Antipsychotic drug use and mortality in older adults in dementia

University of Toronto, Toronto, Ontario, Canada
Annals of internal medicine (Impact Factor: 17.81). 07/2007; 146(11):775-86.
Source: PubMed


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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    • "This study did not show any difference in mortality between those who received antipsychotics at the start of the study and those who did not. Several studies have reported an increased mortality among people prescribed antipsychotics, [13,14] while other studies have not - for example one study that found no association between antipsychotics and cerebrovascular events compared to benzodiazepines [40]. A selection effect, where the healthier persons were possibly prescribed antipsychotics more frequently, might have contributed to our results considering mortality and antipsychotics. "
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    ABSTRACT: Antipsychotic drugs are widely used for the treatment of Behavioral and Psychological Symptoms of Dementia (BPSD), despite their limited efficacy and concerns about safety. The aim of this study was to describe antipsychotic drug therapy among people with dementia living in specialized care units in northern Sweden. This study was conducted in 40 specialized care units in northern Sweden, with a total study population of 344 people with dementia. The study population was described in regard to antipsychotic drug use, ADL function, cognitive function and BPSD, using the Multi-Dimensional Dementia Assessment Scale (MDDAS). These data were collected at baseline and six months later. Detailed data about antipsychotic prescribing were collected from prescription records. This study showed that 132 persons (38%) in the study population used antipsychotic drugs at the start of the study. Of these, 52/132 (39%) had prescriptions that followed national guidelines with regard to dose and substance. After six months, there were 111 of 132 persons left because of deaths and dropouts. Of these 111 people, 80 (72%) were still being treated with antipsychotics, 63/111 (57%) with the same dose. People who exhibited aggressive behavior (OR: 1.980, CI: 1.515-2.588), or passiveness (OR: 1.548, CI: 1.150-2.083), or had mild cognitive impairment (OR: 2.284 CI: 1.046-4.988), were at increased risk of being prescribed antipsychotics. The prevalence of antipsychotic drug use among people with dementia living in specialized care units was high and inappropriate long-term use of antipsychotic drugs was common.
    No preview · Article · Feb 2013 · BMC pharmacology & toxicology
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    • "Controlled trials and observational studies of older adults with dementia have indicated that LTC residents have more advanced age, more severe cognitive impairment, higher rates of comorbidity (Schneider et al., 2006a; Gill et al., 2007; Rochon, 2008), and receive lower quality of routine and preventative care (Fahey et al., 2003) than outpatient or hospital populations. In addition, higher rates of mortality have been observed for LTC residents with dementia newly started on antipsychotics when compared with communitydwelling populations (Gill et al., 2007; Rochon et al., 2008). For these reasons, LTC residents may be particularly susceptible to mortality and other adverse events associated with psychotropic use which may have been underestimated in previous reviews which included both LTC and other populations within the same review. "
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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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    • "Absolute risks, however, varied between studies according to the method employed to control for confounding. Conventional statistical methods adjusting for measured covariates suggested an increased risk over 6 months of between 2 and 3 deaths per 100 patients treated with conventional compared to atypical antipsychotics [22,27,56] while those that used an instrumental variable analysis, to adjust for unmeasured confounding, found an increased risk of between 4 and 7 deaths per 100 patients treated over 6 months [28,29] and up to 10 deaths per 100 over 12 months [31]. Only one observational cohort study [26] and one case–control study [23] found no significant difference between the classes. "
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    ABSTRACT: Antipsychotics are frequently and increasingly prescribed to treat the behavioural symptoms associated with dementia despite their modest efficacy. Evidence regarding the potential adverse events of antipsychotics is limited and little is known about the longer-term safety of these medicines in the elderly. The aim of this review was to determine the impact of the choice of observational study design and methods used to control for confounding on the measurement of antipsychotic risks in elderly patients. We searched PUBMED and the Cochrane controlled trials register for double-blind randomised controlled trials (RCTs), meta-analyses and published observational studies of antipsychotics. Forty four studies were identified for the endpoints; death, cerebrovascular events, hip fracture and pneumonia. RCTs found a 20% to 30% increased risk of death, or an absolute increase of 1extra death per 100 patients with atypical antipsychotics compared to non-use. Cohort and instrumental variable analyses estimated between 2 to 7 extra deaths per 100 patients with conventional compared to atypical antipsychotics. RCTs found a 2 to 3 times increased risk of all cerebrovascular events with atypical antipsychotics compared to placebo and no association with serious stroke that required hospitalisation. Observational studies using cohort and self-controlled case-series designs reported similar results; no association where the endpoint was stroke causing hospitalisation and a doubling of risk when minor stroke was included. No RCTs were available for the outcome of hip fracture or pneumonia. Observational studies reported a 20% to 40% increased risk of hip fracture with both antipsychotic classes compared to non-use. The risk of pneumonia was a 2 to 3 times greater with both classes compared to non-use while a self-controlled case-series study estimated a 60% increased risk. Conventional antipsychotics were associated with a 50% greater hip fracture risk than atypical antipsychotics, while the risk of pneumonia was similar between the classes. Choice of observational study design is critical in studying the adverse effects of antispychotics. Cohort and instrumental variable analyses gave more consistent results to clinical studies for mortality outcomes as have self-controlled case-series for the risk of cerebrovascular events and stroke. Observational evidence has highlighted the potential for antipsychotics to be associated with serious adverse events that were not reported in RCTs including hip fracture and pneumonia. Good quality observational studies are required, that employ appropriate study designs that are robust towards unmeasured confounding, to confirm the potential excess risk of hip fracture and pneumonia with antipsychotics.
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