Gill SS, Rochon PA, Herrmann N, et al. Atypical antipsychotic drugs and risk of ischaemic stroke: population based retrospective cohort study. BMJ 330:445

Harvard University, Cambridge, Massachusetts, United States
BMJ (online) (Impact Factor: 16.38). 03/2005; 330(7489):445. DOI: 10.1136/bmj.38330.470486.8F
Source: PubMed

ABSTRACT To compare the incidence of admissions to hospital for stroke among older adults with dementia receiving atypical or typical antipsychotics.
Population based retrospective cohort study.
Ontario, Canada. Patients 32,710 older adults (< or = 65 years) with dementia (17,845 dispensed an atypical antipsychotic and 14,865 dispensed a typical antipsychotic).
Admission to hospital with the most responsible diagnosis (single most important condition responsible for the patient's admission) of ischaemic stroke. Observation of patients until they were either admitted to hospital with ischaemic stroke, stopped taking antipsychotics, died, or the study ended.
After adjustment for potential confounders, participants receiving atypical antipsychotics showed no significant increase in risk of ischaemic stroke compared with those receiving typical antipsychotics (adjusted hazard ratio 1.01, 95% confidence interval 0.81 to 1.26). This finding was consistent in a series of subgroup analyses, including ones of individual atypical antipsychotic drugs (risperidone, olanzapine, and quetiapine) and selected subpopulations of the main cohorts.
Older adults with dementia who take atypical antipsychotics have a similar risk of ischaemic stroke to those taking typical antipsychotics.

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Available from: Walter Wodchis, Aug 24, 2015
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    • "Both atypical and conventional antipsychotics are used in the management of BPSD (Sink et al., 2005; Kales et al., 2007; Ballard et al., 2011). However, prescribing trends heavily favour atypical antipsychotics because of a modest advantage with respect to tolerability and safety (Gill et al., 2005; Schneider et al., 2005). "
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    ABSTRACT: Objectives People with vascular dementia (VaD) are frequently prescribed atypical antipsychotics to treat behavioural and psychological symptoms, but there is an alarming lack of evidence regarding their safety or efficacy in VaD. This study sought to identify the mortality risk associated with the most commonly prescribed atypical antipsychotics in people with VaD compared with people not exposed to these drugs.MethodsA clinical cohort study of 1531 people with VaD performed using anonymised versions of full electronic health records from the Clinical Record Interactive Search application at the South London and Maudsley NHS Foundation Trust. Patients were identified from 2007 to 2010, of whom 337 were exposed to quetiapine, risperidone or olanzapine. The main outcome measure was mortality.ResultsPatients exposed to atypical antipsychotics were not at increased risk of mortality [hazard ratio (HR) 1.05, 95% confidence interval (CI): 0.87–1.26]. Exposure to risperidone did not result in an increased risk of mortality (HR = 0.85; 95% CI: 0.59–1.24), and patients exposed to quetiapine had a non-significant numerical increase in mortality risk (HR = 1.14; 95% CI: 0.93–1.39; p-value = 0.20) compared with untreated patients. Too few patients were exposed to olanzapine alone to provide reliable results.Conclusions The absence of a significant increase in mortality risk associated with atypical antipsychotics in people with VaD indicates that a clinical trial of antipsychotics focussing on the treatment of aggression and agitation in this patient group will be justified and feasible following further consideration of possible confounders, which will be critical to determine the role of antipsychotics in treatment of VaD. Copyright © 2014 John Wiley & Sons, Ltd.
    International Journal of Geriatric Psychiatry 12/2014; 29(12). DOI:10.1002/gps.4101 · 3.09 Impact Factor
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    • "Evidence of an increased risk of cerebrovascular events in BPSD patients treated with atypical antipsychotics prompted safety alerts by the U.K. Committee on the Safety of Medicines and the U.S. Federal Drug Administration (Duff, 2004; FDA Public Health Advisory, 2005). Further studies of patients receiving antipsychotics for BPSD indicate that the risk of cerebrovascular events and increased mortality is similar for typicals and atypicals (Gill et al., 2005; Trifirò et al., 2007). Since the safety alerts, a number of organizations have issued guidance concerning antipsychotic use for BPSD (e.g. "
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    ABSTRACT: Antipsychotics are widely used for the treatment of behavioral and psychological symptoms of dementia (BPSD). In the light of the increased risk of cerebrovascular events, many countries have issued guidelines concerning their use in treating BPSD. We carried out an audit of antipsychotic prescribing practice for inpatients with BPSD at a tertiary referral centre using standards derived from two U.K. dementia guidelines. We collated case note and prescription data and interviewed consultant psychiatrists. Of the 60 patients with dementia 50 (83%) had BPSD; of these, 28 (56%) were receiving antipsychotics. Those prescribed antipsychotics were more likely to have severe BPSD and to be aggressive and/or agitated. Audit of the 28 patients receiving antipsychotics for BPSD showed generally satisfactory results but there was room for improvement in case note documentation of off-label usage, screening for risk factors of cerebrovascular disease, consultation with relatives and use of an appropriate starting dose and slow titration of the antipsychotic. Audit of the use of antipsychotics for BPSD is important given the increased mortality associated with their use. Simple audit tools as used in this study can inform clinical practice. Even at a tertiary referral centre prescribing practice could be improved.
    International Psychogeriatrics 09/2008; 20(4):790-9. DOI:10.1017/S1041610208006819 · 1.89 Impact Factor
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    • "It is thus possible that some of the actual events could have been characterized as non- " cerebrovascular " in origin, although this does not mitigate concern about their seriousness. c) Typical vs. Atypical Antipsychotics: Gill et al. (2005) in a retrospective cohort study reported that, after adjustment for potential confounders, participants receiving atypical antipsychotics showed no significant increase in the risk of ischemic stroke compared with those receiving typical antipsychotics (adjusted hazard ratio 1.0, 95% CI 0.8, 1.3). This finding was consistent in subgroup analyses of individual atypical antipsychotic drugs (risperidone, olanzapine, and quetiapine) and selected subpopulations of the total sample. "
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    ABSTRACT: In elderly persons, antipsychotic drugs are clinically prescribed off-label for a number of disorders outside of their Food and Drug Administration (FDA)-approved indications (schizophrenia and bipolar disorder). The largest number of antipsychotic prescriptions in older adults is for behavioral disturbances associated with dementia. In April 2005, the FDA, based on a meta-analysis of 17 double-blind randomized placebo-controlled trials among elderly people with dementia, determined that atypical antipsychotics were associated with a significantly (1.6-1.7 times) greater mortality risk compared with placebo, and asked that drug manufacturers add a 'black box' warning to prescribing information for these drugs. Most deaths were due to either cardiac or infectious causes, the two most common immediate causes of death in dementia in general. Clinicians, patients, and caregivers are left with unclear choices of treatment for dementia patients with psychosis and/or severe agitation. Not only are psychosis and agitation common in persons with dementia but they also frequently cause considerable caregiver distress and hasten institutionalization of patients. At the same time, there is a paucity of evidence-based treatment alternatives to antipsychotics for this population. Thus, there is insufficient evidence to suggest that psychotropics other than antipsychotics represent an overall effective and safe, let alone better, treatment choice for psychosis or agitation in dementia; currently no such treatment has been approved by the FDA for these symptoms. Similarly, the data on the efficacy of specific psychosocial treatments in patients with dementia are limited and inconclusive. The goal of this White Paper is to review relevant issues and make clinical and research recommendations regarding the treatment of elderly dementia patients with psychosis and/or agitation. The role of shared decision making and caution in using pharmacotherapy for these patients is stressed.
    Neuropsychopharmacology 05/2008; 33(5):957-70. DOI:10.1038/sj.npp.1301492 · 7.83 Impact Factor
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