Benefits of and Barriers to Pharmacogenomics‐Guided Treatment for Major Depressive Disorder

Ahmed, Ahmed T.; Weinshilboum, Richard M.; Frye, Mark A.

doi:10.1002/cpt.1009

Cited by 10 publications

(7 citation statements)

References 5 publications

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“…Antidepressants reduce the symptom burden in Major Depressive Disorder (MDD) in over 50% of the cases, but ADRs and treatment resistance still present major challenges in over 30% of the cases [19,172]. Some studies did not identify significant predictive effect of PGx in depressive patients [173,174], whereas others found that over 40% of depressive patients receive inappropriate medication, and that with the aid of PGx testing it is possible to reverse inefficacy and unwanted effects after treatment rectification [19,169,175,176].…”

Section: Central Nervous System Disordersmentioning

confidence: 99%

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions

Cacabelos

Naidoo

Corzo

et al. 2021

IJMS

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Adverse drug reactions (ADRs) rank as one of the top 10 leading causes of death and illness in developed countries. ADRs show differential features depending upon genotype, age, sex, race, pathology, drug category, route of administration, and drug–drug interactions. Pharmacogenomics (PGx) provides the physician effective clues for optimizing drug efficacy and safety in major problems of health such as cardiovascular disease and associated disorders, cancer and brain disorders. Important aspects to be considered are also the impact of immunopharmacogenomics in cutaneous ADRs as well as the influence of genomic factors associated with COVID-19 and vaccination strategies. Major limitations for the routine use of PGx procedures for ADRs prevention are the lack of education and training in physicians and pharmacists, poor characterization of drug-related PGx, unspecific biomarkers of drug efficacy and toxicity, cost-effectiveness, administrative problems in health organizations, and insufficient regulation for the generalized use of PGx in the clinical setting. The implementation of PGx requires: (i) education of physicians and all other parties involved in the use and benefits of PGx; (ii) prospective studies to demonstrate the benefits of PGx genotyping; (iii) standardization of PGx procedures and development of clinical guidelines; (iv) NGS and microarrays to cover genes with high PGx potential; and (v) new regulations for PGx-related drug development and PGx drug labelling.

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Section: Central Nervous System Disordersmentioning

confidence: 99%

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions

Cacabelos

Naidoo

Corzo

et al. 2021

IJMS

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“…Other potential uses in BD are mostly limited to metabolic phenotype associated variants. However, in comparison to genetic variation associated with adverse event or quantifiable biological process (i.e., rash, QTc prolongation), the bar to establish pharmacogenomic efficacy is significantly higher and to date, the evidence base for treatment recommendations is significantly less (Ahmed et al 2018). It is important to note that most of these commercial assays vary in content-which may be not fully disclosed-of the genetic tests provided.…”

Section: Discussionmentioning

confidence: 99%

Potential pharmacogenomic targets in bipolar disorder: considerations for current testing and the development of decision support tools to individualize treatment selection

Cuellar‐Barboza

McElroy

Veldić

et al. 2020

Int J Bipolar Disord

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Background: Treatment in bipolar disorder (BD) is commonly applied as a multimodal therapy based on decision algorithms that lack an integrative understanding of molecular mechanisms or a biomarker associated clinical outcome measure. Pharmacogenetics/genomics study the individual genetic variation associated with drug response. This selective review of pharmacogenomics and pharmacogenomic testing (PGT) in BD will focus on candidate genes and genome wide association studies of pharmacokinetic drug metabolism and pharmacodynamic drug response/ adverse event, and the potential role of decision support tools that incorporate multiple genotype/phenotype drug recommendations. Main body: We searched PubMed from January 2013 to May 2019, to identify studies reporting on BD and pharmacogenetics, pharmacogenomics and PGT. Studies were selected considering their contribution to the field. We summarize our findings in: targeted candidate genes of pharmacokinetic and pharmacodynamic pathways, genome-wide association studies and, PGT platforms, related to BD treatment. This field has grown from studies of metabolizing enzymes (i.e., pharmacokinetics) and drug transporters (i.e., pharmacodynamics), to untargeted investigations across the entire genome with the potential to merge genomic data with additional biological information. Conclusions: The complexity of BD genetics and, the heterogeneity in BD drug-related phenotypes, are important considerations for the design and interpretation of BD PGT. The clinical applicability of PGT in psychiatry is in its infancy and is far from reaching the robust impact it has in other medical disciplines. Nonetheless, promising findings are discovered with increasing frequency with remarkable relevance in neuroscience, pharmacology and biology.

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“…Moreover, combinatorial pharmacogenomic testing has been suggested to contribute to the better selection of antidepressant therapy, potentially improving treatment outcomes (Vojvodic et al, 2021). However, the emerging focus on pharmacogenomics in the context of antidepressant treatment also raises considerations regarding the benefits and barriers of pharmacogenomics-guided treatment for major depressive disorder (Ahmed et al, 2018).…”

Section: Antidepressantsmentioning

confidence: 99%

Pharmacogenomics as a Tool in Addressing Genetic VariationDependent Adverse Drug Reactions

Anunobi

2024

dujopas

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Adverse drug reactions (ADRs) are a cause of discontinuing drug development and withdrawal from market, as well as a very common source of morbidity and mortality. Genetic variables may be the primary predictor of drug response for certain medications, but they are estimated to account for 15– 30% of the variability in drug response. Many factors can contribute to adverse drug reactions, including genetics and drug targeting/delivery. Genetic markers, such as single nucleotide polymorphisms (SNPs) in drug-metabolizing enzymes, drug targets, and human leukocyte antigen (HLA) genotypes, have been associated with an increased risk of ADRs. Pharmacogenomics is the study of the genetic variation in the way that different people react to different pharmaceuticals, including variations in the risk of adverse drug reactions, dose requirements, and efficacy. The implementation of genetic data for predicting responses to medications and ADRs is becoming a reality in clinical practice, offering the potential to reduce the incidence of ADRs and improve patient outcomes. As pharmacogenomic research continues to advance, it holds great promise for enhancing drug safety and efficacy, ultimately leading to more tailored and effective therapeutic interventions.

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Benefits of and Barriers to Pharmacogenomics‐Guided Treatment for Major Depressive Disorder

Cited by 10 publications

References 5 publications

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions

Potential pharmacogenomic targets in bipolar disorder: considerations for current testing and the development of decision support tools to individualize treatment selection

Pharmacogenomics as a Tool in Addressing Genetic VariationDependent Adverse Drug Reactions

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