Sebastian Schneeweiss , Soko Setoguchi , Alan Brookhart , Colin Dormuth , Philip S . Wang Risk of death associated with the use of conventional versus atypical antipsychotic drugs among elderly patients

Antipsychotic medications are disproportionately used in elderly populations and have been prescribed to over a quarter of US Medicare beneficiaries in nursing homes. Reasons for their use include dementia, delirium, psychosis, agitation and affective disorders, but much use is outside approved indications. In addition, there have been rapid shifts away from first-generation conventional agents (e.g., chlorpromazine, haloperidol and loxapine) to more actively marketed second-generation atypical agents (e.g., clozapine, olanzapine, quetiapine and risperidone). In a public health advisory issued on June 15, 2005, Health Canada warned that, compared with placebo, atypical antipsychotic medications increased the risk of death by 60% in a pooled analysis of 17 short-term randomized controlled trials involving elderly patients with dementia. Health Canada requested that “all manufacturers of these drugs include a warning and description of this risk in the safety information sheet for each drug.” The advisory did not extend to conventional antipsychotic medications, although the US Food and Drug Administration (FDA) noted that this is an important issue to study in the future. In the absence of data on the risk of death posed by conventional antipsychotic medications, there is mounting concern that clinicians may switch their elderly patients to these older agents, particularly since their replacement by the newer drugs occurred so rapidly and recently. On the basis of extrapolations mainly from younger populations, some have suggested that the conventional formulations could, in theory, pose risks equal to or greater than those associated with the newer, atypical drugs in elderly populations. A cohort study involving US Medicare patients eligible for statefunded low-income pharmacy assistance programs showed a 37% increase in the 180-day mortality associated with the use of conventional antipsychotic medications compared with atypical ones. However, patients enrolled in state-funded pharmacy assistance programs are not representative of the general elderly population, since on average they have lower incomes and higher morbidity and mortality. We conducted a population-based cohort study involving all elderly people in British Columbia to compare the shortterm mortality between those prescribed a conventional antipsychotic medication and those prescribed an atypical antipsychotic medication. We also examined whether the risk of death differed by dose or duration of drug use and by dementia status and residence in a nursing home.