Husna Rahim, PharmD & Kate Choy-Kay Lee
Pharmacogenomics in Mental Health: A Look at Schizophrenia. How can pharmacogenomics (PGx) be leveraged to optimize treatments for patients suffering from mental illness? In contrast to diseases of physical manifestation, mental illness typically requires significant trial and error before the right therapeutic regimen is established for any one patient. PGx has particular appeal in schizophrenia due to highly variable responses to drug treatment, side effects, and enzyme polymorphisms.
Only 20-50% of patients with schizophrenia respond to standard medication. Understanding how a person’s genetics influence the dopamine system and its modulation by antipsychotics helps guide treatment selection and dosing. According to a 2023 clinical investigation, only 20-50% of patients with schizophrenia respond to standard antipsychotic medications (Kang 2023). Many antipsychotics for schizophrenia target dopamine receptors. However, genetic variants and polymorphisms which alter the function of these receptors, such as the COMT gene, differ from person to person (Kang 2021 & Lally 2016). These differences impact how individuals respond to antipsychotic medications, leading to varying levels of efficacy and side effects. By incorporating genetic testing into treatment decisions, healthcare providers may be able to optimize medication selection and dosing for better outcomes in patients with schizophrenia.
Genetic testing can reduce the need for trial-and-error. Antipsychotics are infamous for their large side effect profile.These can often be debilitating, leading patients to discontinue their medication. As the gold standard therapy for treatment-resistant schizophrenia, clozapine’s effects and adverse drug reactions have been linked to genetic variations (Lally 2016). By testing for these genetic markers, clinicians can make more informed decisions about which medications to prescribe, reducing the risk of adverse events and need for trial and error.
Lastly, polymorphisms in the enzymes responsible for metabolizing antipsychotics can alter the efficacy of treatment (Lally 2016). This can be observed with clozapine, which Is metabolized by CYP1A2. A patient with exceptionally high levels of CYP1A2 enzyme activity as a result of a polymorphism would likely not respond to treatment with clozapine whereas a poor metabolizer might experience toxicity (Zhang 2021). Factors beyond just genetic variants, like smoking and diet, can also impact CYP1A2 activity, and should be accounted for.
Personalized approach to mental health. PGx offers a promising solution to the challenges of treating schizophrenia. Continuing to study the relationships between drug efficacy and genetic polymorphisms allows for a streamlined and personalized approach to optimizing treatment for those suffering from a mental illness.
Learn more about UGenome’s Personalized Medication Service, ProPEx, or contact UGenome. You can also find case studies for UGenome’s bioinformatics services Metabolite Identification, Bone Metastasis Risk Analysis in Breast Cancer, Survival Analysis with gene signatures in cancer
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