Dataset Information

Risk of Adverse Outcomes for Older People with Dementia Prescribed Antipsychotic Medication: A Population Based e-Cohort Study.

ABSTRACT:

Introduction

Over recent years there has been growing evidence of increased risk of mortality associated with antipsychotic use in older people with dementia. Although this concern combined with limited evidence of efficacy has informed guidelines restricting antipsychotic prescription in this population, the use of antipsycotics remains common. Many published studies only report short-term outcomes, are restricted to examining mortality and stroke risk or have other limitations. The aim of this study was to assess adverse outcomes associated with the use of antipsychotics in older people living with dementia in Wales (UK).

Methods

This was a retrospective study of a population-based dementia cohort using the Welsh Secure Anonymised Information Linkage databank. The prior event rate ratio (PERR) was used to estimate the influence of exposure to antipsychotic medication on acute cardiac events, venous thromboembolism, stroke and hip fracture, and adjusted Cox proportional hazard models were used to compare all-cause mortality.

Results

A total of 10,339 people aged ≥65 years were identified with newly diagnosed dementia. After excluding those who did not meet the inclusion criteria, 9674 people remained in the main cohort of whom 3735 were exposed to antipsychotic medication. An increased risk of a venous thromboembolic episode [PERR 1.95, 95% confidence interval (CI) 1.83-2.0], stroke (PERR 1.41, 95% CI 1.4-1.46) and hip fracture (PERR 1.62, 95% CI 1.59-1.65) was associated with antipsychotic use. However, there was no long-term increased mortality in people exposed to antipsychotics (adjusted hazard ratio 1.06, 95% CI 0.99-1.13).

Conclusions

The increase in adverse medical events supports guidelines restricting antipsychotic use in this population.

SUBMITTER: Dennis M

PROVIDER: S-EPMC5447553 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ObjectivesTo investigate the association between antidepressant treatment and risk of several potential adverse outcomes in older people with depression and to examine risks by class of antidepressant, duration of use, and dose.DesignCohort study of people aged 65 and over diagnosed as having depression.Setting570 general practices in the United Kingdom supplying data to the QResearch primary care database.Participants60,746 patients diagnosed as having a new episode of depression between the ages of 65 and 100 years from 1 January 1996 to 31 December 2007 and followed up until 31 December 2008.Main outcome measuresHazard ratios associated with antidepressant use for all cause mortality, attempted suicide/self harm, myocardial infarction, stroke/transient ischaemic attack, falls, fractures, upper gastrointestinal bleeding, epilepsy/seizures, road traffic accidents, adverse drug reactions, and hyponatraemia, adjusted for a range of potential confounding variables. Hazard ratios were calculated for antidepressant class (tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants), dose, and duration of use and for commonly prescribed individual drugs.Results54,038 (89.0%) patients received at least one prescription for an antidepressant during follow-up. A total of 1,398,359 antidepressant prescriptions were issued: 764,659 (54.7%) for selective serotonin reuptake inhibitors, 442,192 (31.6%) for tricyclic antidepressants, 2203 (0.2%) for monoamine oxidase inhibitors, and 189,305 (13.5%) for the group of other antidepressants. The associations with the adverse outcomes differed significantly between the antidepressant classes for seven outcomes. Selective serotonin reuptake inhibitors were associated with the highest adjusted hazard ratios for falls (1.66, 95% confidence interval 1.58 to 1.73) and hyponatraemia (1.52, 1.33 to 1.75) compared with when antidepressants were not being used. The group of other antidepressants was associated with the highest adjusted hazard ratios for all cause mortality (1.66, 1.56 to 1.77), attempted suicide/self harm (5.16, 3.90 to 6.83), stroke/transient ischaemic attack (1.37, 1.22 to 1.55), fracture (1.64, 1.46 to 1.84), and epilepsy/seizures (2.24, 1.60 to 3.15), compared with when antidepressants were not being used. Tricyclic antidepressants did not have the highest hazard ratio for any of the outcomes. Significantly different associations also existed between the individual drugs for the same seven outcomes; trazodone (tricyclic antidepressant), mirtazapine, and venlafaxine (both in the group of other antidepressants) were associated with the highest rates for some of these outcomes. Absolute risks over 1 year for all cause mortality were 7.04% for patients while not taking antidepressants, 8.12% for those taking tricyclic antidepressants, 10.61% for selective serotonin reuptake inhibitors, and 11.43% for other antidepressants.ConclusionsSelective serotonin reuptake inhibitors and drugs in the group of other antidepressants were associated with an increased risk of several adverse outcomes compared with tricyclic antidepressants. Among individual drugs, trazodone, mirtazapine, and venlafaxine were associated with the highest risks for some outcomes. As this is an observational study, it is susceptible to confounding by indication, channelling bias, and residual confounding, so differences in characteristics between patients prescribed different antidepressant drugs that could account for some of the associations between the drugs and the adverse outcomes may remain. Further research is needed to confirm these findings, but the risks and benefits of different antidepressants should be carefully evaluated when these drugs are prescribed to older people.

Project description:BackgroundLittle is known about how multimorbidity, dementia and increasing age combine to influence health outcomes or utilization. Our objective was to examine the joint associations between age, dementia and burden of morbidity with mortality and other clinical outcomes.MethodsWe did a retrospective population-based cohort study of all adults aged 65 years and older residing in Alberta, Canada, between 2002 and 2013. We used validated algorithms applied to administrative and laboratory data from the provincial health ministry to assess the presence/absence of dementia and 29 other morbidities, and their associations with mortality (our primary outcome), other clinical outcomes (emergency department visits, all-cause hospital admissions) and a proxy for loss of independent living (discharge to long-term care). Cox and Poisson models were adjusted for year-varying covariates. A 3-way interaction was modelled for dementia, the number of comorbidities, and age.ResultsThere were 610 457 adults aged 65 years and older living in Alberta over the study period. Over median follow-up of 6.8 years, 153 125 (25.1%) participants died and 5569 (0.9%) were discharged to long-term care. The prevalence of people with at least 3 morbidities was 33.7% in 2003 and 50.2% in 2012. The prevalence of dementia rose from 6.2% in fiscal year 2003 to 8.3% in fiscal year 2012, representing a net increase of approximately 13 700 people. The likelihood of all 4 outcomes increased with age and with greater burden of morbidity; the presence of dementia further increased these risks. For example, the risk of mortality increased by 1.54 to 6.38 in the presence of dementia, depending on age and morbidity burden. The risk associated with dementia was attenuated by increasing comorbidity.InterpretationOlder age, multimorbidity and dementia are all strongly correlated with adverse health outcomes as well as a proxy for loss of independent living. The increasing prevalences of dementia and multimorbidity over time suggest the need for coordinated national strategies aimed at mitigating the health challenges associated with the aging of the population.

Project description:Antipsychotic treatments are associated with safety concerns in people with dementia. The authors aimed to investigate whether risk of adverse outcomes related to antipsychotic prescribing differed according to major neuropsychiatric syndromes-specifically psychosis, agitation, or a combination. A cohort of 10,106 patients with a diagnosis of dementia was assembled from a large dementia care database in South East London. Neuropsychiatric symptoms closest to first dementia diagnosis were determined according to the Health of the Nation Outcome Scales' mental and behavioural problem scores and the sample was divided into four groups: 'agitation and psychosis', 'agitation, but no psychosis', 'psychosis, but no agitation', and 'neither psychosis nor agitation'. Antipsychotic prescription in a one-year window around first dementia diagnosis was ascertained as exposure variable through natural language processing from free text. Cox regression models were used to analyse associations of antipsychotic prescription with all-cause and stroke-specific mortality, emergency hospitalisation and hospitalised stroke adjusting for sixteen potential confounders including demographics, cognition, functioning, as well as physical and mental health. Only in the group 'psychosis, but no agitation' (n = 579), 30% of whom were prescribed an antipsychotic, a significant antipsychotic-associated increased risk of hospitalised stroke was present after adjustment (adjusted hazard ratio (HR) 2.16; 95% confidence interval (CI) 1.09-4.25). An increased antipsychotic-related all-cause (adjusted HR 1.14; 95% CI 1.04-1.24) and stroke-specific mortality risk (adjusted HR 1.28; 95% CI 1.01-1.63) was detected in the whole sample, but no interaction between the strata and antipsychotic-related mortality. In conclusion, the adverse effects of antipsychotics in dementia are complex. Stroke risk may be highest when used in patients presenting with psychosis without agitation, indicating the need for novel interventions for this group.

Project description:IntroductionThere are robust associations between use of anticholinergic medicines and adverse effects in older people. However, the nature of these associations for older people living with frailty is yet to be established.ObjectivesThe aims were to identify and investigate associations between anticholinergics and adverse outcomes in older people living with frailty and to investigate whether exposure is associated with greater risks according to frailty status.MethodsMEDLINE, CINAHL, EMBASE, Cochrane Database of Systematic Reviews, Web of Science and PsycINFO were searched to 1 August 2019. Observational studies reporting associations between anticholinergics and outcomes in older adults (average age ≥ 65 years) that reported frailty using validated measures were included. Primary outcomes were physical impairment, cognitive dysfunction, and change in frailty status. Risk of bias was evaluated using the Cochrane Risk of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool. Meta-analysis was undertaken where appropriate.ResultsThirteen studies (21,516 participants) were included (ten community, one residential aged-care facility and two hospital studies). Observed associations included reduced ability for chair standing, slower gait speeds, poorer physical performance, increased risk of falls and mortality. Conflicting results were reported for grip strength, timed up and go test, cognition and activities of daily living. No associations were observed for transitions between frailty states, psychological wellbeing or benzodiazepine-related adverse reactions. There was no clear evidence of differences in risks according to frailty status.ConclusionsAnticholinergics are associated with adverse outcomes in older people living with frailty; however, the literature has significant methodological limitations. There is insufficient evidence to suggest greater risks based on frailty, and there is an urgent need to evaluate this further in well-designed studies stratifying by frailty.

Project description:BackgroundSleep disturbance is common in dementia and often treated with Z-drugs (zopiclone, zaleplon, and zolpidem). While some observational studies suggest that Z-drugs are associated with adverse events such as falls and fracture risks in older people, this has not been studied in dementia.MethodsWe used data from 27,090 patients diagnosed with dementia between January 2000 and March 2016 from the Clinical Practice Research Datalink linked to Hospital Episodes Statistics data in England. We compared adverse events for 3532 patients newly prescribed Z-drugs by time-varying dosage to (1) 1833 non-sedative-users with sleep disturbance; (2) 10,214 non-sedative-users with proximal GP consultation matched on age, sex, and antipsychotic use; and (3) 5172 patients newly prescribed benzodiazepines. We defined higher dose Z-drugs and benzodiazepines as prescriptions equivalent to ≥ 7.5 mg zopiclone or > 5 mg diazepam daily. Cox regression was used to estimate hazard ratios (HRs) for incident fracture, hip fracture, fall, mortality, acute bacterial infection, ischaemic stroke/transient ischaemic attack, and venous thromboembolism over a 2-year follow-up, adjusted for demographic- and health-related covariates.ResultsThe mean (SD) age of patients was 83 (7.7) years, and 16,802 (62%) were women. Of 3532 patients prescribed Z-drugs, 584 (17%) were initiated at higher doses. For patients prescribed higher dose Z-drugs relative to non-users with sleep disturbance, the HRs (95% confidence interval) for fractures, hip fractures, falls, and ischaemic stroke were 1.67 (1.13-2.46), 1.96 (1.16-3.31), 1.33 (1.06-1.66), and 1.88 (1.14-3.10), respectively. We observed similar associations when compared to non-sedative-users with proximal GP consultation. Minimal or inconsistent excess risks were observed at ≤ 3.75 mg zopiclone or equivalent daily, and for mortality, infection, and venous thromboembolism. We observed no differences in adverse events for Z-drugs compared to benzodiazepines, except lower mortality rates with Z-drugs (HR [95% confidence interval] of 0.73 [0.64-0.83]).ConclusionsHigher dose Z-drug use in dementia is associated with increased fracture and stroke risks, similar or greater to that for higher dose benzodiazepines. Higher dose Z-drugs should be avoided, if possible, in people living with dementia, and non-pharmacological alternatives preferentially considered. Prescriptions for higher dose Z-drugs in dementia should be regularly reviewed.Trial registrationENCePP e-register of studies, EUPAS18006.

Project description:BackgroundThe growing burden associated with population aging, dementia and multimorbidity poses potential challenges for the sustainability of health systems worldwide. We sought to examine how the intersection among age, dementia and greater multimorbidity is associated with health care costs.MethodsWe did a retrospective population-based cohort study in Alberta, Canada, with adults aged 65 years and older between April 2003 and March 2017. We identified 31 morbidities using algorithms (30 algorithms were validated), which were applied to administrative health data, and assessed costs associated with hospital admission, provider billing, ambulatory care, medications and long-term care (LTC). Actual costs were used for provider billing and medications; estimated costs for inpatient and ambulatory patients were based on the Canadian Institute for Health Information's resource intensive weights and Alberta's cost of a standard hospital stay. Costs for LTC were based on an estimated average daily cost.ResultsThere were 827 947 people in the cohort. Dementia was associated with higher mean annual total costs and individual mean component costs for almost all age categories and number of comorbidities categories (differences in total costs ranged from $27 598 to $54 171). Similarly, increasing number of morbidities was associated with higher mean total costs and component costs (differences in total costs ranged from $4597 to $10 655 per morbidity). Increasing age was associated with higher total costs for people with and without dementia, driven by increasing LTC costs (differences in LTC costs ranged from $115 to $9304 per age category). However, there were no consistent trends between age and non-LTC costs among people with dementia. When costs attributable to LTC were excluded, older age tended to be associated with lower costs among people with dementia (differences in non-LTC costs ranged from -$857 to -$7365 per age category).InterpretationMultimorbidity, older age and dementia were all associated with increased use of LTC and thus health care costs, but some costs among people with dementia decreased at older ages. These findings illustrate the complexity of projecting the economic consequences of the aging population, which must account for the interplay between multimorbidity and dementia.