Anticholinergics, Antipsychotics and Associated Risks in Dementia Seeking to improve the Safety of Prescribing

To date, there is no cure for dementia and no treatments exist that have been unequivocally shown to interrupt or reverse the disease progression. Therapeutic interventions are therefore targeted at specific symptoms or to improve or slow the decline in cognitive function for a limited period. In view of the limited treatment options available for Alzheimer’s disease, it is imperative to try to prevent dementia where possible as well as trying to improve outcomes and preserve cognitive function for as long as possible. This thesis focusses on exploring ways to improve the safety of prescribing in people with dementia. Over the last 15 years, growing evidence of serious effects associated with anticholinergic agents in older people has emerged. Long-term use of anticholinergic drugs in older people is associated with an increased risk of cognitive decline, dementia and early death. I investigated the effect of anticholinergic burden of drugs on dementia outcomes and found that drugs with a high Anticholinergic Effect on Cognition (AEC) score were associated with increased mortality and hospitalisation compared to those with low scores. This highlights the importance of keeping the central anticholinergic burden to a minimum. When looking at antidepressants and antipsychotic drugs specifically, this association was not seen, suggesting that other properties are considered when prescribing these psychotropic agents, and that there may be other confounding factors not considered. In contrast, when I compared bladder anticholinergic drugs in people with dementia, those with high AEC scores were associated with significantly increased mortality, by 55% compared to those with low AEC scores. Additionally, I led on the development of Medichec, a desktop and phone app that helps to identify drugs that have a high central anticholinergic burden in addition to drugs that are reported to cause QTc prolongation, hyponatraemia, bleeding risk, dizziness, drowsiness and constipation. Medichec can facilitate access to side-effects information for multiple medications at once, aid clinical decision-making and optimise treatment. Finally, because antipsychotic drugs have been associated with increased cerebrovascular accidents and mortality in dementia for nearly 20 years, I led a project in South London and Maudsley (SLaM) NHS Foundation Trust that enhanced the prescribing and monitoring of antipsychotic drugs in people with dementia.<br/