Antipsychotic use in dementia: The relationship between neuropsychiatric symptom profiles and adverse outcomes

Abstract

AbstractBackgroundAntipsychotic treatments are associated with safety concerns in people with dementia. The authors aimed to investigate whether risk of adverse outcomes related to antipsychotic prescribing differed according to major neuropsychiatric syndromes – specifically psychosis, agitation, or a combination – in order to inform a precision medicine approach to management of key neuropsychiatric symptoms.MethodA cohort of 10,106 patients with a diagnosis of dementia was assembled from a large dementia care database in southeast London. Neuropsychiatric symptoms closest to the time of first dementia diagnosis were determined according to Health of the Nation Outcome Scales (HoNOS) mental and behavioural problem scores and the sample was divided into four groups: ‘agitated psychosis’, ‘agitation, but no psychosis’, ‘psychosis, but no agitation’, and ‘neither psychosis nor agitation’. Antipsychotic prescription in a six‐months window around first dementia diagnosis was ascertained as exposure variable through natural language processing from free text. Cox regression models were used to analyse associations of antipsychotic prescription with all‐cause and stroke‐specific mortality, emergency hospitalisation and hospitalised stroke adjusting for sixteen potential confounders including demographics, cognition, functioning, as well as physical and mental health.ResultOnly in the group ‘psychosis, but no agitation’ (n=579), 30% of whom were prescribed an antipsychotic, a significant antipsychotic‐associated increased risk of hospitalised stroke was present after adjustment (adjusted hazard ratio (HR) 2.16; 95% confidence interval (CI) 1.09‐4.25). An increased antipsychotic‐related all‐cause (adjusted HR 1.14; 95% CI 1.04‐1.24) and stroke‐specific mortality risk (adjusted HR 1.28; 95% CI 1.01‐1.63) was detected in the whole sample, but was no interaction between the strata and antipsychotic‐related mortality.ConclusionThe adverse effects of antipsychotics in dementia are complex. Stroke risk may be highest when used in patients presenting with psychosis without agitation, indicating the need for novel interventions for this group.