Combinatorial pharmacogenomic guidance for psychiatric medications reduces overall pharmacy costs in a 1 year prospective evaluation

Winner, Joel G; Carhart, Joseph M; Altar, C. Anthony; Goldfarb, Seth; Allen, Josiah D.; Lavezzari, Gabriela; Parsons, Kelly; Marshak, Andrew G; Garavaglia, Susan B.; Dechairo, Bryan

doi:10.1185/03007995.2015.1063483

Cited by 96 publications

(71 citation statements)

References 24 publications

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“…Furthermore, the GeneSight test was reported to double the likelihood of response compared to treatment as usual in a small prospective randomised doubleblind trial (Winner et al 2013b) and similar findings were obtained in a larger open-label study (HallFlavin et al 2013). Finally, the GeneSight test was recently demonstrated to save $1,035.60 more in total medication costs (both CNS and non-CNS medications) over 1 year compared to a non-tested standard care cohort (Winner et al 2015). In comparison, the commercial pharmacogenetic Genecept Assay includes polymorphisms in CYP2D6, CYP2C19, CYP3A4, SLC6A4, HTR2C, DRD2, CACNA1C, ANK3, COMT, MTHFR, MC4R, ADRA2A, BDNF, OPRM1 and GRIK1.…”

Section: Clinical Applications: Pilot Studiesmentioning

confidence: 99%

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Fabbri

Hosák

Mößner

et al. 2016

The World Journal of Biological Psychiatry

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Major depressive disorder (MDD) is a heritable disease with a heavy personal and socio-economic burden. Antidepressants of different classes are prescribed to treat MDD, but reliable and reproducible markers of efficacy are not available for clinical use. Further complicating treatment, the diagnosis of MDD is not guided by objective criteria, resulting in the risk of under-or overtreatment. A number of markers of MDD and antidepressant response have been investigated at the genetic, epigenetic, gene expression and protein levels. Polymorphisms in genes involved in anti-depressant metabolism (cytochrome P450 isoenzymes), antidepressant transport (ABCB1), glucocorticoid signalling (FKBP5) and serotonin neurotransmission (SLC6A4 and HTR2A) were among those included in the first pharmacogenetic assays that have been tested for clinical applicability. The results of these investigations were encouraging when examining patient-outcome improvement. Furthermore, a nine-serum biomarker panel (including BDNF, cortisol and soluble TNF-a receptor type II) showed good sensitivity and specificity in differentiating between MDD and healthy controls. These first diagnostic and response-predictive tests for MDD provided a source of optimism for future clinical applications. However, such findings should be considered very carefully because their benefit/cost ratio and clinical indications were not clearly demonstrated. Future tests may include combinations of different types of biomarkers and be specific for MDD subtypes or pathological dimensions.

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Section: Clinical Applications: Pilot Studiesmentioning

confidence: 99%

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Fabbri

Hosák

Mößner

et al. 2016

The World Journal of Biological Psychiatry

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“…To appeal to the request for evidence demonstrating clinical utility, the collective clinical utility for a subset of genes in the PGx‐Passport () is being assessed in a cluster randomized controlled trial including 8,100 patients across healthcare institutions in 7 European countries . Several promising studies indicate the (cost‐)effectiveness of PGx panel‐based testing on healthcare utilization in psychiatry and polypharmacy, where observed cost savings ranged from $218 to $2,778 per patient. Others have modeled the cost‐effectiveness of one‐time genetic testing to minimize a lifetime of adverse drug reactions, and concluded an incremental cost‐effectiveness ratio of $43,165 per additional life year and $53,680 per additional quality‐adjusted life year, and, therefore, cost‐effective .…”

Section: Discussionmentioning

confidence: 99%

Development of the PGx‐Passport: A Panel of Actionable Germline Genetic Variants for Pre‐Emptive Pharmacogenetic Testing

Wouden

Rhenen

Jama

et al. 2019

Clin Pharma and Therapeutics

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Pre‐emptive pharmacogenetics (PGx) testing of a panel of germline genetic variants represents a new model for personalized medicine. Clinical impact of PGx testing is maximized when all variant alleles for which actionable clinical guidelines are available are included in the test panel. However, no such standardized panel has been presented to date, impeding adoption, exchange, and continuity of PGx testing. We, therefore, developed such a panel, hereafter called the PGx‐Passport, based on the actionable Dutch Pharmacogenetics Working Group (DPWG) guidelines. Germline‐variant alleles were systematically selected using predefined criteria regarding allele population frequencies, effect on protein functionality, and association with drug response. A PGx‐Passport of 58 germline variant alleles, located within 14 genes (CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A5, DPYD, F5, HLA‐A, HLA‐B, NUDT15, SLCO1B1, TPMT, UGT1A1, and VKORC1) was composed. This PGx‐Passport can be used in combination with the DPWG guidelines to optimize drug prescribing for 49 commonly prescribed drugs.

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“…Evidence to date suggests there may be potential benefits associated with the use of pharmacogenetic decision support tools, such as increased remission rates [36,[46][47][48], reduced adverse effects [36,49], and cost-savings [36,[50][51][52]. However, the clinical utility of these tools remains uncertain due to a lack of high quality randomized clinical trials with adequate statistical power.…”

Section: ) Do You Have Good Reason To Believe That Yourmentioning

confidence: 99%

Antidepressant Prescribing in the Precision Medicine Era: a Prescriber's Primer on Pharmacogenetic Tools

Bousman¹,

Forbes²,

Jayaram³

et al. 2018

FOC

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About half of people who take antidepressants do not respond and many experience adverse effects. These detrimental outcomes are in part a result of the impact of an individual's genetic profile on pharmacokinetics and pharmcodynamics. If known and made available to clinicians, this could improve decision-making and antidepressant therapy outcomes. This has spurred the development of numerous pharmacogenetic-based decision support tools. In this article, we provide an overview of pharmacogenetic decision support tools, with particular focus on tools relevant to antidepressants. We briefly describe the evolution and current state of antidepressant pharmacogenetic decision support tools in clinical practice, followed by the evidence-base for their use. Finally, we present a series of considerations for clinicians contemplating use of these tools and discuss the future of antidepressant pharmacogenetic decision support tools.

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Combinatorial pharmacogenomic guidance for psychiatric medications reduces overall pharmacy costs in a 1 year prospective evaluation

Cited by 96 publications

References 24 publications

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Development of the PGx‐Passport: A Panel of Actionable Germline Genetic Variants for Pre‐Emptive Pharmacogenetic Testing

Antidepressant Prescribing in the Precision Medicine Era: a Prescriber's Primer on Pharmacogenetic Tools

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