Gill SS, Rochon PA, Herrmann N, Lee PE, Sykora K, Gunraj 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: 17.45). 03/2005; 330(7489):445. DOI: 10.1136/bmj.38330.470486.8F
Source: PubMed


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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    • "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.
    Full-text · Article · Dec 2014 · International Journal of Geriatric Psychiatry
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    • "Systematic reviews and meta-analyses have indicated that some typical antipsychotics (Schneider et al., 1990; Lanctot et al., 1998), atypical antipsychotics (Ballard and Waite, 2006; Schneider et al., 2006b), and antidepressants (Seitz et al., 2011) may have benefits in treating certain NPS, although the magnitude of benefit may be limited and potentially outweighed by adverse events. Atypical antipsychotics, the most extensively studied and utilized medications for NPS, are also associated with serious adverse events such as death (Schneider et al., 2005; Wang et al., 2005; Gill et al., 2007) or stroke (Herrmann et al., 2004, Gill et al., 2005), as well as falls (Hien Le et al., 2005), sedation (Schneider et al., 2006a), and cognitive decline (Schneider et al., 2006a; Vigen et al., 2011). Although there has been a decline in the use of antipsychotics with dementia recently, these medications continue to be used frequently (Kales et al., 2011). "
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    ABSTRACT: Background: Medications are frequently prescribed for neuropsychiatric symptoms (NPS) associated with dementia, although information on the efficacy and safety of medications for NPS specifically in long-term care (LTC) settings is limited. The objective of this study was to provide a current review of the efficacy and safety of pharmacological treatments for NPS in LTC. Methods: We searched MEDLINE, EMBASE, PsychINFO, and the Cochrane Library for randomized controlled trials comparing medications with either placebo or other interventions in LTC. Study quality was described using the Cochrane collaboration risk of bias tool. The efficacy of medications was evaluated using NPS symptom rating scales. Safety was evaluated through rates of trial withdrawals, trial withdrawals due to adverse events, and mortality. Results: A total of 29 studies met inclusion criteria. The most common medications evaluated in studies were atypical antipsychotics (N = 15), typical antipsychotics (N = 7), anticonvulsants (N = 4), and cholinesterase inhibitors (N = 3). Statistically significant improvements in NPS were noted in some studies evaluating risperidone, olanzapine, and single studies of aripiprazole, carbamazepine, estrogen, cyproterone, propranolol, and prazosin. Study quality was difficult to rate in many cases due to incomplete reporting of details. Some studies reported higher rates of trial withdrawals, adverse events, and mortality associated with medications. Conclusions: We conclude that there is limited evidence to support the use of some atypical antipsychotics and other medications for NPS in LTC populations. However, the generally modest efficacy and risks of adverse events highlight the need for the development of safe and effective pharmacological and non-pharmacological interventions for this population.
    Full-text · Article · Oct 2012 · International Psychogeriatrics
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    • "In a recent population based retrospective cohort study Gill [51] identified 32,710 older adults with dementia (17,845 dispensed atypical antipsychotics and 14,865 dispensed typical antipsychotics). In this population based cohort, older adults with BPSD who received atypical antipsychotic drugs seem to have a similar risk of admission to hospital for ischemic stroke as those receiving typical antipsychotic drugs. "
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    ABSTRACT: Pharmacological treatment and several drugs of abuse have been associated with ischemic heart disease (IHD) and cerebrovascular diseases (CVD). However, there is a paucity of data on the independent risk of vascular disease (VD) associated with pharmacological treatment and no controlled trials demonstrating a reduction in risk with abstinence. Information about IHD and CVD-related drug abuse is mainly limited to epidemiological studies focused on urban populations. The potential link between some pharmacological treatments (estrogen, some oncologic drugs and some atypical antipsychotics) and cerebrovascular adverse events was analyzed, but disagreement about an association persists. Drugs of abuse, including cocaine, amphetamines and heroin, have been associated with an increased vascular risk. These drugs can cause abrupt changes in blood pressure, vasculitic-type changes, lead to embolization caused by infective endocarditis, and hemostatic and hematologic abnormalities that can result in increased blood viscosity and platelet aggregation. Long-term treatment strategies based on medication, psychological support, and outreach programs play an important role in treatment of drug dependency. In these last years public interest in risk factors for VD has been constantly increasing and the successful identification and management of pharmacological treatment and drug abuse can be challenging. One of the major public health issues for the future will be to focus more on new vascular risk factor recognition and management. The objective of this chapter is to review the relevance of IHD and CVD associated with various pharmacological treatments and drug abuse with focusing on ischemic disease. This chapter reports the clinical evidence of this association and analyzes the experimental role of new drugs as a growing risk factor of VD with the hypothetical new association. In conclusion, in this chapter great attention is paid to evaluating the scientific and real evidence of cerebrovascular effect and drug use and abuse so as to identify a new groups of “modifiable” risk factors.
    Full-text · Article · Jun 2010 · The Open Neurology Journal
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