Differential risk of death in older residents in nursing homes prescribed specific antipsychotic drugs: population based cohort study

• Published in: BMJ Vol. 344; no. 7848; p. 16
• Main Authors: Huybrechts, K F, Gerhard, T, Crystal, S, Olfson, M, Avorn, J, Levin, R, Lucas, J A, Schneeweiss, S
• Format: Journal Article
• Language: English
• Published: England British Medical Journal Publishing Group 23.02.2012; BMJ Publishing Group; BMJ Publishing Group LTD; BMJ Publishing Group Ltd
• Subjects: Aged; Aged, 80 and over; Alzheimer's disease; Antipsychotic agents; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - adverse effects; Antipsychotic Agents - therapeutic use; Antipsychotics; Aripiprazole; Cause of Death; Certification; Cohort analysis; Cohort studies; Comorbidity; Datasets; Death; Dementia; Dementia - drug therapy; Dementia - mortality; Dementia disorders; Dibenzothiazepines - administration & dosage; Dibenzothiazepines - adverse effects; Dibenzothiazepines - therapeutic use; Dose-Response Relationship, Drug; Drug development; Drug dosages; Drug-Related Side Effects and Adverse Reactions - mortality; Drugs: Psychiatry; Epidemiologic Methods; Epidemiologic Studies; Epidemiology; Female; Geriatrics; Haloperidol; Haloperidol - administration & dosage; Haloperidol - adverse effects; Haloperidol - therapeutic use; Health Policy; Health Service Research; Humans; Male; Medicaid; Medical Assistance - statistics & numerical data; Medicare; Memory Disorders (Neurology); Memory Disorders (Psychiatry); Mortality; Nursing homes; Nursing Homes - statistics & numerical data; Olanzapine; Older adults; Population; Population aging; Population studies; Population-based studies; Prescription drugs; Psychotic Disorders (Incl Schizophrenia); Psychotropic drugs; Quetiapine; Quetiapine Fumarate; Research universities; Risperidone; Risperidone - administration & dosage; Risperidone - adverse effects; Risperidone - therapeutic use; Suicides & suicide attempts; United States - epidemiology; Universities; Ziprasidone; United States; USA
• ISSN: 0959-8138; 1468-5833; 1756-1833
• DOI: 10.1136/bmj.e977

Objective To assess risks of mortality associated with use of individual antipsychotic drugs in elderly residents in nursing homes.Design Population based cohort study with linked data from Medicaid, Medicare, the Minimum Data Set, the National Death Index, and a national assessment of nursing home quality.Setting Nursing homes in the United States.Participants 75 445 new users of antipsychotic drugs (haloperidol, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone). All participants were aged ≥65, were eligible for Medicaid, and lived in a nursing home in 2001-5.Main outcome measures Cox proportional hazards models were used to compare 180 day risks of all cause and cause specific mortality by individual drug, with propensity score adjustment to control for potential confounders.Results Compared with risperidone, users of haloperidol had an increased risk of mortality (hazard ratio 2.07, 95% confidence interval 1.89 to 2.26) and users of quetiapine a decreased risk (0.81, 0.75 to 0.88). The effects were strongest shortly after the start of treatment, remained after adjustment for dose, and were seen for all causes of death examined. No clinically meaningful differences were observed for the other drugs. There was no evidence that the effect measure modification in those with dementia or behavioural disturbances. There was a dose-response relation for all drugs except quetiapine.Conclusions Though these findings cannot prove causality, and we cannot rule out the possibility of residual confounding, they provide more evidence of the risk of using these drugs in older patients, reinforcing the concept that they should not be used in the absence of clear need. The data suggest that the risk of mortality with these drugs is generally increased with higher doses and seems to be highest for haloperidol and least for quetiapine.