Alzheimer’s disease is the leading cause of dementia and is characterised by a progressive decline in cognitive function. Agitation is a common complication of dementia which causes distress in people with dementia, complicating the management and care for the patient. It frequently triggers institutionalization, rapid dementia progression, prolonged hospital stay, more difficult discharge from hospital and increased mortality. Antipsychotic medications are prescribed for the management of agitation in dementia. Yet, antipsychotics have been associated with an increased mortality risk, increased incidence of stroke, pneumonia, falls and drowsiness leading to injuries.
The appropriate management of agitation in Alzheimer’s patients is an important treatment goal. We aim to provide evidence of the risk of first falls leading to hospitalisation from the use of antipsychotics and antipsychotics in combination with benzodiazepines for agitation in Alzheimer’s disease.
While there has been research into general antipsychotic use in dementia, there is currently a lack of evidence on the risk of falls from the use of antipsychotics and the new generation of atypical antipsychotics used to treat agitation in Alzheimer’s disease. This study will provide further evidence on the use of antipsychotics to treat agitation in Alzheimer’s disease in the UK and possible complications of their use. This valuable up-to-date information conducted in a large number of people with Alzheimer’s disease will provide further understanding to improve the current clinical management of agitation in Alzheimer’s disease.
We aim to provide evidence of the risk of falls leading to hospitalisation from the use of antipsychotics (AP) to manage agitation in people with Alzheimer´s disease (AD). We will also calculate the excess risk of first falls leading to hospitalisation due to the use of any APs in patients with AD and agitation.
A Self-Controlled Cases Series (SCCS) will be conducted to estimate the incidence rate ratio (IRR) using a conditional Poisson regression model. Only first fall during the study period will be considered in the primary analysis. Time variant variables such as, age, time from AD diagnosis, other AP use, stroke and living situation will need to be accounted for in the analysis.
For each eligible participant, we would classify:
• Antipsychotics as: atypical APs (AAP), AAP in combination with benzodiazepines, typical AP and any AP.
• Exposed periods will be categorised into fully exposed periods followed by a sequence of five 35-day partially exposed periods up to a maximum of 175 days. This will allow to represent a gradual shift from full exposure, to a partially exposed and to an unexposed state (1). Any time in hospital (Immortal time) will be excluded from the exposure period.
A cohort design will be used to calculate the relative excess rate of falls by taking the ratio of the incidence rate (IR) of falls in patients exposed to AP and the IR of fall in those unexposed to AP.
Primary objective
Given that a fall is an event that could affect the likelihood of a future fall, first fall leading to hospitalisation during the study period is the primary outcome. All subsequent falls will be excluded from the primary analysis and will instead be considered in the secondary analysis. History of falls in the 12 months before the index date will be included as covariate.
Secondary objective
• All falls: first and subsequent falls leading to hospitalisations of more than 1 day during the study period that are separated from a previous hospitalisation by more than 15 days from discharge to new admission.
Nawab Qizilbash - Chief Investigator - OXON Epidemiology - Spain
Bélène Podmore - Corresponding Applicant - OXON Epidemiology - Spain
Agueda Azpeitia - Collaborator - OXON Epidemiology - Spain
Ignacio Mendez - Collaborator - OXON Epidemiology - Spain
Itziar Ubillos - Collaborator - OXON Epidemiology - Spain
Jeff Schein - Collaborator - Otsuka America Pharmaceutical Inc
Julia Agúndez - Collaborator - OXON Epidemiology - Spain
Kristian Tore Jørgensen - Collaborator - Lundbeck Limited
Madhusudan Kabra - Collaborator - Otsuka Europe
Michael Frank Mørup - Collaborator - Lundbeck A/S
MIGUEL DESCALZO - Collaborator - OXON Epidemiology - Spain
Ruth Owen - Collaborator - OXON Epidemiology - Spain
HES Admitted Patient Care