Review and Consensus on Pharmacogenomic Testing in
                    Psychiatry

AbstractThe implementation of pharmacogenomic (PGx) testing in psychiatry remains modest, in part due to divergent perceptions of the quality and completeness of the evidence base and diverse perspectives on the clinical utility of PGx testing among psychiatrists and other healthcare providers. Recognizing the current lack of consensus within the field, the International Society of Psychiatric Genetics assembled a group of experts to conduct a narrative synthesis of the PGx literature, prescribing guidelines, and product labels related to psychotropic medications as well as the key considerations and limitations related to the use of PGx testing in psychiatry. The group concluded that to inform medication selection and dosing of several commonly-used antidepressant and antipsychotic medications, current published evidence, prescribing guidelines, and product labels support the use of PGx testing for 2 cytochrome P450 genes (CYP2D6, CYP2C19). In addition, the evidence supports testing for human leukocyte antigen genes when using the mood stabilizers carbamazepine (HLA-A and HLA-B), oxcarbazepine (HLA-B), and phenytoin (CYP2C9, HLA-B). For valproate, screening for variants in certain genes (POLG, OTC, CSP1) is recommended when a mitochondrial disorder or a urea cycle disorder is suspected. Although barriers to implementing PGx testing remain to be fully resolved, the current trajectory of discovery and innovation in the field suggests these barriers will be overcome and testing will become an important tool in psychiatry.

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Pharmacogenetic testing in psychiatry and neurology: an overview of reviews

Pharmacogenomics ◽

10.2217/pgs-2020-0187 ◽

2021 ◽

Author(s):

Danilo Vieira de Lara ◽

Daniela Oliveira de Melo ◽

Rafael Augusto Mantovani Silva ◽

Paulo Caleb Junior Lima de Santos

Keyword(s):

Selective Serotonin Reuptake Inhibitors ◽

Human Leukocyte ◽

Cochrane Library ◽

Drug Selection ◽

Pharmacogenetic Testing ◽

Overview Of Reviews ◽

Leukocyte Antigen ◽

Cytochrome P450 Genes ◽

Potential Benefits ◽

Adequate Design

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 low quality/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.

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Identification of Circulating Nonclassic Human Leukocyte Antigen G (HLA-G)–Like Molecules in Exudates

Clinical Chemistry ◽

10.1373/clinchem.2010.159673 ◽

2011 ◽

Vol 57 (7) ◽

pp. 1013-1022 ◽

Cited By ~ 18

Author(s):

Álvaro Gonzalez ◽

Estibaliz Alegre ◽

Ainhoa Arroyo ◽

Jöel LeMaoult ◽

José Ignacio Echeveste

Keyword(s):

Western Blot ◽

Clinical Utility ◽

Biological Fluids ◽

Human Leukocyte ◽

Disulfide Bridges ◽

Leukocyte Antigen ◽

Molecular Weights ◽

Capture Antibody ◽

Human Leukocyte Antigen G ◽

Culture Supernatants

BACKGROUND HLA-G in biological fluids has been proposed to be useful as a tumor marker as both a diagnostic and prognostic factor. Most HLA-G measurement procedures are based on ELISA methods using highly specific antibodies. However, results of published studies are in conflict regarding the clinical utility and even the nature of HLA-G present in circulation. METHODS We collected 118 exudates, 94 from cancer patients and 24 from patients without tumors. We measured HLA-G concentrations by ELISA using MEM-G/9 or G233 as capture antibody. Samples were immunoprecipitated with an anti–HLA-G antibody and analyzed by Western blot using a different anti–HLA-G antibody. RESULTS Discrepancies in HLA-G concentrations in exudates were observed depending on what capture anti–HLA-G antibody was used for ELISA (r = 0.376). These discrepancies were not observed when the ELISAs were performed using culture supernatants from HLA-G1–transfected cells (r = 0.983). Immunoprecipitation and Western blot of cell culture supernatants with 2 different anti–HLA-G antibodies produced the typical band at 39 kDa assigned to HLA-G. When the immunoprecipitation and western blot were performed with exudates, however, there were bands at 53 kDa and 70–76 kDa, higher molecular weights than those usually assigned to HLA-G. These HLA-G–like molecules were associated with β2-microglobulin and could also form disulfide bridges with other HLA-G–like molecules. CONCLUSIONS The main HLA-G antigenic molecules in exudates are HLA-G–like complexes, a factor that should be considered when analyzing HLA-G in biological fluids.

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Clinical utility of C3d binding donor-specific anti-human leukocyte antigen antibody detection by single antigen beads after kidney transplantation-a retrospective study

Transplant International ◽

10.1111/tri.13106 ◽

2018 ◽

Vol 31 (4) ◽

pp. 424-435 ◽

Cited By ~ 5

Author(s):

Ronald P Pelletier ◽

Ivan Balazs ◽

Pat Adams ◽

Amer Rajab ◽

Nicholas R DiPaola ◽

...

Keyword(s):

Kidney Transplantation ◽

Retrospective Study ◽

Human Leukocyte Antigen ◽

Clinical Utility ◽

Human Leukocyte ◽

Antibody Detection ◽

Leukocyte Antigen ◽

Single Antigen ◽

Antigen Antibody

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An ESHRE PGD Consortium multicentre retrospective cohort study investigating the clinical utility of PGD with human leukocyte antigen (HLA)-matching and factors influencing a positive outcome

10.26226/morressier.573c1513d462b80296c98ae4 ◽

2016 ◽

Author(s):

Joanne Traeger-Synodinos

Keyword(s):

Cohort Study ◽

Human Leukocyte Antigen ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Clinical Utility ◽

Human Leukocyte ◽

Positive Outcome ◽

Hla Matching ◽

Leukocyte Antigen ◽

Factors Influencing

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Pharmacogenomics Testing Confirmation of Carbamazepine Induced DRESS Reaction of an HLA-A*31:01 Positive, Polypharmacy Patient

INNOVATIONS in pharmacy ◽

10.24926/iip.v12i4.4341 ◽

2021 ◽

Vol 12 (4) ◽

pp. 20

Author(s):

Leigh Speicher ◽

Sheena Crosby ◽

Michael J. Schuh

Keyword(s):

Drug Reaction ◽

Drug Interactions ◽

Human Leukocyte Antigen ◽

Adverse Drug Reactions ◽

Human Leukocyte ◽

Drug Reactions ◽

Leukocyte Antigen ◽

Medication Selection ◽

Systemic Symptoms

Pharmacogenomics (PGx) melds well with polypharmacy as another tool to identify medication related problems (MRPs) more specifically so they may be solved most effectively. PGx can pre-emptively assist in medication selection, medication dosing or identify better medications for patients already taking a medication. PGx can also confirm suspect medications of causing MRPs such as adverse drug reactions (ADRs) or drug interactions. In this case, PGx testing confirmed presence of a serious human leukocyte antigen (HLA) drug reaction with eosinophilia and systemic symptoms (DRESS) after a suspect medication had been stopped.

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