quetiapine-fumarate and Dementia

Neuropsychiatric symptoms affect most patients with dementia over the course of the disease. They include a wide variety of symptoms from apathy and depression to psychosis, irritability, impulsivity and agitation. These symptoms are associated with significant distress to the patient and caregivers, as well as more rapid progression of dementia, institutionalisation and higher mortality. The first-line management of the neuropsychiatric symptoms of dementia should be non-pharmacological. If medications are required, antipsychotics are commonly chosen. Second-generation antipsychotics such as risperidone, olanzapine, quetiapine and aripiprazole are prescribed more often than first-generation antipsychotics, such as haloperidol. The aim of this review is to provide an update on findings on adverse outcomes and clinical implications of antipsychotic use in dementia. These medications may increase mortality and can be associated with adverse events including pneumonia, cerebrovascular events, parkinsonian symptoms or higher rates of venous thromboembolism. Risks related to antipsychotic use in dementia are moderated by a number of modifiable and non-modifiable factors such as co-prescribing of other medications, medical and psychiatric co-morbidities, and demographics such as age and sex, making individualised treatment decisions challenging. Antipsychotics have further been associated with an increased risk of reliance on long-term care and institutionalisation, and they might not be cost-effective for healthcare systems. Many of these risks can potentially be mitigated by close physical health monitoring of antipsychotic treatment, as well as early withdrawal of pharmacotherapy when clinically possible.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Dementia; Humans; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone

Dementia-related psychosis (DRP) is characterized by hallucinations and delusions, which may increase the debilitating effects of underlying dementia. This network meta-analysis (NMA) evaluated the comparative efficacy, safety, and acceptability of atypical antipsychotics (AAPs) commonly used off label to treat DRP.. We included 22 eligible studies from a systematic literature review of AAPs (quetiapine, risperidone, olanzapine, aripiprazole, and brexpiprazole) used off label to treat DRP. Study outcomes were: (1) efficacy-neuropsychiatric inventory-nursing home (NPI-NH psychosis subscale), (2) safety-mortality, cerebrovascular events (CVAEs), and others (somnolence, falls, fractures, injuries, etc.), and (3) acceptability-discontinuations due to all causes, lack of efficacy, and adverse events (AEs). We used random-effects modeling to estimate pooled standardized mean differences (SMDs) for NPI-NH psychosis subscale scores and odds ratios (OR) for other dichotomous outcomes, with their respective 95% confidence intervals (CIs).. Compared with placebo, aripiprazole (SMD - 0.12; 95% CI - 0.31, 0.06), and olanzapine (SMD - 0.17; 95% CI - 0.04; 0.02) demonstrated small, non-significant numerical improvements in NPI-NH psychosis scores (5 studies; n = 1891), while quetiapine (SMD 0.04; 95% CI - 0.23, 0.32) did not improve symptoms. The odds of mortality (15 studies, n = 4989) were higher for aripiprazole (OR 1.58; 95% CI 0.62, 4.04), brexpiprazole (OR 2.22; 95% CI 0.30, 16.56), olanzapine (OR 2.21; 95% CI 0.84, 5.85), quetiapine (OR 1.68; 95% CI 0.70, 4.03), and risperidone (OR 1.63; 95% CI 0.93, 2.85) than for placebo. Risperidone (OR 3.68; 95% CI 1.68, 8.95) and olanzapine (OR 4.47; 95% CI 1.36, 14.69) demonstrated significantly greater odds of CVAEs compared to placebo. Compared with placebo, odds of all-cause discontinuation were significantly lower for aripiprazole (OR 0.71; 95% CI 0.51, 0.98; 20 studies; 5744 patients) and higher for other AAPs. Aripiprazole (OR 0.5; 95% CI 0.31, 0.82) and olanzapine (OR 0.48; 95% CI 0.31, 0.74) had significantly lower odds of discontinuation due to lack of efficacy (OR 12 studies; n = 4382) compared to placebo, while results for quetiapine and risperidone were not significant. Compared with placebo, the odds of discontinuation due to AEs (19 studies, n = 5445) were higher for olanzapine (OR 2.62; 95% CI 1.75, 3.92), brexpiprazole (OR 1.80; 95% CI 0.80, 4.07), quetiapine (OR 1.25; 95% CI 0.82, 1.91), aripiprazole (OR 1.38; 95% CI 0.90, 2.13), and risperidone (OR 1.41; 95% CI 1.02, 1.94).. Overall results demonstrate that, compared with placebo, quetiapine is not associated with improvement in psychosis in patients with dementia, while olanzapine and aripiprazole have non-significant small numerical improvements. These off-label AAPs (quetiapine, risperidone, olanzapine, aripiprazole, and brexpiprazole) are associated with greater odds of mortality, CVAEs, and discontinuations due to AEs than placebo. These results underscore the ongoing unmet need for newer pharmacological options with a more favorable benefit-risk profile for the treatment of DRP.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dementia; Humans; Network Meta-Analysis; Off-Label Use; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Dementia; Diagnosis, Differential; HIV Infections; Humans; Male; Quetiapine Fumarate

Behavioral and psychological symptoms of dementia pose management challenges for caregivers and clinicians. Firstline nonpharmacologic treatments include eliminating physical and emotional stressors, modifying the patient's environment, and establishing daily routines. Family members and caregivers benefit from education about dementia symptoms and reminders that the behaviors are normal and unintentional. Cognitive and emotion-oriented interventions, sensory stimulation interventions, behavior management techniques, and other psychosocial interventions are modestly effective. In refractory cases, physicians may choose to prescribe off-label antipsychotics. Aripiprazole has the most consistent evidence of symptom improvement; however, this improvement is small. Olanzapine, quetiapine, and risperidone have inconsistent evidence of benefit. Physicians should use the smallest effective dose for the shortest possible duration to minimize adverse effects, most notably an increased mortality risk. Other adverse effects include anticholinergic and antidopaminergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, postural hypotension, metabolic syndrome, cardiac arrhythmia, and sedation. Patients should be monitored for these effects while receiving treatment; however, laboratory monitoring may be limited to patients receiving long-term therapy.

Topics: Antipsychotic Agents; Aripiprazole; Arrhythmias, Cardiac; Basal Ganglia Diseases; Behavior Therapy; Benzodiazepines; Cognitive Behavioral Therapy; Dementia; Emotions; Humans; Hypotension, Orthostatic; Metabolic Syndrome; Neuroleptic Malignant Syndrome; Olanzapine; Practice Guidelines as Topic; Psychotic Disorders; Quetiapine Fumarate; Risperidone

Topics: Aged; Anticonvulsants; Antipsychotic Agents; Dementia; Epilepsy, Absence; Female; Follow-Up Studies; Humans; Phenytoin; Quetiapine Fumarate; Rare Diseases; Risk Assessment; Severity of Illness Index; Treatment Outcome; Valproic Acid

Quetiapine (Seroquel(®)) is a potent U.S. Food and Drug Administration (FDA)-approved antipsychotic agent that has been used extensively for off-label indications. The current study was performed to ascertain the efficacy of some of the most prevalent off-label uses of this agent. An extensive search of electronic databases was completed using the search terms quetiapine or Seroquel, off-label and anxiety, substance abuse, dementia, delirium, personality disorder, insomnia, and sleep. Data were predictably mixed according to the indication being examined. The strongest evidence exists for anxiety and delirium. Moderate evidence exists for quetiapine as a pharmacological intervention for insomnia, dementia, and specific personality disorders. Evidence for quetiapine as a treatment for substance abuse is limited. More data are needed to establish specific dosing regimens for off-label uses and to examine the dose relationship to metabolic side effects and extrapyramidal side effects to determine whether various off-label uses justify the risk incurred with using this powerful drug.

Topics: Antipsychotic Agents; Anxiety Disorders; Delirium; Dementia; Dibenzothiazepines; Humans; Mental Disorders; Off-Label Use; Personality Disorders; Quetiapine Fumarate; Sleep Initiation and Maintenance Disorders; Substance-Related Disorders; Treatment Outcome

This meta-analysis is aimed to determine the efficacy of quetiapine for the treatment of behavioural and psychological symptoms of dementia (BPSD).. Our electronic search included MEDLINE (1950-2009), Cochrane Central Register of Controlled Trials and PsychINFO. We also did a hand search of the International Psychogeriatric Association poster presentations and checked the National trial registry data bases from USA, UK, RSA, Holland, Australia and New Zealand. We included double-blinded randomised placebo-controlled trials studies that measured BPSD with the Neuropsychiatric Inventory (NPI). The Clinical Global Impression of Change scale (CGI-C) was our secondary outcome.. Six sets of data were included in this meta-analysis. Patients receiving quetiapine improved when compared to placebo with a weighted mean difference of - 3.05 (95% CI: -6.10, -0.01) and -0.31 (95% CI: -0.54, -0.08) respectively on the NPI score and CGI-C score.. This meta-analysis found that quetiapine is statistically more efficacious than placebo in the treatment of BPSD as measured by the NPI and CGI-C. However, improvement is of a small magnitude and observable clinical significance is questionable.

Topics: Antipsychotic Agents; Behavior; Dementia; Dibenzothiazepines; Humans; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Hallucinations and psychosis are common in patients with Parkinson's disease (PD), with reported prevalences of up to 48% and 80%, respectively. However, few randomized, double-blind, placebo-controlled trials evaluating the treatment options have appeared in the literature. The studies that have been published were complicated by lack of agreement on the diagnosis of psychosis in PD, poor completion rates, mixed populations that included dementia, and other issues. Several reviews, guidelines, and consensus statements have sought to establish standards for treating these symptoms of PD. In 2006, the American Academy of Neurology (AAN) published a practice guideline (based on articles published up to 2004) for management of depression, psychosis, and dementia in patients with PD. Since then, a number of relevant studies have been published.. The purpose of this article was to review data that have appeared in the literature since publication of the AAN guideline regarding the management of hallucinations and psychosis in PD.. A literature search of the PubMed, CINAHL, and PsychInfo databases was conducted for human studies published in English from January 2004 to June 2010. All clinical studies were included except case reports and case series. Studies with <20 participants were also excluded. Search terms included psychosis, hallucinosis, hallucination, delusion, Parkinson, atypical antipsychotic, neuroleptic, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone.. Thirteen studies were included in the review: 3 studies of clozapine, 7 studies of quetiapine, 2 head-to-head trials comparing quetiapine and clozapine, and 1 noncomparative trial of clozapine or quetiapine interventions. Most of the studies included participants with a mean age in the early to mid 70s and a mean duration of PD typically >10 years.. Results of the identified studies suggested that patients with PD might benefit from long-term clozapine therapy. Results of the quetiapine studies were conflicting. However, no statistically significant difference in effectiveness was found between quetiapine and clozapine in comparative trials. The significance of the differences in treatment responses between patients with dementia and those without dementia remains unclear, and it was not possible to draw conclusions for or against other atypical antipsychotics because of insufficient evidence. Further studies are needed to address the methodologic issues in the current trials and to assess safety issues in larger cohorts.

Topics: Aged; Antipsychotic Agents; Brief Psychiatric Rating Scale; Clozapine; Comorbidity; Delusions; Dementia; Depression; Dibenzothiazepines; Disease Progression; Guidelines as Topic; Hallucinations; Humans; Middle Aged; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Research Report; Risperidone

The objective of the present study is to systematically review the supporting evidence for the use of antipsychotics in the treatment of behavioral and psychological symptoms in patients with dementia, as well as the controversies and limitations of this prescription. We discuss the available evidence in the light of the high prevalence of behavioral and psychological symptoms of dementia in this population, along with the greater susceptibility of elderly patients to adverse events.. Systematic literature review of the use of typical and atypical antipsychotics in patients with dementia was carried out in the databases PubMed/Medline, Embase and SciELO. The search was limited to clinical trials and meta-analysis of the literature published from 1986 to 2007.. Evidence drawn from randomized, double-blind, placebo controlled trials support the use of both typical and atypical antipsychotics in the treatment of behavioral symptoms of dementia, especially psychotic symptoms and abnormal psychomotor activity. Nevertheless, the use of these drugs in demented patients is not devoid of important adverse events. Although the induction of extrapyramidal symptoms is not as frequent or severe with atypical antipsychotics as it is with first-generation neuroleptics, the former drugs may particularly increase the risk of cerebrovascular events and death.. Although effective, antipsychotic drugs must be prescribed cautiously in patients with dementia. Dose regimens, duration of treatment and a cautious assessment of risk-benefit must be established for each patient.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Cerebrovascular Disorders; Dementia; Dementia, Vascular; Dibenzothiazepines; Double-Blind Method; Evidence-Based Medicine; Haloperidol; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Treatment Outcome

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Behavioral Symptoms; Benzodiazepines; Dementia; Dibenzothiazepines; Drug Approval; Humans; Mental Disorders; Olanzapine; Quetiapine Fumarate; Risk; Risperidone; United States; United States Food and Drug Administration

To review published reports of the usage of atypical antipsychotics for behavioural problems of dementia patients.. The electronic database Medline was searched from 1999 to 2006 with a combination of search terms including 'behavioural problems' and 'atypical antipsychotics'.. Thirteen eligible studies were included in the overall analysis. The total number of participants was 1,683, of whom 1,015 received medication and 668 received placebo. Medications studied were risperidone, olanzapine, and quetiapine. Other studies examined other types of medications, such as typical versus atypical antipsychotics, but only data for atypical antipsychotics were included in the meta-analysis. The mean effect size for 7 placebo-controlled studies was 0.45 (95% CI = 0.16-0.74) for atypical antipsychotics, and 0.32 (95% CI = 0.10-0.53) for placebo. The mean effect size of all 13 studies included in the analysis was 0.31 (95% CI = 0.08-0.54).. In general, effect sizes of atypical antipsychotics for behavioural problems are medium, and there are no statistically or clinically significant differences between atypical antipsychotics and placebo.

Topics: Antipsychotic Agents; Benzodiazepines; Controlled Clinical Trials as Topic; Dementia; Dibenzothiazepines; Follow-Up Studies; Humans; Mental Disorders; Olanzapine; Quetiapine Fumarate; 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

To review practical evidence-based treatment of behavioural symptoms in dementia. SOURCES OF INFORMATION MEDLINE: Was searched from January 1966 to December 2004 and PsycINFO from January 1967 to December 2004 using the key words "BPSD" (behavioural and psychological symptoms of dementia) and "behavioral disturbances dementia." I also reviewed the bibliographies of recent review papers and original articles.. Family physicians who manage hospital inpatients and care for people in nursing homes are asked to prescribe medications for demented patients. This review discusses alternatives to drugs, indications for appropriate use of drugs, frequently encountered side effects of drugs, and considerations for those with neuroleptic sensitivity. I suggest an approach that employs a combination of behavioural, environmental, and pharmacologic interventions to address disruptive behaviour in patients with dementia.. Optimal treatment of behavioural disturbances in patients with dementia involves nonpharmacologic approaches and using medications with demonstrated efficacy. Pharmacologic treatment should target only those symptoms or behaviours that respond to medication. This approach minimizes unnecessary medication use and reduces adverse outcomes.

Topics: Aged; Antipsychotic Agents; Behavior Therapy; Dementia; Dibenzothiazepines; Environment; Humans; Male; Psychotic Disorders; Psychotropic Drugs; Quetiapine Fumarate

Pharmacotherapy in patients with dementia aims to improve distressing behavioral and psychological signs of dementia after nonpharmacologic interventions fail, without causing unacceptable side effects or exacerbating underlying cognitive impairment. We review data describing risperidone (3 published placebo-controlled trials), olanzapine (1 abstract regarding a placebo-controlled trial and a published placebo-controlled trial), quetiapine (1 published open-label trial and an abstract regarding a placebo-controlled trial), and aripiprazole (1 abstract regarding a placebo-controlled trial). For example, a 12-week study of risperidone in patients with Alzheimer's disease showed a dose-related improvement in psychosis and agitation. The frequency of extrapyramidal symptoms (EPS) was also significantly greater in patients receiving the highest doses. A 6-week study of olanzapine showed greater improvement than placebo in agitation/aggression and psychosis with doses of 5 and 10 mg/day, but not 15 mg/day, with side effects including gait disturbance and sedation at all doses. A 52-week, open-label trial of quetiapine (median dose = 138 mg/day) in elderly patients with psychosis suggested good tolerability with apparent behavioral benefit; EPS improved or remained unchanged in most patients. Limited data describing aripiprazole have shown inconclusive evidence regarding relief of psychosis in elderly patients with Alzheimer's disease-related dementia, with apparently good tolerability over the short term. It appears that, in the aggregate, atypical antipsychotics are efficacious for treatment of agitation in dementia, with less clear impact on psychosis, but their tolerability profiles clearly differ. The National Institute of Mental Health-funded Clinical Antipsychotic Trials of Intervention Effectiveness in Alzheimer's Disease project will provide the first head-to-head comparisons of atypicals in dementia and will examine possible drug-drug differences between efficacy and effectiveness.

Topics: Aged; Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Brief Psychiatric Rating Scale; Controlled Clinical Trials as Topic; Dementia; Dibenzothiazepines; Humans; Mental Disorders; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Treatment Outcome

For any treatment, the impact on quality of life (QoL) is a key consideration. These issues are particularly important in the pharmacologic management of behavioral and psychological symptoms in patients with dementia (BPSD). Although these symptoms can be very distressing for some patients, the overall relationship of the symptoms with QoL is far less clear. In addition, although antipsychotic agents have moderate efficacy in the short- to medium-term management of these symptoms, it cannot be assumed that symptom resolution automatically equates with improved QoL. This is of particular concern in light of the adverse side effect profiles of many of these agents. Indeed, the only empirical study in this area conducted to date indicated that antipsychotics are associated with a worse QoL for nursing home patients. Unfortunately, none of the placebo-controlled trials of antipsychotics for the treatment of BPSD have included formal QoL measures, although preliminary evidence indicates that atypical antipsychotics such as quetiapine may result in QoL improvements. The inclusion of systematic QoL measures in future clinical trials is imperative in order to provide evidence to enable the clinician to make informed judgments regarding the potential benefits or risks of pharmacologic treatment for individual patients. In addition, such information will facilitate a better understanding of the likely factors that may contribute to the impact of treatment on QoL (e.g., side effects) and hence enable physicians to make rational treatment choices between different pharmacologic agents.

Topics: Aged; Antipsychotic Agents; Choice Behavior; Controlled Clinical Trials as Topic; Dementia; Dibenzothiazepines; Double-Blind Method; Homes for the Aged; Humans; Mental Disorders; Nursing Homes; Practice Patterns, Physicians'; Quality of Life; Quetiapine Fumarate; Risperidone; Treatment Outcome

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Controlled Clinical Trials as Topic; Dementia; Dibenzothiazepines; Humans; Olanzapine; Parkinson Disease; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles; Treatment Outcome

The use of antipsychotics is common in the elderly Typical antipsychotics are not without risk, especially in tardive dyskinesia, which, when balanced against relatively low efficacy, make their use debatable. Atypical antipsychotics have much less in the way of side-effects and are much less likely to induce tardive dyskinesia. However, there is much less in the published literature about the efficacy of these drugs in the elderly and how best to use them in primary psychosis, Parkinson's disease and the behavioural and psychological symptoms of dementia. This review attempts to summarise the current literature and make some tentative recommendations for each of the commonest atypicals, based on the current evidence.

Topics: Aged; Aged, 80 and over; Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Clozapine; Cognition; Dementia; Dibenzothiazepines; Female; Humans; Male; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone; United Kingdom

Behavioral problems associated with psychosis in the elderly have a significant negative impact on patients' quality of life and can lead to placement in a nursing home. Because of their decreased propensity to produce extrapyramidal symptoms, atypical antipsychotics such as quetiapine hold promise in the treatment of these vulnerable patients. Quetiapine may, in theory, be particularly advantageous in this regard because of its lack of anticholinergic activity and its relatively loose binding to dopamine receptors. This article reviews the somewhat limited number of clinical studies of the use of quetiapine in treating older patients with schizophrenia and other psychotic disorders, patients with psychosis associated with Alzheimer's disease or dementia with Lewy bodies, and patients with Parkinson's disease and drug-induced psychosis.

Topics: Age Factors; Aged; Antiparkinson Agents; Antipsychotic Agents; Basal Ganglia Diseases; Clinical Trials as Topic; Dementia; Dibenzothiazepines; Double-Blind Method; Humans; Parkinson Disease; Psychoses, Substance-Induced; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Schizophrenia; Treatment Outcome

The atypical antipsychotics have a low incidence of extrapyramidal side effects (EPS), have improved tardive dyskinesia profiles, and have a broad range of therapeutic efficacy. These agents offer important therapeutic advantages that extend beyond their initial regulatory approval in several conditions and patient groups. The use of atypical antipsychotics is most relevant in the treatment of mood disorders, where these medications are being used increasingly for acute mood stabilization and in patients who are resistant to other treatments. Similar circumstances and clinical advantages pertain to the use of atypical antipsychotics in the treatment of behavioral disturbances in patients with dementia and in the management of personality disorders-both circumstances where conventional antipsychotics were initially poorly tolerated because of EPS. The low incidence of EPS associated with atypical antipsychotics is highly beneficial in several neuropsychiatric conditions. The extent to which endocrine and metabolic dysregulations associated with atypical antipsychotics will influence antipsychotics' role remains to be determined. As therapeutic opportunities evolve and diversify, atypical antipsychotics, because of favorable adverse-effect profiles, will have enhanced patient tolerability and use in nonpsychiatric conditions.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Child; Child Development Disorders, Pervasive; Clozapine; Dementia; Dibenzothiazepines; Humans; Mood Disorders; Olanzapine; Personality Disorders; Pirenzepine; Quetiapine Fumarate; Risperidone

Elderly patients with schizophrenia and dementia patients with agitation are frequently candidates for antipsychotic treatment. Conventional neuroleptics have relatively little effect on negative symptoms and may cause considerable side effects, especially in elderly patients. The authors have found a 29% cumulative annual incidence of tardive dyskinesia (TD) in middle-aged and elderly outpatients treated with relatively low doses of conventional neuroleptics Newer antipsychotics are less likely to cause extrapyramidal symptoms and may be associated with a lower risk of TD. They are generally effective for both positive and negative symptoms and may also improve some aspects of cognition, but these drugs have their own side effects. Dosing requirements for elderly patients tend to be much lower than those for younger adults.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Dementia; Dibenzothiazepines; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

Atypical antipsychotics have become the treatment of choice for patients experiencing a first episode of schizophrenia. In addition, they are often prescribed for conditions such as bipolar disorder and dementia. While clinical trials have not yet established the efficacy of the atypical antipsychotics for these uses, a number of reports offer preliminary evidence that the atypical antipsychotics may be beneficial for affective disorders, substance abuse disorder, senile dementia, and pathologic aggression. Atypical agents may be particularly effective and tolerable in elderly patients who are especially susceptible to the adverse effects of conventional antipsychotic medication. Lower dosages are more necessary for the elderly than for younger adults. Current evidence suggests that clozapine is the most effective atypical antipsychotic for neuroleptic-resistant patients. Risperidone, olanzapine, and quetiapine may also be effective in a subset of these patients.

Topics: Adult; Age Factors; Aged; Algorithms; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Clozapine; Decision Trees; Dementia; Dibenzothiazepines; Female; Humans; Male; Mood Disorders; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone; Schizophrenia

Topics: Antipsychotic Agents; Central Nervous System Stimulants; Cross-Over Studies; Dementia; Dextroamphetamine; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Humans; Neuropsychological Tests; Quetiapine Fumarate

In this 10-week, double-blind, fixed-dose study, elderly institutionalized patients with dementia and agitation were randomized (3:3:2) to quetiapine 200mg/day, 100mg/day, or placebo. The primary endpoint was change in Positive and Negative Syndrome Scale (PANSS)-Excitement Component (EC) scores at endpoint, analysed using last observation carried forward (LOCF) and observed cases (OC) approaches. Other efficacy measures were the Clinical Global Impression of Change (CGI-C), and response rates (percentage with > or =40% reduction [PANSS-EC]; "much" or "very much improved" [CGI-C]), Neuropsychiatric Inventory-Nursing Home version (NPI-NH), and Cohen-Mansfield Agitation Inventory (CMAI). The key safety measure was incidence of adverse events; change in Mini-Mental State Examination (MMSE) was also assessed. Baseline characteristics of 333 participants (quetiapine 200mg/day, n=117; quetiapine 100mg/day, n=124; placebo, n=92) and completion rates (63-65%) were comparable among groups. Compared with placebo, quetiapine 200mg/day was associated with clinically greater improvements in PANSS-EC (LOCF, p=0.065; OC, p=0.014 [ANCOVA]), CGI-C (LOCF, p=0.017; OC, p=0.002 [ANOVA]), and CGI-C response rates (LOCF, p=0.002; OC, p<0.001 [Chi-square test]). Quetiapine 100mg/day did not differentiate from placebo on these measures. There were no between-group differences in NPI-NH or CMAI. Incidences of cerebrovascular adverse events, postural hypotension, and falls were similar among groups. MMSE did not change in any group. Mortality was numerically higher in the quetiapine groups; rates were not statistically different from placebo. The results of this study suggest that quetiapine 200mg/day was effective and well-tolerated for treating agitation associated with dementia. However, caution should be exercised given the concerns regarding increased mortality with atypical antipsychotics in this vulnerable patient population.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Antipsychotic Agents; Dementia; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Psychomotor Agitation; Quetiapine Fumarate; Retrospective Studies; 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

In this study we directly compared the efficacy and tolerability of the atypical antipsychotics quetiapine and risperidone in elderly patients with dementia and symptoms of disturbed perception, thought content, mood or behaviour (behavioural and psychological symptoms of dementia-BPSD).. We conducted an 8-week, rater-blinded, randomised study of 72 outpatients (55-85 years) with BPSD (assessed by NPI baseline score), who received flexibly-dosed quetiapine (50-400 mg/day) or risperidone (0.5-2 mg/day). Primary efficacy measure: Neuropsychiatric Inventory (NPI) Parts 1 and 2; secondary efficacy measures: Clinical Global Impression (CGI), Cohen-Mansfield Agitation Inventory (CMAI), Mini-Mental State Examination (MMSE), Age-adjusted concentration test (AKT). Safety evaluations included the incidence of extrapyramidal symptoms (EPS) and adverse events (AEs).. Sixty-nine of 72 patients were evaluable for efficacy (72 were evaluated for safety), 4 patients discontinued (3 due to AEs: quetiapine 2, risperidone 1; 1 lost to follow-up). Sixty-five patients received quetiapine (n=34; mean dose 77+/-40 mg/day) or risperidone (n=31; mean dose 0.9+/-0.3 mg/day). There was no significant difference between treatments on NPI scores; within treatment groups, NPI scores decreased significantly from baseline to Week 8 (P

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Dementia; Dibenzothiazepines; Female; Humans; Male; Mental Disorders; Mental Status Schedule; Middle Aged; Mood Disorders; Neuropsychological Tests; Perceptual Disorders; Quetiapine Fumarate; Risperidone; Single-Blind Method; Thinking; Treatment Outcome

We studied the effect of quetiapine in drug induced psychosis (DIP) in Parkinson's disease (PD) patients with dementia (PDDEM) and without dementia (PDNODEM) in a 6-month open study.. Thirty five consecutive PD patients with DIP (19 of them demented [DSMIV criteria]) were examined. Assessment included Mini-Mental State Examination (MMSE), UPDRS (motor part), Brief Psychiatric Rating Scale (BPRS), Clinical Global Improvement Scale (CGIS) and Hamilton test (for depression). Quetiapine was administered in a flexible dose 25-600 mg daily. Out of the 35 patients included in the study, 24 completed treatment with quetiapine (14 demented and 10 without dementia). Treatment was stopped in 11 patients (5 demented).. Intention to treat patient (ITT) analysis did not show a significant quetiapine effect (BPRS), although in about 30% a good outcome was reported by the family (CGIS). Among the patients who completed the study (n = 24), in the PDNODEM group (n = 10) BPRS improved almost significantly (p = 0.06) while in the PDDEM group the BPRS did not change. According to the CGIS, a good improvement was observed in 50% of the PDDEM group (7/14) and 40% of the PDNODEM group (4/10). Motor features of PD patients worsened mildly (p = 0.05) in the PDDEM group.. In this open trial, quetiapine was not beneficial in the ITT group using the BPRS, although families reported improvement in about 30% of patients (CGIS). Among patients who completed the study, quetiapine was more effective in the PDNODEM group. A double blind study with quetiapine is required.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Brief Psychiatric Rating Scale; Dementia; Dibenzothiazepines; Female; Humans; Male; Neuropsychological Tests; Parkinson Disease; Psychoses, Substance-Induced; Quetiapine Fumarate; Treatment Outcome

Parkinson disease (PD) psychosis (PDP) is a disabling non-motor symptom. Pharmacologic treatment is limited to pimavanserin, quetiapine, and clozapine, which do not worsen parkinsonism. A Food and Drug Administration black box warning exists for antipsychotics, suggesting increased mortality in elderly patients with dementia. However, the reasons for higher mortality are unknown.. Expanding on prior work exploring mortality in treated PDP patients, we conducted a retrospective comparison to understand the links between treatment regimen, clinical characteristics, and negative outcomes.. Electronic medical record data extraction included clinically diagnosed PD patients between 4/29/16-4/29/19 and excluded patients with primary psychiatric diagnoses or atypical parkinsonism. Mortality and clinical characteristics during the study period were compared between untreated patients and those receiving pimavanserin, quetiapine, or both agents (combination). Mortality analyses were adjusted for age, sex, levodopa equivalent daily dose (LEDD), and dementia.. The pimavanserin group (n = 34) had lower mortality than the untreated group (n = 66) (odds ratio = 0.171, 95% confidence interval: 0.025-0.676, p = 0.026). The untreated group had similar mortality compared to the quetiapine (n = 147) and combination (n = 68) groups. All treated groups had a higher LEDD compared to the untreated group, but no other differences in demographics, hospitalizations, medical comorbidities, medications, or laboratory values were found between the untreated and treated groups.. PDP patients receiving pimavanserin had lower mortality than untreated patients. We found no other clear differences in clinical characteristics to explain the mortality risk. Prospective randomized trials are needed to definitively identify the optimal PDP treatment regimen and associated risks.

Topics: Aged; Antipsychotic Agents; Dementia; Humans; Levodopa; Parkinson Disease; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Urea

Topics: Age of Onset; Aged; Anti-Anxiety Agents; Antipsychotic Agents; Aripiprazole; Dementia; Fluvoxamine; Humans; Male; Obsessive-Compulsive Disorder; Psychiatric Status Rating Scales; Quetiapine Fumarate; Self-Injurious Behavior; Tomography, Emission-Computed, Single-Photon

Behavioral and psychological symptoms of dementia are commonly treated with antipsychotic drugs (APDs), which have been associated with adverse health effects. We examine the effect of APDs on long-term care (LTC), nursing home (NH) admission, and death of dementia patients.. We used health claims data of the largest German health insurer from 2004 to 2010 and followed newly-diagnosed dementia patients aged 60 years and older into LTC, NH, and until death. Cox proportional hazards models were estimated to explore whether the risk of these outcomes differed between patients receiving haloperidol, melperone, risperidone, or quetiapine.. In a cohort of 6,930 dementia patients who were initially free of LTC dependency, APD users generally faced a twofold increased risk of LTC relative to nonusers. Quetiapine was the exception, showing a comparatively lower risk (HR = 1.64; CI = 1.35-1.98). Among 9,950 dementia patients initially living in private homes, the risk of moving into a NH was generally increased by about 50% among APD users relative to nonusers. Risk of death (N = 10,921) was significantly higher for haloperidol-, melperone-, and risperidone- but not for quetiapine users (HR = 0.91; CI = 0.78-1.08). The excess mortality associated with haloperidol and melperone was greater among patients living in private households.. In our study, APDs appeared to accelerate adverse health outcomes in German dementia patients. Differentiating between the effect of antipsychotic drug use among dementia patients residing in private households and in NHs, we found that excess mortality for haloperidol and melperone users was higher in private settings.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Butyrophenones; Cohort Studies; Dementia; Female; Germany; Haloperidol; Homes for the Aged; Humans; Institutionalization; Long-Term Care; Male; Middle Aged; Nursing Homes; Proportional Hazards Models; Quetiapine Fumarate; Risk Factors; Risperidone

In the absence of suitable oral or intravenous access for medication administration and when the intramuscular medications are undesirable, alternative routes for drug delivery may be considered. Antipsychotics administered via an inhaled, intranasal, rectal, or topical route have been described in the literature. Topically administered antipsychotics have been previously reported to produce negligible systemic absorption despite being used in clinical practice for nausea and behavioral symptoms associated with dementia. Additionally, the American Academy of Hospice and Palliative Medicine recommends against the use of topical medications that lack supporting literature. Three studies have assessed the systemic absorption of different antipsychotics after administration of only a single, topically applied dose. To evaluate whether the repeated administration of a topically applied antipsychotic may result in detectable serum levels in an accumulating fashion, a pharmacokinetic study was conducted. Five healthy, adult participants consented to receive extemporaneously prepared topical quetiapine in Lipoderm every 4 hours for a total of 5 doses. Blood samples were drawn at baseline and hours 2, 4, 8, 12, 16, and 24, and serum quetiapine concentrations were measured using high-performance liquid chromatography. Quetiapine was undetectable in every sample from 3 participants. Two participants had minimally detectable serum quetiapine levels no sooner than hour 12 of the study period. Extemporaneously prepared quetiapine in Lipoderm resulted in nonexistent or minimal serum level following repeated topical administration. The use of topically applied quetiapine should still be questioned.

Topics: Administration, Cutaneous; Adult; Antipsychotic Agents; Dementia; Drug Delivery Systems; Female; Humans; Male; Middle Aged; Quetiapine Fumarate

This study was to investigate the prescribing patterns for antipsychotic drugs in elderly hospitalized patients with a diagnosis of schizophrenia or dementia at a psychiatric hospital in Taiwan from 2007 to 2012. This study also explored the predictors of antipsychotic polypharmacy (APP).. We collected patients' demographic data, including year of admission, age, gender, and length of hospital stay, and drug-related information.. Second-generation antipsychotic (SGA) monotherapy was the most common type of therapy in both those with dementia and with schizophrenia, and quetiapine and risperidone were the most commonly prescribed drugs for these conditions, respectively. In late-life schizophrenia, 33.8% of the patients used first-generation antipsychotics (FGA) alone. Regarding APP, a combination of FGA and SGA and combinations of SGA were most commonly noted in schizophrenia patients and dementia patients, respectively. Overall, APP increased from 2007 to 2012. It was significantly more common in patients with dementia (odds ratio: 3.49, 95% confidence interval: 1.29-9.39, P = 0.014), less concurrent use of hypnotics and sedatives (odds ratio: 0.41, 95% confidence interval: 0.17-0.99, P = 0.046), and a higher-than-recommended dose of antipsychotic drugs (odds ratio: 4.98, 95% confidence interval: 2.75-9.02, P < 0.001).. FGA are still commonly used for the late-life schizophrenia at our hospital. Given their potentially hazardous side effects, FGA must be employed with caution. The use of APP involving SGA increased over the 6 years of the study period, especially among patients with dementia. However, the use of SGA in dementia began to decline after the US Food and Drug Administration's 2005 warning about SGA being associated with increased mortality in dementia patients, which contrasts with the trends examined in this study. Further controlled trials exploring the efficacy, safety, and tolerability of APP in this population are warranted to gain an additional insight into this practice.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Dementia; Drug Therapy, Combination; Female; Hospitalization; Hospitals, Psychiatric; Humans; Male; Middle Aged; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Taiwan

The USA Food and Drug Administration (FDA) issued warnings regarding the use of antipsychotics in patients with dementia in 2003 and 2005. We aimed to study the dose and duration of antipsychotic treatment in dementia, and to examine whether physicians' prescription behaviors changed after the FDA warnings.. Medical charts of outpatients who had Alzheimer's disease, vascular dementia, or mixed dementia were reviewed. Patients must have achieved a clinically stable state for at least 4 weeks after receiving antipsychotic treatment for agitation or psychosis. Demographics, clinical correlates, and duration of antipsychotic treatment were compared among different antipsychotic groups. Because the quetiapine group had the largest sample size, the optimal dose and duration of quetiapine treatment were compared among three time periods (before 2003, 2003-2005, after 2005).. Stable state was achieved in 215 patients (80 had Alzheimer's disease, 117 vascular dementia, and 18 mixed dementia). Most patients (177) took quetiapine, 25 took risperidone, and 13 took sulpiride. The whole sample had a long total duration of antipsychotic treatment (median 525 days, mean 707 days). The median dose and total duration of antipsychotic treatment were 1.0mg/day and 238 days for risperidone, 100mg/day and 390 days for sulpiride, and 25mg/day and 611 days for quetiapine, respectively. The optimal dose and total duration of quetiapine treatment decreased significantly after FDA warning in 2005, although the duration remained long.. The optimal doses of antipsychotics were not higher than those of western reports, but the total duration of antipsychotic treatment was quite long. Although our study suggests the prescription dosage and duration of antipsychotic treatment decreased significantly after FDA warning in 2005, the duration of treatment was still long. Given the serious safety concerns, more effort should be made to avoid unnecessary and prolonged prescription.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Dementia; Female; Humans; Male; Middle Aged; Outpatients; Psychomotor Agitation; Quetiapine Fumarate; Retrospective Studies; Risperidone; Severity of Illness Index; Sulpiride; Taiwan; Treatment Outcome

Prescribing practice patterns and factors associated with treatment changes in older patients initiating antipsychotic treatment for the behavioral and psychological symptoms of dementia is not well known.. The objective of this study is to study 90-day prescribing practice patterns across the three most commonly prescribed antipsychotics.. This is a retrospective study using national data from the US Department of Veterans Affairs (VA). The study included patients older than 65 years diagnosed with dementia who began outpatient treatment with an antipsychotic medication between 2005 and 2008. Patients were followed for 90 days from their antipsychotic start. The primary event of interest was changing to another psychotropic medication. Cumulative incidence of treatment change was determined with antipsychotic discontinuation and death as competing risks. Covariate-adjusted hazard ratios for treatment change were determined using competing risk regression models.. During the study period, 15,435 patients initiated an atypical antipsychotic; 14,791 started olanzapine, quetiapine, or risperidone. Over half (55%) of the patients discontinued index treatment within 90 days, 36% continued, 3% died while on index treatment, and 6% changed to another psychotropic medication. Compared with quetiapine, the adjusted hazard of treatment change was higher by 43% (p = 0.005) for olanzapine and by 12% (p = 0.08) for risperidone.. The higher hazard of treatment change with olanzapine suggests patients either responded worse to or experienced more adverse events with olanzapine compared with quetiapine.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Dementia; Follow-Up Studies; Humans; Male; Olanzapine; Practice Patterns, Physicians'; Quetiapine Fumarate; Retrospective Studies; Risperidone; United States

Antipsychotic medications are associated with increased mortality in older adults with dementia, yet their absolute effect on risk relative to no treatment or an alternative psychotropic is unclear.. To determine the absolute mortality risk increase and number needed to harm (NNH) (ie, number of patients who receive treatment that would be associated with 1 death) of antipsychotic, valproic acid and its derivatives, and antidepressant use in patients with dementia relative to either no treatment or antidepressant treatment.. A retrospective case-control study was conducted in the Veterans Health Administration from October 1, 1998, through September 30, 2009. Participants included 90,786 patients 65 years or older with a diagnosis of dementia. Final analyses were conducted in August 2014.. A new prescription for an antipsychotic (haloperidol, olanzapine, quetiapine, and risperidone), valproic acid and its derivatives, or an antidepressant (46,008 medication users).. Absolute change in mortality risk and NNH over 180 days of follow-up in medication users compared with nonmedication users matched on several risk factors. Among patients in whom a treatment with medication was initiated, mortality risk associated with each agent was also compared using the antidepressant group as the reference, adjusting for age, sex, years with dementia, presence of delirium, and other clinical and demographic characteristics. Secondary analyses compared dose-adjusted absolute change in mortality risk for olanzapine, quetiapine, and risperidone.. Compared with respective matched nonusers, individuals receiving haloperidol had an increased mortality risk of 3.8% (95% CI, 1.0%-6.6%; P < .01) with an NNH of 26 (95% CI, 15-99); followed by risperidone, 3.7% (95% CI, 2.2%-5.3%; P < .01) with an NNH of 27 (95% CI, 19-46); olanzapine, 2.5% (95% CI, 0.3%-4.7%; P = .02) with an NNH of 40 (95% CI, 21-312); and quetiapine, 2.0% (95% CI, 0.7%-3.3%; P < .01) with an NNH of 50 (95% CI, 30-150). Compared with antidepressant users, mortality risk ranged from 12.3% (95% CI, 8.6%-16.0%; P < .01) with an NNH of 8 (95% CI, 6-12) for haloperidol users to 3.2% (95% CI, 1.6%-4.9%; P < .01) with an NNH of 31 (95% CI, 21-62) for quetiapine users. As a group, the atypical antipsychotics (olanzapine, quetiapine, and risperidone) showed a dose-response increase in mortality risk, with 3.5% greater mortality (95% CI, 0.5%-6.5%; P = .02) in the high-dose subgroup relative to the low-dose group. When compared directly with quetiapine, dose-adjusted mortality risk was increased with both risperidone (1.7%; 95% CI, 0.6%-2.8%; P = .003) and olanzapine (1.5%; 95% CI, 0.02%-3.0%; P = .047).. The absolute effect of antipsychotics on mortality in elderly patients with dementia may be higher than previously reported and increases with dose.

Topics: Aged; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Case-Control Studies; Dementia; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Psychotropic Drugs; Quetiapine Fumarate; Registries; Retrospective Studies; Risk; Risperidone; United States; Veterans

The aims of this study are to analyse, in community-dwelling people aged 65+ living in Italy's Lombardy Region, electrocardiographic (ECG) monitoring for new users of the atypical antipsychotic quetiapine co-prescribed with acetylcholinesterase inhibitors (AChEIs) or memantine and to find independent predictors of ECG monitoring before and after the starting of this prescription.. The Lombardy Region's administrative health database was used to retrieve prescriptions of ECG exams as well as prevalence rates of subjects aged 65+ who were prescribed such psychotropic drugs from 2005 to 2009. Multivariable analyses were adjusted for age, sex, number of drugs, treatment with beta-blockers, digoxin, verapamil or diltiazem, any antiarrhythmic drug and antidepressants.. Overall 2,623 community-dwelling older people started therapy with quetiapine, co-prescribed with AChEIs or memantine, during these 5 years. At least one ECG was performed in 714 cases (27.2 %) in the 6 months before-and in 398 cases (15.2 %) within 3 months after-the starting of this prescription. ECG monitoring was performed both before and after starting quetiapine in only 160 cases (6.1 %). At multivariable analyses, number of drugs taken, beta-blocker and antiarrhythmic drug use were found to be independent correlates of ECG monitoring whereas female sex was associated with a lower probability of receiving an ECG within 3 months after the initiation of quetiapine (odds ratio 0.78, 95 % CI 0.62-0.98).. ECG monitoring for new prescriptions of quetiapine in older people suffering from behavioural and psychological symptoms in dementia was actually performed infrequently, independently of the age of drug users, especially in women. Our results support the need for greater awareness within the medical community of the importance of such ECG monitoring.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Cholinesterase Inhibitors; Dementia; Dibenzothiazepines; Electrocardiography; Female; Humans; Italy; Male; Memantine; Quetiapine Fumarate

A recent large-scale randomized controlled clinical trial, the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease study, found a significant worsening of cognitive functioning in a sample of patients with Alzheimer's disease. To date there have been no equally powered studies examining the cognitive effects of atypical antipsychotics in patients with dementia with Lewy bodies, the second most prevalent neurodegenerative disorder. This case report describes a significant cognitive improvement observed through the use of an atypical antipsychotic in a patient with dementia with Lewy bodies. The observed divergence in cognitive responsiveness is discussed mechanistically on both the clinical and neuromolecular level. Limitations to this case study design are presented and discussed. The prudence of caution in importing the results of the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease study to the dementia with Lewy bodies population is summarized and presented for psychiatrists, neurologists and primary care providers, with an intent to stimulate discussion and further research.

Topics: Antipsychotic Agents; Cognition; Dementia; Dibenzothiazepines; Humans; Lewy Bodies; Lewy Body Disease; Male; Middle Aged; Quetiapine Fumarate; Treatment Outcome

Despite concerns over the potential for severe adverse events, antipsychotic medications remain the mainstay of treatment of behaviour disorders and psychosis in elderly patients. Second-generation antipsychotic agents (SGAs; e.g., risperidone, olanzapine, quetiapine) have generally shown a better safety profile compared to the first-generation agents (FGAs; e.g., haloperidol and phenothiazines), particularly in terms of a lower potential for involuntary movement disorders. Risperidone, the only SGA with an official indication for the management of inappropriate behaviour in dementia, has emerged as the antipsychotic most commonly prescribed to older patients. Most clinical trials evaluating the risk of movement disorders in elderly patients receiving antipsychotic therapy have been of limited sample size and/or of relatively short duration. A few observational studies have produced inconsistent results.. A population-based retrospective cohort study of all residents of the Canadian province of Manitoba aged 65 and over, who were dispensed antipsychotic medications for the first time during the time period from April 1, 2000 to March 31, 2007, was conducted using Manitoba's Department of Health's administrative databases. Cox proportional hazards models were used to determine the risk of extrapyramidal symptoms (EPS) in new users of risperidone compared to new users of FGAs.. After controlling for potential confounders (demographics, comorbidity and medication use), risperidone use was associated with a lower risk of EPS compared to FGAs at 30, 60, 90 and 180 days (adjusted hazard ratios [HR] 0.38, 95% CI: 0.22-0.67; 0.45, 95% CI: 0.28-0.73; 0.50, 95% CI: 0.33-0.77; 0.65, 95% CI: 0.45-0.94, respectively). At 360 days, the strength of the association weakened with an adjusted HR of 0.75, 95% CI: 0.54-1.05.. In a large population of elderly patients the use of risperidone was associated with a lower risk of EPS compared to FGAs.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Canada; Dementia; Dibenzothiazepines; Female; Humans; Male; Olanzapine; Phenothiazines; Proportional Hazards Models; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone

Topics: Aged; Anticoagulants; Antipsychotic Agents; Dementia; Dibenzothiazepines; Drug Therapy, Combination; Hemorrhage; Humans; International Normalized Ratio; Male; Quetiapine Fumarate; Venous Thrombosis; Warfarin

The use of antipsychotics to treat the behavioral symptoms of dementia is associated with greater mortality. The authors examined the mortality risk of individual agents to augment the limited information on individual antipsychotic risk.. The authors conducted a retrospective cohort study using national data from the U.S. Department of Veterans Affairs (fiscal years 1999-2008) for dementia patients age 65 and older who began outpatient treatment with an antipsychotic (risperidone, olanzapine, quetiapine, or haloperidol) or valproic acid and its derivatives (as a nonantipsychotic comparison). The total sample included 33,604 patients, and individual drug groups were compared for 180-day mortality rates. The authors analyzed the data using multivariate models and propensity adjustments.. In covariate-adjusted intent-to-treat analyses, haloperidol was associated with the highest mortality rates (relative risk=1.54, 95% confidence interval [CI]=1.38-1.73) followed by risperidone (reference), olanzapine (relative risk=0.99, 95% CI=0.89-1.10), valproic acid and its derivatives (relative risk=0.91, 95% CI=0.78-1.06), and quetiapine (relative risk=0.73, 95% CI=0.67-0.80). Propensity-stratified and propensity-weighted models as well as analyses controlling for site of care and medication dosage revealed similar patterns. The mortality risk with haloperidol was highest in the first 30 days but decreased significantly and sharply thereafter. Among the other agents, mortality risk differences were most significant in the first 120 days and declined in the subsequent 60 days during follow-up.. There may be differences in mortality risks among individual antipsychotic agents used for treating patients with dementia. The use of valproic acid and its derivatives as alternative agents to address the neuropsychiatric symptoms of dementia may carry associated risks as well.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Dementia; Dibenzothiazepines; Female; Haloperidol; Humans; Male; Olanzapine; Propensity Score; Quetiapine Fumarate; Retrospective Studies; Risk; Risperidone; Time Factors; Valproic Acid

To assess risks of mortality associated with use of individual antipsychotic drugs in elderly residents in nursing homes.. Population based cohort study with linked data from Medicaid, Medicare, the Minimum Data Set, the National Death Index, and a national assessment of nursing home quality.. Nursing homes in the United States.. 75,445 new users of antipsychotic drugs (haloperidol, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone). All participants were aged ≥ 65, were eligible for Medicaid, and lived in a nursing home in 2001-5.. Cox proportional hazards models were used to compare 180 day risks of all cause and cause specific mortality by individual drug, with propensity score adjustment to control for potential confounders.. Compared with risperidone, users of haloperidol had an increased risk of mortality (hazard ratio 2.07, 95% confidence interval 1.89 to 2.26) and users of quetiapine a decreased risk (0.81, 0.75 to 0.88). The effects were strongest shortly after the start of treatment, remained after adjustment for dose, and were seen for all causes of death examined. No clinically meaningful differences were observed for the other drugs. There was no evidence that the effect measure modification in those with dementia or behavioural disturbances. There was a dose-response relation for all drugs except quetiapine.. Though these findings cannot prove causality, and we cannot rule out the possibility of residual confounding, they provide more evidence of the risk of using these drugs in older patients, reinforcing the concept that they should not be used in the absence of clear need. The data suggest that the risk of mortality with these drugs is generally increased with higher doses and seems to be highest for haloperidol and least for quetiapine.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Cause of Death; Comorbidity; Dementia; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Epidemiologic Methods; Female; Haloperidol; Humans; Male; Medical Assistance; Mortality; Nursing Homes; Quetiapine Fumarate; Risperidone; United States

Differences between atypical antipsychotics in their potential to cause parkinsonism and risk factors for antipsychotic-induced parkinsonism are not well established. There is a particular paucity of information on this in real-world use of these drugs, outside of clinical trial settings.. We compared the incidence of parkinsonism after new treatment with risperidone, olanzapine, or quetiapine in patients with dementia and examined the effects of dose and sex on the risk of parkinsonism.. Administrative data from Ontario, Canada between 2002 and 2010 were used to compare the incidence of a diagnostic code for parkinsonism or prescription of an anti-Parkinson medication among patients with dementia who were newly prescribed quetiapine, olanzapine, or risperidone.. From 15,939 person-years of observation, 421 patients developed parkinsonism. Using low-dose risperidone as the reference group, the adjusted hazard ratios for developing parkinsonism were 0.49 (95% CI, 0.07-3.53) for low-dose olanzapine and 1.18 (95% CI, 0.84-1.66) for low-dose quetiapine. Comparing across drugs within the most commonly prescribed dose ranges, the incidence of parkinsonism was higher in the medium-dose olanzapine group compared with the low-dose risperidone group (hazard ratio 1.66; 95% CI 23-2.23). The adjusted hazard ratio for developing parkinsonism for men (compared with women) was 2.29 (95% CI, 1.88- 2.79).. We found no evidence that the risk of drug-induced parkinsonism in older adults with dementia was different among quetiapine, olanzapine, or risperidone, challenging the notion that the drugs differed in their propensity to cause parkinsonism. Men appeared to be at higher risk of parkinsonism as a adverse event than women.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cohort Studies; Dementia; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Incidence; Male; Olanzapine; Parkinson Disease, Secondary; Proportional Hazards Models; Quetiapine Fumarate; Retrospective Studies; Risk Factors; Risperidone; Sex Factors

The use of off-label atypical antipsychotic drugs (AA) has been noted for the treatment of behavior disorders in older patients affected by Alzheimer's or by other forms of dementia, even though effectiveness data are limited and use seems to be associated with severe cerebrovascular risks. The data concerning such risks caused the Italian Ministry of Health to release a statement discouraging doctors from prescribing olanzapine and risperidone outside of the registered indications, in May 2004. This study aimed to analyze the prescriptive profile of AAs in patients with dementia, in terms of the choice of active substance and of the clinical characteristics of the patients.. Patients with a diagnosis of dementia and in treatment with AA (risperidone, olanzapine, and quetiapine) were selected from three main Alzheimer Evaluation Centers (Geriatrics, Neurology, Internal Medicine) of the University Hospital in Ferrara, in the period 05/2003-04/2006. For each subject, the following information was collected: the frequency of prescriptions, the drug received, and the amount of AAs in the considered period. In the third year of observation, the intensity of treatment was evaluated (intense treatment: >300 tablets of any AA; weak treatment: <300 tablets of any AA or up to three packages of risperidone drops). Such data were analyzed in terms of the type of dementia, the behavioral disturbance, and the possible presence of psychomotor agitation. In addition, the adverse reactions that occurred during the treatment were gathered. Lastly, the use of acetylcholinesterase inhibitors among the selected subjects was described.. Among the 392 subjects (63% female), Alzheimer's (49%) was the most frequent form of dementia, hallucinations were present in 50% of the cases and aggression in 53%.The statement by the Ministry of Health resulted in a foreseeable increase in the consumption of quetiapine and a parallel decrease in risperidone and olanzapine; subsequently, the distribution among the drugs stabilized to similar percentages. The doses used for the control of behavioral disturbances during dementia were on average much lower than those for treating more severe psychoses. Among the patients followed in the third year of observation (n = 159), the number of subjects in intense treatment was greater than those in weak treatment (60 vs 40%). Olanzapine was the AA most frequently used in intense dosages. Among the patients in weak treatment, about 50% used risperidone, available as oral droplets. In the patients at the Geriatric Center (n = 174), in the initial period of analysis 10 adverse events were observed and out of these 10 subjects, all of whom were under intense treatment , 8 out of 10 took quetiapine. The most frequently observed adverse events were tremors, a typical extrapyramidal symptom.. As physicians await next studies helping to identify specific classes of drugs for specific symptoms or subpopulations, they should turn to pharmacological treatment only after a careful risk-benefit evaluation. They should consider both the important role of the relationship between patient and carers and the adverse effects of antipsychotics, which are particularly dangerous in the elderly.

Topics: Antipsychotic Agents; Behavioral Symptoms; Benzodiazepines; Cholinesterase Inhibitors; Dementia; Dibenzothiazepines; Drug Prescriptions; Female; Hospitals, University; Humans; Italy; Male; Olanzapine; Practice Patterns, Physicians'; Quetiapine Fumarate; Risperidone

To estimate mortality risk associated with individual commonly prescribed antipsychotics.. Five-year retrospective study.. Veterans national healthcare data.. Predominantly male, aged 65 and older, with a diagnosis of dementia and no other indication for an antipsychotic. Subjects who received an antipsychotic were compared with randomly selected controls who did not. Exposed and control cohorts were matched according to their date of dementia diagnosis and time elapsed from diagnosis to the start of antipsychotic therapy.. Mortality during incident antipsychotic use.. Cohorts who were exposed to haloperidol (n=2,217), olanzapine (n=3,384), quetiapine (n=4,277), or risperidone (n=8,249) had more comorbidities than their control cohorts. During the first 30 days, there was a significant increase in mortality in subgroups prescribed a daily dose of haloperidol greater than 1 mg (hazard ratio (HR)=3.2, 95% confidence interval (CI)=2.2-4.5, P<.001), olanzapine greater than 2.5 mg (HR=1.5, 95% CI=1.1-2.0, P=.01), or risperidone greater than 1 mg (HR=1.6, 95% CI=1.1-2.2, P=.01) adjusted for demographic characteristics, comorbidities, and medication history using Cox regression analyses. Greater mortality was not seen when a daily dose of quetiapine greater than 50 mg (HR=1.2, 95% CI=0.7-1.8, P=.50) was prescribed, and there was no greater mortality associated with a dose less than 50 mg (HR=0.7, 95% CI=0.5-1.0, P=.03). No antipsychotic was associated with greater mortality after the first 30 days.. Commonly prescribed doses of haloperidol, olanzapine, and risperidone, but not quetiapine, were associated with a short-term increase in mortality. Further investigations are warranted to identify patient characteristics and antipsychotic dosage regimens that are not associated with a greater risk of mortality in elderly patients with dementia.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cohort Studies; Comorbidity; Dementia; Dibenzothiazepines; Female; Haloperidol; Humans; Male; Olanzapine; Proportional Hazards Models; Quetiapine Fumarate; Retrospective Studies; Risk Factors; Risperidone; Sex Factors; Veterans

Although atypical antipsychotics (AA) provoke fewer extra-pyramidal symptoms (ES) than classic antipsychotics, their use in patients greater than or equal to 75 years old with dementia must be under compassionate-use. This is an important limitation. We performed a descriptive analysis of the use of atypical antipsychotics under compassionate-use (AACU) in the Ferrol health area.. We retrospectively assessed all the patients who were receiving an AACU from March, 2004 (that is the date when prescription under compassionate-use of AA came into force in Spain) to November 30, 2008.. One hundred and thirty-three of 164 patients (63.6% women; median ages, 81.9 ± 4.95 years) were included. Diagnostic aetiologies were: 42.9% Alzheimer's disease, 30.8% Parkinson-dementia/Lewy body disease, and 15.8% vascular/mixed dementia. A total of 68.4% of patients had received other anti-psychotic drugs previously and 32.3% had ES due to antipsychotics. The AACU received were: quetiapine (76.7%), ziprasidone (18.8%), and olanzapine (4.5%). Median follow-up time was 20.25 ± 20.38 months. Side effects were observed in 19.7% of patients. Improvement of NPI (Neuropsychiatric Inventory) was 33.3 ± 24.75 points. Agitation/aggressiveness (5.6 ± 4.55), delirious ideas (4.94 ± 5.07), irritability (4.38 ± 4.94), and anxiety (4.32 ± 4.83) were the symptoms that most improved. Although there were no differences between AACU, quetiapine was associated with significant maintenance in monotherapy (94.1% vs 72% for ziprasidone and 83.3% for olanzapine; p < 0.0001).. AACU are effective and well tolerated drugs. Quetiapine was the most frequently used AACU. An excessive percentage of patients previously received other antipsychotics and present with ES.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Compassionate Use Trials; Dementia; Dibenzothiazepines; Female; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Retrospective Studies; Spain; Thiazoles; Treatment Outcome

to examine the use of quetiapine for sleep in patients with dementia admitted to a geriatric psychiatry ward.. retrospective cross-sectional study (January 2007 to December 2009).. geriatric psychiatric unit located near a metropolitan city in North Carolina.. all patients admitted with a diagnosis of dementia who were also receiving quetiapine were eligible. One hundred one patients met the criteria and were included in the study.. none.. descriptive statistics defining quetiapine prescribing. Based on a priori criteria, quetiapine was considered to be used for sleep if it were prescribed: 1) only at bedtime, as needed, for sleep, 2) once daily, only at bedtime, or 3) multiple times daily, but with at least 75% of the daily dose administered at bedtime.. forty-three of the 101 patients included in the study were prescribed quetiapine, probably for sleep. Quetiapine, when used as a sedative-hypnotic, was generally employed at doses between 50 mg and 100 mg nightly. Several published studies report beneficial sleep-promoting effects of quetiapine and other atypical antipsychotics for primary and secondary sleep complaints; however, most of these trials involve young and middle-aged adults, have diagnostic variability, and are limited methodologically.. quetiapine prescribed as a sedative-hypnotic in patients with dementia, while common, is understudied and not without risk.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Cross-Sectional Studies; Dementia; Dibenzothiazepines; Female; Humans; Male; Middle Aged; North Carolina; Off-Label Use; Quetiapine Fumarate; Retrospective Studies; Sleep Initiation and Maintenance Disorders; Treatment Outcome

Delusional jealousy or Othello syndrome (OS) is a well-described psychiatric disorder with paranoid features reported in both organic and functional psychoses. In organic psychoses, the disorder occurs more frequently among chronic male alcoholics and in demented patients. To date, only 2 anecdotal cases of OS have been reported in Parkinson disease (PD) during dopaminergic treatment.. To investigate the presence of OS in PD patients and to study the relationship between dopaminergic treatment, avoiding the possible influence of dementia.. Five hundred sixty-three PD patients without dementia encountered in our movement disorders practice were included in the study. All patients who developed OS were studied. Relationships between clinical and familial history and dopaminergic therapy and OS were assessed.. Six patients with OS were identified. They were all male, with a relatively recent diagnosis of PD characterized by mild-moderate motor deficit. Dopaminergic treatment had been prescribed at low dosages. Neither confusional states (including agitated confusion) nor delirium were associated with OS. The disorder became manifest mainly at time of introduction/increment of antiparkinson treatment. Invariably, OS decreased or receded after reduction/suspension of the antiparkinson drug and prescription of an atypical neuroleptic, usually clozapine or quetiapine.. We hypothesize that nondemented PD patients affected by OS do not necessarily present with severe motor complications and may well have a biologic predisposition for psychiatric disorders. In our opinion this paranoid delusion is rarely considered in PD.

Topics: Adult; Antiparkinson Agents; Antipsychotic Agents; Clozapine; Delusions; Dementia; Dibenzothiazepines; Humans; Jealousy; Male; Middle Aged; Parkinson Disease; Quetiapine Fumarate; Retrospective Studies; Schizophrenia, Paranoid

Topics: Aged, 80 and over; Antipsychotic Agents; Dementia; Dibenzothiazepines; Dystonia; Humans; Male; Parkinson Disease; Psychomotor Agitation; Quetiapine Fumarate

Frontotemporal dementia (FTD) often presents with behavioural changes warranting treatment with antipsychotic medications. It is known that patients with Lewy body dementia are sensitive to developing extrapyramidal symptoms (EPS) from these medications. This has not been emphasized in FTD. We report three patients with FTD that developed parkinsonism and prominent antecollis after treatment with newer antipsychotics, including olanzapine, risperidone and quetiapine. Patients with FTD might have increased sensitivity to antipsychotic medications as with Lewy body dementia. Although newer antipsychotics have favourable side effect profiles, there is increasing evidence that EPS develop more frequently than previously thought.

Topics: Antipsychotic Agents; Benzodiazepines; Dementia; Dibenzothiazepines; Dystonia; Humans; Male; Middle Aged; Neck Muscles; Olanzapine; Parkinsonian Disorders; Quetiapine Fumarate; Risperidone

This study examined the determinants of atypical antipsychotic use among antipsychotic users in community-dwelling elderly in the United States.. The study involved analysis of household and prescription files of the Medical Expenditure Panel Survey (MEPS) data from 1996 to 2004. The analysis focused on the use of six atypical antipsychotic agents namely, clozapine, olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole among the elderly of 60 years or older. Multiple logistic regression analysis within the conceptual framework of Andersen's Behavioral Model was used to examine the determinants of atypical antipsychotic use among antipsychotic users in community-dwelling elderly.. An average of 0.62 million elderly received antipsychotic agents annually during the study period. A majority of the elderly using antipsychotic agents were female (70%), white (86%), non-Hispanic (95%), and living in metropolitan statistical areas (79%). Frequently reported diagnoses among the elderly taking antipsychotic agents were dementia (26.12%), anxiety (20.42%), and schizophrenia (6.62%). Of the elderly receiving antipsychotic agents, 50.39% received atypical agents and 51.88% received typical agents during the study period. The most frequently used atypical agents were risperidone, olanzapine, and quetiapine. Multivariate logistic regression analysis revealed that need (perceived mental health, p < 0.01) and enabling (time, p < 0.01) factors were significantly associated with atypical antipsychotic use after controlling for predisposing factors. The study found that elderly patients with relatively poor perception of mental health (need) and utilization of antipsychotic agents after 1998 (enabling) were more likely to involve the use of atypical agents.. This study was limited to the use of antipsychotic agents in community settings and cannot be extrapolated to other settings. Correlates examined in this study were limited to variables available from the data source and those used by previous researchers.. Need and enabling factors play a vital role in the use of atypical agents in the elderly. The findings have important implications in understanding the use and outcomes of atypical agents in the elderly. Future pharmacoepidemiological research can use these variables to control for confounding and selection bias when evaluating health care outcomes in observational studies.

Topics: Age Factors; Aged; Aged, 80 and over; Antipsychotic Agents; Anxiety; Benzodiazepines; Cross-Sectional Studies; Dementia; Dibenzothiazepines; Female; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Residence Characteristics; Risperidone; Schizophrenia; Serotonin Antagonists; United States

This article describes the spectrum of recurrent thoughts and behaviors that can result from frontotemporal dementia (FTD) and its variants. Although repetitive behaviors can result from a range of brain disorders, FTD is the most common neurologic cause of new-onset recurrent thoughts and behaviors in middle or late life. Patients with FTD can manifest typical or bizarre compulsions, hoarding, verbal and motor stereotypies and complex tics; self-injurious acts, perseverations; and fixed, obsessional thoughts. The frequency and variability of these repetitive behaviors suggest a common disturbance of orbitofrontal-basal ganglia circuits involved in response inhibition. The amelioration of these recurrent events with the administration of serotonin selective reuptake inhibitors further suggests a serotonergic deficit.

Topics: Aged; Antipsychotic Agents; Basal Ganglia; Cognition Disorders; Dementia; Dibenzothiazepines; Dopamine Agents; Female; Humans; Magnetic Resonance Imaging; Memantine; Neuropsychological Tests; Quetiapine Fumarate; Recurrence; Sertraline; Stereotypic Movement Disorder; Thinking

Pisa syndrome (or pleurothotonus), consisting of a tonic flexion of the trunk, has been recently reported also in association with atypical antipsychotics. We describe the first case of Pisa syndrome during aripiprazole treatment in an elderly (77-year-old) woman, admitted to hospital for behavioural and psychological symptoms of dementia. The ongoing treatment with quetiapine was rapidly tapered and stopped, and a switch to aripiprazole (15 mg/die) was attempted the subsequent day. Six days later, an acute tonic flexion of trunk and head towards the right was observed. Aripiprazole was discontinued and the Pisa syndrome completely disappeared within 3 days, without any adjunctive treatment.

Topics: Aged; Antipsychotic Agents; Aripiprazole; Dementia; Dibenzothiazepines; Dystonia; Female; Humans; Piperazines; Quetiapine Fumarate; Quinolones

Quetiapine was approved in Germany as an atypical antipsychotic for treatment of schizophrenia in 2000, followed by the approval as an antipsychotic for treatment of bipolar mania in 2003. The approval of quetiapine for treatment of bipolar depression is expected. We hypothesized that the psychogeriatric prescription pattern for quetiapine shifts from the psychotic to the affective spectrum.. Retrospectively we screened discharge reports of all geriatric inpatients of the psychiatric department of the Ruhr-University of Bochum in the period from January 2001 until March 2006 and identified 208 individual patients aged over 60 years, who had received quetiapine as final medication. Age, gender, daily drug dose, year of treatment and diagnosis (according to ICD-10) were recorded and analyzed.. Over the six-year time span, the proportion of affective disorders (F3) as indication for quetiapine in the elderly increased, whereas the proportion of dementia (F0) as indication for quetiapine decreased significantly. The proportion of schizophrenic disorders (F2) treated with quetiapine did not change significantly.. Since the decision of the German Federal Court in 2002 'off label' use goes to the expenses of the prescriber. So the decrease of quetiapine in dementia is probably due to its 'off label' status in dementia. The psychogeriatric indication shift for quetiapine towards affective disorders could be the consequence of good clinical experiences with the drug and growing evidence for its antidepressant effect.. In addition to controlled pharmacological trials prospective clinical research is needed to evaluate the prescription attitudes of clinicians.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Bipolar Disorder; Dementia; Dibenzothiazepines; Drug Utilization; Female; Germany; Humans; Male; Middle Aged; Mood Disorders; Psychomotor Agitation; Quetiapine Fumarate; Schizophrenia

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

Topics: Adult; Antipsychotic Agents; Behavioral Symptoms; Brain; Dementia; Dibenzothiazepines; Disease Progression; Frontal Lobe; Humans; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Obsessive-Compulsive Disorder; Positron-Emission Tomography; Quetiapine Fumarate; Urination Disorders

Topics: Administration, Oral; Aged; Antipsychotic Agents; Aripiprazole; Arrhythmias, Cardiac; Benzodiazepines; Clozapine; Databases, Factual; Dementia; Dibenzothiazepines; Drug Utilization Review; Health Services for the Aged; Humans; Olanzapine; Pharmaceutical Services; Piperazines; Quetiapine Fumarate; Quinolones; Risk Assessment; Risperidone; Stroke; Thiazoles; Treatment Outcome

Topics: Antipsychotic Agents; Behavioral Symptoms; Bipolar Disorder; Dementia; Dibenzothiazepines; Female; Humans; Mental Status Schedule; Middle Aged; Quetiapine Fumarate; Syndrome; Treatment Outcome; Valproic Acid

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

Topics: Aged; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Dementia; Dibenzothiazepines; Drug Approval; Drug Labeling; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles; United States; United States Food and Drug Administration

New onset diabetes mellitus (DM) and diabetic ketoacidosis (DKA) among patients using atypical antipsychotics is of clinical importance [1,2,5,7-10]. Recently, atypical antipsychotics have been more widely used in the treatment of behavioral and psychological symptoms with dementia (BPSD) than conventional neuroleptics because of a reduced tendency for movement disorders and psychomotor retardation. We report a case of reversible DKA and new-onset DM that developed in a demented patient who was treated with quetiapine for 14 days.

Topics: Aged; Alcoholism; Antipsychotic Agents; Dementia; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Dibenzothiazepines; Humans; Male; Quetiapine Fumarate

Following changes in the safety information on the use of risperidone and olanzapine in elderly patients with dementia, data from prescription-event monitoring (PEM) studies of risperidone, quetiapine and olanzapine were examined. The aim was to compare incidence rates for events reported as cerebrovascular accident (CVA) and transient ischaemic attack (TIA) during the first 180 days of treatment in patients prescribed atypical antipsychotics for dementia or other indications, because of the possible association between dementia and stroke in users of atypical antipsychotics. A retrospective analysis of data from the three observational studies was conducted using Poisson regression modelling and survival analysis. Within the risperidone, quetiapine and olanzapine cohorts, 23 (0.30%), 6 (0.35%) and 10 (0.11%) patients respectively, were reported to have had a CVA/TIA event. Age, sex and indication (dementia or other) were identified as important confounding variables; age being the most important. The crude rate ratios (RRs) for CVA/TIA for risperidone or quetiapine vs. olanzapine indicated an approximate threefold relative difference in rate during the first six months but after adjustment for age, sex and indication, the RRs were non-significant (1.2 (95% CI 0.5,3.0) and 2.1 (95% CI 0.6,7.7), respectively). For risperidone vs. quetiapine, crude and adjusted RRs were not significantly different. Of the three drugs, the time to event was shortest for risperidone and also shortest for risperidone or quetiapine users where the indication was dementia. The age and sex adjusted RR of CVA/TIA in patients prescribed risperidone for dementia vs. other indications was 6.7 (95% CI 2.4,18.9). The adjusted RRs for quetiapine, according to indication, could not be calculated due to missing information on age and sex. There were no cases of CVA/TIA with dementia for olanzapine, thus the RRs and time to event curves according to indication could not be examined. This study revealed no significant difference in the adjusted RR of CVA/TIA events in the first 180 days of treatment in patients prescribed risperidone or quetiapine when compared with olanzapine. However, dementia appears to be an important risk factor. These results should be considered alongside other pharmacoepidemiological studies on this topic.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cohort Studies; Data Interpretation, Statistical; Dementia; Dibenzothiazepines; England; Family Practice; Female; Humans; Incidence; Ischemic Attack, Transient; Male; Middle Aged; Olanzapine; Product Surveillance, Postmarketing; Quetiapine Fumarate; Retrospective Studies; Risk Factors; Risperidone; Stroke; Survival Analysis; Time Factors; Treatment Outcome

The possibility that low-dose antipsychotic treatment is associated with increased risk of cerebrovascular events (CVEs) in elderly patients with dementia has been raised. The objective was to determine whether risperidone is associated with an increased risk of CVEs relative to other commonly considered alternative treatments.. An analysis of Medicaid data from 1999 to 2002, representing approximately 8 million enrollees from multiple states, was conducted. The primary outcome was the incidence of acute inpatient admission for a CVE within 3 months following initiation of treatment with atypical antipsychotics (risperidone, olanzapine, quetiapine, or ziprasidone), haloperidol, or benzo-diazepines.. Descriptive analyses found similar rates of incident CVEs across evaluated agents. Multivariate analyses found no differences in comparisons of risperidone with olanzapine or quetiapine. Risperidone and other antipsychotics as a group were also not associated with a higher odds ratio (OR) of incident CVE than either haloperidol or benzodiazepines. With risperidone as the reference group: olanzapine, OR = 1.05, 95% CI 0.63-1.73; quetiapine, OR = 0.66, 95% CI 0.23-1.87; haloperidol, OR = 1.91, 95% CI 1.02-3.60; benzodiazepines, OR = 1.97, 95% CI 1.30-2.98. With benzodiazepines as the reference group, the OR of incident CVE for all antipsychotics as a class was 0.49, 95%CI 0.35-0.69.. This study found no significant difference in the incidence of CVEs between patients taking risperidone and those taking other atypical antipsychotics. Risperidone and all atypical antipsychotics were not associated with higher risk than two common treatment alternatives (haloperidol and benzodiazepines). These findings do not support the conclusion that risperidone is associated with a higher risk of CVE than other available treatment alternatives. The data also suggest that patient characteristics other than antipsychotic use are more significant predictors of CVEs. Given the relatively low rates of incident CVEs, a larger sample of patients with groups closely balanced on a wide spectrum of potential risk factors could provide a more precise assessment of risk.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cerebrovascular Disorders; Cohort Studies; Dementia; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Haloperidol; Hospitalization; Humans; Male; Middle Aged; Olanzapine; Patient Admission; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risk Factors; Risperidone; Thiazoles

Increasingly, atypical antipsychotic drugs are prescribed for elderly patients with symptoms of psychosis and behavioral disturbances. These symptoms often occur in patients with Alzheimer's disease, other dementias, or Parkinson's disease. As the average age of Americans increases, the prevalence of Alzheimer's disease and Parkinson's disease will rise accordingly. Although nonpharmacologic treatments for behavioral disturbances should be tried first, medications often are needed to enable the patient to be adequately cared for. Current guidelines recommend using risperidone and olanzapine to treat psychosis in patients with Alzheimer's dementia. Quetiapine and clozapine are recommended for treatment of psychosis in patients with Parkinson's disease. Additional research is needed for a recently approved agent, ziprasidone. To minimize side effects, these medications should be started at low dosages that are increased incrementally. Drug interactions, especially those involving the cytochrome P450 system, must be considered. Clozapine's potentially lethal side effects limit its use in the primary care setting. Informed use of atypical antipsychotic drugs allows family physicians to greatly improve quality of life in elderly patients with dementia and behavior disturbances.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Comorbidity; Dementia; Dibenzothiazepines; Humans; Mental Disorders; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone

Side effects of antipsychotic medications are particularly problematic in elderly patients, who experience many age-related changes that may exacerbate medication side effects. Side effects of particular concern in the elderly include anticholinergic reactions, parkinsonian events, tardive dyskinesia, orthostatic hypotension, cardiac conduction disturbances, reduced bone mineral density, sedation, and cognitive slowing. In addition, elderly patients with schizophrenia often have comorbid medical illnesses-such as cardiovascular disease and dementia of the Alzheimer's type-and are thus likely to be taking multiple medications. The effects of polypharmacy must be carefully considered. Patients, caregivers, and family often have different perspectives on side effects. This article addresses the side effects of the currently available antipsychotic medications in light of these concerns.

Topics: Age Factors; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Clinical Trials as Topic; Clozapine; Comorbidity; Dementia; Dibenzothiazepines; Humans; Movement Disorders; Neuroleptic Malignant Syndrome; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Dementia; Dibenzothiazepines; Humans; Male; Paraphilic Disorders; Quetiapine Fumarate