Can genomics enhance care and quality of life in psychosis? Investigating the cost-effectiveness of pharmacogenomics in mental health.

Schizophrenia is a complex psychotic disorder which is a leading cause of disability and reduced quality of life worldwide. Individuals with schizophrenia have an increased risk of mortality due to poor physical health, such as metabolic syndrome. In this thesis, I aim to address whether a genomics-guided approach can individualise antipsychotic treatment to improve care and quality of life for individuals with psychosis, and whether this approach is cost-effective. In Chapter 2, I conducted a systematic review to investigate whether the use of pharmacogenetics to optimise the prescribing of antipsychotics improves health or economic outcomes. Chapter 2 revealed a lack of studies to assess the clinical utility and cost-effectiveness of pharmacogenetic testing in the UK. Chapter 3 involves an investigation of the causal relationship between schizophrenia and cardiovascular abnormalities, such as diabetes. No evidence of a causal relationship was identified, suggesting that the relationship is likely to be explained by other factors, such as antipsychotic-induced adverse drug reactions. In Chapter 4, I explored whether genetic variation in a pharmacogene (CYP2D6) was associated with healthcare costs from a sample of individuals with psychosis participating in the ongoing Pharmacogenetics in Mental Health Study, which showed that intermediate metabolisers had significantly higher primary care costs compared to normal metabolisers. Finally, in Chapter 5, I ran a cost-effectiveness analysis investigating the use of pharmacogenetic testing for CYP2D6 and CYPC19 to guide prescribing for individuals with schizophrenia, using a decision tree and Markov model, from a healthcare perspective. The genomics-guided approach was found to be cost-effective, although further evidence demonstrating clinical utility is required. This thesis suggests that while a genomics-guided approach could potentially improve health and economic outcomes in schizophrenia, further research is ultimately required to support these findings.