AntipSychotic discontinuation and restarT and its association with cardiOvascular events and all-cause mortality in PatienTs witH dEMentia (STOP-THEM)

Dementia is a group of symptoms related to an ongoing decline of brain functioning, usually affecting older people. Although more related to cognitive deterioration, most patients also experience behavioural and mood symptoms, including depression, sleep disturbance, agitation, and aggression. These symptoms can complicate the interactions with family and assistance from carers. When the symptoms start turning severe, antipsychotic medications are often prescribed to manage them. However, antipsychotics have been linked to an increased risk of developing cardiovascular diseases and mortality. This evidence motivated updating clinical guidelines, which now encourage reducing antipsychotic prescriptions; for example, recommending doctors to prescribe them in low doses and for short periods (<6 months). However, people stopping antipsychotics risk relapse and may therefore need to restart the treatment. Previous research has mainly focused on the benefits of antipsychotic discontinuation in physical health, but there is a lack of knowledge on the impact of dose reduction and/or intermittent antipsychotic treatment and their association with cardiovascular events and mortality in people with dementia living in the community.

We aim to investigate antipsychotic discontinuation and restart and its association with physical health in people with dementia. Our objectives are to 1) describe the antipsychotic prescription patterns over time (including discontinuation, restart, change of medication and dose), and 2) examine the association between these patterns and cardiovascular morbidity and mortality.

For performing this research, we will use medical data routinely collected in UK primary care. We will observe people diagnosed with dementia aged 60 to 85 years who were incident users of antipsychotics between 2006 and 2020. Using statistical and machine learning tools, we will determine how often antipsychotic discontinuation and restart occur in this population, whether time to discontinuation typically follows recommendations from guidelines, and the average time people with dementia usually need to restart antipsychotic treatment. We will also describe what is the usual change in the type of medication and prescribed dose over time, identifying the sociodemographic, lifestyle and clinical characteristics of people prescribed different types of medications and doses. Finally, we will explore how extended exposure to antipsychotics (e.g., when people restart treatment) is associated with future cardiovascular events and mortality by performing a statistical analysis called 2-stage dynamic landmark modelling.

We expect all this evidence will be of great value for patients and clinicians, helping to generate informative materials -for specialists and a bigger audience- and to improve guidelines for clinical practice.

Amount awarded: £61,066