This population based cohort study assessed whether the risk of overall and cause specific mortality is equal across antipsychotic drugs in older residents of nursing homes in the United States. Data for the study were extracted using information on Medicaid and Medicare claims, the Minimum Data Set, the National Death Index, and a national assessment of nursing home quality. The cohort consisted of all patients aged ≥65 who were eligible for Medicare and Medicaid, who started treatment with an antipsychotic drug during a stay in a nursing home, and who had six months’ continuous Medicaid coverage before the date they started the antipsychotic drug (index date). The antipsychotic drugs considered included haloperidol, aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone. Overall, from 2001 to 2005, 75,445 older residents of nursing homes started treatment with antipsychotic drugs. Statistical modelling was 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. The following results are reported:

• 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 that the effect measure was modified by the presence of a recorded diagnosis of dementia or behavioural disturbances

• There was a dose-response relation for all drugs except quetiapine.

The researchers discuss the main strengths and weaknesses of their study, citing the population size as a major strength. They conclude, “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.”  The researchers also add that there may be circumstances where the clinician might need to consider these agents, for example, if the patient poses a risk to themselves or others. They write, “If the clinician faces a situation in which use of these drugs seems inevitable, our findings underscore the importance of always prescribing the lowest possible dose and of closely monitoring patients, especially shortly after the start of treatment. The evidence accumulated so far implies that use of haloperidol in this vulnerable population cannot be justified because of the excess harm. Quetiapine might be somewhat safer than other atypical drugs, but these findings will require replication in other studies.”

In a related editorial, the authors further discuss this issue and the results of the study and note that more research is required into non-drug based interventions and service structures.