Pharmacogenetics: Matching the Right Foundation at Personalized Medicine in the Right Genomic Era

Taușer, Roxana-Georgiana

doi:10.5772/25824

Cited by 2 publications

(8 citation statements)

References 74 publications

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“…Clinical, demographic and genetic specific profiles could contribute in different ratios to significant interpatient variability noticed in both therapeutic efficacy and adverse drug reactions (ADR) (Moore, Hill & Panguluri, 2014;Tauser 2012). "Antipsychotic Trials of Intervention Effectiveness" (CATIE) estimates that over 70% of chronic schizophrenia patients stopped the antipsychotics because of sub-optimal efficacy or safety and treatment-resistant schizophrenia (TRS) affects ~30% of patients (Eum, Lee, & Bishop, 2016).…”

Section: Pharmacogenomics: the Promise Of Personalized Psychotropic Tmentioning

confidence: 99%

“…"Sequenced Treatment Alternatives to Relieve Depression" (STAR*D) trial -the largest and longest evaluation of antidepressants -has proven that: only 37% of non-psychotic major depression cases reported remission to a selective serotonin reuptake inhibitor (SSRI) as first choice drug, and 16.3% of patients stopped the therapy because of poor tolerance; only 50% antidepressant-treated patients are responsive and about 55% experience at least one ADR; at least four antidepressant drugs by classical approach of prescription "trial-and error" and "one dose fits all patients", for more than 50 weeks, were necessary to obtain a cumulative remission rate of 67%; the antidepressant therapy was interrupted after 3 months in 42% of cases, and only 45% were compliant to longer treatment; a great variability (up to 40%) in pharmacokinetic plasmatic parameters is noticed for some antidepressants administered in the same standard therapeutic dose to different patients. Moreover, genetic polymorphisms could explain up to 42-50% of the differences in both positive clinical outcomes and ADR of antidepressants (Bousman et al, 2017;Tauser, 2012).…”

Section: Pharmacogenomics: the Promise Of Personalized Psychotropic Tmentioning

confidence: 99%

“…Pharmacogenetics has mainly associated monogenic polymorphisms to the patients' variability in drugs' metabolism, with the potential to diminish the risk of ADR to the carriers (i.e., persons who do not "average" respond). Pharmacogenomics investigates in an integrative approach the differences in genes' expression caused by the systemic interactions between medications and the whole genome, exploiting the acquisitions from genomics, proteomics, transcriptomics, metabolomics and epigenomics in the medical practice (Tauser, 2012). The two terms are still used interchangeably and will be here abbreviated by PGx.…”

Section: Pharmacogenomics: the Promise Of Personalized Psychotropic Tmentioning

confidence: 99%

“…The test is recommended for the pretreatment dose adjustements in non-responders or outliers (UM, PM, IM), so as to assure therapeutic efficacy and to minimise severe ADR. Despite its commercial availability, it costs over $600/test and requires about 14 days to perform, whilst delaying initiation of therapy associated with the clinical deterioration could be ethically inappropriate (Leucht et al, 2013;Tauser, 2012). Genotyping key alleles of CYP2D6 and CYP2C19 was approved by FDA only as informational test on labels of drugs mainly metabolized by these enzymes, for instance: CYP2D6 for atomoxetine, fluoxetine, paroxetine, amitriptyline, aripiprazole, risperidone.…”

Section: Predictive Pharmacokinetics Pgx Testing: Amplichip™ Cyp450 Testmentioning

confidence: 99%

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Pharmacogenomics in Psychiatric Disorders

Taușer

2020

BRAIN

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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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Section: Pharmacogenomics: the Promise Of Personalized Psychotropic Tmentioning

confidence: 99%

Section: Pharmacogenomics: the Promise Of Personalized Psychotropic Tmentioning

confidence: 99%

Section: Pharmacogenomics: the Promise Of Personalized Psychotropic Tmentioning

confidence: 99%

Section: Predictive Pharmacokinetics Pgx Testing: Amplichip™ Cyp450 Testmentioning

confidence: 99%

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Pharmacogenomics in Psychiatric Disorders

Taușer

2020

BRAIN

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“…Before administering certain medications to a patient, it is mandatory to perform some pharmacogenomic analyses. For some medications pharmacogenomic testing is just recommended, but for the majority of drugs, the testing used today is only informative (41). Introducing routine pharmacogenomic testing into clinical practice enables patients to get an adequate therapy (correct medications and correct drug dose) in accordance with their genotype (42).…”

Section: Pharmacogenetics and Pharmacogenomicsmentioning

confidence: 99%

Molecular Genetic Markers as a Basis for Personalized Medicine / MOLEKULARNO-GENETIČKI MARKERI KAO OSNOV ZA PERSONALIZOVANU MEDICINU

Pavlović¹,

Zukić²,

Petrović³

2014

Journal of Medical Biochemistry

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Summary Nowadays, genetics and genomics are fully integrated into medical practice. Personalized medicine, also called genome-based medicine, uses the knowledge of the genetic basis of disease to individualize treatment for each patient. A number of genetic variants, molecular genetic markers, are already in use in medical practice for the diagnosis, prognosis and follow-up of diseases (monogenic hereditary disorders, fusion genes and rearrangements in pediatric and adult leukemia) and presymptomatic risk assessment (BRCA 1/2 for breast cancer). Additionally, the application of pharmacogenomics in clinical practice has significantly contributed to the individualization of therapy in accordance with the patient’s genotype and gene expression profile. Genetic testing for several pharmacogenomic markers (TPMT, UGT1A1, CYP2C9, VKORC1) is mandatory or recommended prior to the initiation of therapy. The most important achievement of genome-based medicine is molecular-targeted therapy, tailored to the genetic profile of a disease. Testing for gene variants in cancer (BCR-ABL, PML/RARa, RAS, BCL-2) is part of the recommended evaluation for different cancers, in order to achieve better management of the disease. The ultimate goal of medical science is to develop gene therapy which will fight or prevent a disease by targeting the disease causing genetic defect. Gene therapy technology is rapidly developing, and has already been used with success. Although medicine has always been essentially »personal« to each patient, personalized medicine today uses modern technology and knowledge in the field of molecular genetics and genomics, enabling a level of personalization which leads to significant improvement in health care.

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Pharmacogenetics: Matching the Right Foundation at Personalized Medicine in the Right Genomic Era

Cited by 2 publications

References 74 publications

Pharmacogenomics in Psychiatric Disorders

Pharmacogenomics in Psychiatric Disorders

Molecular Genetic Markers as a Basis for Personalized Medicine / MOLEKULARNO-GENETIČKI MARKERI KAO OSNOV ZA PERSONALIZOVANU MEDICINU

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