The Potential of Pharmacometabonomics and Pharmacogenomics Approach to Determine Clozapine Response among Schizophrenia Patients

Main Article Content

Abdulkader Ahmad Bawadikji
Mohsen Huraybi M Alshammari
Badr Jarallah Alenezi
Jamal Mohammed Alshammari
Obaid J Alanzi
Bader Awadh A Almutairi
Bader Ayed Alqarni
Majed Eqab Alshammary
Baharudin Ibrahim

Keywords

Schizophrenia, Clozapine, Pharmacogenomics, Pharmacometabonomics, Nuclear Magnetic Resonance

Abstract

Schizophrenia and related disorders are severe mental illnesses characterized by profound disruptions in emotional processes, speech, behaviour, thinking, and sense of self. It, moreover, has specific antisuicidal and anti-aggressive properties. Clozapine is the most efficacious antipsychotic drug in treatment-resistant schizophrenia, mainly when other antipsychotic medications do not work. It improves negative symptoms (e.g., poverty of speech and withdrawal) and positive symptoms (e.g., hallucinations and delusions). However, it is unclear the most effective dose/response of clozapine with the most negligible side effects. Pharmacogenomics has been recommended to predict clozapine response. However, this might be insufficient to predict the response. Pharmacometabonomics analysis using proton nuclear magnetic resonance (1H-NMR) spectroscopy can help to identify novel biomarkers of clozapine. Many factors could influence the metabolism of clozapine, changing clozapine response, drug dosage standard, and clinical characteristics such as drug-drug interactions, dietary interactions, and age explanation for the critical part of the variability in clozapine dosing/response. Integrating pharmacogenetics and pharmacometabonomics has the advantage of getting more extensive and comprehensive information on variations in drug response.

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