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Speaker at Pharma Conferences - Daisy Mills
Daisy Mills
University College London, United Kingdom
Title : The influence of CYP450 variation and smoking on clozapine metabolism: a mixed- effects model using longitudinal patient data

Abstract:

Clozapine is an atypical antipsychotic regarded as the gold-standard for treatment-resistant schizophrenia, yet its metabolism remains highly variable. The cytochrome P450 enzymes CYP1A2, CYP2D6, and CYP2C19 are involved in clozapine metabolism, though the clinical significance of genetic variation in these enzymes remains unclear. Tobacco, a known inducer of CYP1A2, has a well-established influence on clozapine metabolism, but the effects of cannabis remain unknown. In this study, we investigate the influence of these CYP450 polymorphisms and smoking behaviours on dose-adjusted clozapine concentrations using longitudinal data from ~400 plasma samples collected from schizophrenia patients. We apply linear mixed-effects models to assess these associations while accounting for key confounders, including C-reactive protein (CRP), co-medications, smoking status, metabolic parameters, age, ethnicity, and gender. Preliminary results indicate [tbc] significant effects of CYP450 variants, tobacco, and cannabis use on clozapine metabolism (p = tbc]). These findings suggest that CYP1A2, CYP2D6 or CYP2C19 polymorphisms may have [tbc] clinical utility in guiding clozapine dosing. In the future, this work could have direct clinical applications, offering actionable insights to optimise clozapine dosing based on individual genetic and environmental factors. By addressing gaps in pharmacogenetic studies, particularly the underexplored role of cannabis, this work contributes to advancing personalized psychiatry.

Audience Take Away Notes:   

  • The detriment to patients of trial-and-error prescribing in psychiatry.
  • Practical guidance on incorporating pharmacogenetic insights into psychiatric treatment, allowing healthcare professionals to look towards personalised medication plans.
  • Offering a research framework for researchers to further explore drug metabolism, precision psychiatry, and the role of substance use in antipsychotic treatment.
  • Current barriers to personalised medicine in psychiatry.
  • The importance of accounting for factors like inflammation (CRP), co-medications, and demographics when evaluating clozapine response.

Biography:

I am Daisy Mills, a Research Assistant at University College London (UCL), working as part of a team aimed at advancing the use of pharmacogenetics in mental health. I earned my BSc in Biochemistry from Imperial College London, followed by an MRes in Brain Sciences at UCL, where I joined Professor Elvira Bramon’s research team. My research focuses on understanding how genetic and environmental factors influence treatment response, particularly in antipsychotic medications. Identifying key gaps in this area, I am now dedicated to expanding this work to improve personalised treatment approaches in psychiatry.

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