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

Abstract

Background Antipsychotic 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. Method A 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. Result Only 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. Conclusion The 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.

Antipsychotic Use and Risk of Stroke Among Community-Dwelling People With Alzheimer’s Disease

“…Other studies have reported no increased risk of cerebrovascular events in risperidone or quetiapine users compared with nonusers with dementia. 15,17,19 Similarly, no difference in stroke risk between risperidone vs other antipsychotics or quetiapine vs other antipsychotics was observed in a recent study of people with dementia. 15 Several mechanisms for the association between antipsychotics and strokes have been proposed.…”

“…15,17,19 Similarly, no difference in stroke risk between risperidone vs other antipsychotics or quetiapine vs other antipsychotics was observed in a recent study of people with dementia. 15 Several mechanisms for the association between antipsychotics and strokes have been proposed. In addition to blockade of dopamine receptors, different antipsychotics act on serotonergic, histaminergic, muscarinic, and alpha-adrenergic receptors.…”

“…16 Similarly, a recent study found no difference in stroke risk associated with antipsychotics between different types of dementia. 15 A key difference between the studies included in the meta-analysis, 6 the recent study, 15 and ours is the outcome definition. The meta-analysis did not conduct subanalyses for TIAs and stroke as an outcome.…”

“…One previous study did not identify an association between antipsychotic use and stroke in 4320 persons with AD. 15 Unlike in the majority of other studies, 15e20 our outcome was restricted to stroke and did not include other cerebrovascular events like transient ischemic attacks (TIAs).…”

Effect of trazodone on cognitive decline in people with dementia: Cohort study using UK routinely collected data

“…This bespoke application is designed to identify medications that are currently prescribed to the patient and was developed through expert annotation, which means that domain experts coded whether the medication prescription was present in a particular document based on pre-defined coding rules and/or their expert experience. 21 This searched for any reference to trazodone (and common mis-spellings or molipaxin, the UK trade name) and comparator drugs, citalopram or mirtazapine, and extracted the date of the record. Any relevant record of the drugs of interest during the study window would be detected by the GATE algorithm so drug exposure was measured longitudinally.…”