-
Clinical Pharmacology and Therapeutics Sep 2021The evidence for pharmacogenetics has grown rapidly in recent decades. However, the strength of evidence required for the clinical implementation of pharmacogenetics is... (Review)
Review
The evidence for pharmacogenetics has grown rapidly in recent decades. However, the strength of evidence required for the clinical implementation of pharmacogenetics is highly debated. Therefore, the purpose of this review is to summarize different perspectives on the evidence required for the clinical implementation of pharmacogenetics. First, we present two patient cases that demonstrate how knowledge of pharmacogenetic evidence affected their care. Then we summarize resources that curate pharmacogenetic evidence, types of evidence (with an emphasis on randomized controlled trials [RCT]) and their limitations, and different perspectives from implementers, clinicians, and patients. We compare pharmacogenetics to a historical example (i.e., the evidence required for the clinical implementation of pharmacokinetics/therapeutic drug monitoring), and we provide future perspectives on the evidence for pharmacogenetic panels and the need for more education in addition to evidence. Although there are differences in the interpretation of pharmacogenetic evidence across resources, efforts for standardization are underway. Survey data illustrate the value of pharmacogenetic testing from the patient perspective, with their providers seen as key to ensuring maximum benefit from test results. However, clinicians and practice guidelines from medical societies often rely on RCT data to guide treatment decisions, which are not always feasible or ethical in pharmacogenetics. Thus, recognition of other types of evidence to support pharmacogenetic implementation is needed. Among pharmacogenetic implementers, consistent evidence of pharmacogenetic associations is deemed most critical. Ultimately, moving pharmacogenetics into practice will require consideration of multiple stakeholder perspectives, keeping particularly attuned to the voice of the ultimate stakeholder-the patient.
Topics: Drug Monitoring; Humans; Pharmacogenetics; Reference Standards; Surveys and Questionnaires
PubMed: 34101169
DOI: 10.1002/cpt.2327 -
Pharmacopsychiatry Jul 2020This Special Issue on Pharmacogenetics in Psychiatry consists of five selected articles which encompass the first concepts of pharmacogenetics, to implementation...
This Special Issue on Pharmacogenetics in Psychiatry consists of five selected articles which encompass the first concepts of pharmacogenetics, to implementation strategies applyng pharmacogenetic testing into psychiatric clinical practice.
Topics: Humans; Mental Disorders; Pharmacogenetics; Psychiatry
PubMed: 32717764
DOI: 10.1055/a-1212-1101 -
Neuroscience Letters May 2020Anxiety disorders are common and disabling conditions the treatment of which remains a challenge. While different groups of medication are available for their treatment,... (Review)
Review
Anxiety disorders are common and disabling conditions the treatment of which remains a challenge. While different groups of medication are available for their treatment, a substantial proportion of patients remain refractory to pharmacotherapy. The reason for this variation in the individual response to treatment has yet to be understood; however genetic factors have been shown to play an important role. Up to now there have been limited publications about pharmacogenetics of anxiety disorders, compared to studies in depression. Published studies are focused on pharmacogenetics of antidepressants rather than being disease specific. This review summarizes pharmacogenetic findings related to the anxiolytic treatment response and their possible functional mechanisms. This inevitably focuses on genes involved in the pharmacodynamics of the medications used, along with some genes implicated in the disease process, as well as briefly mentioning genetic factors associated with psychotherapeutic response.
Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Anxiety Disorders; Brain-Derived Neurotrophic Factor; Catechol O-Methyltransferase; Humans; Pharmacogenetics
PubMed: 31442515
DOI: 10.1016/j.neulet.2019.134443 -
Drug and Therapeutics Bulletin Nov 2023There is considerable interindividual variability in the effectiveness and safety of medicines. Although the reasons for this are multifactorial, it is well recognised... (Review)
Review
There is considerable interindividual variability in the effectiveness and safety of medicines. Although the reasons for this are multifactorial, it is well recognised that genetic changes impacting the absorption or metabolism of these drugs play a significant contributory role. Understanding how these pharmacogenetic variants impact response to medicines, and leveraging this knowledge to guide prescribing, could have significant benefits for patients and health services. This article provides an introduction to the field of pharmacogenetics, including its nomenclature, the existing evidence base and the current state of implementation globally. We discuss the challenges in translating pharmacogenetic research into clinical practice and highlight the considerable benefits which can emerge in those health services where implementation is successful.
Topics: Humans; Pharmacogenetics
PubMed: 37788890
DOI: 10.1136/dtb.2023.000009 -
Psychiatry Research Oct 2020In this narrative, we evaluate the role of pharmacogenetics in psychiatry from a pragmatic clinical perspective and address current barriers of clinical implementation... (Review)
Review
In this narrative, we evaluate the role of pharmacogenetics in psychiatry from a pragmatic clinical perspective and address current barriers of clinical implementation of pharmacogenetics. Pharmacogenetics has been successfully implemented to improve drug therapy in several clinical areas, but not psychiatry. Yet, psychotropics account for more than one-third of the drugs for which pharmacogenetic guidelines are available and drug therapy in mental disorders is suboptimal with insufficient effectiveness and frequent adverse events. The limited application of pharmacogenetics in psychiatry is influenced by several factors; e.g. the complexity of psychotropic drug metabolism, possibly impeding the clinical understanding of the benefits of pharmacogenetics. Also, recommendations for most psychotropics classify pharmacogenetic testing only as (potentially) beneficial, not as essential, possibly because life-threatening adverse events are often not involved in these drug-gene interactions. Implementing pharmacogenetics in psychiatry could improve the current practice of time-consuming switching of therapies causing undue delays associated with worse outcomes. We expect pharmacogenetics in psychiatry to expedite with panel-based genotyping, including clinically relevant variants, which will address the complex enzymatic metabolism of psychotropic drugs. Until then, we stress that available pharmacogenetic testing should be seen as an integrated companion, not a competitor, in current clinical psychiatric care.
Topics: Humans; Mental Disorders; Pharmacogenetics; Pharmacogenomic Testing; Psychiatry; Psychotherapy; Psychotropic Drugs
PubMed: 32739644
DOI: 10.1016/j.psychres.2020.113336 -
Human Molecular Genetics Oct 2001Pharmacogenetics is the variability of drug response due to inherited characteristics in individuals. Drug metabolizing enzymes have been studied for decades, first as... (Review)
Review
Pharmacogenetics is the variability of drug response due to inherited characteristics in individuals. Drug metabolizing enzymes have been studied for decades, first as chemical reactions and, more recently, as specific polymorphisms of known molecules. With the availability of whole-genome single-nucleotide polymorphism (SNP) maps, it will soon be possible to create an SNP profile for patients who experience adverse events (AEs) or who respond clinically to the medicine (efficacy). Proof-of-principle experiments have demonstrated that high density SNP maps in chromosomal regions of genetic linkage facilitate the identification of susceptibility disease genes. Whole-genome SNP mapping analyses aimed at determining linkage disequilibrium (LD) profiles along an ordered human genome backbone are in progress. SNP 'fingerprints' or SNP PRINTs(sm) will be used to identify patients at greater risk of an AE, or those patients with a greater chance of responding to a medicine. As LD maps for various ethnic populations are constructed, the number of SNPs necessary to measure for an individual will decrease. Standardized pharmacogenetic maps for drug registration and post-marketing surveillance will result in safer, more effective and more cost-efficient medicines. The timing of these pharmacogenetic applications will occur over the next 5 years. In contrast, the benefits of pharmacogenomic applications such as the identification of new tractable targets will not be visible as new medicines for 7-12 years, due to the lengthy drug development and registration processes.
Topics: Humans; Pharmacogenetics
PubMed: 11673409
DOI: 10.1093/hmg/10.20.2261 -
Drug Metabolism and Personalized Therapy Mar 2016In the last decade, pharmacogenetic research has been performed in different fields. However, the application of pharmacogenetic findings to clinical practice has not... (Review)
Review
In the last decade, pharmacogenetic research has been performed in different fields. However, the application of pharmacogenetic findings to clinical practice has not been as fast as desirable. The current situation of clinical implementation of pharmacogenetics is discussed. This review focuses on the advances of pharmacogenomics to individualize cancer treatments, the relationship between pharmacogenetics and pharmacodynamics in the clinical course of transplant patients receiving a combination of immunosuppressive therapy, the needs and barriers facing pharmacogenetic clinical application, and the situation of pharmacogenetic testing in Spain. It is based on lectures presented by speakers of the Clinical Implementation of Pharmacogenetics Symposium at the VII Conference of the Spanish Pharmacogenetics and Pharmacogenomics Society, held in April 20, 2015.
Topics: Genetic Testing; Humans; Immunosuppressive Agents; Neoplasms; Organ Transplantation; Pharmacogenetics; Precision Medicine; Spain
PubMed: 26751902
DOI: 10.1515/dmpt-2015-0031 -
Dialogues in Clinical Neuroscience Dec 2014Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect... (Review)
Review
Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h(2)~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future.
Topics: Antipsychotic Agents; Biomarkers; Humans; Pharmacogenetics; Precision Medicine; Psychotic Disorders
PubMed: 25733959
DOI: 10.31887/DCNS.2014.16.4/jpouget -
Drug Metabolism and Drug Interactions 2014Spanning over 2000 years, the Jewish population has a long history of migration, population bottlenecks, expansions, and geographical isolation, which has resulted in a... (Review)
Review
Spanning over 2000 years, the Jewish population has a long history of migration, population bottlenecks, expansions, and geographical isolation, which has resulted in a unique genetic architecture among the Jewish people. As such, many Mendelian disease genes and founder mutations for autosomal recessive diseases have been discovered in several Jewish groups, which have prompted recent genomic studies in the Jewish population on common disease susceptibility and other complex traits. Although few studies on the genetic determinants of drug response variability have been reported in the Jewish population, a number of unique pharmacogenetic variants have been discovered that are more common in Jewish populations than in other major racial groups. Notable examples identified in the Ashkenazi Jewish (AJ) population include the vitamin K epoxide reductase complex subunit 1 (VKORC1) c.106G>T (p.D36Y) variant associated with high warfarin dosing requirements and the recently reported cytochrome P450 2C19 (CYP2C19) allele, CYP2C19*4B, that harbors both loss-of-function [*4 (c.1A>G)] and increased-function [*17 (c.-806C>T)] variants on the same haplotype. These data are encouraging in that like other ethnicities and subpopulations, the Jewish population likely harbors numerous pharmacogenetic variants that are uncommon or absent in other larger racial groups and ethnicities. In addition to unique variants, common multi-ethnic variants in key drug metabolism genes (e.g., ABCB1, CYP2C8, CYP2C9, CYP2C19, CYP2D6, NAT2) have also been detected in the AJ and other Jewish groups. This review aims to summarize the currently available pharmacogenetics literature and discuss future directions for related research with this unique population.
Topics: Cytochrome P-450 Enzyme System; Humans; Jews; Pharmaceutical Preparations; Pharmacogenetics; Population Surveillance
PubMed: 24867283
DOI: 10.1515/dmdi-2013-0069 -
Methods in Molecular Biology (Clifton,... 2014Antipsychotics are the mainstay treatment for schizophrenia. There is large variability between individuals in their response to antipsychotics, both in efficacy and... (Review)
Review
Antipsychotics are the mainstay treatment for schizophrenia. There is large variability between individuals in their response to antipsychotics, both in efficacy and adverse effects of treatment. While the source of interindividual variability in antipsychotic response is not completely understood, genetics is a major contributing factor. The identification of pharmacogenetic markers that predict antipsychotic efficacy and adverse reactions is a growing area of research, and holds the potential to replace the current trial-and-error approach to treatment selection in schizophrenia with a personalized medicine approach.In this chapter, we provide an overview of the current state of pharmacogenetics in schizophrenia treatment. The most promising pharmacogenetic findings are presented for both antipsychotic response and commonly studied adverse reactions. The application of pharmacogenetics to schizophrenia treatment is discussed, with an emphasis on the clinical utility of pharmacogenetic testing and directions for future research.
Topics: Antipsychotic Agents; Genome-Wide Association Study; Humans; Pharmacogenetics; Precision Medicine; Schizophrenia; Treatment Outcome
PubMed: 25150876
DOI: 10.1007/978-1-4939-0956-8_14