olanzapine 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

To evaluate the comparative efficacy, safety, tolerability, and effectiveness of atypical antipsychotics (AAPs) for the treatment of dementia related psychosis (DRP) in older adults.. In this systematic literature review (SLR), we qualitatively synthesized evidence on the comparative efficacy (based on neuropsychiatric inventory), tolerability (weight gain), and safety (cerebrovascular adverse events [CVAE], cardiovascular events, mortality, somnolence, extrapyramidal symptoms [EPS]) of AAPs used to treat DRP. We also assessed effectiveness based on all-cause discontinuations and discontinuations due to lack of efficacy or adverse events (AE). Published articles from through March 2021 from PubMed, EMBASE, PsycINFO, and Cochrane databases evaluated. We included double-blind, active-comparator/placebo-controlled randomized trials, open-label trials, and observational studies.. This qualitative synthesis included 51 eligible studies with sample size of 13,334 and mean age of 79.36 years. Risperidone, olanzapine, quetiapine, and aripiprazole demonstrated numerically small improvement in psychotic symptoms among patients with DRP. Somnolence was the most reported AE for all the AAPs, with weight gain and tardive dyskinesia more common with olanzapine and risperidone, respectively. These AAPs are associated with falls, EPS, cognitive declines, CVAE, and mortality. Aripiprazole and olanzapine had lower odds of discontinuation due to lack of efficacy, with olanzapine having greater discontinuation odds due to AEs.. This SLR demonstrated that AAPs used off-label to treat DRP are associated with small numerical symptom improvement but with a high risk of AEs, including cognitive decline and potentially higher mortality. These results underscore the need for new treatments with a favorable benefit-risk profile for treating DRP.

Topics: Antipsychotic Agents; Aripiprazole; Dementia; Humans; Olanzapine; Psychotic Disorders; Risperidone

Geriatric patients with dementia frequently present with agitation, aggression, psychosis, and other behavioral and psychological symptoms of dementia (BPSD). We present an update of our previously published algorithms for the use of psychopharmacologic agents in these patients taking into account more recent studies and findings in meta-analyses, reviews, and other published algorithms. We propose three algorithms: BPSD in an emergent, urgent, and non-urgent setting. In the emergent setting when intramuscular (IM) administration is necessary, the first-line recommendation is for olanzapine (since IM aripiprazole, previously favored, is no longer available) and haloperidol injection is the second choice, followed by possible consideration of an IM benzodiazepine. In the urgent setting, the first line would be oral second-generation antipsychotics (SGAs) aripiprazole and risperidone. Perhaps next could be then prazosin, and lastly electroconvulsive therapy is a consideration. There are risks associated with these agents, and adverse effects can be severe. Dosing strategies, discontinuation considerations, and side effects are discussed. In the non-emergent setting, medications are proposed for use in the following order: trazodone, donepezil and memantine, antidepressants such as escitalopram and sertraline, SGAs, prazosin, and carbamazepine. Other options with less support but potential future promise are discussed.

Topics: Academic Medical Centers; Aged; Algorithms; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Citalopram; Dementia; Electroconvulsive Therapy; Haloperidol; Humans; Olanzapine; Psychopharmacology; Risperidone

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: Adult; Antipsychotic Agents; Benzodiazepines; Brain; Cognition Disorders; Dementia; Humans; Huntington Disease; Magnetic Resonance Imaging; Male; Memory, Short-Term; Mood Disorders; Olanzapine; Paroxetine

Olanzapine is an atypical antipsychotic agent of the thienobenzodiazepine class. Olanzapine blocks multiple neurotransmitter receptors, including dopaminergic (D(1), D(2), D(3), and D(4)), serotonergic (5-hydroxytryptamine 2A [5-HT(2A)], 5-HT(2C), 5-HT(3), and 5-HT(6)), adrenergic (α(1)), histaminic (H(1)), and muscarinic (M(1), M(2), M(3), and M(4)) receptors. Olanzapine has a high affinity for the 5HT(2A) receptor, which is up to 5 times greater than the dopamine receptor, resulting in less propensity to the development of extrapyramidal side effects. The affinity of olanzapine for multiple receptors has lead to the identification of olanzapine as an important agent in the treatment of delirium, nausea, and vomiting. Olanzapine has been demonstrated to have opioid-sparing properties. Olanzapine is principally metabolized by glucuronidation, with a smaller metabolic contribution from the cytochrome oxidase system. Adverse effects of olanzapine include somnolence, postural hypotension, constipation, dizziness, restlessness, and weight gain. The purpose of this article is to outline the pharmacodynamics, pharmacology, and evidence for the use of olanzapine in palliative care.

Topics: Benzodiazepines; Clinical Trials as Topic; Critical Illness; Dementia; Drug Interactions; Humans; Nausea; Neoplasms; Olanzapine; Pain Management; Palliative Care; Selective Serotonin Reuptake Inhibitors; Vomiting

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

This study was conducted to determine the effect of olanzapine treatment on cognition in elderly patients with behavioral and psychiatric symptoms (BPSD) associated with dementia.. This was a post-hoc analysis of three randomized double-blind, clinical trials of olanzapine (n = 682) vs placebo (n = 257) in dementia patients with BPSD in long-term or continuing-care settings. One study was 6 weeks long; the other two were 10 weeks duration, and their data were combined. Patients were subgrouped according to baseline Mini Mental State Examination (MMSE) scores: Group I = 23-26; Group II = 19-22; Group III = 14-18; Group IV = 7-13; Group V = 1-6. BPSD was assessed by the Neuropsychiatric Inventory (NPI).. Within-treatment group cognitive decline in patients was significant in the combined studies, but not in the 6-week study. Between-treatment cognitive changes were non-significant in the 6-week study, but showed a statistical trend in the combined studies (olanzapine, -0.78 +/- 0.19 vs placebo, -0.32 +/- 0.25; p = 0.06). In the subgroup analysis, there was a significant between-treatment difference in cognitive changes in MMSE subgroup IV in the combined studies (olanzapine, -0.63 +/- 0.26 vs placebo, 0.27 +/- 0.41, p = 0.04). Improvement in BPSD was correlated with better cognitive outcome (r = -0.2; p < 0.01).. Although the overall differences in cognitive changes in patients treated with olanzapine vs placebo were small and non-significant, negative effects on cognition in some patients cannot be excluded, especially in patients with more pronounced cognitive decline or whose behavioral and psychiatric symptoms are not responding to treatment.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Dementia; Double-Blind Method; Female; Humans; Male; Neuropsychological Tests; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Randomized Controlled Trials as Topic; Social Behavior Disorders

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 assess the efficacy and adverse reactions of typical and atypical antipsychotics in the treatment of neuropsychiatric symptoms in dementia, and to examine the evidence for the cerebrovascular events warning for atypical antipsychotics.. Systematic review.. Using Medline, Cinahl, PsyclNFO, Embase and the Cochrane central register of controlled trials (1980-2005), double-blind randomized controlled trials with intention-to-treat analysis were selected, which evaluated efficacy and adverse reactions of antipsychotics in the treatment of neuropsychiatric symptoms in dementia. The studies underwent a standardised validity assessment.. After screening 950 studies, 14 studies on the effect of haloperidol, risperidone, olanzapine, quetiapine, tiapride, loxapine and perphenazine were selected. In 7 out of 10 studies, haloperidol, risperidone and olanzapine appeared to be more effective than placebo in the treatment of aggression and psychosis. Direct comparison between typical and atypical antipsychotics revealed no statistically significant difference. The most common adverse reactions were extrapyramidal symptoms and somnolence. These adverse reactions were less frequent with low-dose risperidone than with haloperidol or olanzapine, but risperidone and olanzapine were found to be associated with a higher risk of cerebrovascular events in two studies.. The efficacy of typical and atypical antipsychotics is comparable, but only low-dose risperidone seems to be associated with fewer (extrapyramidal) side effects. The adverse reactions are inadequately described in the published data and consequently the warning of an increased risk of mortality could not be confirmed.

Topics: Aggression; Antipsychotic Agents; Benzodiazepines; Dementia; Haloperidol; Humans; Olanzapine; Psychotic Disorders; Risperidone; Treatment Outcome

Behavioural and psychological symptoms of dementia (BPSD) are common and can dominate disease presentation. Antidepressions are commonly prescribed for depressive symptoms, but the evidence to support this practice is weak. The atypical antipsychotics risperidone and olanzepine have significant efficacy for the treatment of aggression and risperidone is also efficacious in the treatment of psychosis, but both with substantially increased risk of stroke. There are no newer studies of benzodiazepines in the treatment of anxiety and in old studies the efficacy are doubtful.

Topics: Anti-Anxiety Agents; Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Dementia; Humans; Mental Disorders; Olanzapine; Risperidone; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Agitation is common in patients with acute schizophrenia or bipolar mania, and when severe can result in aggressive or violent behaviour. Pharmacotherapy for acute psychotic agitation includes the use of antipsychotic and benzodiazepine drugs, either alone or in combination. Although oral treatment is preferred, options in the pharmacotherapy of acute agitation include the parenteral administration of antipsychotics in order to facilitate onset of drug action and quickly alleviate symptoms. Until recently only conventional antipsychotic and benzodiazepine drugs were available as intramuscular injections. Olanzapine has been one of the first atypical antipsychotics available for intramuscular administration. Four randomized placebo and comparator controlled , double-blind clinical trials have demonstrated the efficacy of olanzapine in reducing acute agitation in patients with schizophrenia, bipolar mania and Alzheimer and vascular dementia. Evidence from these clinical trials has shown that IM olanzapine associated with faster onset of action and more favorable profile of adverse events, than monotherapy with IM haloperidol. Current clinical experience and one naturalistic study with intramuscular olanzapine suggest that it is efficacious and can be safely used in "real world" patients with severe agitation. Intramuscular olanzapine have shown ease of transition to same agent oral therapy once the acute agitation has diminished. The orally disintegrating tablet formulation of olanzapine was effective rapidly reducing psychopathology, while improving medication compliance, attitudes and behaviours. This new formulation of olanzapine may offer an alternative strategy in the treatment of acutely ill, noncompliant schizophrenic patients. Evidence suggests that the new formulations of olanzapine should be among the first-line choices in the treatment of agitation in acute psychosis.. olanzapine, intramuscular, orally disintegrating tablet, agitation, psychosis.

Topics: Acute Disease; Administration, Oral; Antipsychotic Agents; Attitude; Benzodiazepines; Bipolar Disorder; Dementia; Humans; Injections, Intramuscular; Olanzapine; Patient Compliance; Psychomotor Agitation; Psychotic Disorders; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Post hoc analyses of pooled results from 11 randomised controlled trials of risperidone and olanzapine in elderly dementia subjects revealed an increased incidence of cerebrovascular adverse events compared with placebo. Reanalysis of the risperidone trials suggests that some of the increased incidence may be accounted for by nonspecific events that were not strokes. Large observational administrative health database studies appear to confirm that risperidone and olanzapine are not associated with an increased risk of stroke in elderly patients compared with typical antipsychotics or untreated dementia patients. A larger number of subjects with vascular and mixed dementias were included in the risperidone studies compared with the olanzapine studies, which likely accounts for the increased incidence of cerebrovascular adverse events in the risperidone trials compared with the olanzapine studies. Potential mechanisms proposed to explain an association between atypical antipsychotics and cerebrovascular adverse events include thromboembolic effects, cardiovascular effects (e.g. orthostatic hypotension, arrhythmias), excessive sedation resulting in dehydration and haemoconcentration, and hyperprolactinaemia. However, there is little evidence to support these hypothesised mechanisms at present. The association between atypical antipsychotics and cerebrovascular adverse events requires further clarification. At the present time, this association is another factor that clinicians should consider when weighing the risks and benefits of treating behavioural and psychological disturbances in elderly dementia patients.

Topics: Antipsychotic Agents; Behavioral Symptoms; Benzodiazepines; Dementia; Humans; MEDLINE; Olanzapine; Randomized Controlled Trials as Topic; Risk Factors; Risperidone; Stroke; Treatment Outcome

Post-hoc analysis by the pharmaceutical company Eli Lilly of 5 randomised clinical trials concerning the efficacy ofolanzapine in patients with dementia, has shown that patients taking olanzapine have a risk of experiencing a cerebrovascular accident which is 3 times higher than patients taking placebo. This increased risk has also been found in patients with dementia who take risperidone. Details concerning this relationship cannot be obtained from the sparse information supplied by the producers of risperidone and olanzapine. The pathophysiological mechanisms by which atypical antipsychotics may lead to cerebrovascular accidents are not well understood. Atypical antipsychotics are often prescribed for conditions in which evidence of the efficacy of this group of medications is lacking. This association between antipsychotics and cerebrovascular accidents emphasises the need for a stricter and evidence-based prescription policy for antipsychotics. In cases of adverse drug reaction, more openness on the part of pharmaceutical companies is desirable.

Topics: Antipsychotic Agents; Benzodiazepines; Dementia; Humans; Olanzapine; Randomized Controlled Trials as Topic; Risk Factors; Risperidone; Stroke

To compare the efficacy and safety of risperidone and olanzapine in the treatment of psychotic symptoms and behavioural disturbances in institutionalised patients with dementia and other psychiatric disorders.. We conducted a retrospective chart review of nursing home patients with psychiatric disorders or dementia in 65 long-term care facilities in New Jersey and Pennsylvania who had received treatment with risperidone or olanzapine. We determined the efficacy of the two antipsychotics for the treatment of psychotic symptoms or behavioural disorders in patients with dementia, the incidence of falls in ambulatory patients, and the incidence of adverse events in the total sample of patients.. A total of 289 long-term care patients were included in the analysis. Diagnoses included dementia in 59%, schizophrenia in 20%, bipolar disorder in 8%, schizoaffective disorder in 6% and other diagnoses in 10%. The mean ages were 77 years in patients receiving risperidone and 81 years in patients receiving olanzapine. Risperidone was received by 141 patients and olanzapine by 148 patients. In the 171 patients with dementia, significantly greater improvements in psychotic symptoms and behavioural disturbances were seen in patients receiving risperidone compared with those receiving olanzapine (p < 0.05). In the 222 ambulatory patients, > or = 1 fall was recorded in 19% of patients receiving risperidone and in 38% of patients receiving olanzapine (p = 0.001). The fall rate per month was 0.06 in risperidone recipients and 0.17 in olanzapine recipients (p < 0.001). Adverse events were reported in 6% (9/141) of risperidone-treated patients compared with 34% (42/110) of olanzapine-treated patients (p < 0.001). Adverse events seen only in the olanzapine group were constipation, dry mouth, dysphasia, sedation and dizziness.. The results of this review indicate that risperidone was more efficacious and better tolerated than olanzapine in the treatment of nursing home patients with psychotic symptoms and behavioural disturbances.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Dementia; Homes for the Aged; Humans; Medical Records; Mental Disorders; Nursing Homes; Olanzapine; Retrospective Studies; Risperidone

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

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

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

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

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

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

As the new generation of atypical antipsychotics becomes available, the limitations of the older typical agents become apparent. The new medications, which have benefits other than the alleviation of positive symptoms of schizophrenia, may also be beneficial for psychotic disorders that have responded poorly to conventional neuroleptics. This article will describe the potential use of the atypical antipsychotics, especially olanzapine, for affective mood disturbances in schizophrenia, psychotic depression and mania, first-break schizophrenia, comorbid schizophrenia and substance abuse disorders, dementia in the elderly and those with late-onset schizophrenia, and behavioral problems in patients with mental retardation or developmental delays.

Topics: Antipsychotic Agents; Benzodiazepines; Child; Comorbidity; Dementia; Depressive Disorder; Developmental Disabilities; Diagnosis, Dual (Psychiatry); Humans; Intellectual Disability; Mental Disorders; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia; Substance-Related Disorders

As the world's population ages, increasing numbers of patients with dementia can be expected, the signs and symptoms of which can be extremely disruptive. In particular, behavioral and psychological signs and symptoms of dementia reduce the quality of life of carers (usually family members) and increase the cost of care. Conventional neuroleptics have been used for many years in the management of disturbed and disruptive demented patients, although there are few well-controlled clinical trials demonstrating their efficacy. The use of the low-potency neuroleptics is associated with orthostatic hypotension, cardiac toxicity, anticholinergic side effects and daytime sedation. The high-potency neuroleptics tend to cause extrapyramidal side effects and akathisia. Clozapine although less likely to cause extrapyramidal symptoms than conventional neuroleptics, can cause orthostatic hypotension and requires continual blood monitoring. Early-phase open trials suggest that risperidone is efficacious in patients with behavioral and psychological signs and symptoms of dementia and that it has a low side-effects profile. Further trials are needed to confirm this, but it is likely that the newer antipsychotics, as typified by risperidone, will lead to safer and more effective management of patients with the disruptive and costly behavioral and psychological signs and symptoms of dementia. Non-pharmacologic interventions may also provide benefit, though controls are rare.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Clozapine; Dementia; Humans; Olanzapine; Pirenzepine; Risperidone

Despite modest efficacy, unpredictable individual utility, and a high rate of adverse effects, behavioural and psychological symptoms of dementia (BPSD) are common determinants for antipsychotic drug therapy in nursing home patients.. To explore the impact on BPSD of stopping long-term antipsychotic treatment in nursing home patients with dementia.. Fifty-five patients (43 women; mean age 84.1) taking haloperidol, risperidone, or olanzapine for BPSD were randomly assigned to cessation (intervention group, n=27) or continued treatment with antipsychotic drugs (reference group, n=28) for 4 consecutive weeks. The Neuropsychiatric Inventory (NPI) Questionnaire was used to examine changes in behavioural and psychological symptoms.. By study completion, 23 of the 27 intervention group patients were still off antipsychotics. Symptom scores (NPI) remained stable or even improved in 42 patients (intervention group, 18 out of 27; reference group, 24 out of 28; p=0.18). As compared to patients with stable or improved symptom scores, patients with behavioural deterioration after antipsychotic cessation used higher daily drug doses at baseline (p=0.42).. A large share of elderly nursing home patients on long-term treatment with antipsychotics for BPSD, do well without this treatment. Standardized symptom evaluations and drug cessation attempts should therefore be undertaken at regular intervals.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Dementia; Double-Blind Method; Female; Haloperidol; Humans; Long-Term Care; Male; Neuropsychological Tests; Norway; Nursing Homes; Olanzapine; Risperidone; Withholding Treatment

Older individuals with dementia are highly sensitive to the effects of muscarinic receptor blockade.. This was a 6-week multisite, randomized clinical trial.. Eighty-six patients with probable Alzheimer's disease, vascular dementia, or mixed-etiology dementia (DSM-IV criteria) were randomly assigned to treatment with olanzapine or risperidone.. Anticholinergic activity was measured with a radioreceptor assay, and plasma levels of antipsychotic medications were determined. Primary outcomes were assessed with the Udvalg for Kliniske Undersogelser (UKU) scale and somnolence adverse events; secondary outcome measures included scores on the Neuropsychiatric Inventory (NPI) and other scales.. There were no between-treatment differences in the UKU scale or in somnolence adverse events. Statistically significant improvements (p < .001) from baseline were found for the NPI measures, with no between-treatment group differences. Olanzapine was associated with significant increases from baseline in anticholinergic activity, while risperidone was not; the between-treatment group differences were not statistically significant. Increase in anticholinergic activity was associated with an increase in anticholinergic side effects and slower performance on the Trail Making Test Part A. Higher endpoint anticholinergic activity was associated with higher endpoint scores on several items from the NPI, including delusions, anxiety, and aberrant motor behavior.. Efficacious doses of olanzapine increased anticholinergic activity in older patients with dementia, while similarly efficacious doses of risperidone did not. Patients whose anticholinergic activity increased were more likely to experience anticholinergic side effects and to have worsening in certain cognitive domains. These data suggest that certain patients may be vulnerable to the anticholinergic activity associated with antipsychotic treatment.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Cognition Disorders; Delusions; Dementia; Double-Blind Method; Female; Hallucinations; Humans; Male; Middle Aged; Muscarinic Antagonists; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Radioligand Assay; Receptors, Muscarinic; Risperidone; Sleep Wake Disorders; Trail Making Test; Treatment Outcome

Distinct calming rather than nonspecific sedation is desirable for the treatment of acute agitation. In 3 double-blind studies, acutely agitated patients with schizophrenia (N = 311), bipolar mania (N = 201), or dementia (N = 206) were treated with intramuscular (1-3 injections/24 hrs) olanzapine (2.5-10.0 mg), haloperidol (7.5 mg), lorazepam (2.0 mg), or placebo. The Agitation-Calmness Evaluation Scale (ACES; Eli Lilly and Co.) and treatment-emergent adverse events assessed sedation. Across all studies, 1 patient (lorazepam-treated, bipolar) became unarousable. There were no significant between-group differences in ACES scores of deep sleep or unarousable at any time across. Excluding asleep patients, agitation remained significantly more reduced with olanzapine than placebo (P <.05). The incidences of adverse events indicative of sedation were not significantly different with olanzapine versus comparators. For the treatment of acute agitation associated with schizophrenia, bipolar mania, or dementia, intramuscular olanzapine-treated patients experienced no more sedation than haloperidol- or lorazepam-treated patients and experienced distinct calming rather than nonspecific sedation.

Topics: Adult; Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dementia; Double-Blind Method; Drug Administration Schedule; Haloperidol; Humans; Hypnotics and Sedatives; Injections, Intramuscular; Lorazepam; Olanzapine; Pirenzepine; Psychomotor Agitation; Retrospective Studies; Schizophrenia; Treatment Outcome

In addition to demonstrating their superiority to placebo, there is a need to compare the relative efficacy and side effects of atypical neuroleptics for the acute treatment of dementia-related behavioral disturbances in residents of long-term care facilities.. In a double-blind parallel study allowing dose titration over 14 days, 39 agitated persons with DSM-IV dementia who were residing in long-term care facilities were administered olanzapine (N = 20) or risperidone (N = 19) as acute treatment. Drug was administered once a day at bedtime. The initial dosages were olanzapine, 2.5 mg/day, and risperidone, 0.5 mg/day. Titration was allowed to maximum doses of olanzapine, 10 mg/day, and risperidone, 2.0 mg/day. The primary outcome measures were the Clinical Global Impressions scale (CGI) and the Neuropsychiatric Inventory (NPI). Data were gathered from 2000 to 2002.. Both drugs produced significant reductions in CGI and NPI scores (p <.0001), but there was no significant difference between drugs. The mean olanzapine dose was 6.65 mg/day; for risperidone, the dose was 1.47 mg/day. The positive drug effect was not accompanied by decreased mobility, and there was improvement on a quality-of-life measure. The chief adverse events were drowsiness and falls. At baseline, 42% (16/38) of subjects in both groups had extrapyramidal symptoms that increased slightly, but not significantly, by the end of the study.. Low-dose, once-a-day olanzapine and risperidone appear to be equally safe and equally effective in the treatment of dementia-related behavioral disturbances in residents of extended care facilities.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Dementia; Double-Blind Method; Drug Administration Schedule; Female; Frail Elderly; Geriatric Assessment; Humans; Male; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Quality of Life; Risperidone; Skilled Nursing Facilities; Treatment Outcome

Prolongation of the QTc interval has been reported during treatment with oral antipsychotic agents and may be more pronounced during parenteral administration. Pooled QTc interval data from acutely agitated patients across four double-blind trials were compared. Databases included: placebo-controlled [two schizophrenia, one bipolar mania trials (n=565)]; haloperidol-controlled [two schizophrenia trials (n=482)]; geriatric placebo-controlled [1 dementia trial (n=204)]. Patients received 1-3 injections of intramuscular (IM) olanzapine (2.5-10 mg/injection), IM haloperidol (7.5 mg/injection), or IM placebo. At 2 and 24 h after IM olanzapine treatment, the mean QTc interval decreased approximately 3 ms from baseline in the placebo- and haloperidol-controlled databases. When there was a statistically significant difference between IM olanzapine and IM placebo, QTc intervals decreased during treatment with IM olanzapine and increased with IM placebo. The incidences of prolonged (endpoint >/=99th percentile of healthy adults or >/=500 ms) or lengthened (increase >/=60 ms) QTc intervals during treatment with IM olanzapine (<3% placebo- and haloperidol-controlled databases, <12% geriatric placebo-controlled database) were never significantly greater than with comparators. These data suggest that IM olanzapine has a favorable QTc interval profile in acutely agitated patients with schizophrenia, bipolar mania, or dementia.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dementia; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Haloperidol; Humans; Injections, Intramuscular; Long QT Syndrome; Olanzapine; Psychomotor Agitation; Schizophrenia

To compare the effects of risperidone and olanzapine on cognition in elderly patients with dementia and psychosis, and to compare the side effects of these drugs.. Single-blind, multicenter, observational study.. Four rural nursing care facilities.. Nineteen elderly patients with dementia and psychosis.. Eleven patients were treated with risperidone, eight with olanzapine.. Rating assessments were completed at baseline, 1 month, and 2 months. Simple paired and unpaired t tests determined between- and within-group differences. Social functioning, including activities of daily living, improved over baseline in both groups (p=0.03). Cognition declined significantly (p<0.05) in the risperidone group; comparatively more side effects occurred and blood pressure decreased (p<0.05) in the olanzapine group. When compared with each group cross-sectionally at baseline and end point, however, the two groups did not differ significantly.. Improvements in social functioning in all 19 patients suggest that both risperidone and olanzapine may help improve functioning in elderly patients with dementia and psychosis. Cognitive and side effect profiles of these drugs may differ substantially. Further study is needed to determine patient subpopulations who may be able to tolerate one drug over another.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cognition; Dementia; Female; Humans; Iowa; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Risperidone; Single-Blind Method; Treatment Outcome

This double-blind study investigated the efficacy and safety of rapid-acting intramuscular olanzapine in treating agitation associated with Alzheimer's disease and/or vascular dementia. At 2 h, olanzapine (5.0 mg, 2.5 mg) and lorazepam (1.0 mg) showed significant improvement over placebo on the PANSS Excited Component (PANSS-EC) and Agitation-Calmness Evaluation Scale (ACES), and both 5.0 mg olanzapine and lorazepam showed superiority to placebo on the Cohen-Mansfield Agitation Inventory. At 24 h, both olanzapine groups maintained superiority over placebo on the PANSS-EC; lorazepam did not. Olanzapine (5.0 mg) and lorazepam improved ACES scores more than placebo. Simpson-Angus and Mini-Mental State Examination scores did not change significantly from baseline. Sedation (ACES > or =8), adverse events, and laboratory analytes were not significantly different from placebo for any treatment. No significant differences among treatment groups were seen in extrapyramidal symptoms or in corrected QT interval at either 2 h or 24 h, and no significant differences among treatment groups were seen in vital signs, including orthostasis. Intramuscular injection of olanzapine may therefore provide substantial benefit in rapidly treating inpatients with acute dementia-related agitation.

Topics: Acute Disease; Aged; Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Dementia; Double-Blind Method; Female; Humans; Injections, Intramuscular; Lorazepam; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Psychomotor Agitation

We describe a case of olanzapine-induced hypothermia and hand oedema in an older adult with behavioural and psychological symptoms of dementia (BPSD).. An 82-year-old woman with hypothyroidism and dementia was reviewed by the geriatric team at a nursing home in view of lethargy and an unrecordable oral temperature. She was noted to have a bilateral hand oedema and right basal crackles. Investigations revealed high white cell count and inflammatory markers. She was treated as per hypothermia and communityacquired pneumonia protocols. The patient did not have the expected response to treatment. Olanzapine was tailed down and stopped with good effect as it was suspected to be a contributory cause to both the hypothermia and oedema.. Potentially inappropriate polypharmacy can be specifically targeted with effective deprescribing. Treatment review should be encouraged on a regular basis, especially in frail older adults with polypharmacy.

Topics: Aged; Aged, 80 and over; Dementia; Deprescriptions; Edema; Female; Humans; Hypothermia; Hypothermia, Induced; Olanzapine; Polypharmacy

Topics: Aged; Antipsychotic Agents; Bethanechol; Dementia; Humans; Male; Muscarinic Agonists; Olanzapine; Problem Behavior; Urinary Retention

Antipsychotic (AP) drugs are commonly used to manage the behavioural symptoms of dementia. Nevertheless, international (i.e. the European Medicines Agency in Europe) and national (i.e. the Medicines and Healthcare products Regulatory Agency in the UK and the Italian Drug Agency) regulatory agencies issued safety warnings against AP use in dementia in 2004 and 2009.. The aim of this study is to investigate the short- and long-term impact of safety warnings on the use of APs in UK and Italian persons with dementia using two nationwide databases: The Health Improvement Network (THIN) from the UK and the Health Search Database-Cegedim-Strategic Data-Longitudinal Patient Database (HSD-CSD-LPD) from Italy.. We calculated the overall quarterly prevalence of AP use by class and by individual drug in persons with dementia aged ≥65 years and used generalized linear models to explore the effect of the safety warnings.. We identified 58,497 and 10,857 individuals aged ≥65 years with dementia from the THIN and HSD-CSD-LPD databases, respectively, over the period 2000-2012. After the 2004 warnings, the use of atypical APs decreased, whereas the use of conventional APs increased, in Italy and the UK until 2009. However, the trend for APs individually showed that the use of risperidone/olanzapine decreased, whereas the use of quetiapine increased in both countries. After the 2009 warnings (until 2012), the use of atypical and conventional APs decreased in the UK (from 11 to 9 and 5 to 3 %, respectively), but such use increased in Italy (from 11 to 18 and 9 to 14 %, respectively).. The 2004 warnings led to a reduction in the use of olanzapine and risperidone and increased the use of quetiapine/conventional APs in both countries. From 2009, the use of APs decreased in persons with dementia in the UK but not in Italy. Possible reasons for the difference in AP use between the two countries include a more proactive approach towards reducing the use of APs in the UK than in Italy.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Databases, Factual; Dementia; Drug Prescriptions; Female; Humans; Italy; Male; Olanzapine; Practice Patterns, Physicians'; Retrospective Studies; Risperidone; United Kingdom

The aim of this study was to compare the efficacy and side-effect profile of the typical antipsychotic haloperidol with that of the atypical antipsychotics risperidone, olanzapine, and aripiprazole in the management of delirium.. The Memorial Delirium Assessment Scale (MDAS), the Karnofsky Performance Status (KPS) scale, and a side-effect rating were recorded at baseline (T1), after 2-3 days (T2), and after 4-7 days (T3). Some 21 cases were case-matched by age, preexisting dementia, and baseline MDAS scores, and subsequently analyzed.. The baseline characteristics of the medication groups were not different: The mean age of the patients ranged from 64.0 to 69.6 years, dementia was present in between 23.8 and 28.6%, and baseline MDAS scores were 19.9 (haloperidol), 18.6 (risperidone), 19.4 (olanzapine), and 18.0 (aripiprazole). The doses of medication at T3 were 5.5 mg haloperidol, 1.3 mg risperidone, 7.1 mg olanzapine, and 18.3 mg aripiprazole. Over one week, the decline in MDAS scores between medications was equal, and no differences between individual MDAS scores existed at T2 or T3. After one week, the MDAS scores were 6.8 (haloperidol), 7.1 (risperidone), 11.7 (olanzapine), and 8.3 (aripiprazole). At T2, delirium resolution occurred in 42.9-52.4% of cases and at T3 in 61.9-85.7%; no differences in assessments between medications existed. Recorded side effects were extrapyramidal symptoms (EPSs) in haloperidol- and risperidone-managed patients (19 and 4.8%, respectively) and sedation with olanzapine (28.6%).. Haloperidol, risperidone, aripiprazole, and olanzapine were equally effective in the management of delirium; however, they differed in terms of their side-effect profile. Extrapyramidal symptoms were most frequently recorded with haloperidol, and sedation occurred most frequently with olanzapine.

Topics: Aged; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Delirium; Dementia; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Risperidone

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

In order to target behavioral and psychological symptoms of dementia (BPSD), we used molecular modeling-assisted design to obtain novel multifunctional arylsulfonamide derivatives that potently antagonize 5-HT(6/7/2A) and D2 receptors, without interacting with M1 receptors and hERG channels. In vitro studies confirmed their antagonism of 5-HT(7/2A) and D2 receptors and weak interactions with key antitargets (M1R and hERG) associated with side effects. Marked 5-HT6 receptor affinities were also observed, notably for 6-fluoro-3-(piperidin-4-yl)-1,2-benzoxazole derivatives connected by a 3-4 unit alkyl linker with mono- or bicyclic, lipophilic arylsulfonamide moieties. N-[4-[4-(6-Fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]butyl]benzothiophene-2-sulfonamide (72) was characterized in vitro on 14 targets and antitargets. It displayed dual blockade of 5-HT6 and D2 receptors and negligible interactions at hERG and M1 receptors. Unlike reference antipsychotics, 72 displayed marked antipsychotic and antidepressant activity in rats after oral administration, in the absence of cognitive or motor impairment. This profile is particularly attractive when targeting a fragile, elderly BPSD patient population.

Topics: Animals; Antidepressive Agents; Antipsychotic Agents; Avoidance Learning; Benzoxazoles; Catalepsy; CHO Cells; Cricetulus; Dementia; Dopamine D2 Receptor Antagonists; HEK293 Cells; Humans; Male; Models, Molecular; Motor Activity; Radioligand Assay; Rats, Wistar; Receptors, Serotonin; Serotonin Antagonists; Structure-Activity Relationship; Sulfonamides

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

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

Pisa syndrome or pleurothotonus is the persistent flexion of the body and head to one side giving the appearance of the leaning tower of Pisa. It is most commonly caused by typical and atypical antipsychotic drugs. We report a case of Pisa Syndrome caused by prolonged use of high dose cholinesterase inhibitor, rivastigmine. Symptoms subsided when rivastigmine was withdrawn and did not reappear when a different cholinesterase inhibitor, donepezil was introduced. Physicians should be aware of Pisa syndrome and should alert patient of this possibility when starting and stepping up medications. The purpose of reporting this case is to create awareness among general practitioners as it is a reversible condition which responds to removal of the offending drug.

Topics: Aged; Benzodiazepines; Cholinesterase Inhibitors; Delusions; Dementia; Donepezil; Humans; Indans; Male; Movement Disorders; Olanzapine; Phenylcarbamates; Piperidines; Posture; Rivastigmine; Syndrome

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

We report about a woman of 60 years who received psychiatric inpatient treatment for an affective disorder with psychotic symptoms on several occasions. As time elapsed symptoms of dementia became more and more obvious. Despite a comprehensive workup with neuroimaging methods (SPECT, PET) the correct diagnosis of Huntington's Chorea was not attained until the characteristic movements appeared. Up till then pathologic movements had hardly occurred and there were no known cases of Huntington's Chorea in the family. This case is remarkable as the patient was not only treated with different antidepressants and antipsychotics but with a course of ECT too. Beyond this it shows the enormous stress this illness imposes on patients and their caregivers.

Topics: Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Brain; Combined Modality Therapy; Dementia; Depressive Disorder, Major; Diagnosis, Differential; Disease Progression; Electroconvulsive Therapy; Female; Humans; Huntington Disease; Middle Aged; Olanzapine; Positron-Emission Tomography; Psychotic Disorders; Suicidal Ideation; Tomography, Emission-Computed, Single-Photon; Treatment Failure

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

We discussed a neurosyphilis case who had a risky sexual intercourse history nearly 10 years ago. After the neurosyphilis diagnosis, the patient has clinical symptoms of a demential case starting as a typical manic episode and Jarisch-Herxheimer reaction because of intravenous penicillin treatment that has improved with olanzapine treatment.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dementia; Humans; Male; Neurosyphilis; Olanzapine; Penicillins; Psychotic Disorders

Media reports have discussed how olanzapine was marketed off-label for dementia and subsyndromal bipolar disorder. Much of this marketing occurred in primary care settings. However, these reports have provided few details. In legal proceedings, Lilly disclosed internal documents that detail the strategies utilized to market olanzapine. The current paper addresses the marketing of olanzapine in detail based upon a review of these documents. All 358 documents released by Lilly are publicly available online. Documents were utilized for this review if they were relevant to the marketing of olanzapine in primary care settings in the United States. It was found that olanzapine was marketed off-label in primary care settings for relatively mild symptoms that were framed as bipolar disorder and schizophrenia. A key strategy in this campaign was the use of hypothetical patient profiles in detailing visits, most of which clearly failed to meet diagnostic criteria for any recognized mental disorder. Evidence emerged that olanzapine was also marketed off-label as a treatment for dementia.

Topics: Antipsychotic Agents; Benzodiazepines; Dementia; Documentation; Drug Industry; Humans; Marketing; Olanzapine; Primary Health Care; Schizophrenia

Studies conducted to obtain drug authorization are often of short duration and based on small sample sizes in selected populations. Policies on drug safety rely on the validity of the methods used to achieve rapid and effective communication of new information. No formal evaluation has ever been made of the Spanish communications system, although indirect data have raised questions about its effectiveness.. To evaluate the impact of two safety warnings issued by the Spanish Drug Agency, and of a later prior authorization requirement involving the use of atypical antipsychotic drugs in the elderly.. The study was based on a time-series analysis constructed with data corresponding to monthly invoicing from 2000 to 2006 for olanzapine and risperidone in the Region of Valencia, Spain. Because the safety warnings and the prior authorization policy applied exclusively to prescriptions of these drugs for elderly patients with dementia, we investigated whether these interventions were successful and therefore changed prescription patterns for pensioners receiving low-strength formulations (the available proxy for elderly subjects with dementia), without altering patterns for those receiving the highest-strength formulations (typically used in schizophrenic patients) or for prescriptions for non-pensioners (any strength formulations). These two latter groups were therefore established as the control groups.. Defined daily doses (DDDs) for olanzapine in low-strength pharmaceutical forms showed a clear levelling off after the first warning, while that for risperidone showed less pronounced decline. The prior authorization policy had a dramatic effect on the consumption of risperidone, but not on that of olanzapine. DDDs for low-strength formulations between the 12 months prior to the first warning and the 12 months following the prior authorization showed a substantial reduction (22% for risperidone and 33% for olanzapine). In the high-strength forms and in non-pensioners the upward trends in DDDs remained unaltered after both interventions.. The safety warnings concerning atypical antipsychotic drugs were effective in reducing the prescribing of risperidone and olanzapine in low-strength doses in pensioner prescriptions, and the implementation of a prior authorization policy had a dramatic effect on the prescribing of risperidone.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Dementia; Dose-Response Relationship, Drug; Drug and Narcotic Control; Humans; Information Dissemination; Olanzapine; Practice Patterns, Physicians'; Risperidone; Spain

The treatment of rapidly deteriorating dementia is always very challenging. This case report describes a 78-year-old male patient with rapidly developing dementia treated successfully with orally disintegrating olanzapine, memantine, donepezil, omega-3 and vitamin-B complex. The prevailing fatalism and treatment nihilism regarding treatment of dementia should give way to more hope and optimism. Several important treatment dillemas in rapidly developing dementia are discussed.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Cholinesterase Inhibitors; Dementia; Depression; Disease Progression; Donepezil; Dopamine Agonists; Drug Therapy, Combination; Electrocardiography; Electroencephalography; Humans; Indans; Male; Memantine; Neuropsychological Tests; Olanzapine; Piperidines; Severity of Illness Index

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

Neuroleptic malignant syndrome (NMS) is an idiosyncratic and uncommon but serious adverse effect that has been reported with both typical and atypical antipsychotic agents. We describe a 58-year-old man with Down syndrome and dementia who was receiving low-dose olanzapine and rivastigmine therapy; he developed NMS 4 months after starting olanzapine. The patient presented with altered mental status, rigidity, fever, diaphoresis, and tremor, and his creatine kinase level was elevated. Olanzapine was discontinued, and the patient fully recovered; antipsychotic therapy was not restarted. Based on the Naranjo adverse drug reaction probability scale, olanzapine was the probable cause of the patient's NMS. In addition, use of rivastigmine in combination with olanzapine may have placed the patient at greater risk for NMS, possibly due to an acetylcholine-dopamine imbalance. Clinicians should be aware of the potential for NMS even with low doses of antipsychotics, particularly in patients who have a limited ability to communicate. Concomitant administration of cholinesterase inhibitors such as rivastigmine may represent an unrecognized risk factor for NMS development.

Topics: Antipsychotic Agents; Benzodiazepines; Cholinesterase Inhibitors; Dementia; Down Syndrome; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Olanzapine; Phenylcarbamates; Rivastigmine

Antipsychotic medication is often prescribed to persons with dementia exhibiting behavioural and psychological symptoms (BPSD). Use of atypical antipsychotics in elderly persons with dementia is associated with an increased risk of serious cerebrovascular adverse events and increased mortality. Based on a review of available literature, we conclude that atypical antipsychotics have a modest effect on BPSD and potentially serious side effects and that conventional antipsychotics appear to have even less favourable effects and adverse event profiles. Antipsychotic medication in patients with dementia exhibiting BPSD should only be prescribed for short-term treatment of severe symptoms associated with considerable distress or serious risk. Non-pharmacological interventions should be the first-line treatment approach in most cases.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Dementia; Haloperidol; Humans; Methotrimeprazine; Middle Aged; Olanzapine; Risk Factors; Risperidone; Stroke

Topics: Aged; Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Catatonia; Chlorpromazine; Cholinesterase Inhibitors; Cognition Disorders; Creatine Kinase; Dementia; Disease Progression; Donepezil; Female; Humans; Indans; Lorazepam; Muscle Rigidity; Neuroleptic Malignant Syndrome; Olanzapine; Piperidines; Recurrence; Risperidone

To estimate the association between use of typical and atypical antipsychotics and all-cause mortality in a population of demented outpatients.. The study cohort comprised all demented patients older than 65 years and registered in the Integrated Primary Care Information (IPCI) database, during 1996-2004. First, mortality rates were calculated during use of atypical and typical antipsychotics. Second, we assessed the association between use of atypical and typical antipsychotics and all-cause mortality through a nested case-control study in the cohort of demented patients. Each case was matched to all eligible controls at the date of death by age and duration of dementia. Odds ratios were estimated through conditional logistic regression analyses.. The crude mortality rate was 30.1 (95%CI: 18.2-47.1) and 25.2 (21.0-29.8) per 100 person-years (PY) during use of atypical and typical antipsychotics, respectively. No significant difference in risk of death was observed between current users of atypical and typical antipsychotics (OR = 1.3; 95%CI: 0.7-2.4). Both types of antipsychotics were associated with a significantly increased risk of death as compared to non-users (OR = 2.2, 1.2-3.9 for atypical antipsychotics; OR=1.7, 1.3-2.2 for typical antipsychotics).. Conventional antipsychotic drug should be included in the FDA's Public Health advisory, which currently warns only of the increased risk of death with the use of atypical antipsychotics in elderly demented persons.

Topics: Age Factors; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cardiovascular Diseases; Case-Control Studies; Cause of Death; Dementia; Effect Modifier, Epidemiologic; Female; Follow-Up Studies; Humans; Male; Netherlands; Odds Ratio; Olanzapine; Outpatients; Sex Factors

The use of atypical antipsychotics (AA) is suggested in the treatment of BPSD, although controversial data are available on their safety and efficacy. The aim of this study was to assess the efficacy and safety of AA and whether this therapy could modify cognitive and functional domains in parallel with BPSD modifications. Out of 1,100 patients followed by the psychogeriatric ambulatory of our hospital, 69 patients (6.2%) were in therapy with AA and only 32 of them fulfilled the inclusion criteria of this study. Namely, the availability was required of a complete geriatric assessment, including the evaluation of cognitive (mini mental state examination=MMSE), emotional (the Italian "scala di valutazione del benessere emotivo nell'anziano"=SVEBA), functional (basic and instrumental activities of daily living=ADL and IADL), as well as behavioral (neuropsychological inventory=NPI) status, at the beginning (T(0)) and after a 6 month therapy (T(1)). The AA prescribed were risperidone (42.8%), olanzapine (31.3%), quetiapine (25.9%). The mean age was 80.1 years; 34.4% male; 65.6% female. Educational level was elementary in 90.6% of cases. Only 21.9% were institutionalized. 15.6% had 1 cardiovascular risk factor (CVRF), 50% more than 1, and the remaining with no CVRF. More than the half of them were diagnosed with degenerative dementia (D) (40.6% Alzheimer D=AD; 15.6% fronto-temporal dementia (FTD); 34.4% with vascular dementia (VD) (9.4%) or combined D (25%); 3,1 % with mild cognitive impairment (MCI), classified as F06.7 by the ICD-10 (International Classification of Diseases) and 6.2% with psychiatric disturbances. The most common BPSD were hallucinations, delusions, agitation, verbal and physical aggression. A paired t-test was applied to analyze data. There was a significant improvement with all 3 AA on NPI (mean NPI T(0)=27.50 vs. T(1)=12.13; t=7.49). An improvement was also observed on SVEBA (t=1.97), close to significance. Most people did not have any adverse effects; 5 patients (15.6%) had extrapyramidal symptoms and 1 (3.1%) showed ginecomasty, clinically so relevant to cause the interruption of the treatment. The profile of safety and efficacy described on the whole sample was confirmed when it was subdivided according to kind of drug, illness severity and presence/absence of CVRF. In a large sample of the "real" subjects attending a geriatric service for dementia, the accurate selection of patients treatable with AA leads to identification of a popula

Topics: Activities of Daily Living; Aged; Antipsychotic Agents; Benzodiazepines; Dementia; Female; Follow-Up Studies; Humans; Institutionalization; Male; Olanzapine; Psychomotor Agitation; Retrospective Studies; Risperidone; Severity of Illness Index

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

To establish the instantaneous relative risk (RR) of death associated with individual antipsychotic drugs, carbamazepine and sodium valproate for those 65 years and older.. Subjects dispensed antipsychotic drugs, sodium valproate or carbamazepine in 2003 or 2004 were analyzed as incident (N = 16,634) or prevalent (N = 9,831) users. Survival curves, mortality rates, and Cox proportional hazards models over two time periods were used to explore risk of death. The models were adjusted for age, sex, residential status, and psychotropic and medical drug dispensing. Olanzapine subjects were the reference group in the Cox regression. Subanalyses were performed for incident subjects with more than 30 days of follow-up and those dispensed cholinesterase inhibitors.. In the adjusted Cox proportional hazards models, haloperidol dispensing was consistently associated with an increased risk of death compared with olanzapine users (relative risk [RR] for incident users: 2.26, 95% confidence intervals (CI): 2.08-2.47; Wald statistic: 345.36, df = 1, p < or =0.001). There was some evidence of decreased survival with dispensing of higher haloperidol doses, although confounding by medical comorbidity cannot be excluded. Chlorpromazine (RR: 1.39, 95% CI: 1.15-1.67; Wald statistic: 12.08, df = 1, p <0.001) and risperidone (RR: 1.23, 95% CI: 1.07-1.40; Wald statistic: 9.12, df = 1, p = 0.003) dispensing were associated with increased risk of death in incident users.. These results should be interpreted cautiously because haloperidol and chlorpromazine are used in broader clinical contexts. However, in the absence of data from randomized trials, the safety profile of haloperidol should not be assumed to be benign. Antipsychotic drugs should not be studied as an aggregated group because their associated risks are not uniform.

Topics: Age Factors; Aged; Aged, 80 and over; Anticonvulsants; Antipsychotic Agents; Australia; Benzodiazepines; Carbamazepine; Cause of Death; Chlorpromazine; Cohort Studies; Dementia; Female; Haloperidol; Humans; Male; Mortality; Olanzapine; Proportional Hazards Models; Retrospective Studies; Risk; Risk Factors; Survival Rate; Valproic Acid; Veterans; Widowhood

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

To report a case of delirium probably caused by the atypical antipsychotic olanzapine in a 74-year-old man with dementia.. A 74-year-old white man with a diagnosis of severe dementia of mixed etiology with behavioral disturbances was admitted to an urban teaching hospital for increasing agitation in the context of worsening dementia. Olanzapine 2.5 mg each evening was started for agitation, and the dose was titrated to 5 mg each evening with additional emergent doses. Memantine, an N-methyl-D-aspartate antagonist, was increased from the admission dose of 10 mg/day to 15 mg/day. The patient developed symptoms of delirium on hospital day 4. Neuroleptic malignant syndrome and other causes of delirium were ruled out. Discontinuation of olanzapine resulted in resolution of the delirium.. Antipsychotic medications are commonly used to treat symptoms of delirium. Atypical antipsychotics are better tolerated in the elderly because of their fewer adverse reactions compared with other antipsychotics. Olanzapine has been successfully used in the treatment of delirium. However, there have been case reports of delirium associated with olanzapine, probably related to its intrinsic anticholinergic effect. Application of the Naranjo probability scale indicated a probable relationship between the onset of delirium and the use of olanzapine in this patient. As of December 1, 2005, this was the second such report of a case in the elderly.. Although olanzapine is useful in the treatment of delirium, elderly patients treated with this drug can develop delirium and hence should be closely monitored.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Delirium; Dementia; Humans; Male; Olanzapine

The objective of this study was to evaluate the association of established risk factors for treatment-emergent diabetes (TED) among patients over 65 years of age with dementia who received treatment with olanzapine.. This was a post hoc analysis of data pooled from seven olanzapine clinical trials, which included patients over 65 years of age with dementia. The association of established risk factors for TED was evaluated using categorical and time-to-event analysis. TED was defined as two casual (fasting or nonfasting) glucose values > or =200 mg/dL at any time after baseline or one casual glucose value > or =200 mg/dL at the final visit, initiation of antidiabetic medication, or new clinical diagnosis of diabetes.. Elderly patients subsequently identified with TED (N = 29, 2.1%) had similar baseline body mass indices (24 kg/m(2)) and were similar in age (82 versus 80 years) to those who did not have TED. Cox proportional hazards model identified only elevated casual glucose (> or =140 mg/dL) measure at baseline to be significantly associated with the development of TED (hazard ratio [HR] = 11.2, p <0.0001) in this elderly cohort. Other clinical risk factors, like body mass index > or =25 (HR = 0.86), 7% weight gain (HR = 2.26), and antipsychotic treatment (HR = 1.36) were not significant.. In elderly patients with dementia enrolled in olanzapine clinical trials, an elevated casual glucose (> or =140 mg/dL) at baseline was the only risk factor significantly associated with subsequent development of TED. Risk of diabetes in these studies was not significantly associated with antipsychotic treatment group assignment.

Topics: Aged; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Clinical Trials as Topic; Cohort Studies; Dementia; Diabetes Mellitus, Type 2; Female; Humans; Male; Olanzapine; Retrospective Studies; Risk Factors

In March 2004, the UK Committee of Safety of Medicines (CSM) informed clinicians that risperidone and olanzapine should not be used to treat behavioural and psychological symptoms of dementia (BPSD) because of increased risk of strokes with both drugs and increased risk of mortality with olanzapine. An audit to examine the implications of the implementation of the CSM guidance was undertaken.. All patients receiving these two drugs, in one psychogeriatric service, at the time of CSM guidance were identified and reviewed. Data on clinical and demographic features, patient and carer involvement in the review and clinical outcome of the efficacy of the overall treatment package at 6 month follow-up was ascertained from the case-notes.. The main findings were: (i) all patients receiving risperidone or olanzapine were identified and reviewed at a median interval of 8 days after the CSM guidance; (ii) most patients and carers were involved in the initial review; (iii) risperidone and olanzapine were discontinued in 22 and 12 of the patients respectively, and in 19 of these patients another neuroleptic was substituted; (iv) there was no relationship between discontinuation of these two drugs and presence of cerebrovascular and cardiovascular risk factors; and, (v) there was no relationship between the clinical outcome of efficacy at six months and discontinuation of these two drugs.. This study illustrates that it is possible to identify, review and follow-up patients on these two drugs and involve the patient and carer in the review, and clinical outcome of efficacy of the overall treatment package is not adversely affected by continuation or discontinuation of these two drugs.

Topics: Administration, Oral; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cardiovascular Diseases; Cerebrovascular Disorders; Dementia; Drug Administration Schedule; Female; Humans; Male; Medical Audit; Olanzapine; Practice Guidelines as Topic; Risk Factors; Risperidone; Treatment Outcome; Withholding Treatment

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Benztropine; Dementia; Drug Resistance; Humans; Muscarinic Antagonists; Olanzapine; Psychotic Disorders; Risperidone

Olanzapine and other antipsychotics are not approved by the U.S. Food and Drug Administration to treat behavioral disturbances associated with dementia, but they are often prescribed to these patients. Although antipsychotics may be efficacious in this population, elderly patients with dementia may be particularly vulnerable to adverse events. This article reviews the safety of olanzapine in elderly patients with dementia.. Data from 6 studies comparing olanzapine to placebo, risperidone, or conventional antipsychotics in elderly patients with dementia were analyzed for mortality, cerebrovascular adverse events (CVAEs), and other adverse events. These trials represent all Lilly olanzapine-comparator trials in this population. The data included integration of 5 double-blind, placebo-controlled studies (olanzapine, N = 1184; placebo, N = 478; median age = 79 years; 1 study also compared olanzapine with risperidone, N = 196) and an open-label study comparing olanzapine (N = 150) with conventional antipsychotics (N = 143).. Incidence of mortality was significantly higher in olanzapine- (3.5%) than in placebo-treated patients (1.5%; p = .024). There were no significant differences in the crude incidence of mortality between olanzapine- (2.9%) and risperidone- (2.0%) or olanzapine- (14.8%) and conventional antipsychotic-treated patients (16.1%; p = .871). Risk factors associated with mortality in olanzapine-treated patients included age >/= 80, concurrent benzodiazepine use, treatment-emergent sedation, or treatment-emergent pulmonary conditions. Incidence of CVAEs was approximately 3 times higher in olanzapine- (1.3%) than in placebo-treated patients (0.4%). There were no significant differences in the incidence of CVAEs between olanzapine- (2.5%) and risperidone- (2.0%; p = 1.0) or olanzapine- (3.4%) and conventional antipsychotic-treated patients (4.3%; p = .765).. These findings should be considered if prescribers elect to treat behavioral disturbances associated with dementia in the elderly with olanzapine or other antipsychotics.

Topics: Age Factors; Aged; Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Dementia; Female; Humans; Male; Olanzapine

The objective was to compare survival in a population-based cohort of elderly demented patients with behavioural and psychological symptoms (BPSD) dispensed an atypical antipsychotic (AA) with that of a sample of demented patients not treated with AAs. An observational cohort study was carried out in the province of Modena, Italy (644,000 inhabitants) on a cohort of 294 patients with BPSD diagnosed by a dementia specialist and treated with an AA, and a cohort of 2020 demented adults not dispensed AAs. All patients were 65 years of age or older. Measured outcomes were death by any cause and death by cerebrovascular accident at the end of the study. After a median follow-up of one year, survival was not significantly different between patients treated and not treated with AAs (overall mortality rates: 0.52 vs. 0.55/1000 years/person, respectively; relative risk reduction 0.047, 95% confidence interval -0.251 to 0.286). Multivariate survival analysis showed that older age at entry, male gender, severe dementia and functional impairment were associated with a higher risk of death. Although our sample size does not allow the exclusion of small differences in the short term, age, gender and dementia severity but not treatment with AAs seem to influence survival among elderly demented patients.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cohort Studies; Dementia; Female; Humans; Italy; Male; Multivariate Analysis; Olanzapine; Risk Factors; Risperidone; Survival Analysis

The case presented highlights the difficult differential diagnosis of memory-sparing cognitive decline in an elderly patient with previously stable bipolar illness. Many disorders can contribute to cognitive and behavioral deterioration in this population, including reversible causes, particularly delirium and psychiatric illness, and irreversible structural or progressive processes including vascular disease, dementia with Lewy bodies, normal-pressure hydrocephalus, and frontotemporal dementia.

Topics: Age of Onset; Aged; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Brain; Cognition Disorders; Dementia; Dementia, Vascular; Disease Progression; Humans; Lithium Compounds; Male; Memory; Mental Disorders; Neuropharmacology; Olanzapine; Psychoses, Substance-Induced; Recovery of Function

Topics: Antipsychotic Agents; Benzodiazepines; Dementia; Humans; Olanzapine; Risk Factors; Risperidone; Stroke

Topics: Antipsychotic Agents; Benzodiazepines; Dementia; Humans; Olanzapine; Risk Factors; Risperidone; Stroke

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

As clinicians we talk about "the best interests of our patients". How can a treatment which doubles the rate of cognitive decline, triples the rate of stroke, doubles mortality, substantially increases falls and fractures and reduces quality of life be beneficial, especially, as in real life, once neuroleptics are started they are rarely discontinued with cumulative adverse effects? As there is clearly no rational reason for prescribing, we need to consider other explanations. We would suggest the following: Therapeutic impotence: Doctors, especially specialists feel they need to do something, and prescribing a familiar drug is the easiest option. Ignorance: Doctors are either unaware of the substantial evidence of harm with neuroleptics or are swayed by slick marketing information, portraying atypical neuroleptics in an "over-safe" light that does not reflect the actual data. Placebo effect: If neuroleptics are prescribed, the majority of patients experience an improvement in BPSD symptoms. This reinforces the apparent value of this practice, as we like to take the credit for any improvements that occur. The reality is that the majority of people would have experienced a comparable improvement with monitoring. Bowing to pressure: Sometimes the pressure to respond can be great, and a prescription is an easy way to relieve the pressure. This is understandable, and reflects a similar phenomenon to that of general practioners prescribing antibiotics for sore throats. In neither situation does it represent good practice. Lack of skills to implement non-pharmacological alternatives: The main evidence for alternative treatment options are for therapies that by and large are not a core part of the physician or psychiatrist's skill-base, such as psychological interventions. Doctors therefore feel uncomfortable pursuing these options. Why for example is so little time spent on the nonpharmacological interventions that everyone agrees should be the first line of treatment for BPSD in people with dementia? It is largely assumed that the "enlightened clinician has already appropriately assessed and diagnosed the patient and exhausted all the possible environmental and behavioral interventions before resorting to the prescription pad." Accumulating evidence clearly indicates that the need for psychotropic medication is substantially reduced by proactive services or interventions which can provide training and promote psychological, social and environmental and sensory

Topics: Accidental Falls; Aged; Antipsychotic Agents; Benzodiazepines; Cerebrovascular Disorders; Cognition; Dementia; Humans; Mental Disorders; Olanzapine; Quality of Life; Risperidone

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Dementia; Geriatric Psychiatry; Humans; Ischemic Attack, Transient; Mental Disorders; Olanzapine; Risperidone; Stroke; United States

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

Concern exists about a possible increased risk of cerebrovascular events (CVEs) among elderly patients receiving risperidone or olanzapine. We estimated the effect of atypical and conventional antipsychotics on the risk of CVEs among elderly nursing home patients with dementia.. We conducted a case-control study on residents of nursing homes in 6 U.S. states by using the Systematic Assessment of Geriatric drug use via Epidemiology database, which includes data from the Minimum Data Set linked to Medicare inpatient claims. Participants were diagnosed with Alzheimer's disease or other forms of dementia on the basis of clinical criteria and medical history (including medical records and neuroradiologic documentation). Cases included patients hospitalized for stroke or transient ischemic attack between June 30, 1998, and December 27, 1999. For each case, we identified up to 5 controls hospitalized for septicemia or urinary tract infection residing in the same facility during the same time period. The sample consisted of 1130 cases and 3658 controls.. After controlling for potential confounders, the odds ratio of being hospitalized for CVEs was 0.87 (95% CI = 0.67 to 1.12) for risperidone users, 1.32 (95% CI = 0.83 to 2.11) for olanzapine users, 1.57 (95% CI = 0.65 to 3.82) for users of other atypical agents, and 1.24 (95% CI = 0.95 to 1.63) for conventional antipsychotic users compared to nonusers of antipsychotics. A history of CVEs appeared to modify the effect of atypical antipsychotics other than risperidone on the risk of new events.. Overall, no increased risk of CVEs seems to be conferred by atypical or conventional antipsychotics. Preexisting cerebrovascular risk factors might interact with some atypical antipsychotics to increase the risk of events. These results should be interpreted in light of the limitations of the study and need to be confirmed.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Case-Control Studies; Cerebrovascular Disorders; Clozapine; Comorbidity; Dementia; Female; Geriatric Assessment; Hospitalization; Humans; Ischemic Attack, Transient; Male; Medical Records Systems, Computerized; Nursing Homes; Odds Ratio; Olanzapine; Risk Factors; Stroke; United States

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

Topics: Antipsychotic Agents; Benzodiazepines; Dementia; Humans; Olanzapine; Risk Factors; Risperidone; Stroke

Randomized controlled trials have suggested that at least one atypical antipsychotic may be associated with an increased risk of stroke in older people with dementia. This study examined the association between atypical antipsychotic use and stroke in the elderly.. The authors conducted a retrospective population-based cohort study of patients over the age of 66 by linking administrative health care databases. Three cohorts-users of typical antipsychotics, risperidone, and olanzapine-were identified and compared.. Subjects treated with typical antipsychotics (N=1,015) were compared with those given risperidone (N=6,964) and olanzapine (N=3,421). Model-based estimates adjusted for covariates hypothesized to be associated with stroke risk revealed relative risk estimates of 1.1 (95% CI=0.5-2.3) for olanzapine and 1.4 (95% CI=0.7-2.8) for risperidone.. Olanzapine and risperidone use were not associated with a statistically significant increased risk of stroke compared with typical antipsychotic use.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Cohort Studies; Comorbidity; Dementia; Female; Geriatric Assessment; Humans; Male; Olanzapine; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Risperidone; Stroke

Topics: Adverse Drug Reaction Reporting Systems; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Dementia; Humans; Olanzapine; Risperidone; Stroke; Treatment Outcome; United Kingdom; United States

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Dementia; Dose-Response Relationship, Drug; Hot Temperature; Humans; Male; Neuroleptic Malignant Syndrome; Olanzapine; Pirenzepine

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

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

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

Hallervorden-Spatz disease is a rare autosomal recessive condition, with early onset of predominantly extrapyramidal dysfunction. The symptoms of the disease are dystonia, rigidity, choreoathetosis, pyramidal signs, and intellectual decline. Recent genetic studies mapped the disease to chromosome 20p12.3-p13, and identified mutations in the pantothenate kinase gene. This report describes a childhood onset case of Hallervorden-Spatz disease with schizophreniform psychotic symptoms. Former reports about the psychiatric comorbidity generally included depressive disorder.. A single case report.. A 14-year-old boy with Hallervorden-Spatz disease presented a psychotic episode with prominent auditory hallucinations. Symptoms were relieved after neuroleptic treatment.. To the authors' knowledge, this is the first published report of the disease with psychotic symptoms. The contribution of basal ganglia, with their wide projections, to the emergence of psychotic symptoms was discussed.

Topics: Acute Disease; Adolescent; Antipsychotic Agents; Benzodiazepines; Comorbidity; Dementia; Dominance, Cerebral; Globus Pallidus; Humans; Magnetic Resonance Imaging; Male; Neurologic Examination; Olanzapine; Pantothenate Kinase-Associated Neurodegeneration; Psychotic Disorders

Olanzapine, an atypical antipsychotic, is often regarded as a safe choice for psychosis management. We hereby report an aged case that presented with conscious depression, bradycardia, hypotension, miosis and hypothermia. Olanzapine was thought to be the offending agent. His condition improved with supportive therapy.

Topics: Age Factors; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Bradycardia; Cardiovascular Diseases; Delusions; Dementia; Humans; Hypotension; Hypothermia; Male; Olanzapine

Dementia with Lewy bodies (DLB) is now a well-recognized form of dementia in which psychosis and behavioural disturbance are common. Treatment with conventional neuroleptics is often very poorly tolerated. Olanzapine, a newly introduced atypical neuroleptic which binds to multiple receptor types with relatively low affinity for D2 receptors, may be a useful treatment option in DLB.. The Behavioural Pathology in Alzheimer's Disease Rating Scale, The Neuropsychiatric Inventory, Unified Parkinson's Disease Rating Scale and The Webster Disability Scale.. We present the results of eight DLB patients with associated psychotic and behavioural difficulties. All patients were given olanzapine 2.5-7.5 mg. Their psychotic phenomena and behavioural and extrapyramidal symptoms were monitored at 2-weekly intervals.. Three out of the eight patients could not tolerate olanzapine even at the lowest available dose. Two patients had clear improvement in psychotic and behavioural symptoms. Three patients were able to tolerate olanzapine but gained only minimal benefit.. Olanzapine at the doses used conferred little advantage over conventional neuroleptics and should only be given with great caution to patients with DLB. The utility of smaller doses deserves further evaluation.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Contraindications; Delusions; Dementia; Depression; Dose-Response Relationship, Drug; Female; Hallucinations; Humans; Lewy Bodies; Male; Olanzapine; Parkinson Disease; Pirenzepine; Treatment Outcome

Twenty-one patients with Parkinson's disease and psychosis were included in an open-label 8-week trial of olanzapine. Eight subjects had dementia. Six subjects (29%) discontinued treatment prematurely because of drowsiness. Delusions and hallucinations improved significantly, and 80% were rated as much or very much improved. There was no worsening of parkinsonism or cognition.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Dementia; Dose-Response Relationship, Drug; Female; Humans; Male; Neuropsychological Tests; Olanzapine; Parkinson Disease; Pirenzepine; Prospective Studies; Psychotic Disorders; Severity of Illness Index; Treatment Outcome