Utility of integrated pharmacogenomic testing to support the treatment of major depressive disorder in a psychiatric outpatient setting

Hall‐Flavin, Daniel K.; Winner, Joel G; Allen, Josiah D.; Carhart, Joseph M; Proctor, Brian D.; Snyder, Karen; Drews, Maureen S.; Eisterhold, Linda L.; Geske, Jennifer R.; Mrazek, David A.

doi:10.1097/fpc.0b013e3283649b9a

Cited by 183 publications

(177 citation statements)

References 15 publications

Supporting

Mentioning

173

Contrasting

Order By: Relevance

“…Their findings demonstrated that use of the test would lead to improved outcomes with antidepressant medication. The guided group experienced greater improvement in three depression scores from baseline on the HAMD, QIDS, and PHQ, when compared to the unguided group (153).…”

Section: Dmetmentioning

confidence: 99%

See 1 more Smart Citation

Genetics of antipsychotic drug outcome and implications for the clinician: into the limelight

Changasi

Shams

Pouget

et al. 2014

Translational Developmental Psychiatry

View full text Add to dashboard Cite

Background and purpose: Antipsychotics (APs) are the primary method of treatment for schizophrenia and other psychotic disorders. Unfortunately, lengthy trial-and-error approaches are typically required to find the optimal medication and dosage due to a large interindividual variability with outcome to AP treatment. The literature has shown abundant evidence for a genetic component in individuals' responses to APs. Pharmacogenetic studies analyze specific genetic markers and their association with symptom improvement and occurrence of side effects with APs. This research aims to optimize AP drug treatment by usage of predictive testing and to personalize medicine. Recent findings: This review will highlight the most consistent findings in pharmacogenetics of APs and will update the reader on the clinical implications. This will include how genetic variants modulate AP drug levels, side effects, and therapeutic symptom improvement (i.e. response) to AP treatment. Summary: Several promising findings were obtained implicating gene variants of the dopamine receptor genes in addition to gene variants of serotonin receptors for response and common side effects. Notably, effect sizes appear to be particularly high in the genetics of side effects compared to response. One example is antipsychotic-induced weight gain where the leptin, HTR2C and in particular the melanocortin-4-receptor (MC4R) genes have been implicated in weight gain in children and adolescents. Consistent findings were also obtained for genes implicated in tardive dyskinesia and agranulocytosis. However, the most clinically relevant findings pertain to genes involved in drug metabolism such as the CYP2D6 and CYP2C19 genes which have been included in the first genetic test kits such as the Amplichip †

show abstract

Section: Dmetmentioning

confidence: 99%

“…children and geriatric populations); address potential gender effects; and consider variations due to ethnicity. In addition, further studies comparing pharmacogenetic-guided treatment versus treatment as usual (TAU) are required, such as the study on antidepressants published by Hall-Flavin et al (153).…”

Section: Discussionmentioning

confidence: 99%

Genetics of antipsychotic drug outcome and implications for the clinician: into the limelight

Changasi

Shams

Pouget

et al. 2014

Translational Developmental Psychiatry

View full text Add to dashboard Cite

show abstract

“…The majority of earlier study designs examined a narrow objective, such as looking at only the relationship between a single gene variant of a single gene and a single outcome measure. It has been demonstrated that considering all relevant genes for a particular drug when using pharmacogenetically-guided drug selection, also known as combinatorial pharmacogenetics, results in better outcomes than when compared to either no pharmacogenetic guidance or single gene/single drug-based pharmacogenetic guidance [8,9]. It is reasonable to expect that adoption of combinatorial pharmacogenetic approaches in clinical practice will continue to show superior clinical benefit and become best practice in pharmacogenetic testing.…”

Section: Editorialmentioning

confidence: 99%

Proposed FDA Regulation of Clinical Laboratories and Clinical Implementation of Pharmacogenetics

Massey¹

2017

PPIJ

View full text Add to dashboard Cite

Submit Manuscript | http://medcraveonline.com of very different attributes among the different types of genetic tests. An understanding of the differences between these tests allows one to stratify them according to the degree of scientific evidence supporting their utility, as well as the degree of risk they pose to public safety.It is in the interest of public safety that any test that is used to make medical decisions be accurate and FDA is justifiably concerned regarding the potential harm an inaccurate genetic test result could cause. The draft guidance outlining FDA's proposed regulatory framework for oversight of LDTs acknowledges that the risks posed by the wide varieties of LDTs varies greatly, and the proposed regulatory framework is based on the degree of risk that a particular LDT presents, i.e. a risk-based approach [1]. This is a well-reasoned approach that is consistent with FDA's responsibilities to protect the public health while the regulatory framework is being developed and implemented, without denying access to this information to patients during this implementation period. While there are a wide range of risk levels associated within any of the classes of genetic tests, it is generally recognized that genetic tests that diagnose a disease or risk of disease, especially if the disease is potentially life-threatening, pose a greater risk to the public due to a false result because of the harmful actions that may be taken, or beneficial actions which may not be taken, based on the inaccurate test result (e.g. inaccurate ovarian cancer diagnosis leading to unneeded major medical procedures [2] misdiagnosis and lack of care in the case of a false negative result for HER2 breast cancer [3] etc.). In contrast, genetic information that can help inform the patient (and healthcare provider) about their genetic predisposition for an array of drug metabolizing enzymes poses much less risk, as it does not result in unnecessary treatment, does not put the patient at risk of undergoing unnecessary medical treatment, or just as troubling, does not result in the patient not receiving treatment due to false negative misdiagnosis. These differences in the potential harm that can result from inaccurate test results makes pharmacogenetic tests much safer, from a public health standpoint, than the above-mentioned genetic tests for cancer (disease) diagnosis.In an FDA assessment of any LDT, the potential benefit of the test must also be taken into account so that the relative risk or risk-benefit relationship can be considered in the context of current medical practice. The clinical benefit of pharmacogenetics is explicitly stated by FDA on its own website, where a list of pharmacogenetic markers that appear in the FDA-approved prescribing information of over 100 drugs is posted [4]. FDA provides information that suggests that adverse drug reactions are the 4th leading cause of death in the US, cost the nation billions of dollars annually, and that the majority of these adverse drug reactions have a genetic basis...

show abstract

“…It has been demonstrated that considering all relevant genes for a particular drug when using pharmacogenetically-guided drug selection, also known as combinatorial pharmacogenetics, results in better outcomes than when compared to either no pharmacogenetic guidance or single gene/single drug-based pharmacogenetic guidance. 8,9 It is reasonable to expect that adoption of combinatorial pharmacogenetic approaches in clinical practice will continue to show superior clinical benefit and become best practice in pharmacogenetic testing.…”

Section: Editorialmentioning

confidence: 99%

Untitled

2017

PPIJ

View full text Add to dashboard Cite

different types of genetic tests, these articles have been misleading due to conflation of very different attributes among the different types of genetic tests. An understanding of the differences between these tests allows one to stratify them according to the degree of scientific evidence supporting their utility, as well as the degree of risk they pose to public safety.It is in the interest of public safety that any test that is used to make medical decisions be accurate and FDA is justifiably concerned regarding the potential harm an inaccurate genetic test result could cause. The draft guidance outlining FDA's proposed regulatory framework for oversight of LDTs acknowledges that the risks posed by the wide varieties of LDTs varies greatly, and the proposed regulatory framework is based on the degree of risk that a particular LDT presents, i.e. a risk-based approach.1 This is a well-reasoned approach that is consistent with FDA's responsibilities to protect the public health while the regulatory framework is being developed and implemented, without denying access to this information to patients during this implementation period. While there are a wide range of risk levels associated within any of the classes of genetic tests, it is generally recognized that genetic tests that diagnose a disease or risk of disease, especially if the disease is potentially life-threatening, pose a greater risk to the public due to a false result because of the harmful actions that may be taken, or beneficial actions which may not be taken, based on the inaccurate test result (e.g. inaccurate ovarian cancer diagnosis leading to unneeded major medical procedures 2 misdiagnosis and lack of care in the case of a false negative result for HER2 breast cancer etc.).3 In contrast, genetic information that can help inform the patient (and healthcare provider) about their genetic predisposition for an array of drug metabolizing enzymes poses much less risk, as it does not result in unnecessary treatment, does not put the patient at risk of undergoing unnecessary medical treatment, or just as troubling, does not result in the patient not receiving treatment due to false negative misdiagnosis. These differences in the potential harm that can result from inaccurate test results makes pharmacogenetic tests much safer, from a public health standpoint, than the abovementioned genetic tests for cancer (disease) diagnosis.In an FDA assessment of any LDT, the potential benefit of the test must also be taken into account so that the relative risk or risk-benefit relationship can be considered in the context of current medical practice. The clinical benefit of pharmacogenetics is explicitly stated by FDA on its own website, where a list of pharmacogenetic markers that appear in the FDA-approved prescribing information of over 100 drugs is posted. 4 FDA provides information that suggests that adverse drug reactions are the 4th leading cause of death in the US, cost the nation billions of dollars annually, and that the majority of these adverse drug...

show abstract

Utility of integrated pharmacogenomic testing to support the treatment of major depressive disorder in a psychiatric outpatient setting

Abstract: These findings replicate previous studies and demonstrate significantly improved depression outcomes with use of GeneSight, an integrated, multigenetic pharmacogenomic testing platform.

Cited by 183 publications

References 15 publications

Genetics of antipsychotic drug outcome and implications for the clinician: into the limelight

Genetics of antipsychotic drug outcome and implications for the clinician: into the limelight

Proposed FDA Regulation of Clinical Laboratories and Clinical Implementation of Pharmacogenetics

Untitled

Contact Info

Product

Resources

About