olanzapine and Alzheimer-Disease

To systematically assess the safety and efficacy of olanzapine versus clozapine when treating senile dementia and to provide evidence-based medicine basis for its promotion and use.. PubMed, Embase, ScienceDirect, Cochrane Library, China Knowledge Network Database (CNKI), China VIP Database, Wanfang Database, and China Biomedical Literature Database (CBM) online database were searched for randomized controlled trials (RCT) of olanzapine and clozapine when treating senile dementia. The retrieval time limit is from the establishment of the database to the present. The data were extracted independently by two researchers, and the bias risk of each contained literature was analyzed in accordance with the standard of Cochrane Handbook 5.3. RevMan 5.4 statistical software was used to analyze the collected data by meta-analysis.. Finally, 6 randomized controlled trial articles were included, with a total of 490 samples. Meta-analysis of clinical efficacy showed that the clinical efficacy was similar and there was no significant difference (. Olanzapine and clozapine have similar efficacy when treating mental and behavioral disorders in patients with senile dementia, in which olanzapine is more effective in improving the symptoms of patients with Alzheimer's disease (AD), with less adverse reactions and high safety, which is worth popularizing in clinical practice. However, more studies and follow-up with higher methodological quality and longer intervention time are needed to further verify.

Topics: Alzheimer Disease; Antipsychotic Agents; Clozapine; Humans; Olanzapine; Randomized Controlled Trials as Topic; Treatment Outcome

Capgras delusion (CD) has multiple etiologies including neurodegenerative disorders and can be associated with violent behavior. CD is a common complication of Alzheimer dementia (AD); however, CD with violent behavior is uncommon in AD. We report escalating violent behavior by a patient with advanced AD and CD who presented to the emergency department (ED) and required admission to an academic medical center.. Case analysis with PubMed literature review.. A 75-year-old male with a 13-year history of progressive AD, asymptomatic bipolar disorder, chronic kidney disease, hypertension, hyperlipidemia, and benign prostatic hypertrophy presented to the ED with recurrent/escalating violence toward his wife, whom he considered an impostor. His psychotropic regimen included potentially inappropriate medications (PIMs) for geriatric/AD patients-topiramate/amitriptyline/chlordiazepoxide/olanzapine-that are associated with delirium, cognitive decline, dementia, and mortality. Renal dosing for topiramate, reduction in PIMs/anticholinergic burden, and substituting haloperidol for olanzapine resolved his violent behavior and CD.. CD in AD is a risk factor for violent behavior. As the geriatric population in the United States grows, CD in patients with AD may present more frequently in the ED, requiring proper treatment. Pharmacovigilance is necessary to minimize PIMs in geriatric/AD patients. Clinicians and other caregivers require further education to appropriately address CD in AD.

Topics: Aged; Aggression; Alzheimer Disease; Amitriptyline; Anticonvulsants; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Capgras Syndrome; Chlordiazepoxide; Fructose; Haloperidol; Humans; Hypnotics and Sedatives; Male; Olanzapine; Potentially Inappropriate Medication List; Renal Insufficiency, Chronic; Topiramate; Violence

This manuscript reviews the preclinical in vitro, ex vivo, and nonhuman in vivo effects of psychopharmacological agents in clinical use on cell physiology with a view toward identifying agents with neuroprotective properties in neurodegenerative disease. These agents are routinely used in the symptomatic treatment of neurodegenerative disease. Each agent is reviewed in terms of its effects on pathogenic proteins, proteasomal function, mitochondrial viability, mitochondrial function and metabolism, mitochondrial permeability transition pore development, cellular viability, and apoptosis. Effects on the metabolism of the neurodegenerative disease pathogenic proteins alpha-synuclein, beta-amyloid, and tau, including tau phosphorylation, are particularly addressed, with application to Alzheimer's and Parkinson's diseases. Limitations of the current data are detailed and predictive criteria for translational clinical neuroprotection are proposed and discussed. Drugs that warrant further study for neuroprotection in neurodegenerative disease include pramipexole, thioridazine, risperidone, olanzapine, quetiapine, lithium, valproate, desipramine, maprotiline, fluoxetine, buspirone, clonazepam, diphenhydramine, and melatonin. Those with multiple neuroprotective mechanisms include pramipexole, thioridazine, olanzapine, quetiapine, lithium, valproate, desipramine, maprotiline, clonazepam, and melatonin. Those best viewed circumspectly in neurodegenerative disease until clinical disease course outcomes data become available, include several antipsychotics, lithium, oxcarbazepine, valproate, several tricyclic antidepressants, certain SSRIs, diazepam, and possibly diphenhydramine. A search for clinical studies of neuroprotection revealed only a single study demonstrating putatively positive results for ropinirole. An agenda for research on potentially neuroprotective agent is provided.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Antioxidants; Antipsychotic Agents; Benzodiazepines; Benzothiazoles; Brain; Clonazepam; Desipramine; Dibenzothiazepines; Dopamine Agonists; Humans; Lithium Carbonate; Maprotiline; Melatonin; Neurodegenerative Diseases; Neuroprotective Agents; Olanzapine; Parkinson Disease; Pramipexole; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Valproic Acid

Treatment-emergent weight gain has been reported in younger patients receiving atypical antipsychotics, but less is known about weight gain in adults aged 65 years and older. This was a post hoc analysis of 1267 patients with dementia and behavioral disturbances treated with olanzapine (1 to 20 mg/d) in clinical trials, most of whom were underweight (body mass index <18.5 kg/m2) or of normal weight (body mass index, 18.5-24.9 kg/m2) at baseline. Weight changes over the first 20 weeks of treatment in olanzapine-treated patients, as estimated by a repeated measures analysis model, were significantly greater in the combined categories of underweight and normal weight (1.22 kg and 1.29 kg, respectively) versus overweight and obese (0.56 kg and 0.53 kg, respectively; P = .006). The estimated probability of gaining more than 7% of initial body weight was significantly greater in patients treated with olanzapine versus active comparator (P < .001) or placebo (P < .001). Weight gain in olanzapine-treated older patients with dementia and behavioral disturbances was significantly greater in individuals with a baseline body mass index of less than 25 kg/m2.

Topics: Age Factors; Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Body Weight; Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Mental Disorders; Olanzapine; Product Surveillance, Postmarketing

Aggression, agitation or psychosis occur in the majority of people with dementia at some point in the illness. There have been a number of trials of atypical antipsychotics to treat these symptoms over the last five years, and a systematic review is needed to evaluate the evidence in a balanced way.. To determine whether evidence supports the use of atypical antipsychotics for the treatment of aggression, agitation and psychosis in people with Alzheimer's disease.. The trials were identified from a last updated search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 7 December 2004 using the terms olanzapine, quetiapine, risperidone, clozapine, amisulpride, sertindole, zotepine, aripiprazole, ziprasidone. This Register contains articles from all major healthcare databases and many ongoing trials databases and is updated regularly.. Randomised, placebo-controlled trials, with concealed allocation, where dementia and psychosis and/or aggression were assessed.. 1. Two reviewers extracted data from included trials2. Data were pooled where possible, and analysed using appropriate statistical methods3. Analysis included patients treated with an atypical antipsychotic, compared with placebo. Sixteen placebo controlled trials have been completed with atypical antipsychotics although only nine had sufficient data to contribute to a meta-analysis and only five have been published in full in peer reviewed journals. No trials of amisulpiride, sertindole or zotepine were identified which met the criteria for inclusion. The included trials led to the following results:1. There was a significant improvement in aggression with risperidone and olanzapine treatment compared to placebo.2. There was a significant improvement in psychosis amongst risperidone treated patients.3. Risperidone and olanzpaine treated patients had a significantly higher incidence of serious adverse cerebrovascular events (including stroke), extra-pyramidal side effects and other important adverse outcomes.4. There was a significant increase in drop-outs in risperidone (2 mg) and olanzapine (5-10 mg) treated patients.5. The data were insufficient to examine impact upon cognitive function.. Evidence suggests that risperidone and olanzapine are useful in reducing aggression and risperidone reduces psychosis, but both are associated with serious adverse cerebrovascular events and extra-pyramidal symptoms. Despite the modest efficacy, the significant increase in adverse events confirms that neither risperidone nor olanzapine should be used routinely to treat dementia patients with aggression or psychosis unless there is marked risk or severe distress. Although insufficient data were available from the considered trials, a meta-analysis of seventeen placebo controlled trials of atypical neuroleptics for the treatment of behavioural symptoms in people with dementia conducted by the Food and Drug Administration (using data not in the public domain) suggested a significant increase in mortality (OR 1.7).

Topics: Aggression; Alzheimer Disease; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dibenzothiazepines; Humans; Mental Disorders; Olanzapine; Piperazines; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone

Atypical antipsychotic medications are widely used to treat delusions, aggression, and agitation in people with Alzheimer disease (AD) and other dementia. Several clinical trials have not shown efficacy, and there have been concerns about adverse events. The objective of this study was to assess the evidence for efficacy and adverse events of atypicals for people with dementia.. MEDLINE, the Cochrane Register of Controlled Trials, meetings, presentations, and information obtained from sponsors were used in this study. Published and unpublished randomized, placebo-controlled, double-blind, parallel-group trials in patients with AD or dementia of atypical antipsychotics marketed in the United States were studied. Clinical and trials characteristics, outcomes, and adverse events were extracted. Data were checked by a second reviewer. Fifteen trials including 16 contrasts of atypical antipsychotics with placebo met selection criteria: aripiprazole (k = 3), olanzapine (k = 5), quetiapine (k = 3), and risperidone (k = 5). A total of 3,353 patients were randomized to drug and 1,757 to placebo. Standard meta-analysis methods were used to summarize outcomes.. Quality of the reporting of trials varied. Efficacy on rating scales was observed by meta-analysis for aripiprazole and risperidone, but not for olanzapine. Response rates were frequently not reported. There were smaller effects for less severe dementia, outpatients, and patients selected for psychosis. Approximately one-third dropped out without overall differences between drug and placebo. Adverse events were mainly somnolence and urinary tract infection or incontinence across drugs, and extrapyramidal symptoms or abnormal gait with risperidone or olanzapine. Cognitive test scores worsened with drugs. There was no evidence for increased injury, falls, or syncope. There was a significant risk for cerebrovascular events, especially with risperidone; increased risk for death overall was reported elsewhere.. Small statistical effect sizes on symptom rating scales support the evidence for the efficacy of aripiprazole and risperidone. Incomplete reporting restricts estimates of response rates and clinical significance. Dropouts and adverse events further limit effectiveness. Atypicals should be considered within the context of medical need and the efficacy and safety of alternatives. Individual patient meta-analyses are needed to better assess clinical significance and effectiveness.

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dementia; Dibenzothiazepines; Double-Blind Method; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic

Topics: Alzheimer Disease; Benzodiazepines; Dementia; Donepezil; Galantamine; Ginkgo biloba; Humans; Indans; Memantine; Nootropic Agents; Olanzapine; Phenylcarbamates; Physostigmine; Phytotherapy; Piperidines; Rivastigmine; Selegiline; Tacrine

Topics: Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Cognition; Dementia; Donepezil; Galantamine; Ginkgo biloba; Haloperidol; Humans; Indans; Memantine; Olanzapine; Phenylcarbamates; Physostigmine; Phytotherapy; Piperidines; Risperidone; Rivastigmine; Selegiline; Tacrine; Vitamin E

To evaluate the efficacy and safety of olanzapine for the treatment of psychotic and behavioral disturbances in Alzheimer disease.. MEDLINE (1966-January 2003) and Science Citation Index searches were performed. Key search terms included olanzapine, Alzheimer(s), and dementia.. Four trials of olanzapine and subsequent post hoc analyses were reviewed. Three trials found a benefit associated with olanzapine use, but a fourth trial did not.. Olanzapine appears to be effective in treating psychotic and behavioral disturbances associated with Alzheimer disease. However, the most appropriate dose remains to be determined. The benefit of olanzapine therapy must be weighed against the adverse effect profiles of olanzapine and alternative treatment options.

Topics: Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Humans; Mental Disorders; Olanzapine; Pirenzepine; Psychotic Disorders; Randomized Controlled Trials as Topic; Treatment Outcome

Psychotic symptoms are seen in numerous psychiatric illnesses afflicting the elderly. This article reviews the efficacy of the pharmacologic management of psychotic symptoms in primary psychotic disorders, affective disorders, and neurodegenerative disorders.. A comprehensive literature review.. Evidence to support the use of pharmacologic interventions to manage psychotic symptoms in elderly patients afflicted with primary psychotic disorders and affective disorders is limited by the absence of randomized, placebo-controlled trials (RCTs). The use of low-dose clozapine is supported by RCTs in Parkinson's disease. The efficacy of risperidone and olanzapine for the treatment of psychotic symptoms has been demonstrated by large RCTs in Alzheimer's disease.. There is evidence of the efficacy of antipsychotic medications to manage psychotic symptoms in elderly patients. However, the absence of published evidence from RCTs in primary psychotic and affective disorders, and the limited evidence in the neurodegenerative illnesses, is notable.

Topics: Aged; Alzheimer Disease; Benzodiazepines; Bipolar Disorder; Clozapine; Depressive Disorder; Drug Administration Schedule; Humans; Lewy Body Disease; Olanzapine; Parkinson Disease; Pirenzepine; Psychotic Disorders; Risperidone

Drug-induced iatrogenic hallucinations and psychosis occur in about 30% of Parkinson's disease (PD) patients and are the single most important precipitant for nursing home placement, which carries a grave prognosis. In addition, parkinsonism is a frequent accompaniment to the more common dementing syndromes, Alzheimer's disease (AD), vascular dementia, and dementia with Lewy bodies (DLB). The five most recent antipsychotic drugs approved by the Food and Drug Administration in the United States have been marketed as "atypical" antipsychotics (AA) due to their relative freedom from extrapyramidal symptoms when used in schizophrenia patients. The use of these newer antipsychotic drugs in PD and other parkinson-sensitive populations represents the most stringent test to their freedom from motor side effects. To date, clozapine, risperidone, olanzapine, and quetiapine have been studied in parkinson-vulnerable populations. This article reviews the data and highlights the differences that these four drugs have on motor function. It also emphasizes the challenges in evaluating the available data on the motor effects of AA, especially on the non-PD elderly and cognitively impaired population. Suggestions are made for future research to improve the interpretability of these studies.

Topics: Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Clozapine; Dementia, Vascular; Dibenzothiazepines; Hallucinations; Humans; Iatrogenic Disease; Lewy Body Disease; Olanzapine; Parkinson Disease; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone

The association between Down's syndrome (DS) and Alzheimer's disease is well established. This paper presents a review of the literature, suggesting a possible association between DS and the more recently recognised dementia with Lewy bodies (DLB). Patients with DLB frequently present with changes in affect and behaviour, and in particular with psychotic symptoms. The literature suggests a possible role for atypical neuroleptics in the management of psychosis in DLB.

Topics: Adolescent; Adult; Aged; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Comorbidity; Depressive Disorder; Down Syndrome; Humans; Lewy Body Disease; Middle Aged; Olanzapine; Pirenzepine; Selective Serotonin Reuptake Inhibitors

Olanzapine (OLZ) is unique among currently available antipsychotic medications in its antagonism of a range of receptor systems including dopamine, norepinephrine, serotonin, acetylcholine, and histamine. Olanzapine's mechanistic complexity provides a broad efficacy profile in patients with schizophrenia and acute, pure or mixed mania. Patients experience symptomatic relief of mania, anxiety, hallucinations, delusions, and agitation/aggression and reduced depressive, negative, and some cognitive symptoms. This paper will review the safety profile of OLZ, focusing on the elderly, where data are available.. Preclinical and clinical studies of OLZ are reviewed, with emphasis on its possible effects on the cholinergic system and the histamine H(1) receptor. Weight change and related metabolic considerations, cardiac and cardiovascular safety, and motor function during treatment with OLZ are also reviewed.. In vitro receptor characterization methods, when done using physiologically relevant conditions allow accurate prediction of the relatively low rate of anticholinergic-like adverse events, extrapyramidal symptoms, and cardiovascular adverse events during treatment with OLZ. Currently available clinical data suggest olanzapine is predictably safe in treating adult patients of any age with schizophrenia and acute bipolar mania, as well as in treatment of patients with some types of neurodegenerative disorders.

Topics: Adverse Drug Reaction Reporting Systems; Aged; Alzheimer Disease; Animals; Benzodiazepines; Brain; Drug Evaluation, Preclinical; Humans; Neurologic Examination; Olanzapine; Pirenzepine; Receptors, Neurotransmitter

Prediction of response or nonresponse to antipsychotics is especially important in patients with behavioral and psychological symptoms of dementia (BPSD) in whom antipsychotic exposure increases risks of death. This study examined whether the presence or absence of early improvement of BPSD with antipsychotics is associated with subsequent response or nonresponse.. In a post-hoc analysis of the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) study (2001-2004) (clinicaltrials.gov; NCT00015548) in 45 U.S. sites, 245 subjects (olanzapine, N = 90; quetiapine, N = 81; risperidone, N = 74) with a DSM-IV diagnosis of dementia of the Alzheimer type who presented with a score of 1 or more in the Brief Psychiatric Rating Scale (BPRS) at baseline (phase I of CATIE-AD) were randomly assigned to treatment with olanzapine, quetiapine, risperidone, or placebo in a double-blind manner. Associations were examined between response at week 8 and demographic and clinical characteristics, including BPRS total score reduction at week 2, using logistic regression analyses. Prediction performance of binary classification (presence or absence) of improvement or no improvement at week 2 for response at week 8 was examined.. BPRS total score reduction at week 2 (mean percentage score reduction: 12.6%) was significantly associated with response at week 8 (odds ratio: 1.18; 95% CI: 1.11-1.26). The 5% score reduction cut-off at week 2 showed the highest accuracy (0.71), with sensitivity, specificity, and positive and negative predictivevalues of 0.76, 0.65, 0.69, and 0.72, respectively.. Lack of even a very small early improvement with antipsychotic treatment may be a marker of subsequent nonresponse in BPSD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Behavioral Symptoms; Benzodiazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Risperidone; Time Factors; Treatment Outcome

The impact of the atypical antipsychotics olanzapine, quetiapine, and risperidone on cognition in patients with Alzheimer's disease is unclear. The authors assessed the effects of time and treatment on neuropsychological functioning during the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease study (CATIE-AD).. CATIE-AD included 421 outpatients with Alzheimer's disease and psychosis or agitated/aggressive behavior who were randomly assigned to receive masked, flexible-dose olanzapine, quetiapine, risperidone, or placebo. Based on their clinicians' judgment, patients could discontinue the originally assigned medication and receive another randomly assigned medication. Patients were followed for 36 weeks, and cognitive assessments were obtained at baseline and at 12, 24, and 36 weeks. Outcomes were compared for 357 patients for whom data were available for at least one cognitive measure at baseline and one follow-up assessment that took place after they had been on their prescribed medication or placebo for at least 2 weeks.. Overall, patients showed steady, significant declines over time in most cognitive areas, including in scores on the Mini-Mental State Examination (MMSE; -2.4 points over 36 weeks) and the cognitive subscale of the Alzheimer's Disease Assessment Scale (-4.4 points). Cognitive function declined more in patients receiving antipsychotics than in those given placebo on multiple cognitive measures, including the MMSE, the cognitive subscale of the Brief Psychiatric Rating Scale, and a cognitive summary score summarizing change on 18 cognitive tests.. In CATIE-AD, atypical antipsychotics were associated with worsening cognitive function at a magnitude consistent with 1 year's deterioration compared with placebo. Further cognitive impairment is an additional risk of treatment with atypical antipsychotics that should be considered when treating patients with Alzheimer's disease.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Dibenzothiazepines; Disease Progression; Double-Blind Method; Drug Substitution; Female; Follow-Up Studies; Humans; Male; Mental Status Schedule; Neuropsychological Tests; Olanzapine; Patient Dropouts; Quetiapine Fumarate; Risperidone

The second-generation antipsychotics are associated with metabolic abnormalities in patients with schizophrenia. Elderly patients with Alzheimer's disease are frequently treated with these antipsychotics, but limited data are available on their metabolic effects.. The authors assessed 186 male and 235 female Alzheimer's disease outpatients from the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) for changes in weight, waist circumference, blood pressure, fasting glucose, and lipids in relation to duration of second-generation antipsychotic use (i.e., olanzapine, quetiapine, and risperidone) throughout the 36-week trial, using logistic regression and mixed-effects models.. Women showed significant weight gain (0.14 lb/week of use) while change was nonsignificant in men. Clinically significant weight gain (i.e., > or = 7% of body weight) was seen among patients with antipsychotic use < or = 12 weeks (odds ratio [OR]=1.56, 95% CI=0.53 to 4.58), between 12 and 24 weeks (OR=2.89, 95% CI=0.97 to 8.64), and > 24 weeks (OR=3.38, 95% CI=1.24 to 9.23) relative to patients who did not use antipsychotics during the trial. Olanzapine and quetiapine treatments were significantly associated with weight gain (0.12 and 0.14 lb/week, respectively). In addition, olanzapine was significantly associated with decreases in HDL cholesterol (-0.19 mg/dl/week) and increased girth (0.07 inches/week) relative to the placebo group. No treatment effects were noted for changes in blood pressure, glucose, and triglycerides.. Second-generation antipsychotic use was associated with weight gain in women, with olanzapine and quetiapine in particular, and with unfavorable change in HDL cholesterol and girth with olanzapine. The potential consequences of these effects suggest that patients with Alzheimer's disease treated with second-generation antipsychotics should be monitored closely.

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Double-Blind Method; Drug Monitoring; Female; Humans; Male; Mental Disorders; Obesity; Olanzapine; Quetiapine Fumarate; Risperidone

The study measured the effects of atypical antipsychotics on psychiatric and behavioral symptoms in patients with Alzheimer's disease and psychosis or agitated behavior.. The Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) Alzheimer's disease effectiveness study included 421 outpatients with Alzheimer's disease and psychosis or agitated/aggressive behavior. Patients were assigned randomly to masked, flexible-dose treatment with olanzapine, quetiapine, risperidone, or placebo for up to 36 weeks. Patients could be randomly reassigned to a different medication at the clinician's discretion, which ended phase 1. Psychiatric and behavioral symptoms, functioning, cognition, care needs, and quality of life were measured at regular intervals.. In relation to placebo, the last observation in phase 1 showed greater improvement with olanzapine or risperidone on the Neuropsychiatric Inventory total score, risperidone on the Clinical Global Impression of Changes, olanzapine and risperidone on the Brief Psychiatric Rating Scale (BPRS) hostile suspiciousness factor, and risperidone on the BPRS psychosis factor. There was worsening with olanzapine on the BPRS withdrawn depression factor. Among patients continuing phase 1 treatment at 12 weeks, there were no significant differences between antipsychotics and placebo on cognition, functioning, care needs, or quality of life, except for worsened functioning with olanzapine compared to placebo.. In this descriptive analysis of outpatients with Alzheimer's disease in usual care settings, some clinical symptoms improved with atypical antipsychotics. Antipsychotics may be more effective for particular symptoms, such as anger, aggression, and paranoid ideas. They do not appear to improve functioning, care needs, or quality of life.

Topics: Activities of Daily Living; Aged; Aggression; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Brief Psychiatric Rating Scale; Cognition Disorders; Dibenzothiazepines; Female; Humans; Male; Neuropsychological Tests; Olanzapine; Psychomotor Agitation; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Risperidone; Surveys and Questionnaires

Response to antipsychotics is highly variable, which may be due in part to differences in drug exposure. The goal of this study was to evaluate the magnitude and variability of concentration exposure of olanzapine. Patients with Alzheimer's disease (n = 117) and schizophrenia (n = 406) were treated with olanzapine as part of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). Combined, these patients (n = 523) provided 1527 plasma samples for determination of olanzapine concentrations. Nonlinear mixed-effects modeling was used to determine the population pharmacokinetics of olanzapine, and patient-specific covariates were evaluated as potential contributors to variability in drug exposure. The population mean olanzapine clearance and volume of distribution were 16.1 L/h and 2150 L, respectively. Elimination of olanzapine varied nearly 10-fold (range, 6.66-67.96 L/h). Smoking status, sex, and race accounted for 26%, 12%, and 7% of the variability, respectively (P < .0001). Smokers cleared olanzapine 55% faster than non/past smokers (P < .0001). Men cleared olanzapine 38% faster than women (P < .0001). Patients who identified themselves as black or African American cleared olanzapine 26% faster than other races (P < .0001). Differences in olanzapine exposure due to sex, race, and smoking may account for some of the variability in response to olanzapine.

Topics: Administration, Oral; Adolescent; Adult; Algorithms; Alzheimer Disease; Antipsychotic Agents; Asian People; Benzodiazepines; Black or African American; Chromatography, Liquid; Female; Humans; Indians, North American; Male; Metabolic Clearance Rate; Multivariate Analysis; Olanzapine; Schizophrenia; Sex Factors; Smoking; Tandem Mass Spectrometry; Tissue Distribution; Treatment Outcome; White People

The goal of this study was to compare the efficacy and safety of olanzapine versus haloperidol in the treatment of agitation and aggression in patients with dementia. The subjects were 58 out-patients with dementia and agitation. After baseline assessments and, if necessary, a period of wash-out of a previous antipsychotic drug, they were randomly assigned to 5 weeks of double-blind treatment with either olanzapine or haloperidol. The first 2 weeks were used for dose titration. Subsequently, the patients received a fixed dose of either olanzapine (average dose 4.71 mg) or haloperidol (average dose 1.75 mg) from day 14 to day 35. Both olanzapine and haloperidol decreased agitation significantly (decrease in Cohen-Mansfield Agitation Inventory scores), but there was no significant difference between the two drugs. The two drugs had comparable effects on all secondary outcome measures. They were well tolerated and had a similar side-effect pattern. Our study could not demonstrate the superiority of olanzapine, compared to haloperidol, for the treatment of agitation in patients with dementia.

Topics: Aged; Aggression; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Haloperidol; Humans; Olanzapine; Psychomotor Agitation

Second-generation (atypical) antipsychotic drugs are widely used to treat psychosis, aggression, and agitation in patients with Alzheimer's disease, but their benefits are uncertain and concerns about safety have emerged. We assessed the effectiveness of atypical antipsychotic drugs in outpatients with Alzheimer's disease.. In this 42-site, double-blind, placebo-controlled trial, 421 outpatients with Alzheimer's disease and psychosis, aggression, or agitation were randomly assigned to receive olanzapine (mean dose, 5.5 mg per day), quetiapine (mean dose, 56.5 mg per day), risperidone (mean dose, 1.0 mg per day), or placebo. Doses were adjusted as needed, and patients were followed for up to 36 weeks. The main outcomes were the time from initial treatment to the discontinuation of treatment for any reason and the number of patients with at least minimal improvement on the Clinical Global Impression of Change (CGIC) scale at 12 weeks.. There were no significant differences among treatments with regard to the time to the discontinuation of treatment for any reason: olanzapine (median, 8.1 weeks), quetiapine (median, 5.3 weeks), risperidone (median, 7.4 weeks), and placebo (median, 8.0 weeks) (P=0.52). The median time to the discontinuation of treatment due to a lack of efficacy favored olanzapine (22.1 weeks) and risperidone (26.7 weeks) as compared with quetiapine (9.1 weeks) and placebo (9.0 weeks) (P=0.002). The time to the discontinuation of treatment due to adverse events or intolerability favored placebo. Overall, 24% of patients who received olanzapine, 16% of patients who received quetiapine, 18% of patients who received risperidone, and 5% of patients who received placebo discontinued their assigned treatment owing to intolerability (P=0.009). No significant differences were noted among the groups with regard to improvement on the CGIC scale. Improvement was observed in 32% of patients assigned to olanzapine, 26% of patients assigned to quetiapine, 29% of patients assigned to risperidone, and 21% of patients assigned to placebo (P=0.22).. Adverse effects offset advantages in the efficacy of atypical antipsychotic drugs for the treatment of psychosis, aggression, or agitation in patients with Alzheimer's disease. (ClinicalTrials.gov number, NCT00015548 [ClinicalTrials.gov].).

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Mental Disorders; Olanzapine; Proportional Hazards Models; Quetiapine Fumarate; Risperidone; Survival Analysis; Treatment Outcome

We report on the responsiveness of a previously validated quality-of-life scale, the Quality of Life in Late-Stage Dementia scale (QUALID), as an outcome measure in a clinical trial of two psychotropic medications.. Secondary analyses were conducted comparing outcome measures used in a randomized double-blind trial of two antipsychotics (olanzapine and risperidone) for the treatment of dementia-related behavioral symptoms. The QUALID was completed for 31 of the patients in addition to several measures of behavior-related dementia symptoms including the Neuropsychiatric Inventory, the Withdrawn Behavior subscale of the Multidimensional Observation Scale for Elderly Subjects, the Mini-Mental State Examination, and the Clinical Global Impression. Measures of safety and adverse effects included the Simpson-Angus Scale and records of specific adverse events.. A significant positive relationship was found between QUALID score and improvement in behavioral symptoms, and a negative association was found with adverse medication effects.. The QUALID was sensitive to both the treatment effects and the adverse effects of medication in this sample of patients.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Female; Homes for the Aged; Humans; Long-Term Care; Male; Mental Status Schedule; Nursing Homes; Olanzapine; Psychometrics; Quality of Life; Risperidone; Social Behavior Disorders

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.. 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).. 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.. 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.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Brief Psychiatric Rating Scale; Comorbidity; Conduct Disorder; Dementia, Vascular; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Male; Neuropsychological Tests; Olanzapine; Psychomotor Agitation; Risperidone; Treatment Outcome

The authors report findings from an 8-week, open-label trial conducted to evaluate efficacy of olanzapine in treating negative symptoms in Alzheimer's disease (AD). Subjects were AD patients age 50 and older who exhibited untreated neuropsychiatric symptoms. Findings suggest that a therapeutic profile for olanzapine may be appropriate for AD patients experiencing neuropsychiatric problems.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Behavioral Symptoms; Benzodiazepines; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Schizophrenic Psychology; Treatment Outcome

This was an exploratory study of olanzapine as potential treatment for improvement in cognition in patients with Alzheimer's disease without prominent psychobehavioral symptoms.. Non-psychotic/non-agitated patients (n = 268) with Alzheimer's disease, who had baseline Mini-Mental State Examination (MMSE) scores of 14-26 were randomized to treatment with olanzapine (2.5 to 7.5 mg/d) or placebo for 26 weeks. The primary objectives were to determine if treatment with olanzapine improved cognition as indexed by the Alzheimer's disease Assessment Scale for Cognition (ADAS-Cog) and the Clinician's Interview-Based Impression of Change (CIBIC) after 26 weeks of therapy.. Patients treated with olanzapine vs placebo experienced significant worsening ADAS-Cog scores at weeks 12 (p = 0.03) and 26 (p = 0.004). Changes in CIBIC scores were not significantly different between treatment groups at either assessment. A post hoc analysis revealed that olanzapine-treated patients with more cognitive impairment at baseline (MMSE scores of 14-18) (n = 35) experienced significantly greater deterioration in ADAS-Cog performance than patients in the placebo group (n = 24; p < 0.001); whereas in patients with less cognitive impairment (n = 78, baseline MMSE scores of 23-26) between-group ADAS-Cog changes were not significant.. In this 26-week study non-psychotic/non-agitated patients with Alzheimer's disease treated with olanzapine experienced significant worsening of cognition as compared to placebo.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Disease Progression; Double-Blind Method; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Psychomotor Agitation; Treatment Outcome

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.. 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).. 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.. 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.

Topics: Adult; Aged; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Delusions; Double-Blind Method; Female; Hallucinations; Humans; Male; Middle Aged; Olanzapine; Patient Compliance; Psychiatric Status Rating Scales; Psychotic Disorders; Time Factors; Treatment Outcome

This double-blind study evaluated the efficacy and safety of risperidone or olanzapine vs. promazine in the treatment of behavioral and psychological symptoms in dementia(BPSD). Patients were required to be 65 years or older, to have DSM-IV diagnoses of Alzheimer's disease (AD), vascular dementia (VD) or a combination of both. A brain computerized tomography (CT) was performed for all the patients; 60 demented patients,27 men (45 %) and 33 women (55 %) were selected for this study. The University of California Los Angeles neuropsychiatric inventory (NPI) was administered at baseline, then after 4 and 8 weeks. Patients had at least a score of 24 or more. The Hoehn and Yahr scale was used for evaluating parkinsonism. The scales were administered by an examinator who was not aware of the kind of treatment of the patients. After a wash-out period of 10 days,20 patients, 9 men and 11 women, mean age 76.6 +/- 6.0 years, were randomly assigned torisperidone 1 mg daily in divided doses (morning and bedtime) (Group A); 20 patients, 9 men and 11 women, mean age 82.5 +/- 9.3 years were randomly assigned to olanzapine 5mg at bedtime (Group B), and 20 patients, 9 men and 11 women, mean age 77.6 +/- 4.6 years, were randomly assigned to promazine 50 mg daily (morning and bedtime) (Group C). In case of lack of clinical response, after 4 weeks, the dose could be increased to 2 mg/day of risperidone, 10 mg/day of olanzapine, and to 100 mg/day of promazine in the respective groups. Repeated measures ANOVA was used for the statistical analysis of rating scales over time (baseline, 4 and 8 weeks). At the end of the 8th week, a global improvement was obtained in 80% of patients treated with risperidone and olanzapine, vs. 65 % of patients treated with promazine (p < 0.01). The results show that risperidone in doses of 1-2 mg/day and olanzapine in doses of 5-10 mg/day are effective and safe in the treatment of BPSD. Risperidone presents a major and dose-dependent antidopaminergic action and seems to be preferable when hallucinations and delusions are prevailing symptoms, even if it gives good results on aggression and wandering. Olanzapine seems to be faster in its sedative effect, probably for H1 receptor blockade. Moreover, 5-HT6 antagonism may favor acetylcholine release and this explains why these patients have not presented a cognitive worsening. However, both drugs are comparable or even superior to promazine, with significantly fewer side effects of both anticholinergic

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Brain; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Female; Humans; Magnetic Resonance Imaging; Male; Mental Disorders; Olanzapine; Promazine; Psychomotor Disorders; Risperidone; Tomography, X-Ray Computed

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.. 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.. 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.. These results suggest that, overall, olanzapine effectively attenuated emergence of psychosis in a short-term trial of patients with Alzheimer's disease.

Topics: Aged; Aged, 80 and over; Aggression; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Delusions; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Hallucinations; Humans; Male; Nursing Homes; Olanzapine; Pirenzepine; Psychomotor Agitation; Psychotic Disorders; Treatment Outcome

The authors describe the development of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) protocol for Alzheimer disease (AD), a trial developed in collaboration with the National Institute of Mental Health (NIMH), assessing the effectiveness of atypical antipsychotics for psychosis and agitation occurring in AD outpatients. They provide an overview of the methodology utilized in the trial as well as the clinical-outcomes and effectiveness measures that were implemented.

Topics: Aged; Algorithms; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Citalopram; Cost-Benefit Analysis; Humans; Olanzapine; Patient Compliance; Pirenzepine; Psychomotor Agitation; Psychotic Disorders; Risperidone; Treatment Outcome

The objective of this analysis was to compare the treatment-emergent central anticholinergic-like adverse events experienced during treatment with olanzapine versus placebo in patients with psychosis and/or agitation due to Alzheimer's disease (AD). In addition, changes in cognition were assessed in a subgroup of patients with mild to moderate cognitive impairment.. Double-blind data were compared for placebo and three fixed olanzapine dosages (5 mg/day, 10 mg/day, and 15 mg/day) in 206 nursing home-residing patients with AD for five a priori selected central nervous system anticholinergic-like adverse events: confusion, delirium, delusions, hallucinations, abnormal thinking. Mean change from baseline to endpoint on the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) was measured for a subgroup of 43 patients who had mild to moderate cognitive impairment at baseline.. There were no significant differences in central anticholinergic-like adverse events at any olanzapine dose compared to placebo. Additionally, in the 43-patient subgroup, there were no significant differences in mean change in ADAS-Cog scores between placebo and the three olanzapine dose subgroups.. Olanzapine did not differ significantly from placebo for any of the five central nervous system anticholinergic events nor on the ADAS-Cog. Olanzapine's initially reported potent in vitro muscarinic receptor affinity is not consistent with this clinical study of central nervous system anticholinergic-like adverse events in patients with AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Benzodiazepines; Brain; Cholinergic Fibers; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Neuropsychological Tests; Olanzapine; Pirenzepine; Receptors, Muscarinic; Retrospective Studies

Psychotic symptoms and behavioral disturbances are a leading cause of institutionalization in elderly patients with Alzheimer's disease (AD).. 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.. 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.. 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.. Low-dose olanzapine appears to be effective and well tolerated for treatment of behavioral disturbances and psychotic symptoms due to AD in elderly patients.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Behavioral Symptoms; Benzodiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Female; Homes for the Aged; Humans; Long-Term Care; Male; Neuropsychological Tests; Nursing Homes; Olanzapine; Pirenzepine; Psychotic Disorders; Treatment Outcome

Alzheimer's disease (AD) is associated with both cognitive and behavioral symptoms. Agitation, hallucinations, delusions, aggression, irritability, and anxiety are observed in up to 90% of patients with dementia. Although new information has emerged in recent years on the treatment of psychosis and agitation in dementia, very little information is available about the treatment of anxiety symptoms in this population.. To assess the efficacy and tolerability of olanzapine in the treatment of significant anxiety symptoms in patients with AD.. A post hoc analysis of a previously published study was performed. Those post hoc analysis evaluated the response to treatment with olanzapine of a subgroup of AD patients presenting with significant symptoms of anxiety. Patients were considered to have significant symptoms of anxiety if their baseline in the Nursing home version of the Neuropsychiatric Instrument NPI/NH anxiety scores were > or = 2. The analysis included 120 patients.. Patients receiving olanzapine 5 mg/d were statistically significantly improved on the NPI/NH Anxiety item compared to those receiving placebo (olanzapine, 5 mg/d: -3.72; placebo: -1.67; p = 0.034). In the group of patients with clinically significant anxiety, somnolence was the only treatment-emergent event that was statistically different in any olanzapine treatment group compared with placebo (olanzapine 5 mg/d: 9 patients [25%], p = 0.034; 10 mg/d: 7 [23%], p = 0.054; 15 mg/d: 7 [26%], p = 0.050; placebo: 1 [3.7%]). When controlling for treatment-emergent somnolence, the improvement in anxiety in the olanzapine 5 mg/d group remained statistically significant (p = 0.049).. These findings suggest that olanzapine could be a safe and effective treatment for anxiety in Alzheimer's disease.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Anxiety; Benzodiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Female; Homes for the Aged; Humans; Male; Neuropsychological Tests; Nursing Homes; Olanzapine; Pirenzepine; Treatment Outcome

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.. 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.. 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.. 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.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Behavioral Symptoms; Benzodiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Nursing Homes; Olanzapine; Pirenzepine; Placebos; Psychotic Disorders; Treatment Outcome

Topics: Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Humans; Olanzapine; Pirenzepine; Psychotic Disorders; Tablets

The apolipoprotein E (APOE) ε4 allele confers the strongest risk for late-onset Alzheimer's disease (AD) besides age itself, but the mechanisms underlying this risk are debated. One hypothesis supported by evidence from multiple labs is that apoE4 binds to the amyloid-β (Aβ) peptide and catalyzes its polymerization into neurotoxic oligomers and fibrils. Inhibiting this early step in the amyloid cascade may thereby reduce or prevent neurodegeneration and AD.. Using a design of experiments (DOE) approach, we developed a high-throughput assay to identify inhibitors of apoE4-catalyzed polymerization of Aβ into oligomers and fibrils. We used it to screen the NIH Clinical Collection of small molecule drugs tested previously in human clinical trials. We then evaluated the efficacy and cytotoxicity of the hit compounds in primary neuron models of apoE4-induced Aβ and phosphorylated tau aggregation. Finally, we performed retrospective analyses of the National Alzheimer's Coordinating Center (NACC) clinical dataset, using Cox regression and Cox proportional hazards models to determine if the use of two FDA-approved hit compounds was associated with better cognitive scores (Mini-Mental State Exam), or improved AD clinical diagnosis, when compared with other medications of the same clinical indication.. Our high-throughput screen identified eight blood-brain barrier (BBB)-permeable hit compounds that reduced apoE4-catalyzed Aβ oligomer and fibril formation in a dose-dependent manner. Five hit compounds were non-toxic toward cultured neurons and also reduced apoE4-promoted Aβ and tau neuropathology in a dose-dependent manner. Three of the five compounds were determined to be specific inhibitors of apoE4, whereas the other two compounds were Aβ or tau aggregation inhibitors. When prescribed to AD patients for their normal clinical indications, two of the apoE4 inhibitors, imipramine and olanzapine, but not other (non-hit) antipsychotic or antidepressant medications, were associated with improvements in cognition and clinical diagnosis, especially among APOE4 carriers.. The critical test of any proposed AD mechanism is whether it leads to effective treatments. Our high-throughput screen identified two promising FDA-approved drugs, imipramine and olanzapine, which have no structural, functional, or clinical similarities other than their shared ability to inhibit apoE4-catalyzed Aβ polymerization, thus identifying this mechanism as an essential contribution of apoE4 to AD.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Apolipoprotein E4; Catalysis; Cognition; Humans; Imipramine; Olanzapine; Polymerization; Retrospective Studies

Current methods are not designed to relate the incidence of individual adverse events reported in clinical trials to the plurality of adverse events accumulated in spontaneous reporting databases during real-world use. We have previously reported on a pharmacological class-effect query of clinical trial data defined by a disproportionality analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS) post-marketing data. The aim of the current analysis was to apply a dopamine D. Patient-level adverse event data (n = 4400) from controlled clinical trials of the antipsychotic risperidone in schizophrenia, bipolar disorder, Alzheimer's disease psychosis, and autism were obtained through the Yale University Open Data Access (YODA) project. An Empirical Bayes Geometric Mean analysis was performed, and a three-fold threshold incidence level was applied to determine if a preferred term met criteria for being an antipsychotic class-related adverse event.. In pooled data from seven trials of adult schizophrenia, class-specific adverse events were identified in 49% of patients treated with risperidone; in 49% of risperidone-treated patients in two trials in adolescent schizophrenia; in 65% of risperidone-treated patients in four trials in adult bipolar disorder; in 50% of risperidone-treated patients in two trials in adolescent schizophrenia; in 36% of risperidone-treated patients in one trial in Alzheimer's disease; and in 94% of risperidone-treated patients in one trial in autism.. The cumulative curves of class-specific adverse events in risperidone clinical trials of schizophrenia were similar to those first reported for other atypical antipsychotic drugs. However, the class-specific adverse event curves were notably lower for Alzheimer's disease and higher for autism, suggesting that the diagnostic indication may have an important effect on the cumulative class-specific side-effect burden.

Topics: Adolescent; Adult; Alzheimer Disease; Antipsychotic Agents; Bayes Theorem; Benzodiazepines; Dopamine; Humans; Olanzapine; Risperidone; United States; United States Food and Drug Administration

Topics: Alzheimer Disease; Cholinesterase Inhibitors; Donepezil; Humans; Olanzapine

To investigate the efficacy and safety of olanzapine, aripiprazole, and risperidone in the treatment of mental and behavioral symptoms of Alzheimer's Disease. A retrospective analysis was performed on the clinical data of 126 patients with Alzheimer's Disease from February 2018 to February 2020. The patients were divided into group A (aripiprazole, n=44), group B (olanzapine, n=42) and group C (risperidone, n=40) based on the treatment method. Remarkably differences at different time points among the three groups were observed (P<0.05). Significant differences in the Positive and Negative Syndrome Scale scores of different time points and cross-group comparison among the three groups were detected (P<0.05). The time-point comparison of BEHAVE-AD scores among the three groups indicated a remarkable difference (P<0.05). After 4 weeks of treatment, the Positive and Negative Syndrome Scale and BEHAVE-AD scores of group A were lower than those of groups B and C (P<0.05). The total incidence of adverse reactions in group A was remarkably lower than in groups B and C (P<0.05). Olanzapine, aripiprazole and risperidone are effective in treating Alzheimer's disease and aripiprazole, with a better safety profile and fewer adverse reactions, is more suitable for elderly patients.

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Aripiprazole; Female; Humans; Male; Olanzapine; Retrospective Studies; Risperidone; Time Factors; Treatment Outcome

Alzheimer's disease (AD) is a profoundly debilitating neurodegenerative disorder characterized most notably by progressive cognitive decline, but also agitation and behavioral disturbances that are extremely disruptive to patient and caregiver. Current pharmacological treatments for these symptoms have limited efficacy and significant side effects. We have recently reported the discovery of Compound 24, an M4 positive allosteric modulator (PAM) that is potent, highly selective, and devoid of cholinergic-like side effects in rats. In order to further evaluate the translatability of the effects of compound 24 in primates, here we describe the effect of Compound 24 on three behavioral and cognition assays in rhesus monkeys, the stimulant induced motor activity (SIMA) assay, the object retrieval detour task (ORD), and the visuo-spatial paired-associates learning (vsPAL) task. As far as we know, this is the first such characterization of an M4 PAM in non-human primate. Compound 24 and the clinical standard olanzapine attenuated amphetamine induced hyperactivity to a similar degree. In addition, Compound 24 demonstrated procognitive effects in scopolamine-impaired ORD and vsPAL, and these effects were of similar magnitude to donepezil. These findings suggest that M4 PAMs may be beneficial to diseases such as Alzheimer's disease and schizophrenia, which are marked by behavioral disturbances as well as deficits in cognitive function.

Topics: Alzheimer Disease; Amphetamine; Animals; Association Learning; Behavior, Animal; Central Nervous System Stimulants; Cholinergic Agents; Cognition Disorders; Hyperkinesis; Macaca mulatta; Male; Motor Activity; Olanzapine; Orientation; Receptor, Muscarinic M4; Schizophrenia; Schizophrenic Psychology

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Cost Control; Cost Savings; Drug Costs; Drug Industry; Drugs, Generic; Europe; Forecasting; Fraud; Health Care Costs; Health Expenditures; Health Policy; Health Services for the Aged; Humans; Marketing; National Health Programs; Off-Label Use; Olanzapine; Population Dynamics; Republic of Korea; United States

Olanzapine is an atypical antipsychotic drug that infrequently has been reported to cause seizures and myoclonus despite a small proconvulsant risk. This is the first report of generalized myoclonus induced in a patient who had been maintained on low dose olanzapine for over seven years without any change in her dose. Olanzapine was discontinued, and the myoclonic jerks completely resolved within 48 h.

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Electroencephalography; Female; Humans; Myoclonus; Olanzapine; Psychotic Disorders

Antipsychotics have long been used to treat agitation and psychosis related to Alzheimer's disease, but in a limited fashion because of troubling adverse effects. The new atypical antipsychotics are thought to be at least as effective as first-generation drugs and to cause fewer adverse effects. These drugs, however, are currently not US FDA-approved for use among elderly demented subjects due to a slight increase in the risk of death and serious cardiovascular events within this population. However, their favourable adverse effect profile has led many physicians to prescribe these drugs as first-line therapy for behaviourally disturbed patients with Alzheimer's disease. Clinical trials to evaluate the use of atypical antipsychotics have produced varying results, and clarity has not yet been achieved. Thus, a quantitative summary of the risks and benefits may help inform complex decisions that must be made in this area. In this study we set out to compare the expected costs and outcomes for a community-dwelling cohort of patients with Alzheimer's disease with agitation and/or psychosis who are (a) untreated, or (b) treated with olanzapine.. We constructed a Markov state-transition model using the best published data from several sources for Alzheimer's disease patient progression and treatment. This model allowed us to compare the expected costs and outcomes associated with olanzapine treatment compared with no treatment for a synthetic cohort of US adults aged > or =65 years. The model cycles every 6 months and continues until all patients die from Alzheimer's disease progression or from co-morbid conditions. Outcome estimates included the incremental cost-effectiveness ratio (ICER) and cost per quality-adjusted life-year (QALY) gained. The robustness of the estimates was examined by sensitivity analyses of key parameters, including cost of care, olanzapine effectiveness and Alzheimer's disease progression rates.. Results indicated that olanzapine was a cost-effective treatment for agitation and psychosis related to Alzheimer's disease when compared with no treatment (ICER <$US50,000). In addition, sensitivity analyses demonstrated that olanzapine remained cost effective despite multiple variations of several parameters, both alone and concurrently.. Olanzapine treatment for agitation and psychosis related to Alzheimer's disease is cost effective when compared with no treatment. Further analysis should be performed as atypical antipsychotics become generic, as more information on health utilities in the Alzheimer's disease population becomes available, and to compare atypical antipsychotics with first-generation antipsychotics.

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Cohort Studies; Cost-Benefit Analysis; Drug Costs; Ethnicity; Humans; Markov Chains; Mortality; Olanzapine; Proportional Hazards Models; Psychomotor Agitation; Psychotic Disorders; Quality-Adjusted Life Years; Treatment Outcome; United States

Topics: Aged; Alzheimer Disease; Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Delirium; Depressive Disorder; Diagnosis, Differential; Dibenzothiazepines; Hallucinations; Humans; Male; Olanzapine; Oxazepam; Psychotic Disorders; Quetiapine Fumarate; Tachycardia

The behavioral and psychological symptoms of dementia present a major challenge in the management of these patients. There is no Food and Drug Administration-indicated medication for the management of these symptoms. Even though atypical antipsychotics are considered safer than conventional antipsychotics, safety concerns have emerged.. The FDA has issued warnings regarding the cardiac and metabolic side effects, cerebrovascular events, and, most recently, mortality risk. This study was conducted in 2003 when physicians were notified of the cerebrovascular risks of risperidone. Since then, similar warnings have been issued for olanzapine and aripiprazole.. The medical records of 58 elderly dementia patients who were taking risperidone and were abruptly switched to olanzapine were reviewed. Clinical Global Impressions scale at assigned retrospectively at switch, and weeks 4-6 assessed treatment.. Baseline and follow-up Clinical Global Impressions scale scores were essentially unchanged. Adverse events were mild to moderate in severity. Mean risperidone dose at switch was 1.54 mg/day (range: 0.25-6 mg/day). Mean olanzapine dose after the switch was 5.69 mg/day (range: 2.52-27.5 mg/day).. Most of the 58 patients were switched from risperidone to olanzapine without any deterioration in their clinical status. Even though it is generally not recommended in elderly patients, abrupt switching did not have any negative consequences in this group of patients.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Benzodiazepines; Comorbidity; Dementia, Vascular; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Female; Follow-Up Studies; Homes for the Aged; Humans; Male; Nursing Homes; Olanzapine; Psychotic Disorders; Retrospective Studies; Risk Factors; Risperidone; Schizophrenia; Treatment Outcome

Topics: Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Humans; Olanzapine; Psychomotor Agitation; Quetiapine Fumarate; Risperidone

Topics: Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Data Interpretation, Statistical; Dibenzothiazepines; Dopamine Antagonists; Double-Blind Method; Follow-Up Studies; Humans; Multicenter Studies as Topic; Olanzapine; Outpatients; Placebos; Quetiapine Fumarate; Risk Assessment; Risperidone; Serotonin Antagonists; Time Factors; Treatment Outcome

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Mental Disorders; Olanzapine; Proportional Hazards Models; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Survival Analysis; Treatment Outcome

Autobiographical memory loss is a common and disturbing problem for individuals with Alzheimer's disease (AD). Patients with AD who are taking antipsychotic medications may be at further risk for loss of recent autobiographical memory because of the potential anticholinergic side effects of antipsychotics. The purpose of this post hoc, descriptive study was to compare the recent autobiographical memory scores of patients with AD taking antipsychotics to those who were not taking antipsychotics. The study population was composed of 35 patients with moderate-stage AD. Patients who were taking antipsychotics scored significantly worse on a recent autobiographical memory measure compared with patients who were not taking antipsychotics. This study provides further evidence for judicious use of antipsychotic medications with AD patients.

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Autobiographies as Topic; Benzodiazepines; Dibenzothiazepines; Drug Monitoring; Female; Geriatric Assessment; Haloperidol; Humans; Male; Memory; Mental Status Schedule; Neuropsychological Tests; Nursing Assessment; Olanzapine; Pilot Projects; Quetiapine Fumarate; Retrospective Studies; Risk Assessment; Risk Factors; Risperidone; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

Atypical antipsychotics will continue to be prescribed for the behavioral symptoms of dementia in the absence of more effective, better tolerated, and safer alternatives. The evidence base, although incomplete, suggests that modest treatment effect sizes are offset by risk of considerable adverse effects. How might this information be best applied to clinical practice? Non-pharmacologic strategies should be implemented in routine clinical practice. Placebo-controlled clinical trials of individual antipsychotic agents have historically reported high placebo response rates; CATIE-AD reported that the sum total of the risk/benefit equation of atypical antipsychotic therapy was no greater than that achieved by placebo. CATIE-AD was designed to study the effectiveness of atypical antipsychotic treatment in community dwelling patients with AD. It is uncertain whether the results can be generalized to the populations of dementia patients residing in nursing homes with more severe cognitive and behavioral impairment. There is some suggestion that nursing home patients with dementia complicated by severe behavioral symptoms, particularly agitation and aggression without accompanying psychosis, might achieve greater benefit from atypical antipsychotic treatment than patients with milder behavioral symptoms. The finding that dementia patients without psychosis may respond more robustly to antipsychotic treatment seems counterintuitive, but may support the hypothesis that the neurobiology of the "psychosis of AD" differs from the psychosis of schizophrenia or bipolar disease. Adverse effects associated with antipsychotic therapy should be aggressively monitored throughout therapy. Treatment-emergent sedation was associated with all of the atypical antipsychotics in CATIE-AD and is probably an important mediator of mortality risk in patients with dementia. Sedation exacerbates pre-existing cognitive impairment and increases the risk of complications such as aspiration pneumonia, so concomitant use of benzodiazepines should be discouraged or limited to short periods with careful observation.' Once initiated, the effectiveness and tolerability of antipsychotic therapy should be evaluated routinely. In Alzheimer's disease, the severity and frequency of behavioral symptoms often decreases as illness progresses. In a stable patient, it is prudent to attempt to taper and discontinue the antipsychotic after 2-8 months of therapy. Better understanding of the potential adverse

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Behavioral Symptoms; Benzodiazepines; Dementia; Dibenzothiazepines; Evidence-Based Medicine; Humans; Olanzapine; Psychomotor Agitation; Quetiapine Fumarate; Retrospective Studies; Risperidone; Treatment Outcome

The credibility of an increased risk of cerebrovascular events (CVEs) in elderly patients with dementia being treated with second-generation antipsychotics (SGAs) is debatable. Although early published and unpublished data indicated a risk, much of the subsequent literature has not supported this initial finding. Previously published studies were flawed in part because they lacked a control group and did not stratify by dementia subtype. This study examined the risk of a CVE in patients diagnosed with Alzheimer or vascular dementia while being treated with SGA, first-generation antipsychotics, or no antipsychotic medication.. Data from 14,029 patients aged 65 years and older were evaluated using patient information from Veterans Administration and Medicare databases. Patients who received care for dementia were categorized according to dementia subtype (vascular or Alzheimer) and antipsychotic use during an 18-month period. Patients were observed until they were admitted to a hospital for a CVE, stopped taking or switched antipsychotics, died, or until the 18-month observation period ended.. Overall, CVE risk did not differ whether patients were receiving a first-generation antipsychotic, SGA, or no antipsychotic therapy. However, patients with vascular dementia had an increased risk in hospitalization for a CVE. There was no increase in risk of a CVE for patients treated with quetiapine, olanzapine, or risperidone relative to haloperidol, or for patients receiving olanzapine or risperidone relative to quetiapine. Stratified subgroup analyses demonstrated no difference in risk for CVE-related admission patients with Alzheimer dementia among individual agents. However, patients with vascular dementia receiving risperidone, but not olanzapine or quetiapine, were found to be at decreased risk for CVE admission relative to haloperidol.. This study found no increase in overall risk for CVE-related hospital admission in patients treated with antipsychotic medications.

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Databases, Factual; Dementia, Vascular; Dibenzothiazepines; Female; Haloperidol; Humans; Kaplan-Meier Estimate; Male; Medicare Part A; Multivariate Analysis; Olanzapine; Quetiapine Fumarate; Risk Assessment; Risk Factors; Risperidone; Treatment Outcome; United States; United States Department of Veterans Affairs; Veterans

The objectives of this retrospective, naturalistic study were to provide preliminary data on the effects of 6 months treatment with risperidone, olanzapine and quetiapine on behavioral disturbances, within a sample of outpatients with mild to moderate Alzheimer's disease, and on predictors of response. Between July 2005 and December 2005, data were collected from 58 consecutive outpatients with a DSM-IV-TR diagnosis of Alzheimer's disease with behavioral disturbances, who received a 6-month treatment with risperidone, olanzapine or quetiapine. Primary outcome measures were Neuropsychiatric Inventory (NPI) total score and its items forming the basic core of behavioral disturbances in Alzheimer's disease: delusions, hallucinations and agitation/aggressiveness. Secondary outcome measures were Mini-Mental State Examination (MMSE), Activities of Daily Living, Instrumental Activities of Daily Living and Clinical Insight Rating scale. Correlations between baseline MMSE score and improvements in behavioral disturbances were investigated. At 6 months mean NPI total score had fallen 43.5% in the risperidone group, 45.6% in the olanzapine group and 33.3% in the quetiapine group, with no significant between-group differences. Global cognitive function showed no significant change from baseline to end-point. Incidence of adverse events was low. A significant correlation was found between MMSE score and NPI total score and NPI item agitation decreases. Risperidone, olanzapine and quetiapine produced significant improvements in behavioral disturbances and were well tolerated. No significant differences emerged among treatments. The preliminary results also suggest that baseline cognitive function might influence treatment response.

Topics: Activities of Daily Living; Aged; Alzheimer Disease; Antipsychotic Agents; Behavior; Benzodiazepines; Cognition; Data Interpretation, Statistical; Dibenzothiazepines; Donepezil; Endpoint Determination; Female; Galantamine; Humans; Indans; Long-Term Care; Male; Neuropsychological Tests; Nootropic Agents; Olanzapine; Phenylcarbamates; Piperidines; Psychiatric Status Rating Scales; Quetiapine Fumarate; Retrospective Studies; Risperidone; Rivastigmine; Treatment Outcome

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Cause of Death; Controlled Clinical Trials as Topic; Dementia, Vascular; Humans; Olanzapine; Psychotic Disorders; Risk; Risperidone; Statistics as Topic; Stroke; Survival Analysis

Weight gain and the risk of developing alterations in lipid and glucose metabolism are possible side effects of atypical antipsychotic therapy in young and adult patients. The objective of this study was to examine whether elderly patients with Alzheimer's disease (AD) gain weight or develop disturbances in lipid and glucose metabolism while being treated with atypical antipsychotic drugs.. This retrospective study identified 36 out of 99 patients (mean age: 75.4+/-7.1, 27 female, 9 males) who were taking risperidone (N=9, mean dosage: 1.42+/-0.49 mg/day), olanzapine (N=17: 4.42+/-1.10 mg/day), and quetiapine (N=10: 75+/-27 mg/day) over a 12 months period. Anthropometric parameters, mini nutritional assessment (MNA), total, HDL and LDL cholesterol, triglycerides, glycaemia were assessed at baseline (T0) and 12 (T1) months.. Body weight (BMI=23+/-5 vs 23+/-5), MNA score (21+/-4 vs 21+/-4), blood glucose (5.7+/-2 vs 4.9+/-0.9 mmol/L) or total cholesterol (4.9+/-1.1 vs 4.3+/-0.7 mmol/L), HDL cholesterol (1.3+/-0.3 vs 1.1+/-0.3 mmol/L), LDL cholesterol (3.3+/-0.7 vs 3 +/- 0.4 mmol/L), triglycerides (1.1+/-0 vs 1+/-0.3 mmol/L) did not reveal treatment-induced changes in the patients evaluated (T0 vs T1).. These results suggest that the treatment with low-dose of atypical antipsychotic drugs is not associated with weight gain or increase the risk of developing type II diabetes or abnormalities of lipid metabolism among elderly patients with AD, who were residing in long-term nursing home.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Dibenzothiazepines; Female; Humans; Lipids; Male; Mental Disorders; Nursing Homes; Olanzapine; Quetiapine Fumarate; Retrospective Studies; Risperidone; Weight Gain

Topics: Aggression; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Controlled Clinical Trials as Topic; Dopamine Antagonists; Humans; Olanzapine; Placebos; Risk Assessment; Risperidone; Selective Serotonin Reuptake Inhibitors; Serotonin Antagonists

No medication has received regulatory approval in the U.S.A. for the distressing agitation and aggressive behaviors that often complicate dementia. Although studies suggest that several psychotropic medications are sometimes useful for these behavioral problems, response is variable and adverse effects often limit treatment. Theoretical considerations suggest that increasing estrogenic activity or reducing androgenic activity could reduce agitation and aggression in dementia. Estrogen has been reported helpful for these symptoms, but adverse effects are problematic. Chronic administration of the synthetic gonadotropin (luteinising hormone) releasing hormone analogue, goserelin, reduces testosterone activity. Here we describe the apparently sustained elimination of previously treatment-resistant agitation and aggression with goserelin treatment in a 78-year-old male nursing-home resident with Alzheimer's disease.

Topics: Aged; Aggression; Alzheimer Disease; Amines; Antipsychotic Agents; Benzodiazepines; Cyclohexanecarboxylic Acids; Dibenzothiazepines; Gabapentin; gamma-Aminobutyric Acid; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Olanzapine; Propranolol; Quetiapine Fumarate; Risperidone; Testosterone; Trazodone; Treatment Outcome; Valproic Acid

Topics: Adverse Drug Reaction Reporting Systems; Aged; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Cerebrovascular Disorders; Clinical Trials as Topic; Contraindications; Humans; Olanzapine; Product Surveillance, Postmarketing

The exponential growth in the prevalence of cognitive impairment of old patients leads the physicians to deal with a larger incidence of behavioral disorders (such as excitement,aggressiveness), and psychotic symptoms (such as delirium and visual hallucinations). The presence of psychotic troubles in dementia causes a remarkable distress to caregivers and involves higher difficulties in the patient management. The estimates of such troubles range between 15 and 75 %. Geriatric assessment and the management of behavioral troubles require a prompt evaluation of all their possible causes. As a matter of fact, their appearance often reveals a physical disturbance (pain, fever, etc.), or adverse environmental conditions, or it could also be a consequence of a multiple drug therapy. For this reason,the use of antipsychotics should always be preceded by an accurate clinical diagnosis.Anxiolytic, anti-depressive, anti-convulsive and anti-psychotic drugs are among the therapeutic strategies for the management of the psychogeriatric patient. Atypical antipsychotics seem to be able to decrease the psychotic symptoms, with low levels of therapeutic failure. They also reduce extrapyramidal effects and the growth of prolactine hormone, which is quite useful when dealing with very old patients. Risperidone and olanzapine are two atypical anti-psychotics, which already proved to be adequate and well tolerated during the treatment of schizophrenia and of acute maniacal disorders. Our experience, with a population of patients followed by our Alzheimer Evaluation Unit (AEU), confirms that a low dose of olanzapine (5mg/day) and risperidone (0.5-1.0 mg/day) are effective in lowering behavioral disturbances, and psychotic symptoms due to dementia. Even in the long run,low doses of these drugs are still well tolerated. Higher levels of risperidone (> 1 mg/die)often caused extra-pyramidal symptoms such as rigidity and dyskinesia, whereas higher levels of olanzapine (> 5 mg/day) lead to an exceeding sedation. The management of behavioral disturbances is one of the most important goals in the global treatment of patients affected by dementia, to the extent of improving the quality of life. Atypical antipsychotics are preferable compared to old-generation drugs, therefore, they are the key therapeutic strategy we cannot renounce.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Aggression; Alzheimer Disease; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Cognition Disorders; Female; Humans; Male; Mental Disorders; Middle Aged; Olanzapine; Psychotic Disorders; Risperidone

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Cerebral Infarction; Dementia, Vascular; Humans; Olanzapine; Psychotic Disorders; Randomized Controlled Trials as Topic; Risk Factors; Risperidone; Treatment Outcome

This study evaluated length of stay (LOS) associated with atypical antipsychotic monotherapy in inpatients with Alzheimer's disease. In addition to sociodemographic information, data were also obtained on severity of illness, medications, used, patient satisfaction, and hospitalization. Sociodemographics and severity of illness at admission were similar in groups taking olanzapine (N = 66), quetiapine (N = 41), and risperidone (N = 147). The mean LOS for risperidone was significantly shorter than that for quetiapine (12.3 vs. 16.4 days, respectively; P < .02), but the difference between risperidone and olanzapine did not reach statistical significance (12.3 vs. 14.9 days, respectively; P < .08). The savings associated with risperidone versus quetiapine therapy, based on an estimated daily hospital care cost of $492, was $2,017.20 per patient.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Cost Savings; Dibenzothiazepines; Drug Costs; Drug Utilization Review; Female; Geriatric Assessment; Health Services Research; Humans; Length of Stay; Male; Mental Disorders; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone; United States

Orally disintegrating olanzapine is a recently marketed form of olanzapine that dissolves rapidly on contact with saliva. We describe six demented patients resistant to treatment with common oral antipsychotic medications who were successfully treated with the formulation. The importance of these case reports is to make physicians aware that orally disintegrating olanzapine may be useful for the management of psychobehavioral disturbances in demented patients who resist or have difficulty taking standard oral medications.

Topics: Administration, Oral; Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Biological Availability; Brain Injury, Chronic; Dementia; Dementia, Vascular; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Humans; Male; Mental Disorders; Mental Status Schedule; Olanzapine; Pirenzepine; Psychotic Disorders; Treatment Outcome

This paper examines the effects of medical center budget stress on the use of expensive atypical antipsychotic medications for the treatment of schizophrenia in the Department of Veterans Affairs (VA). VA prescription drug records were collected for patients diagnosed with schizophrenia. Generalized estimation equations were used to identify patient and facility characteristics (especially fiscal stress) that are associated with the use of atypical antipsychotics. Of the 34,925 patients in the final sample, over half received an atypical antipsychotic, usually either olanzapine or risperidone. Unexpectedly, increased fiscal stress was associated with increased likelihood of receiving atypical antipsychotics. Among patients who receive atypicals, however, fiscal stress was associated with reduced likelihood of receiving the more expensive atypicals (clozapine and olanzapine) but positively associated with receiving the least expensive atypical (risperidone). Institutional fiscal pressure does not seem to reduce the broad availability of these medications overall but does affect which drug is prescribed.

Topics: Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Budgets; Clozapine; Comorbidity; Depressive Disorder; Drug Costs; Female; Health Care Costs; Health Facilities; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Practice Patterns, Physicians'; Regression Analysis; Risperidone; Schizophrenia; Treatment Outcome; United States; United States Department of Veterans Affairs

Behavioral/psychological symptoms of dementia (BPSD) affect caregiver burden and transition from home to hospital or long-term care. The authors examined change in BPSD for dementia patients (from hospital admission to discharge) who were prescribed haloperidol (n= 289), olanzapine (n=209), or risperidone (n=500). Olanzapine was associated with significantly greater overall improvement in BPSD (based on the Psychogeriatric Dependency Rating Scale total score) than risperidone or haloperidol. Olanzapine was significantly superior on measures of active-, verbal-, and passive-aggression and delusions/hallucinations to risperidone or haloperidol, and, on manipulative behavior and noisiness, to risperidone. Results support the effectiveness of olanzapine in improving several BPSD in hospitalized dementia patients.

Topics: Aged; Aged, 80 and over; Aggression; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Female; Hallucinations; Hospitalization; Humans; Male; Mental Disorders; Middle Aged; Olanzapine; Pirenzepine; Severity of Illness Index; Treatment Outcome

Neuroleptic-induced tardive dyskinesia, which often appears in middle-aged and older adults early in the course of treatment with low doses of conventional antipsychotics, is 5 to 6 times more prevalent in elderly than in younger patients. In addition to age, other risk factors for tardive dyskinesia include early extrapyramidal symptoms (EPS), cumulative amounts of neuroleptics, duration of neuroleptic treatment, and history of alcohol abuse and/or dependence. The atypical antipsychotics, which have a low liability for EPS, are likely to also have low potential for tardive dyskinesia, despite the paucity of controlled studies. Starting and maintenance doses of the atypical antipsychotics should generally be lower in older than in younger adults.

Topics: Adult; Age Factors; Aged; Alzheimer Disease; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clinical Trials as Topic; Clozapine; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Humans; Incidence; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risk Factors; Risperidone

Topics: Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Clozapine; Double-Blind Method; Drug Costs; Drugs, Investigational; Humans; Olanzapine; Pirenzepine; Placebos; Pyridines; Randomized Controlled Trials as Topic; Schizophrenia; Thiadiazoles