Overview: pharmacogenomics of psychiatric disorders--separating the dreams from the realities.
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Personalized medicine is a hot topic in the literature of the psychiatric field but it seems that regular clinical application of valid tests are awaited. Urgent requirement of objective tools for screening high-risk patients is postulated by prominent authors because long-term set up time, serious side effects or ineffectiveness of psychiatric agents mean a great challenge for clinicians to find optimal therapy on time. Unwanted suffering from inaccurate medicine, progression of the disorder and mistrust or in adherence of the patients are dramatic consequences of the delay of adequate therapy which is linked with irreversible health and mental damages and financial loss. On the other hand, a growing body of data are published on pharmacogenomic studies in association with psychiatric conditions. Although several pharmacogenetic tests are commercially available, accurate use of these tools are absent from clinical protocols. Here we give a short review on the most important pharmacogenomic results and a discussion on possible conflict of interests around pharmacogenetic tests. We conclude that all participants of the health care system could benefit from personalized medicine in psychiatry.
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Recent research has revealed that patients may metabolize the same drug differently.Why and how does this occur?Investigation into the expanding field of pharmacogenomics can help answer these two questions.Pharmacogenomics is the study of all genes in the genome that may determine drug response. 1Looking into studies where psychiatric patients have been diagnosed with the same disease, it has been observed that a large sample of patients react differently to similar or the same medications.In pharmacogenomics of the psychiatric population, drugs are divided into three categories based on safety and effectiveness: red category, yellow category, and green category; red-zone, yellow-zone, and green-zone.The subjects of the studies cited herein are a sampling of those who took either red, yellow, or green categorized FDA-approved drugs.There is also a small sample of subjects who took a combination of yellow and green drugs simultaneously.However, there are no subjects that took a combination of red and yellow or a combination of red and green; and there are also no subjects that took drugs from all three categories.Drugs that treat depression are the focus of this research, as psychiatric medicines, such as antidepressants, have a large sampling of patients who have or have not done well with the various medications.Pharmacogenomic testing will help treat patients more effectively using medications that better correspond to the patient's genetic makeup.This results in a more personalized approach to treatment with medicines..
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The broad arsenal of psychotropic medications is characterised by significant interindividual variability in clinical response and adverse effects, stringent monitoring requirements, potential drug-drug interactions, difficult long-term adherence and high costs.Pharmacogenomics investigates the correlation between genetic polymorphisms and responsiveness to drugs and could provide a valuable guide to fulfill the promise of personalized therapy in the context of the genomic medicine era, by tailoring treatment based on the patient's specific genetic markers.The present paper overviews the current advances in the clinical applications of pharmacogenomics to individualized psychotropic therapy.Material and methods.The relevant recent pharmacogenomics literature is selected and analysed in order to illustrate the impact on the clinical outcomes and quality of life in psychiatric patients of the genetic variants in the neurotransmitter receptors (dopamine and serotonin), metabolic pathways of drugs (cytochrome CYP450 2D6 and 2C19) and the human leukocyte antigen system.The paper focuses on some of the major psychotropic drug classes, such as: antipsychotics, antidepressants and mood stabilizers.Validation of statistically significant pharmacogenomics relationships has enabled the development and market approval of some predictive tests which are already integrated into some psychotropic drugs label.Results and discussions.Predictive pharmacogenomics tests have changed the classical approach of prescription "trial-and error" and "one dose fits all patients" towards personalized therapy.In addition, in new therapeutic candidates' clinical development, pharmacogenomics practically guides the clinical studies design, by substantially reducing the failure rates, costs and exposure risks of non-responders patients to new drugs.Current translation barriers of predictive pharmacogenomic tests from bench to clinical practice are also discussed.Conclusion.The paper emphasizes the current progress and future prospects in the field of pharmacogenomics as a guide to personalized therapy of psychiatric disorders, by: a) pretreatment selection of the right drug, prescribed in its optimized dose, to the right patient, according to one's specific genetic biomarkers; b) by improved clinical trials design based on genetic stratification of patients' population into responders versus nonresponders, especially in the costly phases III and IV.
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Background The prevalence of psychiatric disorders is increased in children and adults with intellectual disability. Brain damage or dysfunction interacts with social and family factors to increase susceptibility to mental illness. Current concepts in drug therapy often attempt treatment of large patient populations as groups, irrespective of the potential for individual, genetically-based differences in drug response.
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Realizing the promise of precision medicine in psychiatry is a laudable and beneficial endeavor, since it should markedly reduce morbidity and mortality and, in effect, alleviate the economic and social burden of psychiatric disorders. This review aims to summarize important issues on pharmacogenomics in psychiatry that have laid the foundation towards personalized pharmacotherapy and, in a broader sense, precision medicine. We present major pharmacogenomic biomarkers and their applications in a variety of psychiatric disorders, such as depression, attention-deficit/hyperactivity disorder (ADHD), narcolepsy, schizophrenia, and bipolar disorder. In addition, we extend the scope into epilepsy, since antiepileptic drugs are widely used to treat psychiatric disorders, although epilepsy is conventionally considered to be a neurological disorder.
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