quetiapine-fumarate and Alzheimer-Disease

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

Topics: Alzheimer Disease; Amyloid beta-Peptides; Antipsychotic Agents; Brain; Cholinesterase Inhibitors; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Donepezil; Humans; Indans; Neurofibrils; Piperidines; Plaque, Amyloid; Quetiapine Fumarate; Reference Standards; Selective Serotonin Reuptake Inhibitors; tau Proteins

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

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

Behavioral and psychological symptoms of dementia (BPSD) affect 60-90% of patients with Alzheimer's disease (AD).. To determine if environmental therapy is an effective strategy to reduce BPSD, we tested 163 patients with AD with Neuropsychiatric Inventory (NPI) before and after 6 months of an indoor therapeutic garden (TG) or standard environment.. A single-blind randomized controlled trial on AD patients with BPSD. Participants were randomized to an indoor TG (N = 82), or standard environment (control, N = 81) for 6 months.. change in the NPI score from baseline (T0) to end of treatment (T1).. change in use of quetiapine, cognition, activities of daily living, salivary cortisol, blood pressure from T0 to T1.. NPI score significantly ameliorated (TG versus control: -31.8 points), quetiapine dosage (-150 mg), blood pressure (-2.6 mm Hg), and salivary cortisol (-6.4 to -2.1 Nmol/l) were significantly reduced, the Mini-Mental State Examination significantly improved (1.8 points) in the TG versus control arm at T1 (p < 0.001). No adverse events were reported.. The indoor TG seems safe and may reduce BPSD, medication intake, and cortisol levels in AD.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Blood Pressure; Environment; Female; Gardening; Gardens; Humans; Hydrocortisone; Male; Mental Status and Dementia Tests; Neuropsychological Tests; Quetiapine Fumarate; Single-Blind Method; Treatment Outcome

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 objective of this study was to assess the safety and tolerability of extended-release quetiapine fumarate (quetiapine XR) compared with quetiapine immediate-release (quetiapine IR) in older patients with Alzheimer's disease with symptoms of psychosis and/or agitation.. This was a 6-week, double-blind, double-dummy, randomised study. Of the 109 patients screened, 100 were randomised to receive quetiapine XR (n = 68) or quetiapine IR (n = 32), at doses of 50 and 25 mg/day, respectively. Treatment was escalated to 100 mg/day by Day 4. At Day 8, a flexible-dose (50-300 mg/day) period began when dose adjustment was made at the investigator's discretion. The primary variable was incidence and type of adverse events (AEs). Secondary variables included efficacy and other safety assessments.. Mean daily doses were 143.6 and 142.0 mg in the quetiapine XR and quetiapine IR groups, respectively. Ninety patients completed the study; only one withdrew (in the quetiapine XR group) because of an AE. Laboratory evaluations identified severe neutropaenia (one patient), mild neutropaenia (three patients) and eosinophilia (five patients); however, these were not reported, as AEs and confounding factors, such as patient age, concomitant illness and medication, made it difficult to determine any relationship to quetiapine treatment. Numerical improvements from baseline were seen across both treatment groups in Neuropsychiatric Inventory frequency × severity total, Neuropsychiatric Inventory-Nursing Home version, Cohen-Mansfield Agitation Inventory, Clinical Global Impression-Severity of Illness and Clinical Global Impression-Improvement scores.. Quetiapine XR dosed up to 300 mg/day was generally well tolerated, with a similar profile to that of quetiapine IR.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate

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

Treating elderly patients with Alzheimer's disease (AD) and behavioral and psychological symptoms of dementia (BPSD) is challenging due to the increased risk of iatrogenic movement disorders with old neuroleptics and the seemingly increasing risk of cardiovascular events with newer atypical agents. Quetiapine is an atypical antipsychotic agent that warrants further investigation.. To assess tolerability, safety, and clinical benefit of quetiapine in AD patients with BPSD.. AD patients with BPSD participated in a 6-week randomized, double-blind, placebo-controlled trial. Quetiapine was increased on the basis of clinical response and tolerability. Primary efficacy assessments included the Neuropsychiatric Inventory (NPI) and Clinical Global Impression of Change (CGI-C). Secondary efficacy measures included the Mini-Mental State Examination (MMSE), the Simpson-Angus Scale (SAS) and the Abnormal Involuntary Movement Scale (AIMS).. Forty patients (26 women), mean age 82.2 (SD 6.4) years were enrolled, 27 completed treatment. Median dose of quetiapine was 200 mg/day. Significant NPI total scores reductions (79% for placebo and 68.5% for quetiapine) were observed. The CGI-C score decreased significantly in the quetiapine group (p = 0.009 at 6 weeks) and did not change significantly in the placebo group (p = 0.48). The MMSE, AIMS, SAS scores and adverse events did not differ significantly between the two arms.. Quetiapine did not significantly improve psychosis scores. It did not cause cognitive and motor deterioration. These results might possibly be due to small sample size.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Social Behavior Disorders; Treatment Outcome

To assess the efficacy and tolerability of quetiapine for agitation or psychosis in patients with dementia and parkinsonism.. Multicenter randomized, double-blind, placebo-controlled parallel groups clinical trial involving 40 patients with dementia with Lewy bodies (n = 23), Parkinson disease (PD) with dementia (n = 9), or Alzheimer disease with parkinsonian features (n = 8). The main outcome measure for efficacy was change in the Brief Psychiatric Rating Scale (BPRS) from baseline to 10 weeks of therapy. For tolerability it was change in the Unified PD Rating Scale (UPDRS) motor section over the same time period. The trial was confounded by the need for a design change and incomplete recruitment.. No significant differences in the primary or secondary outcome measures of efficacy were observed. An unexpectedly large placebo effect, inadequate dosage (mean 120 mg/day), and inadequate power may have contributed to lack of demonstrable benefit. Quetiapine was generally well-tolerated and did not worsen parkinsonism, but was associated with a trend toward a decline on a measure of daily functioning.. Quetiapine was well-tolerated and did not worsen parkinsonism. Although conclusions about efficacy may be limited, the drug in the dosages used did not show demonstrable benefit for treating agitation or psychosis in patients with dementia and parkinsonism. These findings are in keeping with prior studies reporting limited efficacy of various medications for reducing behavioral problems in demented patients.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Alzheimer Disease; Antiparkinson Agents; Antipsychotic Agents; Cholinesterase Inhibitors; Confounding Factors, Epidemiologic; Dementia; Dibenzothiazepines; Donepezil; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Indans; Lewy Body Disease; Male; Neuropsychological Tests; Parkinson Disease; Patient Selection; Piperidines; Placebo Effect; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate; Research Design; Severity of Illness Index; Treatment Failure

This 5-wk, open-label, comparative study investigated the effects of quetiapine and haloperidol on behavioural, cognitive and circadian rest-activity cycle disturbances in patients with Alzheimer's disease (AD). Out of a total of 30 patients enrolled in the study, there were 22 completers, 11 in the quetiapine group (mean age 81.9+/-1.8 yr, mean baseline MMSE 19.9+/-1.3, mean dose 125 mg) and 11 in the haloperidol group (mean age 82.3+/-2.5 yr, mean baseline MMSE 18.1+/-1.3, mean dose 1.9 mg). As shown in the Neuropsychiatric Inventory, both medications reduced delusion and agitation, whereas quetiapine additionally improved depression and anxiety. Haloperidol worsened aberrant motor behaviour and caused extrapyramidal symptoms. In the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological test battery which assessed cognitive parameters, quetiapine improved word recall; significant interaction terms revealed differences between quetiapine and haloperidol in word-list memory and constructional praxis. According to the Nurses' Observation Scale for Geriatric Patients (NOSGER) quetiapine improved instrumental activities of daily living. Actimetry documented the circadian rest-activity cycle before and after treatment. Sleep analysis revealed that patients receiving quetiapine had shorter wake bouts during the night, whereas patients receiving haloperidol had fewer though longer immobile phases. The study provides evidence that quetiapine at a moderate dose may be efficacious in treating behavioural disturbances in AD, with better tolerability than haloperidol.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Alzheimer Disease; Analysis of Variance; Antipsychotic Agents; Behavior; Chronobiology Disorders; Cognition; Dibenzothiazepines; Female; Geriatric Assessment; Haloperidol; Humans; Male; Neuropsychological Tests; Psychiatric Status Rating Scales; Quetiapine Fumarate

Topics: Alzheimer Disease; Cholinesterase Inhibitors; Cognition Disorders; Dibenzothiazepines; Disease Progression; Double-Blind Method; Humans; Phenylcarbamates; Psychomotor Agitation; Quetiapine Fumarate; Rivastigmine

The objectives of this study were to evaluate the efficacy, safety, and tolerability of quetiapine for treating psychosis in patients with probable/possible Alzheimer disease and assess its impact on other psychopathology and social and daily functioning.. The authors conducted a multicenter, double-blind, placebo-controlled, randomized trial of flexibly dosed quetiapine and haloperidol. Primary outcomes were change in total Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impressions-Severity of Illness (CGI-S) scores at week 10. Secondary outcomes included BPRS factors, Neuropsychiatric Inventory (NPI), Multidimensional Observation Scale for Elderly Subjects (MOSES), and Physical Self-Maintenance Scale (PSMS).. Two hundred eighty-four participants (mean age: 83.2 years) were randomized; 63.4% completed; and mean Mini-Mental State Examination score was 12.8. Median of the mean daily dose was 96.9 mg for quetiapine and 1.9 mg for haloperidol. No differential benefit was seen on any psychosis measure. BPRS agitation factor scores improved with quetiapine versus placebo and not quetiapine versus haloperidol. BPRS anergia scores worsened with haloperidol versus quetiapine but not quetiapine versus placebo. No NPI factors showed change, including the agitation factor. MOSES Withdrawal Subscale and PSMS total scores worsened with haloperidol versus quetiapine. Somnolence occurred in 25.3%, 36.2%, and 4.1% of the quetiapine, haloperidol, and placebo groups, respectively; parkinsonism was most prevalent in the haloperidol group; other safety and tolerability measures differed little among groups.. All treatment groups showed improvement in measures of psychosis without significant differences between them when planned comparisons were performed. Participants treated with quetiapine or haloperidol showed inconsistent evidence of improvement in agitation. Tolerability was better with quetiapine compared with haloperidol.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Basal Ganglia Diseases; Brain; Brief Psychiatric Rating Scale; Cholinesterase Inhibitors; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Drug Tolerance; Female; Haloperidol; Humans; Male; Middle Aged; Neuropsychological Tests; Parkinson Disease, Secondary; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate; Severity of Illness Index; Substance Withdrawal Syndrome

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

To determine the respective efficacy of quetiapine and rivastigmine for agitation in people with dementia in institutional care and to evaluate these treatments with respect to change in cognitive performance.. Randomised double blind (clinician, patient, outcomes assessor) placebo controlled trial.. Care facilities in the north east of England.. 93 patients with Alzheimer's disease, dementia, and clinically significant agitation.. Atypical antipsychotic (quetiapine), cholinesterase inhibitor (rivastigmine), or placebo (double dummy).. Agitation (Cohen-Mansfield agitation inventory) and cognition (severe impairment battery) at baseline and at six weeks and 26 weeks. The primary outcome was agitation inventory at six weeks.. 31 patients were randomised to each group, and 80 (86%) started treatment (25 rivastigmine, 26 quetiapine, 29 placebo), of whom 71 (89%) tolerated the maximum protocol dose (22 rivastigmine, 23 quetiapine, 26 placebo). Compared with placebo, neither group showed significant differences in improvement on the agitation inventory either at six weeks or 26 weeks. Fifty six patients scored > 10 on the severe impairment battery at baseline, 46 (82%) of whom were included in the analysis at six week follow up (14 rivastigmine, 14 quetiapine, 18 placebo). For quetiapine the change in severe impairment battery score from baseline was estimated as an average of -14.6 points (95% confidence interval -25.3 to -4.0) lower (that is, worse) than in the placebo group at six weeks (P = 0.009) and -15.4 points (-27.0 to -3.8) lower at 26 weeks (P = 0.01). The corresponding changes with rivastigmine were -3.5 points (-13.1 to 6.2) lower at six weeks (P = 0.5) and -7.5 points (-21.0 to 6.0) lower at 26 weeks (P = 0.3).. Neither quetiapine nor rivastigmine are effective in the treatment of agitation in people with dementia in institutional care. Compared with placebo, quetiapine is associated with significantly greater cognitive decline.

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Cholinesterase Inhibitors; Cognition Disorders; Dibenzothiazepines; Double-Blind Method; Humans; Middle Aged; Phenylcarbamates; Psychomotor Agitation; Quetiapine Fumarate; Rivastigmine; Treatment Failure

The purpose of this study was to assess the effect of quetiapine in the treatment of behavioral and psychological symptoms of dementia (BPSD) in patients with senile dementia of Alzheimer type (SDAT). Sixteen SDAT patients with BPSD were recruited and quetiapine (25- 200 mg/day) was prescribed for 8 weeks. BPSD were evaluated with the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) and Cohen-Mansfield Agitation Inventory (CMAI) at week 0 (baseline) and week 8 (endpoint). The severity of the extrapyramidal symptoms was also assessed by the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) at baseline and endpoint. Significant improvements were seen in the CMAI total score and in the BEHAVE-AD subscales of delusions, activity disturbances, aggressiveness, diurnal rhythm disturbances and in the BEHAVE-AD overall severity. There was no significant difference between the baseline and endpoint in the DIEPSS score. These data indicate that quetiapine is effective in controlling BPSD with favorable adverse-event profiles.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Behavioral Symptoms; Dibenzothiazepines; Dose-Response Relationship, Drug; Equipment and Supplies; Female; Humans; Male; Neuropsychological Tests; Psychiatric Status Rating Scales; Psychometrics; Quetiapine Fumarate; Treatment Outcome

Antipsychotic use for neuropsychiatric symptoms in Alzheimer's disease (AD) is common despite the increased risk of cardiovascular events and mortality. There is limited and inconsistent evidence on the possible risk of stroke. We assessed whether antipsychotic initiation increases the risk of stroke in people with a verified diagnosis of AD and whether there is a difference in stroke risk between the 2 most commonly used antipsychotics, risperidone and quetiapine.. Register-based exposure-matched cohort study.. The Medication Use and Alzheimer's Disease (MEDALZ) cohort included 70,718 community-dwelling people with AD in Finland during 2005-2011. People with previous strokes were excluded.. For each incident antipsychotic user (n = 20,467), 1 nonuser was matched according to sex, age, and time since AD diagnosis. Analyses were conducted with inverse probability of treatment-weighted (IPTW) Cox proportional hazards models.. Compared with nonuse, antipsychotic use was associated with an increased risk of stroke within 60 days of antipsychotic initiation [IPTW hazard ratio (HR) 1.73, 95% confidence interval (CI) 1.32-2.28]. However, there was no significant overall association between antipsychotic use and the risk of stroke (IPTW HR 1.09, 95% CI 0.98-1.22). There was no difference in stroke risk between risperidone and quetiapine (IPTW HR 1.12, 95% CI 0.91-1.37).. Stroke risk is increased shortly after antipsychotic initiation in people with AD, suggesting that even short-term use of antipsychotics should be avoided if possible. If antipsychotics are prescribed, effectiveness and safety should be assessed soon after initiation and treatment limited to the shortest possible duration.

Topics: Alzheimer Disease; Antipsychotic Agents; Cohort Studies; Humans; Independent Living; Quetiapine Fumarate; Risperidone; Stroke

Quetiapine combined with sodium valproate is an effective and more suitable drug treatment for Alzheimer's disease. At present, there are relatively few studies on the combined action mechanism of these two drugs. This study has certain practical value. Alzheimer's disease is a multifaceted, highly genetically heterogeneous neurodegenerative disease. The main clinical manifestations are memory loss, abnormal mental behavior, and loss of various cognitive functions. In order to improve the symptoms of patients with Alzheimer's disease, especially those with mental symptoms, this article combines quetiapine and sodium valproate, two commonly used drugs for the treatment of mental illnesses, and applies them to different levels of Alzheimer's and observes the results of the combination's curative effect. This article introduces Alzheimer's disease and its potential mental behaviors in the method section, and it also introduces the mechanism of action of quetiapine and sodium valproate. For the algorithm, this paper introduces a data mining algorithm to understand the effect of drug efficacy. In the experimental part, firstly, it introduces the experimental objects, the proportion of medicines, and the statistical methods. Secondly, this article covers adverse reactions, inflammatory factors and vascular endothelial indicators, Alzheimer's disease performance, MOAS score, treatment effect evaluation, and satisfaction surveys. It can be seen from the experiment that, in mental behavior, the experimental group decreased from 8.2 before treatment to 0.5, and the control group decreased from 7.1 before treatment to 2.6. It can be seen that the scores of the experimental group changed after receiving the treatment of quetiapine combined with sodium valproate.

Topics: Alzheimer Disease; Antipsychotic Agents; Behavioral Symptoms; Dibenzothiazepines; Humans; Neurodegenerative Diseases; Quetiapine Fumarate; Valproic Acid

The aim of this study was to assess the potency of selected antipsychotic drugs (haloperidol (HAL), bromperidol (BRMP), benperidol (BNP), penfluridol (PNF), pimozide (PIM), quetiapine (QUET) and promazine (PROM)) on the main pathological hallmarks of Alzheimer's disease (AD). Binary mixtures of donepezil and antipsychotics produce an anti-BuChE effect, which was greater than either compound alone. The combination of rivastigmine and antipsychotic drugs (apart from PNF) enhanced AChE inhibition. The tested antipsychotics (excluding HAL and PNF) significantly reduce the early stage of Aβ aggregation. BRMP, PIM, QUET and PROM were found to substantially inhibit Aβ aggregation after a longer incubation time. A test of human erythrocytes hemolysis showed that short-term incubation of red blood cells (RBCs) with QUET resulted in decreased hemolysis. The antioxidative properties of antipsychotics were also proved in human umbilical vein endothelial cells (HUVEC); all tested drugs were found to significantly increase cell viability. In the case of astrocytes, BNP, PNF, PIM and PROM showed antioxidant potential.

Topics: Alzheimer Disease; Antipsychotic Agents; Cholinesterase Inhibitors; Endothelial Cells; Hemolysis; Humans; Quetiapine Fumarate; Rivastigmine

We assessed psychotropic prescribing patterns in the clinical treatment of agitation and aggressive behavior in patients with Alzheimer's disease (AD) treated at specialist outpatient clinics in the Federal District of Brazil. This was a naturalistic, observational, multicenter study of a convenience sample of patients with AD (according to DSM-5) who had behavioral symptoms of aggression and/or agitation at outpatient visits, as assessed by the Neuropsychiatric Inventory (NPI), and required pharmacologic intervention. Participants were recruited in 2018-2019 from 11 AD treatment centers. Sociodemographic and clinical data were collected during routine visits. The sample consisted of 369 older adults with a mean age of 82.3 (SD, 7.7) years. The medications most commonly used in patients with behavioral disorders were antidepressants (79.1%), antipsychotics (70.2%), benzodiazepines (10.6%), and mood stabilizers (9.5%). Quetiapine was the most frequently prescribed antipsychotic medication (48.5%), at a mean dose of 57.4 (SD, 40.7) mg. Citalopram was the most widely used antidepressant medication (32.0%), at a mean daily dose of 24.1 (SD, 8.1) mg. In this sample, two or more pharmacologic agents were frequently used together to control aggression and agitation. Benzodiazepine was not frequently used.

Topics: Aged; Aged, 80 and over; Aggression; Alzheimer Disease; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Brazil; Citalopram; Female; Humans; Male; Psychomotor Agitation; Psychotropic Drugs; Quetiapine Fumarate; Treatment Outcome

Older adults are the leading users of medications, where this can be associated with a high number of potentially inappropriate medications (PIMs) and of potentially inappropriate prescribing (PIP) and consequent harm to health. No Brazilian study evaluating potentially inappropriate prescribing in older patients with Alzheimer's disease (AD) was found. This study determined and analyzed the prevalence of PIP and PIM prescribed for older people with AD.A cross-sectional study was carried out at the Specialty Drugs Pharmacy in the city of Sorocaba, São Paulo State, Brazil. The MEDEX system provided the register in older people with AD and data were collected during interviews with patients and/or caregivers between June and September 2017. The PIMs were identified according to the 2019 Beers Criteria. The association between PIMs and independent variables was analyzed by Poisson regression.This study included 234 older patients with AD. The prevalence of PIP prescribed was 66.7% (n = 156). Of the 1073 medications prescribed, 30.5% (n = 327) were inappropriate with most affecting the central nervous system or cardiovascular, particularly quetiapine (12.8%) and acetylsalicylic acid (11.6%), respectively. Around 45.2% of the PIMs should be avoided in older people, especially sertraline (14.2%) and clonazepam (7.4%). After adjusted analysis, the PIMs were associated with the diagnosis of depression (P = 0.010) and the number of comorbidities (P = 0.005).There was a high number of PIMs among older people, a substantial number of which should have been avoided in this population. Health care professionals can apply these findings to improve safety in the use of medications for treating patients with AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Aspirin; Brazil; Cardiovascular Agents; Central Nervous System Agents; Clonazepam; Cross-Sectional Studies; Drug Interactions; Female; Humans; Inappropriate Prescribing; Male; Polypharmacy; Quetiapine Fumarate; Sertraline

To compare the accumulation of hospital days, a proposed proxy for overall drug safety, between antipsychotic initiators and noninitiators with Alzheimer's disease (AD).. Nationwide exposure-matched cohort.. Finnish community dwellers who received an incident AD diagnosis in 2005‒2011 (n = 70,718). For each antipsychotic initiator, 1 noninitiator was matched on age, sex, and time since AD diagnosis (n = 19,909 matched pairs).. Accumulation of hospital days was measured during a 2-year follow-up from the national hospital discharge register. Antipsychotic use was ascertained from the National Prescription Register. Association between antipsychotic initiation and accumulation of hospital days was analyzed using negative binomial model.. During the 2-year follow-up, antipsychotic initiators were hospitalized on average for 52.5 (standard deviation 97.7) days and matched noninitiators for 34.7 (standard deviation 72.4) days. Of antipsychotic initiators 23.8% and of noninitiators, 34.1% did not have any hospital days. Antipsychotic initiators had 53% more hospital days (adjusted incidence rate ratio 1.53; 95% confidence interval 1.47‒1.59) than noninitiators. Strongest associations were observed during the first 6 months. Antipsychotic initiators had more hospital days with primary diagnosis codes of dementia; mental and behavioral disorders; factors influencing health status; diseases of the respiratory, genitourinary, and circulatory system; certain infectious and parasitic diseases; and symptoms not elsewhere classified, than noninitiators.. Antipsychotic initiators accumulated more hospital days than noninitiators, especially within the first 6 months after initiation. This may indicate adverse events or difficulties in treating the most severe behavioral and psychological symptoms of dementia and health problems triggering them. After initiating antipsychotics, careful and regular monitoring is needed to assess response and decrease the risk of adverse effects and events.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Cohort Studies; Female; Finland; Follow-Up Studies; Health Status; Hospitalization; Humans; Length of Stay; Male; Matched-Pair Analysis; Quetiapine Fumarate; Registries; Risperidone

Alzheimer's disease is a common cause of dementia, and is usually treated with medications that elevate acetylcholine levels. The objective of the present study was to identify drugs with anticholinergic properties prescribed to patients diagnosed with Alzheimer's disease in Colombia.. A cross-sectional study was carried out in outpatients diagnosed with Alzheimer's disease who were identified from a population database from Colombia, and had been treated with cholinesterase inhibitors and glutamate N-methyl-D-aspartate receptor antagonists. The anticholinergic burden was evaluated using the Anticholinergic Cognitive Burden scale, and patients were classified on a scale of 0-3 points according to anticholinergic potential, and were grouped into those with mild-to-moderate (1-2 points) or high (≥3 points) anticholinergic load.. The study included 4134 Alzheimer's disease patients. The mean age was 81.50 ± 8.16 years, and 67.8% were women. At least 22.9% of patients took anticholinergic drugs. Of these, the most frequently prescribed medication was quetiapine (8.6%). Age >85 years was associated with a high risk of having an anticholinergic burden ≥3 points (OR 2.19, 95%CI 1.159-4.162). Potential interactions between cholinesterase inhibitors and anticholinergic drugs were identified in 7.8% of patients.. The majority of patients who were prescribed anticholinergic drugs were older women, had a significant total anticholinergic burden and had frequent pharmacological interactions with cholinesterase inhibitors. The use of anticholinergics reduces the clinical effectiveness of antidementia drugs and increases the risk of adverse reactions. Geriatr Gerontol Int 2019; 19: 913-917.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cholinergic Antagonists; Cholinesterase Inhibitors; Colombia; Cross-Sectional Studies; Female; Humans; Inappropriate Prescribing; Male; Medication Therapy Management; Muscarinic Antagonists; Outpatients; Pharmacovigilance; Potentially Inappropriate Medication List; Psychotropic Drugs; Quetiapine Fumarate

Previous studies approved the important roles of CD68, as scavenger receptors, in Alzheimer's disease (AD). The aim of this study was to evaluate the effect of treatment with anti-psychotic drugs and vitamin B12 on the expression levels of CD68 in monocytes of psychotic AD patients.. Expression of CD68 on the monocytes was evaluated in the following groups: 1. age and sex matched healthy controls (Group 1), 2. non-psychotic AD patients (Group 2), 3. psychotic AD patients (Group 3), 4. psychotic AD patients treated with Risperidone (Group 4), 5. psychotic AD patients treated with Risperidone plus vitamin B12 (Group 5), 6. psychotic AD patients treated with Quetiapine (Group 6), psychotic AD patients treated with Quetiapine plus vitamin B12 (Group 7). The expression of CD68 has been performed using flow cytometry technique.. The results showed that CD68 levels were significantly increased in AD patients in comparison to healthy controls and in psychotic AD patients in comparison to non-psychotic AD patients. Treatment with anti-psychotic drugs decreased the expression of CD68. Expression of CD68 has a positive correlation with pain, dementia and mental disorders symptoms in psychotic AD patients.. CD68 may play key roles in the pathogenesis of AD and its complications may be via induction of inflammation. Therefore, it may be concluded that CD68 may be considered as a risk factor for development of AD and also psychotic symptoms in the patients.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antipsychotic Agents; Case-Control Studies; Drug Therapy, Combination; Female; Flow Cytometry; Humans; Inflammation; Male; Monocytes; Psychotic Disorders; Quetiapine Fumarate; Risk Factors; Risperidone; Vitamin B 12

To study whether antipsychotic use is associated with a risk of hip fracture among individuals with Alzheimer's disease and to compare the risk according to the duration of use and the 2 most frequently used antipsychotics.. The MEDALZ (Medication and Alzheimer's disease) cohort consisted of community-dwelling Finnish persons with clinically verified diagnoses of Alzheimer's disease, including 70,718 persons newly diagnosed according to NINCDS-ADRDA and DSM-IV criteria between 2005 and 2011. Antipsychotic use was modeled from prescription register data, and hip fractures (ICD-10 S72.0-72.2) were identified from the Hospital Discharge Register. The incidence of hip fractures was compared between new users and nonusers of antipsychotics, among various time durations of antipsychotic use, and between quetiapine users and risperidone users.. Antipsychotic use versus nonuse was associated with an increased risk of hip fractures (adjusted hazard ratio [HR] = 1.54; 95% CI, 1.39-1.70). The risk was increased from the first days of use and remained increased thereafter. Quetiapine was associated with a similar risk of hip fracture as risperidone for the first 2.7 years of use (adjusted HR = 0.98; 95% CI, 0.79-1.21). Compared with low-dose (≤ 0.5 mg) risperidone use, higher risperidone doses (> 0.5 mg) were associated with a higher risk of hip fracture (adjusted HR = 1.72; 95% CI, 1.32-2.24).. Since the risk of hip fracture was increased from the first days of use, our results confirm the need for setting a high threshold for initiating antipsychotic use among persons with Alzheimer's disease to avoid serious adverse events. If antipsychotic use is initiated, the duration of use should be limited, as the risk of hip fracture does not attenuate with long-term use.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Cohort Studies; Cross-Sectional Studies; Dose-Response Relationship, Drug; Female; Finland; Hip Fractures; Humans; Long-Term Care; Male; Proportional Hazards Models; Quetiapine Fumarate; Risk; Risperidone

Antipsychotics are recommended only for short-term treatment of severe behavioral and psychological symptoms of dementia. Our objective was to study the duration of antipsychotic use and factors associated with long-term use (365 days or over) among community-dwelling persons with Alzheimer׳s disease (AD) during a 7-year follow-up. This was a nationwide register-based cohort study including all community-dwelling residents in Finland diagnosed with AD in 2005 (n=7217). The follow-up for antipsychotic use started 3 years before the diagnosis of AD and we applied a 7-year washout period to ascertain truly incident antipsychotic use. Follow-up ended on institutionalization, death or at the end of study period (December 31, 2009). Duration of antipsychotic use was modeled from individual purchase histories recorded in the Finnish Prescription Register. During the 7-year follow-up, 34% (2287/6740) of persons initiated antipsychotic use. Median duration of the first antipsychotic use period was 219 (interquartile range 85-583) days. Of those who discontinued antipsychotic use (n=1303), 44% restarted use later. Among users with at least one year of follow-up time after initiating antipsychotic use, prevalence of long-term use was 57% (893/1563). Long-term use was associated with initiation of use after AD diagnosis and choice of antipsychotic. Duration of use was more likely to be shorter among haloperidol users and longer among quetiapine users compared with risperidone users. In conclusion, long-term use of antipsychotics is frequent among community-dwelling persons with AD. Duration of use is not in line with the guidelines recommending time-limited use of antipsychotics.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Cohort Studies; Female; Finland; Follow-Up Studies; Haloperidol; Humans; Male; Prevalence; Quetiapine Fumarate; Registries; Risperidone; Time Factors; Treatment Outcome

Quetiapine, an atypical antipsychotic drug, may have beneficial effects in Alzheimer's disease (AD), and the effect of quetiapine on object recognition memory in AD has never been measured. The aim of the present study was to evaluate the effects of quetiapine on object recognition memory and on oxidative stress that could be involved in the AD pathogenesis in an amyloid precursor protein/presenilin-1 double transgenic mouse model of AD. Nontransgenic and transgenic mice were treated with quetiapine (0 or 5 mg/kg/day) in drinking water from the age of 2 months. After 10 months of continuous quetiapine administration, object recognition memory impairment and the increased hippocampal protein expression of nitrotyrosine, a protein marker of oxidative stress, were attenuated in the AD mice. These results suggest that quetiapine can attenuate object recognition memory impairment and brain oxidative stress in an amyloid precursor protein/presenilin-1 transgenic mouse model of AD and indicate that the antioxidative effect of early quetiapine intervention may be associated with the beneficial effect of quetiapine on memory in AD.

Topics: Alzheimer Disease; Animals; Antipsychotic Agents; Behavior, Animal; Dibenzothiazepines; Disease Models, Animal; Female; Hippocampus; Memory Disorders; Mice; Mice, Transgenic; Oxidative Stress; Quetiapine Fumarate; Recognition, Psychology

In Alzheimer's disease, growing evidence has shown that uncontrolled glial activation and neuroinflammation may contribute independently to neurodegeneration. Antiinflammatory strategies might provide benefits for this devastating disease. The aims of the present study are to address the issue of whether glial activation and proinflammatory cytokine increases could be modulated by quetiapine in vivo and in vitro and to explore the underlying mechanism.. Four-month-old amyloid precursor protein (APP) and presenilin 1 (PS1) transgenic and nontransgenic mice were treated with quetiapine (5mg/kg/d) in drinking water for 8 months. Animal behaviors, total Aβ levels, and glial activation were evaluated by behavioral tests, enzyme-linked immunosorbent assay, immunohistochemistry, and Western blot accordingly. Inflammatory cytokines and the nuclear factor kappa B pathway were analyzed in vivo and in vitro.. Quetiapine improves behavioral performance, marginally affects total Aβ40 and Aβ42 levels, attenuates glial activation, and reduces proinflammatory cytokines in APP/PS1 mice. Quetiapine suppresses Aβ1-42-induced activation of primary microglia by decresing proinflammatory cytokines. Quetiapine inhibits the activation of nuclear factor kappa B p65 pathway in both transgenic mice and primary microglia stimulated by Aβ1-42.. The antiinflammatory effects of quetiapine in Alzheimer's disease may be involved in the nuclear factor kappa B pathway. Quetiapine may be an efficacious and promising treatment for Alzheimer's disease targeting on neuroinflammation.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Antipsychotic Agents; Cells, Cultured; Cerebral Cortex; Cytokines; Dibenzothiazepines; Disease Models, Animal; Exploratory Behavior; Gene Expression Regulation; Humans; Mice; Mice, Transgenic; Microglia; Mutation; NF-kappa B; Presenilin-1; Quetiapine Fumarate; Recognition, Psychology; Signal Transduction

Our previous study has shown the preventive effects of quetiapine, an atypical antipsychotic drug, on memory impairment and brain pathological changes in a mouse model of Alzheimer's disease (AD). The aim of the present study was to evaluate the therapeutic effects of quetiapine on memory deficit and neuropathology in an amyloid precursor protein (APP)/presenilin-1 (PS1) double transgenic mouse model of AD. The APP/PS1 mice started to have detectable brain β-amyloid (Aβ) at 3 months of age. Non-transgenic and transgenic mice were treated with quetiapine (0, 2.5, or 5 mg/(kg day)) in drinking water from the age of 4 months. After 8 months of continuous quetiapine administration, memory deficit was reversed and brain Aβ plaque pathology was attenuated in the AD mice. Quetiapine also decreased the soluble Aβ peptide levels in brain and cerebrospinal fluid (CSF), and attenuated the decreased synaptic protein levels in the AD mice. Furthermore, quetiapine normalized the abnormal activity of glycogen synthase kinase-3β (GSK-3β), an AD-involved kinase, in the AD mice. These results suggest that quetiapine can treat and alleviate the neuropathology in an APP/PS1 transgenic mouse model of AD, and indicate that quetiapine may have therapeutic effects in the treatment of AD.

Topics: Alzheimer Disease; Animals; Blotting, Western; Brain; Dibenzothiazepines; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Humans; Maze Learning; Memory; Memory Disorders; Mice; Mice, Transgenic; Neuroprotective Agents; Plaque, Amyloid; Quetiapine Fumarate

Quetiapine, an atypical antipsychotic drug, is effective in treating the behavioral and psychological symptoms in Alzheimer's disease (AD). However, it is presently unclear whether quetiapine has beneficial effects on memory and whether the effects of quetiapine on psychological symptoms are associated with its effect on memory in AD. The present study was designed to examine the effect of chronic administration of quetiapine on the conditioned (generalized) anxiety that is related to learning experience of open arm exposure in the elevated T-maze (ETM) test in an amyloid precursor protein (APP)/presenilin 1 (PS1) double transgenic mouse model of AD. In a 2nd experiment, the effect of quetiapine on memory per se was investigated in a Y-maze test in AD mice. Non-transgenic and transgenic mice were treated with quetiapine in drinking water from the age of 2 months. After continuous treatment with quetiapine (5 mg/kg/day) for 10 months, mice were tested for conditioned anxiety on the ETM task. After ETM testing, the expression of brain-derived neurotrophic factor (BDNF), a neuroprotective protein, was examined by immunohistochemistry in the basolateral amygdala (BLA) and hippocampus. In the 2nd experiment, the effect of quetiapine (2.5 or 5 mg/kg/day) on the short-term memory in AD mice was tested in a Y-maze test. After 10 months of administration, quetiapine prevented the decrease of conditioned anxiety and cerebral BDNF in AD mice. In addition, quetiapine also prevented memory impairment in the Y-maze test in AD mice. These findings suggest that the therapeutic mechanism of quetiapine on anxiety in AD may be associated with its beneficial effect on memory and its neuroprotective effect on cerebral BDNF expression.

Topics: Alzheimer Disease; Amyloid beta-Protein Precursor; Analysis of Variance; Animals; Antipsychotic Agents; Anxiety; Avoidance Learning; Behavior, Animal; Brain; Brain-Derived Neurotrophic Factor; Dibenzothiazepines; Disease Models, Animal; Dose-Response Relationship, Drug; Drinking; Drug Administration Schedule; Humans; Learning Disabilities; Maze Learning; Mice; Mice, Transgenic; Motor Activity; Mutation; Presenilin-1; Quetiapine Fumarate; Reaction Time; Time Factors

We investigated the change of antipsychotic treatment of elderly persons with dementia after several publications indicated an association between use of antipsychotics and cerebrovascular events in this population.. Twice a year, the complete medication, age, diagnosis and gender of all inpatients in 30 German psychiatric sites is collected anonymously in a data base for statistical analysis.. The treatment changed for the benefit of Quetiapine and Haloperidol. The use of both Risperidone and Olanzapine decreased markedly.. The antipsychotic treatment changed due to critical publication. But, the evidence for the risk profile is still a matter of debate.

Topics: Adverse Drug Reaction Reporting Systems; Aged; Alzheimer Disease; Antipsychotic Agents; Cerebral Infarction; Dibenzothiazepines; Drug Therapy, Combination; Drug Utilization; Drug-Related Side Effects and Adverse Reactions; Evidence-Based Medicine; Female; Germany; Humans; Male; Practice Patterns, Physicians'; Publication Bias; Quetiapine Fumarate; Risk; Risperidone

The Numbers of elderly people are gradually increasing in our society, and mood disorders are progressively increasing among older people. Old age depression may also occur after life events: the death of the significant other, economical reasons, health problems (neurological and/or cardiovascular diseases, arthritis, cancer, nutritional deficiency) and can develop into a depressive state. Old age depression is often mistreated, or undertreated, and also underdiagnosed, and this for several reasons: older people reduce their social relations, depression very often presents as a comorbidity with organic diseases (that cover and mask depressive symptoms); finally,the patient may believe that a depressive state is a normal course of life in older people. Recovering from depression is really feasible both in young/adults and in old people, but in older people we can find a higher frequency of admission to hospital, or mortality or suicidality. The depressive symptoms in old age depression is similar to those in adults, however the following aspects require special care, in order to ensure a correct diagnosis despite the presence of comorbidities: - the mood: in contrast with the young and adult, old people often do not complain about their low mood; - the psychotic simptoms: hypocondriacal and psychotic, including hallucinatory symptoms are often present; - the anxiety symptoms: these are often present together with neuro-sensory symptoms; - the somatic symptoms: the comorbidity with organic diseases can mask and overlap the depressive state; - reduction of congnitive functioning: in these cases, which are quite frequent, it is essential to make a differential diagnosis from "pseudodementia" and "dementia". In conclusion, several factors contribute to the onset of depression in old age, so that we can assert that it is a really a multifactorial disease.

Topics: Aged; Alzheimer Disease; Antidepressive Agents; Antipsychotic Agents; Anxiety Disorders; Benzodiazepines; Comorbidity; Dementia, Vascular; Depressive Disorder, Major; Dibenzothiazepines; Drug Therapy, Combination; Humans; Life Change Events; Psychomotor Agitation; Quetiapine Fumarate; Risk Factors; Selective Serotonin Reuptake Inhibitors

Previous studies have suggested that quetiapine, an atypical antipsychotic drug, may have beneficial effects on cognitive impairment, and be a neuroprotectant in treating neurodegenerative diseases. In the present study, we investigated the effects of quetiapine on memory impairment and pathological changes in an amyloid precursor protein (APP)/presenilin-1 (PS-1) double transgenic mouse model of Alzheimer's disease (AD). Non-transgenic and transgenic mice were treated with quetiapine (0, 2.5, or 5mg/(kg day)) for 1, 4, and 7 months in drinking water from the age of 2 months. After 4 and 7 months of continuous quetiapine administration, memory impairment was prevented, and the number of beta-amyloid (Abeta) plaques decreased in the cortex and hippocampus of the transgenic mice. Quetiapine also decreased brain Abeta peptides, beta-secretase activity and expression, and the level of C99 (an APP C-terminal fragment following cleavage by beta-secretase) in the transgenic mice. Furthermore, quetiapine attenuated anxiety-like behavior, up-regulated cerebral Bcl-2 protein, and decreased cerebral nitrotyrosine in the transgenic mice. These findings suggest that quetiapine can alleviate cognitive impairment and pathological changes in an APP/PS1 double transgenic mouse model of AD, and further indicate that quetiapine may have preventive effects in the treatment of AD.

Topics: Aging; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Amyloid Precursor Protein Secretases; Animals; Antipsychotic Agents; Anxiety; Brain; Dibenzothiazepines; Disease Models, Animal; Female; Male; Memory Disorders; Mice; Mice, Transgenic; Plaque, Amyloid; Presenilin-1; Protease Nexins; Proto-Oncogene Proteins c-bcl-2; Quetiapine Fumarate; Receptors, Cell Surface; Tyrosine

We have shown that quetiapine, a new antipsychotic drug, protects cultured cells against oxidative stress-related cytotoxicities induced by amyloid beta (Abeta)25-35, and that quetiapine prevents memory impairment and decreases Abeta plaques in the brains of amyloid precursor protein (APP)/presenilin-1 (PS-1) double-mutant mice. The aim of this study was to understand why quetiapine has these protective effects. Because the cytotoxicity of both Abeta(25-35) and Abeta(1-40) requires fibril formation, our first experiments determined the effect of quetiapine on Abeta(25-35) aggregation. Quetiapine inhibited Abeta(25-35) aggregation in cell-free aqueous solutions and blocked the fibrillar aggregation of Abeta(25-35), as observed under an electron microscope. We then investigated why quetiapine inhibits Abeta(25-35) aggregation. During the aggregation of Abeta(25-35), a hydroxyl radical (OH*) was released, which in turn amplified Abeta(25-35) aggregation. Quetiapine blocked OH*-induced Abeta(25-35) aggregation and scavenged the OH* produced in the Fenton system and in the Abeta(25-35) solution, as analyzed using electron paramagnetic resonance spectroscopy. Furthermore, new compounds formed by quetiapine and OH* were observed in MS analysis. Finally, we applied Abeta(25-35) to PC12 cells to observe the effect of quetiapine on living cells. Abeta(25-35) increased levels of intracellular reactive oxygen species and calcium in PC12 cells and caused cell death, but these toxic effects were prevented by quetiapine. These results demonstrate an anti-oxidative stress mechanism of quetiapine, which contributes to its protective effects observed in our previous studies and explains the effectiveness of this drug for Alzheimer's disease patients with psychiatric and behavioral complications.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Antioxidants; Antipsychotic Agents; Dibenzothiazepines; Free Radical Scavengers; Hydroxyl Radical; Oxidative Stress; PC12 Cells; Peptide Fragments; Quetiapine Fumarate; Rats; Reactive Oxygen Species

Atypical antipsychotics (AA) are generally associated with weight gain. We determined body mass index (BMI) change in Parkinson's disease (PD) before and after taking AA and compared against PD controls and Alzheimer's disease (AD) patients on AA. In 66 consecutive PD subjects started on AA who had accurate weights for more than 6 months before and after initiation of AA, we compared weight change before and after AA use, against a control group of sixty-one sex-matched PD subjects, and against twenty-eight AD subjects taking AA. A linear regression model was created to compare weight changes. Fifty-nine PD subjects had complete data, quetiapine (n=53) and clozapine (n=6). The mean BMI change in the period before starting AA was 0.00 kg/m(2)/month over 1.95+/-1.41 years. After starting AA, subjects lost 0.03 kg/m(2)/month (95% CI 0.62-1.21, P<0.0001), comparing PD before AA to the same PD patients after AA. In 61 PD controls, the mean BMI loss was 0.01 kg/m(2)/month (95% CI 0.15-0.94, P=0.007) comparing PD on AA vs. PD controls. The BMI for 28 AD subjects on AA increased 0.01 kg/m(2)/month (95% CI 0.26-0.83, P<0.0001), comparing PD on AA vs. AD on AA. The weight loss seen in the PD/AA group, compared to AD, suggest uniquely altered weight homeostasis in PD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Body Mass Index; Body Weight; Case-Control Studies; Clozapine; Confidence Intervals; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Odds Ratio; Parkinson Disease; Quetiapine Fumarate

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

Topics: Alzheimer Disease; Antipsychotic Agents; Clozapine; Dibenzothiazepines; Humans; Mental Disorders; Quetiapine Fumarate

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

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: Alzheimer Disease; Antipsychotic Agents; Cholinesterase Inhibitors; Dementia; Dibenzothiazepines; Humans; Phenylcarbamates; Practice Guidelines as Topic; Quetiapine Fumarate; Rivastigmine; Withholding Treatment

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

Quetiapine, an atypical antipsychotic, is effective for psychosis in younger patients, with limited adverse effects reported. This open-label naturalistic study was conducted to assess the 4-week efficacy and safety of quetiapine for treatment of geriatric psychosis. Clinical efficacy was evaluated using the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression Improvement (CGI-I) instruments before and after 4 weeks of quetiapine treatment. The sample population consisted of 100 geropsychiatric inpatients with psychosis, with the therapeutic evaluation completed by 91. Eighty-one of these 91 patients (89.0%) experienced mild-to-substantial improvement, as determined from the CGI-I. Further, a mean reduction in BPRS score of 39.5% (from baseline) was also determined. The mean daily dose of quetiapine for the fourth week was 276.1 177.2mg/day (range 50-800). Higher quetiapine dosages were administered for patients with functional psychoses compared to an analogous group with organic mental disorders. The most common adverse effects were somnolence (30.0%), lower-limb weakness (28.0%) and dizziness (27.0%). Body weight and fasting triglyceride were significantly elevated after quetiapine treatment (2.2% and 8.9% from baseline, respectively). Based on the results of this study, it appears that quetiapine is an efficacious and safe treatment for geriatric inpatients with psychosis, however, there is a wide dosing range and optimal dosage is diagnosis-dependent.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Brief Psychiatric Rating Scale; Delusions; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Geriatric Assessment; Humans; Male; Mood Disorders; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; 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

To report a case of seizures in a patient with Alzheimer disease, who was receiving quetiapine for psychoses.. A 75-year-old white man with Alzheimer disease was observed to have seizures while receiving quetiapine 500 mg/d and carbamazepine 200 mg/d. He had been taking quetiapine for 18 months prior to the event. No other toxic, metabolic, or anatomic abnormalities were identified to explain the seizures. After cessation of quetiapine treatment, the patient remained seizure free. An objective causality assessment revealed that the adverse drug reaction was possible.. The patient was taking a relatively high dose of quetiapine. An increased risk of seizures has been associated with Alzheimer disease. Using a relatively high dose of quetiapine may have resulted in seizures in our patient with Alzheimer disease.. As with other antipsychotics, quetiapine should be used cautiously in elderly patients with conditions that can lower the seizure threshold, and special monitoring should be performed for this serious adverse effect.

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Carbamazepine; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Male; Psychotic Disorders; Quetiapine Fumarate; Seizures

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Cost of Illness; Dibenzothiazepines; Humans; Nursing Homes; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; United States

Neuroleptic malignant syndrome (NMS) is an uncommon but potentially life-threatening adverse effect associated with conventional antipsychotic agents. The syndrome is characterized by muscular rigidity, hyperpyrexia, altered consciousness, and autonomic dysfunction. Few cases of quetiapine-induced NMS have been reported. A 54-year-old man was unsuccessfully challenged with quetiapine after conventional antipsychotic-induced NMS.

Topics: Alzheimer Disease; Antipsychotic Agents; Chlorpromazine; Dibenzothiazepines; Haloperidol; Humans; Hyperthyroidism; Lorazepam; Male; Middle Aged; Neuroleptic Malignant Syndrome; Psychomotor Agitation; Quetiapine Fumarate

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