Long-term antipsychotic use, orthostatic hypotension and falls in older adults with Alzheimer's disease

AimWe assessed longitudinal relationships between long-term antipsychotic use, orthostatic hypotension and falls/syncope in older adults living with mild-to-moderate dementia due to Alzheimer disease (AD).FindingsOver 18 months, long-term antipsychotic use in older adults with dementia due to AD was associated with a greater likelihood of experiencing sit-to-stand orthostatic hypotension (ssOH), measured on eight separate study visits. Both ssOH and antipsychotic use were independently associated with incident falls/syncope over 18 months.MessageOur findings provide supportive evidence that long-term antipsychotic use is associated with both ssOH and falls/syncope in older adults with mild-moderate dementia due to AD-highlighting the need for medication review and screening for symptoms of OH/falls/syncope in older adults with AD prescribed these medications. PurposeAntipsychotic use in Alzheimer disease (AD) is associated with adverse events and mortality. Whilst postulated to cause/exacerbate orthostatic hypotension (OH), the exact relationship between antipsychotic use and OH has never been explored in AD-a group who are particularly vulnerable to neuro-cardiovascular instability and adverse effects of medication on orthostatic blood pressure (BP) behaviour.MethodsWe analysed longitudinal data from an 18-month trial of Nilvadipine in mild-moderate AD. We assessed the effect of long-term antipsychotic use (for the entire 18-month study duration) on orthostatic BP phenotypes measured on eight occasions, in addition to the relationship between antipsychotic use, BP phenotypes and incident falls.ResultsOf 509 older adults with AD (aged 72.9 +/- 8.3 years, 61.9% female), 10.6% (n = 54) were prescribed a long-term antipsychotic. Over 18 months, long-term antipsychotic use was associated with a greater likelihood of experiencing sit-to-stand OH (ssOH) (OR: 1.21; 1.05-1.38, p = 0.009) which persisted on covariate adjustment. Following adjustment for important clinical confounders, both antipsychotic use (IRR: 1.80, 1.11-2.92, p = 0.018) and ssOH (IRR: 1.44, 1.00-2.06, p = 0.048) were associated with a greater risk of falls/syncope over 18 months in older adults with mild-moderate AD.ConclusionEven in mild-to-moderate AD, long-term antipsychotic use was associated with ssOH. Both antipsychotic use and ssOH were associated with a greater risk of incident falls/syncope over 18 months. Further attention to optimal prescribing interventions in this cohort is warranted and may involve screening older adults with AD prescribed antipsychotics for both orthostatic symptoms and falls.