PhD PROPOSAL: Can genomics enhance care and quality of life in psychosis?

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Psychotic disorders are severe mental illnesses affecting 3% of the population (Bogren et al. 2009). The annual economic burden of psychosis is £9 billion in England and 93 billion in Europe, including both direct healthcare as well as indirect costs to society (McCrone et al. 2008, Olesen et al. 2012). More than 20 medications have demonstrated efficacy to treat psychosis (Joint Formulary Committee 2018). Drug choices and dose adjustments are empirical and it is common for patients to need several medication changes (Taylor et al. 2018). However, there is compelling evidence that genetic factors influence response and adverse drug reactions (van der Wouden et al. 2017). For about 200 medications, including some antipsychotics, there are clinical guidelines and Food and Drug Administration or European Medicines Agency labels recommending dose adjustments based on genetic profile (Clinical Pharmacogenetics Implementation Consortium 2017, Stingl et al. 2016, Swen et al. 2011, U.S. Food and Drug Administration 2015). In psychosis care we face two major challenges: Firstly, as many as 60% of people stop taking their medication, which increases risk of relapsing (Velligan et al. 2020, Velligan et al. 2017); Secondly, there is a major problem of polypharmacy (Broekema et al. 2007, Young et al. 2015), with 20-40% of people treated with drug combinations contrary to National Institute for Health and Care Excellence guidelines (NICE 2014). Genetic testing is now available to the general public for affordable fees and the 100,000 and the 5 million Genomes Projects are transforming our healthcare services in an unprecedented way (Genomics England December 2020). Recent studies indicate that using genetic data to guide medication choices is cost-saving (Verbelen et al. 2017). The only trial of genetic-guided antipsychotic treatment run in Denmark revealed significant savings in direct healthcare costs both in mental health and primary care (Herbild et al. 2013, Jurgens et al. 2020). However, in UK mental health practice we do not use pharmacogenomics testing yet, due to insufficient evidence of its benefits and of its cost-effectiveness (Just et al. 2017, Walden et al. 2015).