d olanzapine group compared with placebo (-2.7 vs -1.5; P =.008). Somnolence was significantly more common among patients receiving olanzapine (25.0%-35.8%), and gait disturbance occurred in those receiving 5 or 15 mg/d (19.6% and 17.0%, respectively). No significant cognitive impairment, increase in extrapyramidal symptoms, or central anticholinergic effects were found at any olanzapine dose relative to placebo., Conclusion: Low-dose olanzapine (5 and 10 mg/d) was significantly superior to placebo and well tolerated in treating agitation/aggression and psychosis in this population of patients with AD.