Risk of death associated with the use of conventional versus atypical antipsychotic drugs among elderly patients

Abstract

A ntipsychotic medications are disproportionately used in elderly populations and have been prescribed to over a quarter of US Medicare beneficiaries in nursing homes.1-3 Reasons for their use include dementia, delirium, psychosis, agitation and affective disorders, but much use is outside approved indications. 4 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). 5In 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.6 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. 7,8In 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, 9 particularly since their replacement by the newer drugs occurred so rapidly and recently.5 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.10-13 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.14 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. MethodsWe conducted a cohort study involving all British Columbia residents aged 65 years or more who filled a first-recorded (index) prescription for an oral antipsychotic medication between Risk of death associated with the use of conventional versus atypical antipsychotic drugs among elderly patients Background: Public health advisories have warned that the use of atypical antipsychotic medications increases the risk of death among elderly patients. We assessed the shor...

ACNP White Paper: Update on Use of Antipsychotic Drugs in Elderly Persons with Dementia

“…Typical antipsychotic medications were associated with a significantly higher adjusted risk of death than were atypical antipsychotic medications at all intervals studied (p180 days: relative risk, 1.4; 95% CI, 1.3-1.5; o40 days: relative risk, 1.6; 95% CI, 1.4-1.8; 40-79 days: relative risk, 1.4; 95% CI, 1.2-1.6; and 80-180 days: relative risk, 1.3; 95% CI, 1.1-1.4), and in all subgroups defined according to the presence or absence of dementia or nursing home residency. Similar results (ie higher mortality with typical than with atypical antipsychotics among older adults) were reported in two other retrospective analyses of large health system databases (Nasrallah et al, 2004;Schneeweiss et al, 2007). A Finnish study of 254 frail elderly patients with dementia in nursing homes and hospitals found no increase in mortality with either typical or atypical antipsychotics over a 2-year period (Raivio et al, 2007).…”

A review comparing the safety and tolerability of memantine with the acetylcholinesterase inhibitors

“…Haloperidol may alleviate delusional behaviour but may cause motor-related AEs, while concerns have been raised about atypical antipsychotics such as risperidone, quetiapine and olanzapine in elderly patients with dementia due to an increased risk of stroke and increased mortality rates (Lawlor, 2004;Lee et al, 2004;Tariot et al, 2004;Schneider et al, 2005). Among elderly patients, the mortality risk associated with conventional antipsychotics has also been reported as comparable to and possibly greater than the risk of death associated with atypical antipsychotics (Schneeweiss et al, 2007). A recent cohort study reported the risk of elderly patients with dementia developing a short-term serious adverse event to be increased more than three-fold in those receiving either typical or atypical antipsychotics (Rochon et al, 2008).…”

Clarifying Delirium Management: Practical, Evidenced-Based, Expert Recommendations for Clinical Practice

“…This warning is based on a number of limited studies. [100][101][102][103][104][105][106][107] Other studies have not replicated these findings. 108 These data do not address the risk of short-term use of antipsychotics to manage delirium and cannot be extrapolated to this situation.…”