About the Project
Schizophrenia is a serious and debilitating psychiatric disorder affecting approximately 1% of the population. Antipsychotic medications can be effective for managing schizophrenia, but there is limited guidance to identify the most appropriate antipsychotic for a given patient. There is often a ‘trial and error’ approach, with some patients needing to be prescribed several different types of antipsychotic before an effective medication and dose is identified; a process which can take several months. Furthermore, antipsychotics can cause adverse drug reactions which are often unpleasant, and in some cases life-threatening. For these reasons, some antipsychotics are considered to be high risk medicines.
Tools or knowledge for medicines optimisation, namely a better choice of medication that is efficacious and with fewer side effects for an individual, would be highly beneficial to both patients and practitioners, improving patient outcomes and cost, for example by reducing length of hospital stay.
There is a particular opportunity for pharmacogenomics (PGx) testing to improve prescribing decisions and medicines optimisation for patients with psychoses. Genetic variants that cause differences in the activities of proteins responsible for the metabolism and excretion of medicines that impact upon antipsychotic efficacy and side-effects have been identified. However, little research has been conducted in UK settings to date to evaluate and understand whether and how real-life implementation of pharmacogenomic testing might be achieved in this patient population and how PGx information may be used to influence prescribing decisions. The NHS wishes to implement PGX nationally within the next 5 years, therefore it is important to establish how this technology can be used effectively in clinical settings.
The aim of this PhD is to explore the potential of PGx, to develop a tool to improve antipsychotic prescribing decisions. Our knowledge gaps are to determine and identify whether:
1. pharmacogenomic testing is feasible in this setting
2. pharmacogenomic test information would be an improvement on treatment as usual in predicting antipsychotic efficacy and side-effect profile
3. symptom profile and other patient characteristics would also contribute to predicting antipsychotic efficacy and side-effect profile
4. pharmacogenomic testing would be acceptable and useful to patients and clinicians
The overall aim of introducing PgX into practice in the prescription of antipsychotics is to provide an evidence base and tools to enable clinical decisions to improve patient outcomes by identifying the most appropriate therapy for each individual patient. These tools are predicted to reduce the time taken to effectively manage the patients’ symptoms, and to minimise side-effects and adverse effects, providing patient benefit and significant cost saving to the NHS. This research therefore has a pathway to impact as it will define an implementation pathway for technology-enabled clinical intervention for patient benefit in an area of national and international priority that aligns with NHS forward view.
This PhD studentship based in the School of Pharmacy & Medical Sciences will align with the NIHR Yorkshire & Humber Patient Safety Translational Research Centre (Safe Use of Medicines theme). The PhD student will be situated mostly in the Wolfson CAHR, with one day per week at the University campus, and one day per week (or more) in the clinical environment. The successful applicant will initially be registered on the MSc in Social Sciences Research for Healthcare programme followed by a 3 year PhD studentship.
If you would like further information or details about this project, please contact Dr Samantha McLean ([Email Address Removed]) or Jaspreet Sohal ([Email Address Removed]).
References
• Hjorth S, Waters S, Waters N, Tedroff J, Svensson P, Fagerberg A, Edling M, Svanberg B, Ljung E, Gunnergren J, McLean SL, Grayson B, Idris NF, Neill JC and Sonesson C (2020) (3S)‐3‐(2,3‐difluorophenyl)‐3methoxypyrrolidine (IRL752) – a novel cortical-preferring catecholamine transmission- and cognition-promoting agent. Journal of Pharmacology and Experimental Therapeutics, in press
• Mitchell EJ, Thomson DM, Openshaw RL, Bristow GC, Dawson N, Pratt JA, Morris BJ (2020). Drug-responsive autism phenotypes in the 16p11.2 deletion mouse model: a central role for gene-environment interactions. Scientific Reports, 10(1):12303.
• Bristow GC, Thomson DM, Openshaw RL, Mitchell EJ, Pratt JA, Dawson N, Morris BJ (2020). 16p11 Duplication Disrupts Hippocampal-Orbitofrontal-Amygdala Connectivity, Revealing a Neural Circuit Endophenotype for Schizophrenia. Cell Reports, 31(3):107536.
• Watremez W, Jackson J, Almari B, McLean SL, Grayson B, Neill JC, Pillot T, Harte MK (2018). Stabilised low-n amyloid-β oligomers induce robust cognitive deficits associated with inflammatory, synaptic and GABAergic dysfunction in the rat. Journal of Alzheimer’s Disease, 62: 213-226.
• Mclean SL, Harte MK, Neill JC, Young AM (2017). Dopamine dysregulation in the prefrontal cortex relates to cognitive deficits in the sub-chronic PCP-model for schizophrenia: A preliminary investigation. Journal of Psychopharmacology, 31: 660-666.
• McLean SL, Grayson B, Marsh S, Zarroug SHO, Harte MK, Neill JC (2016). Nicotinic α7 and α4ß2 agonists enhance the formation and retrieval of recognition memory: Potential mechanisms for cognitive performance enhancement in neurological and psychiatric disorders. Behavioural Brain Research, 302: 73–80.
• Bristow GC, Bostrom JA, Haroutunian V, Sodhi MS (2015). Sex differences in GABAergic gene expression occur in the anterior cingulate cortex in schizophrenia. Schizophrenia Research, 167(1-3):57-63.
• McLean SL Blenkinsopp A, Bennett MI (2013). Using haloperidol as an anti-emetic in palliative care: informing practice through evidence from cancer treatment and post-operative contexts. Journal of Pain and Palliative Care Pharmacotherapy, 27: 132-5.
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