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Translational Psychiatry Oct 2021Pharmacogenomics (PGx) is the study of genetic influences on an individual's response to medications. Improvements in the quality and quantity of PGx research over the... (Review)
Review
Pharmacogenomics (PGx) is the study of genetic influences on an individual's response to medications. Improvements in the quality and quantity of PGx research over the past two decades have enabled the establishment of commercial markets for PGx tests. Nevertheless, PGx testing has yet to be adopted as a routine practice in clinical care. Accordingly, policy regulating the commercialization and reimbursement of PGx testing is in its infancy. Several papers have been published on the topic of challenges, or 'barriers' to clinical adoption of this healthcare innovation. However, many do not include recent evidence from randomized controlled trials, economic utility studies, and qualitative assessments of stakeholder opinions. The present paper revisits the most cited barriers to adoption of PGx testing: evidence for clinical utility, evidence for economic effectiveness, and stakeholder awareness. We consider these barriers in the context of reviewing PGx literature published over the past two decades and emphasize data from commercial PGx testing companies, since they have published the largest datasets. We conclude with a discussion of existing limitations to PGx testing and recommendations for progress.
Topics: Attitude; Pharmacogenetics; Pharmacogenomic Testing; Psychiatry
PubMed: 34615849
DOI: 10.1038/s41398-021-01600-7 -
Circulation. Genomic and Precision... Jun 2022Statin-associated muscle symptoms (SAMS) are the most frequently reported adverse events for statin therapies. Previous studies have reported an association between the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Statin-associated muscle symptoms (SAMS) are the most frequently reported adverse events for statin therapies. Previous studies have reported an association between the p.Val174Ala missense variant in and SAMS in simvastatin-treated subjects; however, evidence for genetic predictors of SAMS in atorvastatin- or rosuvastatin-treated subjects is currently lacking.
METHODS
ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; n=18 924) was a double-blind, randomized, placebo-controlled study evaluating the efficacy and safety of alirocumab (a PCSK9 [proprotein convertase subtilisin/kexin type 9] inhibitor) in acute coronary syndrome patients receiving high-intensity statin therapy. The goal of this pharmacogenomic analysis was to identify genetic variants associated with atorvastatin- and rosuvastatin-mediated SAMS among ODYSSEY OUTCOMES subjects who consented to participate in the genetic study (n=11 880). We performed multi-ancestry exome-wide and genome-wide association studies and gene burden analysis across 2 phenotypes (clinical SAMS [n=10 617] and creatine kinase levels [n=9630]).
RESULTS
A novel genome-wide significant association for an intronic variant (rs6667912) located within (odds ratio [95% CI], 1.39 [1.24-1.55]; =3.71×10) for patients with clinical SAMS (cases=894, controls=9723) was identified. This variant is located ≈30 kb upstream of , a locus associated with severe SAMS. We replicated 2 loci, at and , previously associated with creatine kinase levels during statin treatment. No association was observed between p.Val174Ala (rs4149056) in and SAMS (odds ratio [95% CI], 1.03 [0.90-1.18]; =0.69).
CONCLUSIONS
This study comprises the largest discovery exome-wide and genome-wide association study for atorvastatin- or rosuvastatin-mediated SAMS to date. These novel genetic findings may provide biological/mechanistic insight into this drug-induced toxicity, and help identify at-risk patients before selection of lipid-lowering therapies.
Topics: Acute Coronary Syndrome; Antigens, CD; Atorvastatin; Cholesterol, LDL; Creatine Kinase; Genome-Wide Association Study; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Membrane Proteins; Muscles; PCSK9 Inhibitors; Pharmacogenomic Testing; Receptors, Immunologic; Rosuvastatin Calcium
PubMed: 35543701
DOI: 10.1161/CIRCGEN.121.003503 -
Patient Education and Counseling Apr 2021Pharmacogenomic testing (PGx) is expanding into psychiatric care. PGx could potentially offer a unique benefit to psychiatric patients, providing information about...
OBJECTIVE
Pharmacogenomic testing (PGx) is expanding into psychiatric care. PGx could potentially offer a unique benefit to psychiatric patients, providing information about patients' reaction to medications that could reduce the time and financial burdens of drug optimization. The aims of this study were to: (1) examine psychiatry patients' familiarity and interest in PGx, and (2) explore how Uncertainty Management Theory relates to PGx testing in psychiatry.
METHOD
We surveyed psychiatric patients, measuring their PGx familiarity and interest, attitudes toward PGx testing, and preference for managing illness uncertainty.
RESULTS
We analyzed data from 598 patients. Patients' familiarity of PGx was low, but interest was high. Thirty percent of patients were familiar with the test from communication with their healthcare provider or their own online health information seeking. A preference for seeking information was a significant positive predictor of testing interest (p < .001).
CONCLUSION
Psychiatric patients were interested in PGx testing, regardless of their uncertainty management preferences.
PRACTICE IMPLICATIONS
This study is one of the first to examine psychiatric patients' perspectives on PGx testing in mental health care. Our findings show that psychiatric patients are interested in the test and are familiar enough with PGx to be included in future research on the topic.
Topics: Health Personnel; Humans; Pharmacogenetics; Pharmacogenomic Testing; Psychiatry; Uncertainty
PubMed: 33414028
DOI: 10.1016/j.pec.2020.12.021 -
Journal of the American Pharmacists... 2019To explore the implications of direct-to-consumer pharmacogenomic testing for community pharmacy practice.
OBJECTIVE
To explore the implications of direct-to-consumer pharmacogenomic testing for community pharmacy practice.
SUMMARY
In October 2018, the U.S. Food and Drug Administration provided approval for direct-to-consumer genetic testing company, 23andMe (Mountain View, CA), to return select pharmacogenomic test results to their customers. Given the community pharmacist's high accessibility to the public and in-depth knowledge of pharmacology, and the availability of direct-to-consumer genetic testing kits at pharmacies, it is likely that patients will present their pharmacogenomic test results to their pharmacists and expect them to incorporate those results into their care. It is important, therefore, that community pharmacists are aware of the clinical implications of these results, know where to turn for evidence-based clinical pharmacogenomics information, and be mindful of the need for confirmatory testing before changing therapy.
CONCLUSION
Community pharmacists are at the frontlines of health care, and as such will be at the frontlines of direct-to-consumer pharmacogenomic testing. In the near future, it is likely that community pharmacists will need to counsel patients on the interpretation and appropriate use of direct-to-consumer pharmacogenomic test results.
Topics: Community Pharmacy Services; Diagnostic Tests, Routine; Direct-To-Consumer Screening and Testing; Education, Pharmacy; Health Knowledge, Attitudes, Practice; Humans; Medication Therapy Management; Patient Care; Pharmacists; Pharmacogenetics; Pharmacogenomic Testing; Professional Role
PubMed: 31327749
DOI: 10.1016/j.japh.2019.06.008 -
Clinical and Translational Science Mar 2021Although pharmacogenetic testing is becoming increasingly common across medical subspecialties, a broad range of utilization and implementation exists across pediatric...
Although pharmacogenetic testing is becoming increasingly common across medical subspecialties, a broad range of utilization and implementation exists across pediatric centers. Large pediatric institutions that routinely use pharmacogenetics in their patient care have published their practices and experiences; however, minimal data exist regarding the full spectrum of pharmacogenetic implementation among children's hospitals. The primary objective of this nationwide survey was to characterize the availability, concerns, and barriers to pharmacogenetic testing in children's hospitals in the Children's Hospital Association. Initial responses identifying a contact person were received from 18 institutions. Of those 18 institutions, 14 responses (11 complete and 3 partial) to a more detailed survey regarding pharmacogenetic practices were received. The majority of respondents were from urban institutions (72%) and held a Doctor of Pharmacy degree (67%). Among all respondents, the three primary barriers to implementing pharmacogenetic testing identified were test reimbursement, test cost, and money. Conversely, the three least concerning barriers were potential for genetic discrimination, sharing results with family members, and availability of tests in certified laboratories. Low-use sites rated several barriers significantly higher than the high-use sites, including knowledge of pharmacogenetics (P = 0.03), pharmacogenetic interpretations (P = 0.04), and pharmacogenetic-based changes to therapy (P = 0.03). In spite of decreasing costs of pharmacogenetic testing, financial barriers are one of the main barriers perceived by pediatric institutions attempting clinical implementation. Low-use sites may also benefit from education/outreach in order to reduce perceived barriers to implementation.
Topics: Hospitals, Pediatric; Humans; Pharmacogenomic Testing; Practice Patterns, Physicians'; Reimbursement Mechanisms; United States
PubMed: 33325650
DOI: 10.1111/cts.12931 -
Clinical Chemistry and Laboratory... Jun 2017Pharmacogenomics has significantly added to our understanding of drug responses in clinical pharmacology, changing the paradigm of treatment decisions. Interrogations of... (Review)
Review
Pharmacogenomics has significantly added to our understanding of drug responses in clinical pharmacology, changing the paradigm of treatment decisions. Interrogations of both inherited and somatic variations for therapeutic purposes are increasingly being adopted in clinics, where quality control (QC) materials are required. However, for many pharmacogenomic tests, the acquisition of well-characterized QC materials is often difficult or impossible. In this review, several sources of appropriate QC materials for therapy-associated genetic testing are discussed. Among them, the novel methods for producing renewable controls that resemble patient samples are highlighted. Owing to technological complexity, more efforts are needed to develop proper controls for next-generation sequencing-based assay.
Topics: Genetic Testing; Humans; Mutation; Neoplasms; Pharmacogenomic Testing; Quality Control
PubMed: 27845879
DOI: 10.1515/cclm-2016-0755 -
Psychiatria Danubina Sep 2022Quarantine measures with self-isolation of varying duration have been significant psychosocial stressors in the context of the COVID-19 pandemic. The serotonin selective... (Review)
Review
BACKGROUND
Quarantine measures with self-isolation of varying duration have been significant psychosocial stressors in the context of the COVID-19 pandemic. The serotonin selective reuptake inhibitor fluvoxamine has been considered as a prophylaxis against depression in early COVID-19 patients, with additional benefits apparently arising from its antiviral activity. In this narrative review, we draw attention to the body of evidence showing efficacy of fluvoxamine in protecting against depressive disorders in COVID-19 patients, while also attenuating the severity of COVID-19 disease, with a notable reduction in the need for intubation and lower mortality. We consider this potential two-fold action of fluvoxamine in the light of its pharmacogenetic and pharmacological profiles.
SUBJECTS AND METHODS
Full-text publications in English and Russian in Google Scholar, PubMed, NCBI, Web of Science, and E-Library databases were selected by keywords, solitary and in combination (fluvoxamine, COVID-19, depression, anxiety, antidepressants, adverse reactions) for the period from March 01, 2020 to June 06, 2022. We also analyzed the full-text publications in English and Russian language reporting adverse reactions caused by fluvoxamine use for the period from 2012 to 2022.
RESULTS
The literature search yielded 10 papers reporting on the efficacy fluvoxamine in relieving depressive symptoms in COVID-19 patients, and 3 papers on its effect on medical outcome. The preponderance of data indicated a dual therapeutic action of fluvoxamine, and our further literature investigation was informative about drug-drug interactions and genetic factors moderating the antidepressant efficacy of fluvoxamine.
CONCLUSIONS
Patients with COVID-19 seeking psychopharmacological treatment for depressive symptoms must be informed of the benefits and risks of fluvoxamine use. Several lines of findings indicate this agent to possess an additional antiviral action. However, optimal dosage regimens and the trade-off with drug-drug interactions remain unclear. Pharmacogenetic testing may assist in evidence-based optimization of fluvoxamine dosages in the context of COVID-19 infection with comorbid depression.
Topics: Antidepressive Agents; Antiviral Agents; Depression; Fluvoxamine; Humans; Pandemics; Pharmacogenetics; Pharmacogenomic Testing; Serotonin; Selective Serotonin Reuptake Inhibitors; COVID-19 Drug Treatment
PubMed: 36170697
DOI: No ID Found -
Clinical and Translational Science Jul 2022Actionable drug-gene pairs relevant to depression treatment include CYP2D6 and CYP2C19 with specific antidepressants. While clinical use of pharmacogenetic testing is...
Actionable drug-gene pairs relevant to depression treatment include CYP2D6 and CYP2C19 with specific antidepressants. While clinical use of pharmacogenetic testing is growing, little is known about pharmacogenetic testing for depression treatment in managed care. We determined the incidence of single-gene CYP2D6 and CYP2C19 testing following a new depression episode among US managed care patients, and described characteristics and antidepressant use of patients receiving tests. We used paid medical and pharmacy claims for patients from commercial health plans in the US. For adult patients with a new depression episode from January 1, 2013 to June 30, 2018, we identified covered claims for single-gene CYP2D6 and CYP2C19 pharmacogenetic tests and antidepressant fills. Fewer than 1% (n = 1795) of the depressed cohort (n = 438,534) received a single-gene CYP2D6 or CYP2C19 test through their insurance within 365 days of their earliest depression episode. The percentage of patients who received a test nearly tripled from 0.2% in 2013 to 0.5% in 2014 before plateauing at 0.4% from 2014 to 2017. Among the patients who received a single-gene CYP2D6 or CYP2C19 test and filled an antidepressant within 365 days of their depression diagnosis, up to 30% may have had their initial antidepressant informed by the test result. Our findings describe the use of antidepressants before and after pharmacogenetic testing, which is clinically relevant as pharmacogenomic testing becomes more common in clinical practice. Our study also emphasizes the need for procedure and billing codes that capture multiple-gene panel tests to be more widely implemented in administrative databases.
Topics: Adult; Antidepressive Agents; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2D6; Depression; Humans; Managed Care Programs; Pharmacogenomic Testing
PubMed: 35385214
DOI: 10.1111/cts.13279 -
Psychiatry Research Feb 2021We evaluated the clinical validity of a combinatorial pharmacogenomic test and single-gene Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines against...
Clinical validation of combinatorial pharmacogenomic testing and single-gene guidelines in predicting psychotropic medication blood levels and clinical outcomes in patients with depression.
We evaluated the clinical validity of a combinatorial pharmacogenomic test and single-gene Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines against patient outcomes and medication blood levels to assess their ability to inform prescribing in major depressive disorder (MDD). This is a secondary analysis of the Genomics Used to Improve DEpression Decisions (GUIDED) randomized-controlled trial, which included patients with a diagnosis of MDD, and ≥1 prior medication failure. The ability to predict increased/decreased medication metabolism was validated against blood levels at screening (adjusted for age, sex, smoking status). The ability of predicted gene-drug interactions (pharmacogenomic test) or therapeutic recommendations (single-gene guidelines) to predict patient outcomes was validated against week 8 outcomes (17-item Hamilton Depression Rating Scale; symptom improvement, response, remission). Analyses were performed for patients taking any eligible medication (outcomes N=1,022, blood levels N=1,034) and the subset taking medications with single-gene guidelines (outcomes N=584, blood levels N=372). The combinatorial pharmacogenomic test was the only significant predictor of patient outcomes. Both the combinatorial pharmacogenomic test and single-gene guidelines were significant predictors of blood levels for all medications when evaluated separately; however, only the combinatorial pharmacogenomic test remained significant when both were included in the multivariate model. There were no substantial differences when all medications were evaluated or for the subset with single-gene guidelines. Overall, this evaluation of clinical validity demonstrates that the combinatorial pharmacogenomic test was a superior predictor of patient outcomes and medication blood levels when compared with guidelines based on individual genes.
Topics: Adult; Depressive Disorder, Major; Genomics; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Pharmacogenetics; Pharmacogenomic Testing; Predictive Value of Tests; Psychotropic Drugs; Reproducibility of Results; Treatment Outcome
PubMed: 33360967
DOI: 10.1016/j.psychres.2020.113649 -
Medecine Sciences : M/S Dec 2019Therapeutic antibodies have been increasingly used for the treatment of various diseases, including cancers and chronic inflammatory diseases. The pharmacokinetic... (Review)
Review
Therapeutic antibodies have been increasingly used for the treatment of various diseases, including cancers and chronic inflammatory diseases. The pharmacokinetic interindividual variability of mAbs is large and influences, at least in part, the clinical response to antibody treatment. This variability is explained by a number of individual sources of variability, which are reviewed here. Some of them are major because they are frequently reported to greatly influence the interindividual variability; notably, increased body size, the presence of anti-drug antibodies, and high antigen mass are associated with decreased antibody concentrations. Other individual sources of variability are of less critical importance. They include sex, age, co-treatments, or genetic polymorphisms of IgG Fc receptors (FcgRs). The interindividual variability of antibody pharmacokinetics should be soundly described in order to design optimal dosing strategy.
Topics: Age Factors; Antibodies, Monoclonal; Biomarkers, Pharmacological; Comorbidity; Dose-Response Relationship, Immunologic; Female; Humans; Individuality; Male; Pharmacogenomic Testing; Polymorphism, Genetic; Precision Medicine; Sex Factors
PubMed: 31903927
DOI: 10.1051/medsci/2019210