The use of atypical antipsychotics in nursing homes

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.     

Antipsychotic and antidepressant drug use in the elderly and the risk of venous thromboembolism

BACKGROUND: Preliminary evidence suggests that use of antipsychotic drugs is associated with an increased risk of venous thromboembolism. OBJECTIVE: To evaluate the relationship between antipsychotic or antidepressant drug use and venous thromboembolism among adults aged 65 years and older. DESIGN: Retrospective cohort study using linked health care administrative databases over a nine year period. SETTING: The entire province of Ontario, Canada. PARTICIPANTS: Individuals aged 65 years and over exclusively prescribed either antipsychotic drugs (n = 22,514), antidepressant drugs (n = 75,649) or thyroid replacement hormones (33,033), the referent control group. We excluded those with an antecedent history of cardiovascular disease, venous thromboembolism or cancer, as well as those dispensed warfarin before study entry. MEASUREMENTS: Diagnosis of deep vein thrombosis or pulmonary embolism. RESULTS: Relative to those prescribed thyroid hormones, neither antidepressant (adjusted hazard ratio 1.02, 95% CI 0.91-1.14) nor antipsychotic (adjusted hazard ratio 1.13, 95% CI 0.96-1.32) drug use was associated with an increased risk for deep vein thrombosis. Similar risk estimates were found for deep vein thrombosis or pulmonary embolism. In a sub-group analysis, only butyrophenone use was found to be associated with a slightly increased risk of deep vein thrombosis (adjusted HR 1.51, 95% CI 1.23-1.86) as well as deep vein thrombosis or pulmonary embolism (adjusted HR 1.43, 95% CI 1.18-1.74). CONCLUSIONS: In a large cohort of adults aged 65 years and older, neither antipsychotic or antidepressant drug use was associated with an increased risk of venous thromboembolism, with the exception of a slightly increased risk among those prescribed butyrophenones. Further data are required before use of these psychoactive drugs can be considered a risk factor for venous thromboembolism.     

Risk of death associated with antipsychotic drug dispensing in residential aged care facilities

OBJECTIVE: To establish the instantaneous relative risk (RR) associated with the dispensing of individual antipsychotic drugs, carbamazepine and valproate for those > or = 65 years who resided in an aged care facility. METHOD: The risk of death for incident users of antipsychotic drugs, carbamazepine and valproate in 2003 or 2004 who resided in an aged care facility was established using mortality rates and Cox proportional hazards models over two time periods. The regression models were adjusted for age, gender, medical and psychotropic drug dispensing, and a measure of overall medical comorbidity. Olanzapine users formed the referent group. RESULTS: Haloperidol and chlorpromazine use were associated with the highest death rates. The instantaneous RR for those dispensed haloperidol was 1.67 (95% confidence intervals (CI) = 1.50-1.84, p < 0.001) and for chlorpromazine it was 1.75 (95%CI = 1.31-2.34, p < 0.001). The RR of death for haloperidol and chlorpromazine was higher in the regression model restricted to 60 days follow up (haloperidol RR = 2.17, 95%CI = 1.86-2.53, p < 0.001, chlorpromazine RR = 2.72, 95%CI = 1.84-4.01). CONCLUSIONS: The increased risk associated with haloperidol and chlorpromazine dispensing should be interpreted cautiously because confounding by medical illness cannot be excluded despite adjusting the model for multiple variables. This study supports the findings from other data linkage studies that atypical antipsychotic medications are not associated with increased risk of death compared with conventional antipsychotic drugs.     

Differential effects of risperidone,olanzapine, clozapine,and conventional antipsychotics on type 2 diabetes: findings from a large health plan database

BACKGROUND: Case series suggest that some antipsychotics may induce or exacerbate type 2 diabetes. This study measured the association of antipsychotic treatments with diabetes at a population level. METHOD: Claims data for psychosis patients (ICD-CM-9 290.xx-299.xx) within health plans encompassing 2.5 million individuals were analyzed. Patients reporting preexisting type 2 diabetes up to 8 months prior to observation were excluded. The frequency of newly reported type 2 diabetes in untreated patients and among patients treated with antipsychotics from 5 categories (risperidone, olanzapine, clozapine, and high-potency and low-potency conventionals) was compared. Logistic regression models compared the odds of diabetes based on exposure to each of the antipsychotic categories. RESULTS: Based on 12 months of exposure, the odds of type 2 diabetes for risperidone-treated patients (odds ratio = 0.88, 95% CI = 0.372 to 2.070) was not significantly different from that for untreated patients, whereas patients receiving other antipsychotics had a significantly greater risk of diabetes than untreated patients (p < .05): olanzapine, 3.10 (95% CI = 1.620 to 5.934); clozapine, 7.44 (95% CI = 0.603 to 34.751); high-potency conventionals, 2.13 (95% CI = 1.097 to 4.134); and low-potency conventionals, 3.46 (95% CI = 1.522 to 7.785). Older age and greater use of non-antipsychotic psychotropic medications also contributed to risk of type 2 diabetes. Olanzapine also showed significantly higher (p < .01) odds of diabetes associated with increasing dose. CONCLUSION: Consistent with previously published literature, these data suggest that olanzapine, clozapine, and some conventional antipsychotics appear to increase the risk of acquiring or exacerbating type 2 diabetes and that the effect may vary by drug. In contrast to these agents, risperidone was not associated with an increased risk of type 2 diabetes.     

Cerebrovascular events among elderly nursing home patients treated with conventional or atypical antipsychotics

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.     

Atypical antipsychotics and risk of cerebrovascular accidents

OBJECTIVE: Randomized controlled trials have suggested that at least one atypical antipsychotic may be associated with an increased risk of stroke in older people with dementia. This study examined the association between atypical antipsychotic use and stroke in the elderly. METHOD: The authors conducted a retrospective population-based cohort study of patients over the age of 66 by linking administrative health care databases. Three cohorts-users of typical antipsychotics, risperidone, and olanzapine-were identified and compared. RESULTS: Subjects treated with typical antipsychotics (N=1,015) were compared with those given risperidone (N=6,964) and olanzapine (N=3,421). Model-based estimates adjusted for covariates hypothesized to be associated with stroke risk revealed relative risk estimates of 1.1 (95% CI=0.5-2.3) for olanzapine and 1.4 (95% CI=0.7-2.8) for risperidone. CONCLUSIONS: Olanzapine and risperidone use were not associated with a statistically significant increased risk of stroke compared with typical antipsychotic use.     

Antipsychotics and the risk of sudden cardiac death

BACKGROUND: Case reports link antipsychotic drugs with sudden cardiac deaths, which is consistent with dose-related electrophysiologic effects. Because this association has not been confirmed in controlled studies, we conducted a retrospective cohort study in Tennessee Medicaid enrollees, which included many antipsychotic users; there were also computer files describing medication use and comorbidity. The study was conducted before the introduction of risperidone and, thus, did not include the newer atypical agents. METHODS: The cohort included 481,744 persons with 1,282,996 person-years of follow-up. This included 26,749 person-years for current moderate-dose antipsychotic use (>100-mg thioridazine equivalents), 31,864 person-years for current low-dose antipsychotic use, 37,881 person-years for use in the past year only, and 1 186,501 person-years for no use. The cohort had 1487 confirmed sudden cardiac deaths; from these, we calculated multivariate rate ratios adjusted for potential confounding factors. RESULTS: When current moderate-dose antipsychotic use was compared with nonuse, the multivariate rate ratio was 2.39 (95% confidence interval, 1.77-3.22; P<.001). This was greater than that for current low-dose (rate ratio, 1.30; 95% confidence interval, 0.98-1.72; P=.003) and former (rate ratio, 1.20; 95% confidence interval, 0.91-1.58; P<.001) use. Among cohort members with severe cardiovascular disease, current moderate-dose users had a 3.53-fold (95% confidence interval, 1.66-7.51) increased rate relative to comparable nonusers ( P<.001), resulting in 367 additional deaths per 10,000 person-years of follow-up. CONCLUSIONS: Patients prescribed moderate doses of antipsychotics had large relative and absolute increases in the risk of sudden cardiac death. Although the study data cannot demonstrate causality, they suggest that the potential adverse cardiac effects of antipsychotics should be considered in clinical practice, particularly for patients with cardiovascular disease.     

Increased risk of extrapyramidal side-effect treatment associated with atypical antipsychotic polytherapy

OBJECTIVE: To determine whether atypical antipsychotic polytherapy is a risk factor for drug treatment for extrapyramidal side-effects (anti-EPS drugs) and whether the risk is attributable to antipsychotic dose. METHOD: We studied Iowa Medicaid beneficiaries aged 18-64 years with an active atypical and no conventional antipsychotic on January 1, 2001. The association of atypical antipsychotic polytherapy with anti-EPS drug treatment was determined. Multiple logistic regression was utilized to adjust for covariates in two models, the first adjusting for age, sex and the specific antipsychotic(s) prescribed, and the second also adjusting for doses. RESULTS: Among 4400 patients, the unadjusted odds of anti-EPS treatment were increased two-fold with polytherapy. Polytherapy remained a risk factor in the first model (OR 1.5, 95% CI 1.1-2.0), but not after adjusting for doses (OR 1.0, 95% CI 0.7-1.4). CONCLUSION: Atypical antipsychotic polytherapy is a risk factor for anti-EPS drug treatment, apparently because of higher cumulative doses.     

New-onset type-2 diabetes associated with atypical antipsychotic medications

PURPOSE: This study compared the one-year incidence of new-onset type-2 diabetes mellitus (DM) and changes in weight in patients with a variety of psychiatric diagnoses prescribed olanzapine, risperidone, or quetiapine, compared to a reference group receiving haloperidol and no other antipsychotic medication. RESEARCH DESIGN AND METHODS: Data was abstracted from charts of subjects newly initiated and then maintained for one year on olanzapine (n=112), risperidone (n=100), quetiapine (n=100), and haloperidol (n=100). Baseline and one-year DM status, height, and weight were collected, as well as concurrent psychotropic medications, medical and psychiatric comorbidities. FINDINGS: Using a multivariate model, logistic regression identified a significant association between olanzapine (but not other atypical agents) and the development of diabetes compared to haloperidol over the one-year period (odds ratio 8.4, 95% CI 1.8-38.7). Baseline obesity was independently associated with new-onset DM, but only marginally greater weight gain was found among olanzapine users. CONCLUSIONS: The middle-aged American veterans in this study cohort were highly vulnerable to the diabetogenic effects of olanzapine, but a close correlation with weight change was not found. Patients administered olanzapine should receive careful laboratory monitoring for elevated plasma glucose in addition to weight measurement.     

Antipsychotic medication dispensing and risk of death in veterans and war widows 65 years and older.

OBJECTIVE: To establish the instantaneous relative risk (RR) of death associated with individual antipsychotic drugs, carbamazepine and sodium valproate for those 65 years and older. METHODS: Subjects dispensed antipsychotic drugs, sodium valproate or carbamazepine in 2003 or 2004 were analyzed as incident (N = 16,634) or prevalent (N = 9,831) users. Survival curves, mortality rates, and Cox proportional hazards models over two time periods were used to explore risk of death. The models were adjusted for age, sex, residential status, and psychotropic and medical drug dispensing. Olanzapine subjects were the reference group in the Cox regression. Subanalyses were performed for incident subjects with more than 30 days of follow-up and those dispensed cholinesterase inhibitors. RESULTS: In the adjusted Cox proportional hazards models, haloperidol dispensing was consistently associated with an increased risk of death compared with olanzapine users (relative risk [RR] for incident users: 2.26, 95% confidence intervals (CI): 2.08-2.47; Wald statistic: 345.36, df = 1, p < or =0.001). There was some evidence of decreased survival with dispensing of higher haloperidol doses, although confounding by medical comorbidity cannot be excluded. Chlorpromazine (RR: 1.39, 95% CI: 1.15-1.67; Wald statistic: 12.08, df = 1, p <0.001) and risperidone (RR: 1.23, 95% CI: 1.07-1.40; Wald statistic: 9.12, df = 1, p = 0.003) dispensing were associated with increased risk of death in incident users. CONCLUSION: These results should be interpreted cautiously because haloperidol and chlorpromazine are used in broader clinical contexts. However, in the absence of data from randomized trials, the safety profile of haloperidol should not be assumed to be benign. Antipsychotic drugs should not be studied as an aggregated group because their associated risks are not uniform.     

Prevalence of diabetes mellitus among outpatients with severe mental disorders receiving atypical antipsychotic drugs

BACKGROUND: Recent studies have suggested that patients receiving atypical antipsychotic drugs are at increased risk for developing diabetes mellitus. The purpose of this study is to examine the prevalence of diabetes in a group of adults with schizophrenia and other severe mental disorders receiving atypical antipsychotic drugs within a community mental health center setting. METHOD: A retrospective chart review was conducted on 436 outpatients receiving either atypical antipsychotic or decanoate antipsychotic drugs at a community mental health center. Diagnosis of diabetes was established through the presence of documentation in the medical record. Patients with a history of diabetes prior to age 18 years were excluded. Data were gathered from April 2001 through September 2002. RESULTS: The mean (SD) age of patients was 42.5 (10.8) years, and 57.3% were men. Patients were 61.5% white, 31.8% black, 5.3% Hispanic, and 2.3% other. Seventeen percent of patients had a positive family history of diabetes. Point prevalence of diabetes was 14.2% for the entire group. Chi-square analysis for the group revealed significant effects of age (chi(2) = 16.514, p <.001), family history of diabetes (chi(2) = 27.128, p <.001), and gender (chi(2) = 14.114, p <.001). A trend was noted toward a higher prevalence of diabetes among patients receiving atypical drugs (15.2%) compared with those receiving decanoate drugs (6.3%) (chi(2) = 2.984, p =.078). CONCLUSION: Prevalence of diabetes mellitus among outpatients with severe mental disorders receiving atypical antipsychotic drugs is substantially higher than that reported in the general population. Results of this study are limited by the retrospective methodology, which may underestimate actual prevalence by failing to detect undiagnosed cases.