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      Movement Disorders in Elderly Users of Risperidone and First Generation Antipsychotic Agents: A Canadian Population-Based Study

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          Abstract

          Background

          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.

          Methods

          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.

          Results

          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.

          Conclusions

          In a large population of elderly patients the use of risperidone was associated with a lower risk of EPS compared to FGAs.

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          Most cited references27

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          Atypical antipsychotic drugs and the risk of sudden cardiac death.

          Users of typical antipsychotic drugs have an increased risk of serious ventricular arrhythmias and sudden cardiac death. However, less is known regarding the cardiac safety of the atypical antipsychotic drugs, which have largely replaced the older agents in clinical practice. We calculated the adjusted incidence of sudden cardiac death among current users of antipsychotic drugs in a retrospective cohort study of Medicaid enrollees in Tennessee. The primary analysis included 44,218 and 46,089 baseline users of single typical and atypical drugs, respectively, and 186,600 matched nonusers of antipsychotic drugs. To assess residual confounding related to factors associated with the use of antipsychotic drugs, we performed a secondary analysis of users of antipsychotic drugs who had no baseline diagnosis of schizophrenia or related psychoses and with whom nonusers were matched according to propensity score (i.e., the predicted probability that they would be users of antipsychotic drugs). Current users of typical and of atypical antipsychotic drugs had higher rates of sudden cardiac death than did nonusers of antipsychotic drugs, with adjusted incidence-rate ratios of 1.99 (95% confidence interval [CI], 1.68 to 2.34) and 2.26 (95% CI, 1.88 to 2.72), respectively. The incidence-rate ratio for users of atypical antipsychotic drugs as compared with users of typical antipsychotic drugs was 1.14 (95% CI, 0.93 to 1.39). Former users of antipsychotic drugs had no significantly increased risk (incidence-rate ratio, 1.13; 95% CI, 0.98 to 1.30). For both classes of drugs, the risk for current users increased significantly with an increasing dose. Among users of typical antipsychotic drugs, the incidence-rate ratios increased from 1.31 (95% CI, 0.97 to 1.77) for those taking low doses to 2.42 (95% CI, 1.91 to 3.06) for those taking high doses (P<0.001). Among users of atypical agents, the incidence-rate ratios increased from 1.59 (95% CI, 1 .03 to 2.46) for those taking low doses to 2.86 (95% CI, 2.25 to 3.65) for those taking high doses (P=0.01). The findings were similar in the cohort that was matched for propensity score. Current users of typical and of atypical antipsychotic drugs had a similar, dose-related increased risk of sudden cardiac death. 2009 Massachusetts Medical Society
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            Development and application of a population-oriented measure of ambulatory care case-mix.

            This article describes a new case-mix methodology applicable primarily to the ambulatory care sector. The Ambulatory Care Group (ACG) system provides a conceptually simple, statistically valid, and clinically relevant measure useful in predicting the utilization of ambulatory health services within a particular population group. ACGs are based on a person's demographic characteristics and their pattern of disease over an extended period of time, such as a year. Specifically, the ACG system is driven by a person's age, sex, and ICD-9-CM diagnoses assigned during patient-provider encounters; it does not require any special data beyond those collected routinely by insurance claims systems or encounter forms. The categorization scheme does not depend on the presence of specific diagnoses that may change over time; rather it is based on broad clusters of diagnoses and conditions. The presence or absence of each disease cluster, along with age and sex, are used to classify a person into one of 51 ACG categories. The ACG system has been developed and tested using computerized encounter and claims data from more than 160,000 continuous enrollees at four large HMOs and a state's Medicaid program. The ACG system can explain more than 50% of the variance in ambulatory resource use if used retrospectively and more than 20% if applied prospectively. This compares with 6% when age and sex alone are used. In addition to describing ACG development and validation, this article also explores some potential applications of the system for provider payment, quality assurance, utilization review, and health services research, particularly as it relates to capitated settings.
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              Antipsychotic drug use and mortality in older adults with dementia.

              Antipsychotic drugs are widely used to manage behavioral and psychological symptoms in dementia despite concerns about their safety. To examine the association between treatment with antipsychotics (both conventional and atypical) and all-cause mortality. Population-based, retrospective cohort study. Ontario, Canada. Older adults with dementia who were followed between 1 April 1997 and 31 March 2003. The risk for death was determined at 30, 60, 120, and 180 days after the initial dispensing of antipsychotic medication. Two pairwise comparisons were made: atypical versus no antipsychotic use and conventional versus atypical antipsychotic use. Groups were stratified by place of residence (community or long-term care). Propensity score matching was used to adjust for differences in baseline health status. A total of 27,259 matched pairs were identified. New use of atypical antipsychotics was associated with a statistically significant increase in the risk for death at 30 days compared with nonuse in both the community-dwelling cohort (adjusted hazard ratio, 1.31 [95% CI, 1.02 to 1.70]; absolute risk difference, 0.2 percentage point) and the long-term care cohort (adjusted hazard ratio, 1.55 [CI, 1.15 to 2.07]; absolute risk difference, 1.2 percentage points). Excess risk seemed to persist to 180 days, but unequal rates of censoring over time may have affected these results. Relative to atypical antipsychotic use, conventional antipsychotic use was associated with a higher risk for death at all time points. Sensitivity analysis revealed that unmeasured confounders that increase the risk for death could diminish or eliminate the observed associations. Information on causes of death was not available. Many patients did not continue their initial treatments after 1 month of therapy. Unmeasured confounders could affect associations. Atypical antipsychotic use is associated with an increased risk for death compared with nonuse among older adults with dementia. The risk for death may be greater with conventional antipsychotics than with atypical antipsychotics.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                16 May 2013
                : 8
                : 5
                : e64217
                Affiliations
                [1 ]Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada
                [2 ]Department of Accounting and Finance, Asper School of Business, University of Manitoba, Winnipeg, Manitoba, Canada
                [3 ]Department of Psychiatry, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
                University of Montreal, Canada
                Author notes

                Competing Interests: Silvia Alessi-Severini is an academic editor for PLOS ONE. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: IV RGB CJM MWE SAS. Performed the experiments: IV RGB SAS. Analyzed the data: IV RGB SAS. Wrote the paper: SAS IV MWE CJM.

                Article
                PONE-D-13-03065
                10.1371/journal.pone.0064217
                3656145
                23696870
                32cca983-8a33-42c6-8fb9-296d9e115b34
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 18 January 2013
                : 12 April 2013
                Page count
                Pages: 7
                Funding
                This work was funded in part by a grant from the Manitoba Medical Service Foundation. Irina Vasilyeva was supported by the Manitoba Health Research Council Graduate Studentship Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Population Biology
                Epidemiology
                Medicine
                Drugs and Devices
                Adverse Reactions
                Pharmacoepidemiology
                Psychopharmacology
                Epidemiology
                Pharmacoepidemiology
                Geriatrics
                Mental Health
                Psychiatry
                Public Health

                Uncategorized
                Uncategorized

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