Pharmacogenetic Testing In Psychiatry Research Articles

Predictive Pharmacogenetic Testing in Psychiatry: Pros and Cons

Pharmacogenetic testing (PGx) is an important diagnostic tool for achieving an optimal balance between the effectiveness and safety of psychotropic drugs, especially those requiring long-term use. The most prescribed medications in psychiatric practice are antipsychotics (APs). Despite the long period of use of APs, their safety profile remains insufficiently high. Due to the high incidence of adverse drug reactions (ADRs), from the central nervous system (CNS) and other organs and tissues of the human body. Therapeutic drug monitoring can help predict and diagnose AP-induced ADRs only if the patient is receiving APs. PGx helps to individually select an AP, its dose and clarify the risk of ADRs before prescribing an AP, or at the start of therapy. This explains the importance of PGx in psychiatrist practice. However, to date, most practicing psychiatrists rarely use predictive PGx or do not use this method. PGx is more often prescribed in the case of a long history of un-successful AP-therapy, or in the case of the development of serious ADRs, the risk of which could be significantly reduced if predictive PGx was used. This case report of PGx in a 56-year-old woman with severe bipolar disorder demonstrates that the trajectory of ADRs and socialization could be significantly improved if this method was prescribed before the initiation of APs, rather than in the event of the development of serious ADRs.

Pharmacogenetic testing in psychiatry: Perspective on clinical utility.

Pharmacogenetic studies the influence of inherited characteristics on medication. While different from pharmacogenomics, which is a study of the entire genome in relation to medication effect, their distinction remains inconsistent, and the two terms are used interchangeably. Although the potential of pharmacogenomics in psychiatry is apparent and its clinical utility is suboptimal, the uptake of recommendations and guidelines is minimal and research into PGx is not diverse. This article offers an overview of pharmacogenetics (PGx) in psychiatry, explores the difficulties, and provides recommendations on improving its applicability and clinical utility.

Use of a consultation service following pharmacogenetic testing in psychiatry.

The emerging discipline of pharmacogenetics(PGx) has the goal of aiding the selection of effective therapies and personalized dosing, decreasing the likelihood of adverse drug reactionsand optimizing resource utilization. Simultaneously, the rapid evolution of economically feasible genetic testing technologies has resulted in a raft of commercial entities that provide genetic data to providers for use with their complex patients. The adoption of pharmacogenomics in psychiatry is growing, but itis limited by severalfactors, including the limitless permutations of drugs, comorbid conditions and concomitant medications and provider understanding of phenomena such as phenoconversion. We established an expert PGx consultation service for psychiatric providers who utilize our commercial PGx assay. To date, this service has provided ∼16,000 consults with extremely high levels of satisfaction; in an anonymous survey, 96% of respondents reported a rating of "very helpful" or "extremely helpful".

The use of pharmacogenetic testing in psychiatry.

Psychiatric pharmacogenetic testing is commonly used by providers in primary care and mental health settings. The purpose of this article is to describe the extent to which psychiatric pharmacogenetic testing supports clinical practice. human leukocyte antigen (HLA)-A and HLA-B should be tested before initiating carbamazepine and oxcarbazepine due to risk of serious skin reactions. For psychotropic medications metabolized through the liver, limited evidence suggests testing for variation in metabolism through CYP2D6 and CYP2D19. For specific medication and genotype-phenotype variations, guidance through the Clinical Pharmacogenetics Implementation Consortium (CPIC) or the International Society of Psychiatric Genetics (ISPG) should be reviewed. Commercial tests interpret this information differently and should not be used for broad guidance. Clinicians should follow current guidelines from professional bodies such as CPIC or ISPG and test for HLA-A or HLA-B before initiating carbamazepine or oxcarbazepine. Evidence is limited for psychiatric pharmacogenetic testing. Clinicians should continue to follow best practice and clinical practice guidelines.

Pharmacogenetic testing in psychiatry and neurology: an overview of reviews.

Pharmacogenetic testing is available to healthcare professionals to guide drug selection and prevent adverse events. However, its implementation in the clinical practice of psychiatry/neurology still has barriers, mainly due to a lack of evidence. We conducted a literature search on Cochrane Library, Embase and Pubmed, from their inception to 18 June 2020. We included 16 published systematic reviews. The most studied drug categories were anticonvulsants and selective serotonin reuptake inhibitors associated with human leukocyte antigen and cytochrome P450 genes (HLA-A, HLA-B, CYP2C9, CYP2D6, CYP2C19), classified as critically lowquality/low quality. There is a need for more robust studies with adequate design to assess the potential benefits of adopting pharmacogenetics in health systems and services.

How Can Drug Metabolism and Transporter Genetics Inform Psychotropic Prescribing?

Many genetic variants in drug metabolizing enzymes and transporters have been shown to be relevant for treating psychiatric disorders. Associations are strong enough to feature on drug labels and for prescribing guidelines based on such data. A range of commercial tests are available; however, there is variability in included genetic variants, methodology, and interpretation. We herein provide relevant background for understanding clinical associations with specific variants, other factors that are relevant to consider when interpreting such data (such as age, gender, drug–drug interactions), and summarize the data relevant to clinical utility of pharmacogenetic testing in psychiatry and the available prescribing guidelines. We also highlight areas for future research focus in this field.

Commercial Pharmacogenetic Tests in Psychiatry: Do they Facilitate the Implementation of Pharmacogenetic Dosing Guidelines?

Expert groups have created dosing guidelines to facilitate the implementation of pharmacogenetic knowledge into clinical practice and commercial pharmacogenetic tests are becoming increasingly accessible. However, the extent to which these commercial tests facilitate the implementation of dosing guidelines is not clear. Gene-drug pairs included on 22 commercial pharmacogenetic test panels were extracted and cross-referenced with the 74 gene-drug pairs with dosing guidelines in the Pharmacogenetics Knowledgebase, with particular attention given to the 28 gene-drug pairs relevant to psychiatry. On average, 70% of the 28 gene-drug pairs most relevant to psychiatry were covered by the examined tests. Six gene-drug pairs (CYP2D6-venlafaxine, CYP2D6-paroxetine, CYP2D6-amitriptyline, CYP2C19-sertraline, CYP2C19-citalopram, CYP2C19-amitriptyline) were included by all tests. Gene-drug pairs included on less than half of the test panels included HLA-B-phenytoin (14%), HLA-A-carbamazepine (24%), HLA-B-carbamazepine (29%), and CYP2D6-zuclopenthixol (43%). Most commercial pharmacogenetic tests we examined are well-equipped to facilitate implementation of the majority of dosing guidelines relevant to psychiatry but are limited in their ability to facilitate implementation of the full spectrum of dosing guidelines currently available.

Towards the integration of pharmacogenetics in psychiatry: a minimum, evidence-based genetic testing panel.

The implementation of pharmacogenetic testing in psychiatry is underway but is not yet standard protocol. Barriers to pharmacogenetics becoming standard practice are the lack of translation of evidence-based recommendations and standardization of genetic testing panels. As for the latter, there are currently no regulatory standards related to the gene and allele content of testing panels used to derive medication selection and dosing advice. To address these barriers, we summarize the current gene-drug interaction knowledgebase and proposed a minimum gene and allele set for pharmacogenetic testing in psychiatry. The Pharmacogenomics Knowledgebase has cataloged 448 gene-drug interactions relevant to psychiatry based on the current scientific literature, drug labels, and pharmacogenetic-based implementation guidelines. A majority of these interactions involved two cytochrome P450 enzymes (CYP2D6 and CYP2C19) and antidepressant medications, however, CYP2C9, HLA-A, and HLA-B are relevant to mood stabilizers/anticonvulsants. On the basis of evidence base, we proposed a minimum gene and allele set for pharmacogenetic testing in psychiatry that includes 16 variant alleles within five genes (CYP2C9, CYP2C19, CYP2D6, HLA-A, HLA-B). The intent is to assist clinicians in judging the gene and allele content of pharmacogenetic tests and to facilitate pharmacogenetic testing as a standard protocol and companion tool for psychotropic medication selection and dosing.

What Pharmacogenetic Testing Can, Can’t Tell You About Your Patient

What Pharmacogenetic Testing Can, Can’t Tell You About Your Patient

Pharmacogenetics in psychiatry: state of the art

In this article, the current literature on pharmacogenetics of antidepressants, antipsychotics and lithium are summarized by the section of Neurobiology and Genetics of the German Society of Psychiatry, Psychotherapy and Neurology (DGPPN). The publications of international expert groups and regulatory authorities are reviewed and discussed. In Germany, astatement on pharmacogenetics was also made by the gene diagnostics committee of the Ministry of Health. The DGPPN supports two recommendations: 1)to perform CYP2D6 genetic testing prior to prescription of tricyclic antidepressants and 2)to determine the HLA-B*1502 genotype in patients of Asian origin before using carbamazepine. The main obstacle for abroad application of pharmacogenetic tests in psychiatry remains the lack of large prospective studies, for both single gene-drug pair and cobinatorial pharmacogenetic tests, to evaluate the benefits of genetic testing. Psychiatrists, geneticists and funding agencies are encouraged to increase their efforts for the future benefit of psychiatric patients.

Implementation of Therapeutic Drug Monitoring and Pharmacogenetic Tests in Psychiatry: How About ABCB1?

Implementation of Therapeutic Drug Monitoring and Pharmacogenetic Tests in Psychiatry: How About ABCB1?

Systematic evaluation of commercial pharmacogenetic testing in psychiatry: a focus on CYP2D6 and CYP2C19 allele coverage and results reporting.

The aim of this study was to systematically assess commercial pharmacogenetic tests relevant to prescribing in psychiatry, with specific attention on CYP2D6 and CYP2C19 star allele coverage as well as compliance with consensus recommendations for pharmacogenetic test result reporting. The CYP2D6 and CY2C19 star (*) allele contents of 20 pharmacogenetic test panels were compared and their test results reports were evaluated on the basis of consensus reporting recommendations published by The Centers for Disease Control and Prevention as well as the Clinical Pharmacogenetics Implementation Consortium. Most test panels included the major CYP2D6 (*2, *4, *5, *10, *17) and CYP2C19 (*2, *3, *17) alleles, but no two test panels contained the same combination of CYP2D6 and CYP2C19 alleles. Of the 20 pharmacogenetic reports that we evaluated, none fulfilled all the recommendations and no recommendation was fulfilled by all tests. Consensus has yet to be reached on which CYP2D6 and CYP2C19 star alleles to include on pharmacogenetic testing panels and pharmacogenetic results reporting could be considerably improved. Collaboration between test manufacturers and end-users is required to narrow the gap between the availability and integration of these pharmacogenetic-based decision-support tools into routine practice.

Pharmacogenetic testing in psychiatry: not (quite) ready for primetime.

To the extent that genetic factors are associated with the efficacy, tolerability, and safety of different drugs, pharmacogenetic tests may be used to personalize medication treatments for an individual. Pharmacogenetic tests, such as GeneSight Psychotropic and the Genecept Assay, are being marketed directly to patients and prescribers despite a relative lack of evidence to support their clinical validity or utility. Pharmacogenetic testing is potentially useful in certain clinical situations, but its usefulness will depend on the knowledge base of the prescriber to be able to interpret the findings for a particular patient. Proposed guidelines on laboratory developed tests will likely encourage, if not require, evidence for the clinical validity and utility of pharmacogenetic tests before they are approved for marketing.

The potential utility of pharmacogenetic testing in psychiatry.

Over the last decade, pharmacogenetics has become increasingly significant to clinical practice. Psychiatric patients, in particular, may benefit from pharmacogenetic testing as many of the psychotropic medications prescribed in practice lead to varied response rates and a wide range of side effects. The use of pharmacogenetic testing can help tailor psychotropic treatment and inform personalized treatment plans with the highest likelihood of success. Recently, many studies have been published demonstrating improved patient outcomes and decreased healthcare costs for psychiatric patients who utilize genetic testing. This review will describe evidence supporting the clinical utility of genetic testing in psychiatry, present several case studies to demonstrate use in everyday practice, and explore current patient and clinician opinions of genetic testing.

Do guidelines recommending pharmacogenetic testing of psychiatric patients affect treatment costs and the use of healthcare services?

To identify the effects of local recommendations of pharmacogenetic testing in psychiatry with respect to treatment costs. Based on Danish patient registers, individual treatment costs within a 365-day period at three psychiatric hospitals recommending and using pharmacogenetic testing is compared retrospectively with treatment costs at other Danish psychiatric hospitals using alternate treatment strategies. Primary outcome of interest is total direct costs analyzed by multilevel modelling. Secondary outcome measures are healthcare consumption within specific sectors analyzed by Tobitregressions. Costs among patients treated at hospitals recommending and using pharmacogenetic testing were not found to be statistically significantly different from costs among patients treated at sites using alternate treatment strategies. In spite of recommendations to test all patients the uptake of the test was, however, low (26-31 %). Treatment practice using routine therapeutic drug monitoring (in Ãrhus) shows a trend towards lower costs. Based on this natural experiment we were not able to document statistically significant differences in total costs between treatment sites that had guidelines recommending pharmacogenetic testing, relative to sites without such guidelines, over a period of one year. However, guidelines of pharmacogenetic testing and possibly also therapeutic drug monitoring seem to lead to reductions in costs for primary care services. In the case of the former, reductions do, however, seem to be outweighed by increases in costs for psychiatric and non-psychiatric inpatient stays. In conclusion, no statistically significant differences in total direct costs across sites with different treatment strategies were found.

Optimisation of psychopharmacotherapy: Clinical relevance of pharmacogenetic tests and therapeutic drug monitoring

More than 100 psychoactive drugs are available for the treatment of psychiatric disorders. However, remission rates are far from being optimal, as a significant number of patients poorly respond or are intolerant to many drugs. The fate of drugs in the organism depends on environmental (diet, smoking habits, comorbidities, comedications) and genetic factors. Therapeutic plasma level monitoring (TDM) of psychotropic drugs represents a useful tool for optimising pharmacotherapy. It is recommended in patients mentioned above, but also in situations of poor compliance, longterm treatment, in elderly and very young patients, and in somatically ill and comedicated patients. The introduction of phenotyping and genotyping procedures allows taking account of the pharmacogenetic status (e.g. cytochrome P–450, P-glycoprotein) of the patients not only for adjustment of their medication, but also for interpreting pharmacokinetic interactions with clinical consequences. In this respect, TDM and pharmacogenetic tests (phenotyping, genotyping) have now also to be considered as a tool in pharmacovigilance. Recently, the AGNP-TDM expert group published consensus guidelines for TDM of psychotropic drugs (Baumann et al., Pharmacopsychiatry 37: 243–265, 2004). In addition, recommendations on the optimal use of TDM in combination with pharmacogenetic tests in psychiatry were summarized.

C-07. Educational course: Therapeuticdrug monitoring of psychotropic drugs and pharmacogenetic tests in psychiatry

C-07. Educational course: Therapeuticdrug monitoring of psychotropic drugs and pharmacogenetic tests in psychiatry

Developing Functional Routines for TDM and Pharmacogenetic Tests in Psychiatry

Developing Functional Routines for TDM and Pharmacogenetic Tests in Psychiatry