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Objective: The proportion of long-term care (LTC) residents being treated with antipsychotic medication is high, and these medications may exacerbate behavioral symptoms. We used propensity scores to investigate the effect of antipsychotic use on the worsening of behavioral symptoms among residents in LTC facilities., Design: A retrospective study., Setting and Participants: Residents in LTC in 8 provinces and 1 territory in Canada, without severe aggressive behavior at baseline and reassessed at follow-up, between March 2000 and March 2022., Methods: We used propensity score matching and weighting to balance baseline covariates and logistic regression to estimate the effect of antipsychotics on the worsening of behavioral symptoms in the original, matched, and weighted cohorts. The treatment variable was use of antipsychotic medication at baseline and the outcome was worsening of behavior at follow-up., Results: A total of 494,215 participants were included [318,234 women and 175,981 men; mean age 82.8 years (SD 10.1; range 18-112)].130 558 (26.4%) used antipsychotics at baseline and 88,632 (17.9%) had worsening behavior in follow-up. In the matched cohort, there were 249,698 participants, and 124,849 were matched (1:1) in each treatment group. There was a significant association between antipsychotic use at baseline and worsening in behavior at follow-up in the adjusted regression models [OR 1.27 (95% CI 1.25-1.29), <0.0001] as well as in matched [OR 1.20 (95% CI 1.17-1.21), <0.0001] and weighted [OR 1.26 (95% CI 1.24-1.28), <0.0001] cohorts., Conclusions and Implications: This study further evidence to support the cautious use of antipsychotics in LTC facilities. Future research in LTC facilities could include a more granular analyses of behavior change, including bidirectional analyses between different symptom severity classifications., Competing Interests: Disclosures The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Little is known about the comparative risk of death with atypical or conventional antipsychotics (APs) among persons with cardiovascular or cerebrovascular disease (CCD)., Research Design and Methods: A cohort study was conducted using five Italian claims databases. New atypical AP users with CCD aged ≥65 (reference) were matched to new conventional AP users. Mortality per 100 person-years (PYs) and hazard ratios (HR), estimated using Cox models, were reported. Incidence and risk of death were estimated for persons having drug-drug interactions. Outcome occurrence was evaluated 180 days after AP initiation., Results: Overall 24,711 and 27,051 elderly new conventional and atypical AP users were identified. The mortality rate was 51.3 and 38.5 deaths per 100 PYs for conventional and atypical AP users. Mortality risk was 1.33 (95%CI: 1.27-1.39) for conventional APs. There was no increased mortality risk with single drug-drug interactions (DDIs) vs. no DDI. AP users with ≥1 DDI had a 29% higher mortality risk compared to no DDI in the first 90 days of treatment (HR: 1.29 (95% CI: 1.00-1.67))., Conclusions: Conventional APs had a higher risk of death than atypical APs among elderly persons with CCD. Having ≥1 DDI was associated with an increased risk of death.

Objective: Among elderly individuals with dementia, the use of antipsychotics has been associated with serious adverse events including ischemic stroke and death. Multiple medications can interact with antipsychotics and increase the risk of such adverse events. The purpose of this retrospective, longitudinal cohort study was to estimate the prevalence of potential antipsychotic drug interactions and their effect on increasing the risk of death among cognitively impaired elderly individuals treated with antipsychotics., Methods: We conducted a retrospective longitudinal cohort study in 59 nursing homes of 7 European Union countries and Israel. The study was conducted during the years 2009 to 2011. Participants were cognitively impaired individuals aged 65 years or older residing in the participating nursing homes and being treated with antipsychotics (N = 604). Risk of death associated with potential antipsychotic drug interactions was the main outcome. The inter-Resident Assessment Instrument for Long Term Care Facilities (interRAI LTCF) was used to assess participants. Follow-up time was 12 months., Results: The prevalence of potential antipsychotic drug interactions was 46.0%. Antipsychotic drug interactions were associated with higher mortality (incidence rate of 0.26 per person-year in the antipsychotic drug-interaction group versus 0.17 per person year in the no antipsychotic drug-interaction group). After adjusting for potential confounders, risk of death was higher in the group of residents with potential antipsychotic drug interactions relative to those unexposed to such interactions (hazard ratio = 1.71; 95% CI, 1.15-2.54)., Conclusions: Part of the observed excess risk of death associated with the use of antipsychotic medications in elderly individuals with cognitive impairment may be attributable to antipsychotic drug interactions. Antipsychotics should be used with extreme caution especially among those individuals receiving concomitant cardiovascular or psychotropic medications., (© Copyright 2017 Physicians Postgraduate Press, Inc.)

Purpose: To explore antipsychotic (AP) medications and physical restraint use and their effects on physical function and cognition in older nursing home residents., Methods: This retrospective cohort studied involved 532 residents with dementia from 57 nursing homes participating in the Services and Health for Elderly in Long-Term Care study. Poisson log regression models explored the effect of physical restraint and/or AP medication use on cognitive or functional decline at 6 months., Results: Physical restraint use was associated with a higher risk of both functional and cognitive decline compared with AP medication use alone. These risks were highest among residents receiving both AP medications and physical restraints, suggesting additive effects., Discussion: Physical restraint use, and even more strongly, concurrent physical restraint and AP medication use, is related to function and cognitive decline in nursing home residents with dementia. Antipsychotic use is cautioned, but these results suggest physical restraint use is potentially more risky., (Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Use of antipsychotic (AP) medications is high and often inappropriate among institutionalized populations. Little is known about the correlates of new AP drug use following admission to long-term care (LTC) settings. This study investigated the frequency and correlates of new AP drug use among newly admitted LTC residents., Methods: This longitudinal, retrospective study used data from the interRAI - Nursing Home Minimum Data Set version 2.0 (MDS 2.0) instrument. Data about demographic, clinical and social characteristics, and medication use, were collected in Ontario, Canada, from 2003-2011 by trained nurses. Residents with complete admission and 3-6 month follow-up data were included (N = 47,768). Multivariate logistic regression analyses, stratified by gender, explored correlates of new AP drug use upon admission to LTC., Results: New AP drug users comprised 7 % of the final cohort. Severe cognitive impairment, dementia, and motor agitation were significantly associated with new AP drug use among both sexes. Additionally, behavioural problems, conflicts with staff and reduced social engagement were strong correlates of new AP drug use., Conclusions: Social factors were as strongly associated with new AP drug use after LTC admission as clinical factors. Strategies to prevent the potential misuse of AP drugs upon LTC admission should consider the social determinants of such prescribing.

Background: Behavioral and psychological symptoms of dementia (BPSD) are common reasons for use of antipsychotic drugs among older individuals with dementia. These drugs are not approved for such use and both the Food and Drug Administration and European Medicines Agency have issued warnings to limit such use., Objectives: This study aimed to describe patterns of antipsychotic drug use in a sample of nursing home residents with dementia in 7 European countries and Israel., Design: This cross-sectional, retrospective cohort study used data from the SHELTER study that collected comprehensive resident data using the interRAI Long-Term Care Facility instrument., Methods: Fifty-seven long-term care facilities participated from 8 countries, and the sample included 4156 long-term care residents from these settings. Individuals with dementia, both Alzheimer and non-Alzheimer types, were identified. Potential correlates of any antipsychotic and atypical versus conventional antipsychotic drug use among residents with dementia were identified using generalized estimation equation modeling., Results: A total of 2091 individuals with dementia were identified. Antipsychotic drug use among these individuals varied by country, with overall prevalence of use being 32.8% (n = 662). Among antipsychotic users, 7 in 10 were receiving atypical agents. Generalized estimation equation analysis revealed that the strongest correlate of any antipsychotic drug use was severe behavioral symptoms, which increased the likelihood by 2.84. Correlates of atypical versus conventional antipsychotic drug use included psychiatric services, more than 10 medications, moderate behavioral symptoms, and female gender., Conclusion: Despite recommendations to avoid the use of antipsychotic drugs in patients with dementia, a large proportion of residents in European long-term care facilities continue to receive such agents. Future work should not only establish the appropriateness of such use through outcomes studies, but explore withdrawal strategies as well as alternative treatment modalities., (Copyright © 2014 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: A recent meta-analysis has indicated that, in patients with dementia, the use of atypical antipsychotics is associated with an excess mortality. Later observational studies have suggested that conventional antipsychotics may pose an even greater risk of death. None of these studies could evaluate the risk associated with single antipsychotics nor could they provide any conclusive evidence concerning the risk among nursing home residents. We conducted a retrospective cohort study to compare the risk of death associated with atypical and conventional antipsychotics in a large population of nursing home residents with dementia., Method: We identified 6,524 new users of atypical antipsychotics and 3,205 new users of conventional antipsychotics living in 1,581 Medicare- or Medicaid-certified nursing homes in 5 US states during the years 1998-2000. The outcome measure was all-cause mortality, which was determined during 6-months of follow-up., Results: After adjusting for potential confounders relative to users of atypicals, the rate of death was increased for users of conventional antipsychotics (hazard ratio [HR], 1.26; 95% CI, 1.13-1.42). Relative to risperidone, a higher rate of death was documented for haloperidol (HR, 1.31; 95% CI, 1.13-1.53), phenothiazines (HR, 1.17; 95% CI, 1.00-1.38) and other conventional medications (HR, 1.32; 95% CI, 0.99-1.80). No atypical antipsychotic was associated with a differential risk relative to risperidone., Conclusions: Conventional antipsychotics are associated with a higher risk of all-cause mortality than atypical agents. It seems advisable that they are not used in substitution for atypical antipsychotics among nursing home residents with dementia even when short-term therapy is being prescribed., (Copyright 2009 Physicians Postgraduate Press, Inc.)

Objective: Conventional antipsychotics have been linked to an increased risk of femur fracture. Despite a lower propensity of atypical agents to cause gait and movement disorders, a correlation between these medications and the risk of femur fracture remains to be established. The aim of this study was to estimate the effect of atypical and conventional antipsychotics on the risk of hospitalization for femur fracture., Method: We conducted a case-control study on nursing home residents in 6 U.S. states by using the Systematic Assessment of Geriatric drug use via Epidemiology (SAGE) database, which includes data from the Minimum Data Set linked to Medicare inpatient claims. Cases were residents hospitalized for femur fracture between July 1, 1998, and December 31, 1999. For each case, we identified up to 5 controls residing in the same facility during the same period of time. The sample consisted of 1787 cases and 5606 controls., Results: After control for potential confounders, the risk of hospitalization for femur fracture was increased for users of atypical (OR = 1.37, 95% confidence interval [CI] = 1.11 to 1.69) and conventional antipsychotics (OR = 1.35, 95% CI = 1.06 to 1.71) relative to nonusers. With respect to individual agents, an excess risk was estimated for risperidone (OR = 1.42, 95% CI = 1.12 to 1.80), olanzapine (OR = 1.34, 95% CI = 0.87 to 2.07), and haloperidol (OR = 1.53, 95% CI = 1.18 to 2.26). No other antipsychotic could be analyzed individually., Conclusion: Conventional and atypical antipsychotics appear to increase the risk of hospitalization for femur fracture in a population of institutionalized elderly patients. These medications should be used with caution, especially among patients with a high risk of falls.

A 77-year-old patient with initial behavioral and psychological symptoms of dementia was treated with clozapine (50 mg/daily). Since no clinical benefit was apparent, clozapine was discontinued after six weeks and the patient started on paroxetine (20 mg/daily). After three weeks on paroxetine, he was given another trial of clozapine at a starting dosage of 25 mg/daily. While clozapine had previously been well tolerated, this time he rapidly developed fever, mental confusion, lethargy, muscle spasms and rigidity. The diagnosis of neuroleptic malignant syndrome was delayed, because there was no leukocytosis and serum creatine phosphokinase was initially not elevated. Subcutaneous apomorphine was then given but, after an initial improvement, the patient developed a multiple organ failure syndrome and died.

Background: Some antipsychotic agents have been indicated as a possible risk factor for venous thromboembolism (VTE) in adult patients with psychiatric disorders. The aim of this study was to estimate the effect of atypical and conventional antipsychotic agents on the risk of hospitalization for VTE among elderly patients., Methods: We conducted a retrospective cohort study on nursing home residents in 5 states. We used data from the Minimum Data Set to identify 19 940 new users of antipsychotic agents and 112 078 nonusers. Hospitalization with VTE as primary discharge diagnosis was determined during a 6-month follow-up period using Medicare inpatient claims. Cox proportional hazards models provided estimates of effect adjusted for confounders., Results: The rate of hospitalization for VTE was 0.91 per 100 person-years. Venous thrombosis accounted for 77.6% of events and 22.4% were pulmonary embolisms. Relative to nonusers, the rate of hospitalization for VTE was increased for users of atypical antipsychotic agents, including risperidone (adjusted hazard ratio [HR], 1.98; 95% confidence interval [CI], 1.40-2.78), olanzapine (adjusted HR, 1.87; 95% CI, 1.06-3.27), and clozapine and quetiapine fumarate (adjusted HR, 2.68; 95% CI, 1.15-6.28). No increased rate was associated with phenothiazines (adjusted HR, 1.03; 95% CI, 0.60-1.77) or other conventional agents (adjusted HR, 0.98; 95% CI, 0.52-1.87)., Conclusions: Atypical antipsychotic agents appear to increase the risk of VTE. However, these events are rare, and in clinical practice the absolute risk should be weighed against the effectiveness of these medications in the elderly population.

Objective: Concern exists about a possible increased risk of cerebrovascular events (CVEs) among elderly patients receiving risperidone or olanzapine. We estimated the effect of atypical and conventional antipsychotics on the risk of CVEs among elderly nursing home patients with dementia., Method: We conducted a case-control study on residents of nursing homes in 6 U.S. states by using the Systematic Assessment of Geriatric drug use via Epidemiology database, which includes data from the Minimum Data Set linked to Medicare inpatient claims. Participants were diagnosed with Alzheimer's disease or other forms of dementia on the basis of clinical criteria and medical history (including medical records and neuroradiologic documentation). Cases included patients hospitalized for stroke or transient ischemic attack between June 30, 1998, and December 27, 1999. For each case, we identified up to 5 controls hospitalized for septicemia or urinary tract infection residing in the same facility during the same time period. The sample consisted of 1130 cases and 3658 controls., Results: After controlling for potential confounders, the odds ratio of being hospitalized for CVEs was 0.87 (95% CI = 0.67 to 1.12) for risperidone users, 1.32 (95% CI = 0.83 to 2.11) for olanzapine users, 1.57 (95% CI = 0.65 to 3.82) for users of other atypical agents, and 1.24 (95% CI = 0.95 to 1.63) for conventional antipsychotic users compared to nonusers of antipsychotics. A history of CVEs appeared to modify the effect of atypical antipsychotics other than risperidone on the risk of new events., Conclusion: Overall, no increased risk of CVEs seems to be conferred by atypical or conventional antipsychotics. Preexisting cerebrovascular risk factors might interact with some atypical antipsychotics to increase the risk of events. These results should be interpreted in light of the limitations of the study and need to be confirmed.

Background: Conventional antipsychotic drugs have been implicated as a cause of ventricular arrhythmias and cardiac arrest, but no definitive information is available regarding atypical antipsychotics. We compared the effect of conventional and atypical antipsychotics on the risk of hospitalization for ventricular arrhythmias and cardiac arrest., Methods: We conducted a case-control study on residents of nursing homes in 6 US states by using data from the Minimum Data Set linked to Medicare inpatient claims. Cases were residents hospitalized for ventricular arrhythmias or cardiac arrest between July 4, 1998, and December 30, 1999. For each case, we identified up to 5 controls residing in the same facility during the same period. The sample consisted of 649 cases and 2962 controls., Results: Use of conventional antipsychotics was associated with a nearly 2-fold increase in risk of hospitalization for ventricular arrhythmias or cardiac arrest (adjusted odds ratio, 1.86; 95% confidence interval, 1.27-2.74). There was no increased risk associated with the use of atypical antipsychotics (odds ratio, 0.87; 95% confidence interval, 0.58-1.32). The risk of hospitalization for ventricular arrhythmias or cardiac arrest was highest among conventional users with cardiac disease (odds ratio, 3.27; 95% confidence interval, 1.95-5.47). However, cardiac disease and conventional antipsychotics did not show a synergistic effect (synergy index, 1.19)., Conclusions: Conventional but not atypical antipsychotics are associated with an increased risk of hospitalization for ventricular arrhythmias and cardiac arrest. The prescription of conventional antipsychotics in patients with cardiac disease should be carefully weighed.

Background: Use of atypical antipsychotics for "off-label" indications, such as behavioral and psychological symptoms of dementia, depression, and bipolar disorder, have been frequently reported, although not systematically studied. We describe the pattern of atypical antipsychotic use among nursing home residents and identify demographic and clinical correlates., Method: We conducted a cross-sectional study on 139,714 nursing home residents living in 1732 nursing homes in 5 U.S. states from Jan. 1, 1999, to Jan. 31, 2000. Data were obtained from the computerized Minimum Data Set (MDS) assessment records., Results: Behavior problems associated with cognitive impairment were manifest in 86,514 residents, and, of these, 18.2% received an antipsychotic. Approximately 11% received an atypical antipsychotic, while 6.8% received a conventional agent. Clinical correlates of atypical antipsychotic use were Parkinson's disease (adjusted odds ratio [OR] = 1.57, 95% confidence interval [CI] = 1.34 to 1.84), depression (OR = 1.35, 95% CI = 1.24 to 1.46), antidepressant use (OR = 1.38, 95% CI = 1.27 to 1.49), Alzheimer's disease (OR = 1.21, 95% CI = 1.12 to 1.32), non-Alzheimer dementia (OR = 1.15, 95% CI = 1.07 to 1.24), and cholinesterase inhibitor use (OR = 1.74, 95% CI = 1.52 to 1.98). Severe functional impairment was inversely related to atypical antipsychotic use (OR = 0.76, 95% CI = 0.65 to 0.89)., Conclusion: Atypical antipsychotics are now used more than conventional antipsychotic agents in U.S. nursing homes. Indications and dosages seem appropriate relative to labeling. Clinical and demographic differences between atypical and conventional antipsychotic users tend to be relatively small, suggesting that other factors may explain the choice of prescribing physicians. The impact of facility factors, economic forces, and physician characteristics needs to be investigated.