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.

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.

Antipsychotic medication dispensing and associated odds ratios of death in elderly veterans and war widows, 2001.

OBJECTIVES: To explore the odds ratios (ORs) of death associated with antipsychotic (AP) medications dispensed to elderly subjects. METHOD: Subjects were veterans and war widows 65 years and older dispensed an AP drug in 2001 in NSW or ACT. For all subjects, dispensing records for AP medication, benzodiazepines, lithium, carbamazepine, sodium valproate and antidepressant medication were extracted and combined with age, gender and date of death. A study date was allocated, either the date of death or a random date from 1.5.01 to 31.12.01. Subjects dispensed an AP in 2001, but not dispensed an AP or other psychotropic medication in the 120 days prior to their study date, formed a reference group. Psychotropic dispensing in the 120 days prior to the study date was analysed using nested logistic regression models to produce ORs of death associated with various AP drugs. The ORs for risperidone, olanzapine and pericyazine were compared. Haloperidol ORs were established for those dispensed the drug 0-30 days prior to study date or 31-120 days prior to the study date. RESULTS: The ORs associated with haloperidol, olanzapine, risperidone, pericyazine, thioridazine and chlorpromazine were significant when compared with the reference group. Odds ratios for all three haloperidol periods were significant when compared with olanzapine, risperidone and pericyazine 120 day ORs. Although there was a trend favouring olanzapine when compared with risperidone, the difference in the ORs failed to reach significance (p=0.066). CONCLUSIONS: Haloperidol is associated with significantly higher mortality rates than other AP medication but it is not clear whether this represents drug toxicity or the medical conditions for which it was dispensed. There was no evidence that the conventional AP pericyazine was associated with a higher mortality rate than olanzapine or risperidone.