Search

Purpose Pharmacogenetic testing can identify patients who may benefit from personalized drug treatment. However, clinical uptake of pharmacogenetic testing has been limited. Clinical practice guidelines recommend biomarker tests that the guideline authors deem to have demonstrated clinical utility, meaning that testing improves treatment outcomes. The objective of this narrative review is to describe the current status of pharmacogenetic testing recommendations within clinical practice guidelines in the US. Summary Guidelines were reviewed for pharmacogenetic testing recommendations for 21 gene-drug pairs that have well-established drug response associations and all of which are categorized as clinically actionable by the Clinical Pharmacogenetics Implementation Consortium. The degree of consistency within and between organizations in pharmacogenetic testing recommendations was assessed. Relatively few clinical practice guidelines that provide a pharmacogenetic testing recommendation were identified. Testing recommendations for HLA-B*57:01 before initiation of abacavir and G6PD before initiation of rasburicase, both of which are included in drug labeling, were mostly consistent across guidelines. Gene-drug pairs with at least one clinical practice guideline recommending testing or stating that testing could be considered included CYP2C19 -clopidogrel, CYP2D6 -codeine, CYP2D6 -tramadol, CYP2B6 -efavirenz, TPMT -thiopurines, and NUDT15 -thiopurines. Testing recommendations for the same gene-drug pair were often inconsistent between organizations and sometimes inconsistent between different guidelines from the same organization. Conclusion A standardized approach to evaluating the evidence of clinical utility for pharmacogenetic testing may increase the inclusion and consistency of pharmacogenetic testing recommendations in clinical practice guidelines, which could benefit patients and society by increasing clinical use of pharmacogenetic testing. [ABSTRACT FROM AUTHOR]

Psychoactive medications are increasingly used to treat children and youth with mental health conditions, but individual variations in response highlight the need for precision medicine. Pharmacogenetic (PGx) testing is a key component of precision medicine. The number of commercial pharmacogenetic testing companies promoting PGx, with the promise of achieving individualized and effective treatment of mental health conditions, has grown exponentially in recent years. Scientific evidence supporting the use of PGx to manage mental health conditions is limited, especially for paediatric populations. This practice point outlines steps guiding the use and interpretation of PGx testing for psychoactive medications in clinical settings, along with key supportive resources. Practice guidelines have been developed for variants in pharmacogenes encoding cytochrome P450 drug-metabolizing enzymes (e.g. CYP2C19 , CYP2D6 , CYP2C9) as one determinant of drug concentrations in blood, which can support both drug choice and dosing strategy for certain anti-psychotics, anti-depressants, and anti-epileptics. Adverse drug reactions to some anti-epileptic drugs (e.g. carbamazepine and phenytoin) have been associated with certain human leukocyte antigen types and variants in DNA polymerase gamma (POLG ; valproic acid). Evidence remains limited for genetic variants of drug target proteins, making it challenging to identify patients with altered treatment responses at a therapeutic blood concentration. [ABSTRACT FROM AUTHOR]

INTRODUCTION. Pharmacogenetic (PGx) testing plays a significant role in predicting the risk of adverse drug reactions (ADRs) associated with valproic acid (VPA) products, which are among the most prescribed medicinal products in neurology and psychiatry. However, the sensitivity and specificity of PGx screening panels may be insufficient as individual valproate metabolism varies across ethnically/racially diverse patient populations.AIM. The study aimed to identify implementation areas for a personalised approach to the development of PGx panels for assessing the safety and risk of valproate therapy in various ethnic and racial groups residing in the Russian Federation.DISCUSSION. The authors reviewed the results of population studies concerning the frequency of non-functional and low-function alleles of genes encoding isoenzymes that play key roles in VPA P-oxidation in the liver. This review focused on studies published in eLIBRARY.RU, PubMed, Scopus, and Google Scholar in 2012–2022. The inclusion criteria were full-text original articles, systematic reviews, meta-analyses, Cochrane reviews, and clinical cases in Russian or English. The analysis revealed that the need for personalised assessment of the risk and safety of VPA may depend on the frequency of risk alleles for slowing down VPA P-oxidation in the liver across racial and ethnic groups worldwide, and particularly in Russia. The authors identified new areas to implement the personalised approach to the development of PGx panels for assessing the safety and risk of valproate therapy with consideration of the rates of hepatic VPA P-oxidation in patients of different ethnic and racial backgrounds. However, the review of population-based associative genetic research from around the world demonstrated the current lack of clarity in the prospects of translating international findings directly into Russian clinical practice through the development of PGx panels due to Russia’s ethnic/racial diversity and vast territory.CONCLUSIONS. To increase the sensitivity and specificity of Russian PGx panels, bridging studies are required to extrapolate the associations established between the most common risk alleles and VPA P-oxidation disorders in other ethnic groups to a specific population of a specific Russian region.

INTRODUCTION. The variability in patient response to non-steroidal anti-inflammatory drugs (NSAIDs) may be due to genetic polymorphisms. Decreased-function or non-functional CYP2C9 alleles are known to be significant contributors to response variability, and research is being conducted on the potential contribution of polymorphisms in the PTGS1 and PTGS2 genes that encode for the NSAID targets, cyclooxygenases 1 and 2.AIM. This study aimed to demonstrate the contribution of pharmacogenetic characteristics to the development of adverse reactions to NSAIDs in clinical cases.MATERIALS AND METHODS. This study reports two clinical cases observed in a multidisciplinary hospital in Moscow. The first case report demonstrates a neurosurgical patient with spondylodiscitis who showed signs of renal failure associated with ketorolac administration during 13 days of inpatient treatment. The second case report presents a patient with gastrointestinal bleeding that developed after 3 weeks of ketorolac self-administration and ultimately required gastric resection surgery. According to real-time polymerase chain reaction results, these patients have single-nucleotide polymorphisms, including rs179985 (CYP2C9*2) and rs1057910 (CYP2C9*3) in the CYP2C9 gene, rs10306135 and rs12353214 in the PTGS1 gene, and rs20417 in the PTGS2 gene.RESULTS. The described adverse reactions to ketorolac are attributable to the patients’ pharmacogenetic characteristics and other factors (exceeding the recommended duration of ketorolac therapy, concomitant conditions, drug interactions, and older age). In the case of nephrotoxicity, the patient has the CYP2C9*1/*2 genotype, which is associated with decreased NSAID metabolism. Additionally, this patient has the PTGS1 (C>T) rs12353214 genotype, which may be associated with variations in the activity of cyclooxygenase 1 and may lead to an increased risk of adverse reactions to NSAIDs. In the case of gastrointestinal bleeding, the patient also has genetic characteristics that affect the response to NSAIDs, as the CYP2C9*1/*3 genotype is associated with significantly decreased NSAID metabolism. Patients with this genotype should take the lowest doses or switch to alternatively metabolised NSAIDs.CONCLUSIONS. To reduce the risk of nephrotoxicity and gastrointestinal bleeding in patients when prescribing ketorolac, healthcare providers should strictly follow the recommended dosing regimen and consider individual comorbidities and potential drug interactions that may potentiate adverse drug reactions. Additionally, patient risk management requires pharmacogenetic testing, including the determination of decreased-function or non-functional CYP2C9 alleles and the rs12353214 polymorphism in the PTGS1 gene.

Copyright of Psychiatrie Pro Praxi is the property of SOLEN sro and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Medical Management & Health Policy / Meditsinski Menidgmant i Zdravna Politika is the property of Medical University - Sofia, Central Medical Library and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Previous results demonstrated that CYP2D6 and CYP2C19 gene variants affect serum concentrations of antidepressants. We implemented a PGx service determining gene variants in CYP2D6 and CYP2C19 in our clinical routine care and report on our first patient cohort. We analysed CYP2D6 and CYP2C19 allele, genotype, and phenotype frequencies, and actionable pharmacogenetic variants in this German psychiatric inpatient cohort. Two-tailed z-test was used to investigate for differences in CYP2D6 and CYP2C19 phenotypes and actionable/non-actionable genetic variant frequencies between our cohort and reference cohorts. Out of the 154 patients included, 44.8% of patients were classified as CYP2D6 normal metabolizer, 38.3% as intermediate metabolizers, 8.4% as poor metabolizers, and 2.6% as ultrarapid metabolizers. As for CYP2C19, 40.9% of patients were classified as normal metabolizers, 19.5% as intermediate metabolizers, 2.6% as poor metabolizers, 31.2% as rapid metabolizers, and 5.8% as ultrarapid metabolizers. Approximately, 80% of patients had at least one actionable PGx variant. There is a high prevalence of actionable PGx variants in psychiatric inpatients which may affect treatment response. Physicians should refer to PGx-informed dosing guidelines in carriers of these variants. Pre-emptive PGx testing in general may facilitate precision medicine also for other drugs metabolised by CYP2D6 and/or CYP2C19. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorders (ASDs) encompass a broad range of phenotypes characterized by diverse neurological alterations. Genomic studies have revealed considerable overlap between the molecular mechanisms implicated in the etiology of ASD and genes involved in the pharmacokinetic (PK) and pharmacodynamic (PD) pathways of antipsychotic drugs employed in ASD management. Given the conflicting data originating from candidate PK or PD gene association studies in diverse ethnogeographic ASD populations, dosage individualization based on "actionable" pharmacogenetic (PGx) markers has limited application in clinical practice. Additionally, off-label use of different antipsychotics is an ongoing practice, which is justified given the shortage of approved cures, despite the lack of satisfactory evidence for its safety according to precision medicine. This exploratory study aimed to identify PGx markers predictive of risperidone (RIS) exposure in autistic Saudi children. Methods: This prospective cohort study enrolled 89 Saudi children with ASD treated with RIS-based antipsychotic therapy. Plasma levels of RIS and 9-OH-RIS were measured using a liquid chromatography--tandem mass spectrometry system. To enable focused exploratory testing, genotyping was performed with the Axiom PharmacoFocus Array, which included a collection of probe sets targeting PK/PD genes. A total of 720 PGx markers were included in the association analysis.Results: A total of 27 PGx variants were found to have a prominent impact on various RIS PK parameters; most were not located within the genes involved in the classical RIS PK pathway. Specifically, 8 markers in 7 genes were identified as the PGx markers with the strongest impact on RIS levels (p < 0.01). Four PGx variants in 3 genes were strongly associated with 9-OH-RIS levels, while 5 markers in 5 different genes explained the interindividual variability in the total active moiety. Notably, 6 CYP2D6 variants exhibited strong linkage disequilibrium; however, they significantly influenced only the metabolic ratio and had no considerable effects on the individual estimates of RIS, 9-OH-RIS, or the total active moiety. After correction for multiple testing, rs78998153 in UGT2B17 (which is highly expressed in the brain) remained the most significant PGx marker positively adjusting the metabolic ratio. For the first time, certain human leukocyte antigen (HLA) markers were found to enhance various RIS exposure parameters, which reinforces the gut--brain axis theory of ASD etiology and its suggested inflammatory impacts on drug bioavailability through modulation of the brain, gastrointestinal tract and/or hepatic expression of metabolizing enzymes and transporters. Conclusion: Our hypothesis-generating approach identified a broad spectrum of PGx markers that interactively influence RIS exposure in ASD children, which indicated the need for further validation in population PK modeling studies to define polygenic scores for antipsychotic efficacy and safety, which could facilitate personalized therapeutic decision-making in this complex neurodevelopmental condition. [ABSTRACT FROM AUTHOR]

The efficacy and tolerability of psychotropic medications can vary significantly among children and adolescents, and some of this variability relates to pharmacogenetic factors. Pharmacogenetics (PGx) in child and adolescent psychiatry can potentially improve treatment outcomes and minimize adverse drug reactions. This article reviews key pharmacokinetic and pharmacodynamic genes and principles of pharmacogenetic testing and discusses the evidence base for clinical decision-making concerning PGx testing. This article reviews current guidelines from the United States Food and Drug Administration (FDA), the Clinical Pharmacogenetics Implementation Consortium (CPIC), and the Dutch Pharmacogenetics Working Group (DPWG) and explores potential future directions. This review discusses key clinical considerations for clinicians prescribing psychotropic medications in children and adolescents, focusing on antidepressants, antipsychotics, stimulants, norepinephrine reuptake inhibitors, and alpha-2 agonists. Finally, this review synthesizes the practical use of pharmacogenetic testing and clinical decision support systems. [ABSTRACT FROM AUTHOR]

Introduction: Combinatorial pharmacogenetic testing panels are widely available in clinical practice and often separate medications into columns/bins associated with low, medium, or high probability of gene-drug interactions. The objective of the Adolescent Management of Depression (AMOD) study was to determine the clinical utility of combinatorial pharmacogenetic testing in a double-blind, randomized, controlled effectiveness study by comparing patients who had genetic testing results at time of medication initiation to those that did not have results until week 8. The objective of this post hoc analysis was to assess and report additional outcomes with respect to significant gene-drug interactions (i.e., a medication in the high probability gene-drug interaction bin as defined by a proprietary algorithm) compared with patients taking a medication with minimal to moderate gene-drug interactions (i.e., a medication from the low or medium probability gene-drug interaction bin, respectively). Methods: Adolescents 13–18 years (N = 170) with moderate to severe major depressive disorder received pharmacogenetic testing. Symptom improvement and side effects were assessed at baseline, week 4, week 8, and 6 months. Patients were grouped into three categories based on whether the medication they were prescribed was associated with low, medium, or high risk for gene-drug interactions. Patients taking a medication from the low/medium gene-drug interaction bin were compared with patients taking a medication from the high gene-drug interaction bin. Results: Patients taking a medication from the high gene-drug interaction bin were more likely to endorse side effects compared with patients taking a medication in the low/medium gene-drug interaction bin at week 8 (p = 0.001) and 6 months (p < 0.0001). Depressive symptom severity scores did not differ significantly across the medication bins. Conclusions: This study demonstrates the utility of gene-drug interaction testing to guide medication decisions to minimize side effect burden rather than solely prioritizing the search for the most efficacious medication. (Clinical Trials Registration Identifier: NCT02286440). [ABSTRACT FROM AUTHOR]

Clinical implementation of pharmacogenetics (PGx) into routine care will elevate the current paradigm of treatment decisions. However, while PGx tests are increasingly becoming reliable and affordable, several barriers have limited their widespread usage in Canada. Globally, over ninety successful PGx implementors can serve as models. The purpose of this paper is to outline the PGx implementation barriers documented in Quebec (Canada) to suggest efficient solutions based on existing PGx clinics and propose an adapted clinical implementation model. We conclude that the province of Quebec is ready to implement PGx. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorders (ASDs) encompass a broad range of phenotypes characterized by diverse neurological alterations. Genomic studies have revealed considerable overlap between the molecular mechanisms implicated in the etiology of ASD and genes involved in the pharmacokinetic (PK) and pharmacodynamic (PD) pathways of antipsychotic drugs employed in ASD management. Given the conflicting data originating from candidate PK or PD gene association studies in diverse ethnogeographic ASD populations, dosage individualization based on “actionable” pharmacogenetic (PGx) markers has limited application in clinical practice. Additionally, off-label use of different antipsychotics is an ongoing practice, which is justified given the shortage of approved cures, despite the lack of satisfactory evidence for its safety according to precision medicine. This exploratory study aimed to identify PGx markers predictive of risperidone (RIS) exposure in autistic Saudi children.Methods: This prospective cohort study enrolled 89 Saudi children with ASD treated with RIS-based antipsychotic therapy. Plasma levels of RIS and 9-OH-RIS were measured using a liquid chromatography–tandem mass spectrometry system. To enable focused exploratory testing, genotyping was performed with the Axiom PharmacoFocus Array, which included a collection of probe sets targeting PK/PD genes. A total of 720 PGx markers were included in the association analysis.Results: A total of 27 PGx variants were found to have a prominent impact on various RIS PK parameters; most were not located within the genes involved in the classical RIS PK pathway. Specifically, 8 markers in 7 genes were identified as the PGx markers with the strongest impact on RIS levels (p < 0.01). Four PGx variants in 3 genes were strongly associated with 9-OH-RIS levels, while 5 markers in 5 different genes explained the interindividual variability in the total active moiety. Notably, 6 CYP2D6 variants exhibited strong linkage disequilibrium; however, they significantly influenced only the metabolic ratio and had no considerable effects on the individual estimates of RIS, 9-OH-RIS, or the total active moiety. After correction for multiple testing, rs78998153 in UGT2B17 (which is highly expressed in the brain) remained the most significant PGx marker positively adjusting the metabolic ratio. For the first time, certain human leukocyte antigen (HLA) markers were found to enhance various RIS exposure parameters, which reinforces the gut–brain axis theory of ASD etiology and its suggested inflammatory impacts on drug bioavailability through modulation of the brain, gastrointestinal tract and/or hepatic expression of metabolizing enzymes and transporters.Conclusion: Our hypothesis-generating approach identified a broad spectrum of PGx markers that interactively influence RIS exposure in ASD children, which indicated the need for further validation in population PK modeling studies to define polygenic scores for antipsychotic efficacy and safety, which could facilitate personalized therapeutic decision-making in this complex neurodevelopmental condition.

Shimaa Aboelbaha,1 Monica Zolezzi,2 Oraib Abdallah,3 Yassin Eltorki3 1College of Pharmacy, QU Health, Qatar University, Doha, Qatar; 2Clinical Pharmacy and Practice, College of Pharmacy, QU Health, Qatar University, Doha, Qatar; 3Mental Health Service, Hamad Medical Corporation, Doha, QatarCorrespondence: Shimaa Aboelbaha, College of Pharmacy, QU Health, Qatar University, Doha, Qatar, Tel +974 74748700, Email sa1401981@qu.edu.qaObjective: A wide variety of commercial pharmacogenetic (PGx) tools are available worldwide to guide treatment selection for depression based on individuals’ genetic profiles. However, the use of genetic testing to inform psychiatric care has faced challenges due to the limited training and education for mental health clinicians. The aim of this study was to explore the knowledge, level of engagement, and perspectives on the use of PGx testing when making depression management decisions among practicing psychiatrists within the Middle East and North Africa (MENA) region.Methods: This is a qualitative study using semi-structured interviews. Consenting psychiatrists were interviewed through an online platform (SkypeTM or Microsoft TeamsTM). Interviews were audio recorded, transcribed, and thematically analyzed with the assistance of NVivo® software.Results: Eighteen interviews from 12 countries have been conducted. Analysis of the current interviews produced five major themes including: (1) Overall perceptions and attitudes; (2) Knowledge and awareness; (3) Education, training, and professional experience; (4) Facilitators and barriers; and (5) Ethical dilemmas. These themes support the notion that there is limited, mostly basic, education, knowledge, and training regarding genetic testing in the management of depression, although there is significant interest and willingness in the part of prescribers to adopt this strategy in their practice.Conclusion: The findings of the study suggest that psychiatrists practicing in the MENA region appear to be interested in implementing PGx testing when managing people with depression. However, it is also important to recognize that this cannot be achieved unless more supporting strategies are implemented within their current health system environment.Keywords: pharmacogenetic testing, depression, qualitative study, MENA region, psychiatry, mental health

Pharmacogenetic testing (PT) is a modern tool in the doctor’s practice, which allows to make the right clinical decision in diffi cult cases, when the expected result of medical measures is not achieved. It is clear that certain metabolic processes in the human body, as well as a number of diseases, are genetically programmed. Therefore, despite the large number of unexplained mechanisms of individual response to drugs, genetic testing occupies one of the leading positions among methods of selecting drug therapy in complex clinical cases. However, the successful implementation of this promising method must overcome a number of obstacles, including limited evidence of eff ectiveness, ethical, legal, and social factors. The purpose of this review is to highlight modern concepts and practical aspects of the use of PT. The article addresses the problem of expanding the indications for PT when it is not limited to preventive use only. PT allows to identify drugs associated with an increased risk of causing side eff ects, with a narrow therapeutic index, to reduce the number of drugs in treatment, to choose the dosage of the drug. A variety of PT platforms can be used in a physician’s offi ce, which can be broadly divided into two categories – genotyping- based tests and sequencing- based tests. Depending on the gene being tested, diff erent algorithms can be used to generate results. Some gene variants can be described in terms of metabolic activity or general function, while others can only be described as present or absent. Results for gene variants can also be reported as normal, intermediate or low function for the corresponding gene. Pharmacogenetic clinical decision support systems (CDSS) are computer- based systems that assist healthcare providers in prescribing medications at the point of care. These systems provide physicians and other healthcare providers with appropriately fi ltered pharmacogenetic information, such as drug-gene interaction alerts or patient- specifi c treatment recommendations. A pharmacogenetic CDSS can either be integrated into a local hospital information system or used as a stand- alone application such as a web service or mobile application. Pharmacogenetics can increase the quantity and quality of information available to pregnant women and their physicians about medication use during pregnancy. Implementation of PT recommendations into routine pediatric practice requires carefully coordinated strategies at the national, regional, and health system levels. To date, pharmacogenetics provides mosaic information on the association between response to drug therapy and genetic background. It is expected that the next step will be a study in a larger group of participants to investigate the contribution of epigenetic factors and to provide clinical recommendations for adjusting or selecting therapy based on the personal characteristics of the patient.

Psychotropic medications are typically prescribed in a trial-and-error fashion, and some providers are beginning to utilize pharmacogenetic testing (PGx) as a supplemental prescribing tool in treatment decision making. PGx testing shows potential in enhancing provider insights into personalized prescribing for patients by examining genetic information related to drug metabolism. Literature points to providers’ lack of knowledge in PGx interpretation as a main barrier, including psychiatric mental health nurse practitioners (PMHNPs). The aim of this study was to measure a difference, if any, in the knowledge and perceptions of PGx after implementation using a pre-post design. This study implemented an educational intervention on graduate nursing students (n = 15). Data were collected by using a pre- and post-interventional questionnaire. Results demonstrated a significant difference in findings related to students’ knowledge (p < 0.001), students’ skills related to pharmacogenetics, (p < 0.001), as well as students’ perceived ability to implement pharmacogenetics into their practice, (p = 0.028). The authors propose that the knowledge gained from the study demonstrates the importance of introducing PGx education into the PMHNP curricula and to prepare future PMHNPs to confidently utilize PGx in their clinical practice. [ABSTRACT FROM AUTHOR]

Pharmacogenetic testing (PT) is a modern tool in the doctor's practice, which allows to make the right clinical decision in difficult cases, when the expected result of medical measures is not achieved. It is clear that certain metabolic processes in the human body, as well as a number of diseases, are genetically programmed. Therefore, despite the large number of unexplained mechanisms of individual response to drugs, genetic testing occupies one of the leading positions among methods of selecting drug therapy in complex clinical cases. However, the successful implementation of this promising method must overcome a number of obstacles, including limited evidence of effectiveness, ethical, legal, and social factors. The purpose of this review is to highlight modern concepts and practical aspects of the use of PT. The article addresses the problem of expanding the indications for PT when it is not limited to preventive use only. PT allows to identify drugs associated with an increased risk of causing side effects, with a narrow therapeutic index, to reduce the number of drugs in treatment, to choose the dosage of the drug. A variety of PT platforms can be used in a physician's office, which can be broadly divided into two categories - genotyping-based tests and sequencing-based tests. Depending on the gene being tested, different algorithms can be used to generate results. Some gene variants can be described in terms of metabolic activity or general function, while others can only be described as present or absent. Results for gene variants can also be reported as normal, intermediate or low function for the corresponding gene. Pharmacogenetic clinical decision support systems (CDSS) are computer-based systems that assist healthcare providers in prescribing medications at the point of care. These systems provide physicians and other healthcare providers with appropriately filtered pharmacogenetic information, such as drug-gene interaction alerts or patient-specific treatment recommendations. A pharmacogenetic CDSS can either be integrated into a local hospital information system or used as a stand-alone application such as a web service or mobile application. Pharmacogenetics can increase the quantity and quality of information available to pregnant women and their physicians about medication use during pregnancy. Implementation of PT recommendations into routine pediatric practice requires carefully coordinated strategies at the national, regional, and health system levels. To date, pharmacogenetics provides mosaic information on the association between response to drug therapy and genetic background. It is expected that the next step will be a study in a larger group of participants to investigate the contribution of epigenetic factors and to provide clinical recommendations for adjusting or selecting therapy based on the personal characteristics of the patient. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether it is feasible to perform pharmacogenetic testing and implement the test results as part of medication reviews during hospitalization of multimorbid patients. Methods: Patients with ≥2 chronic conditions and ≥5 regular drugs with at least one potential gene‐drug interaction (GDI) were included from one geriatric and one cardiology ward for pharmacogenetic testing. After inclusion by the study pharmacist, blood samples were collected and shipped to the laboratory for analysis. For patients still hospitalized at the time when the pharmacogenetic test results were available, the information was used in medication reviews. Recommendations from the pharmacist on actionable GDIs were communicated to the hospital physicians, who subsequently decided on potential immediate changes or forwarded suggestions in referrals to general practitioners. Results: The pharmacogenetic test results were available for medication review in 18 of the 46 patients (39.1%), where median length of hospital stay was 4.7 days (1.6‐18.3). The pharmacist recommended medication changes for 21 of 49 detected GDIs (42.9%). The hospital physicians accepted 19 (90.5%) of the recommendations. The most commonly detected GDIs involved metoprolol (CYP2D6 genotype), clopidogrel (CYP2C19 genotype) and atorvastatin (CYP3A4/5 and SLCOB1B1 genotype). Conclusions: The study shows that implementation of pharmacogenetic testing for medication review of hospitalized patients has the potential to improve drug treatment before being transferred to primary care. However, the logistics workflow needs to be further optimized, as test results were available during hospitalization for less than half of the patients included in the study. [ABSTRACT FROM AUTHOR]

To test the hypothesis that implementation of a cytochrome P-450 2D6 (CYP2D6) genotype–guided perioperative metoprolol administration will reduce the risk of postoperative atrial fibrillation (AF), the authors conducted the Preemptive Pharmacogenetic-Guided Metoprolol Management for Atrial Fibrillation in Cardiac Surgery pilot study. Clinical pilot trial. Single academic center. Seventy-three cardiac surgery patients. Patients were classified as normal, intermediate, poor, or ultrarapid metabolizers after testing for their CYP2D6 genotype. A clinical decision support tool in the electronic health record advised providers on CYP2D6 genotype–guided metoprolol dosing. Using historical data, the Bayesian method was used to compare the incidence of postoperative AF in patients with altered metabolizer status to the reference incidence. A logistic regression analysis was performed to study the association between the metabolizer status and postoperative AF while controlling for the Multicenter Study of Perioperative Ischemia AF Risk Index. Of the 73 patients, 30% (n = 22) developed postoperative AF; 89% (n = 65) were normal metabolizers; 11% (n = 8) were poor/intermediate metabolizers; and there were no ultrarapid metabolizer patients identified. The estimated rate of postoperative AF in patients with altered metabolizer status was 30% (95% CI 8%-60%), compared with the historical reference incidence (27%). In the risk-adjusted analysis, there was insufficient evidence to conclude that modifying metoprolol dosing based on poor/intermediate metabolizer status was associated significantly with the odds of postoperative AF (odds ratio 0.82, 95% CI 0.15-4.55, p = 0.82). A CYP2D6 genotype–guided metoprolol management was not associated with a reduction of postoperative AF after cardiac surgery. [ABSTRACT FROM AUTHOR]

Since the rebirth of pharmacogenomics (PGx) in the 1990s and 2000s, with new discoveries of genetic variation underlying adverse drug response and new analytical technologies such as sequencing and microarrays, there has been much interest in the clinical application of PGx testing. The early involvement of pharmacists in clinical studies and the establishment of organizations to support the dissemination of information about PGx variants have naturally resulted in leaders in clinical implementation. This paper presents an overview of the evolving role of pharmacists, and discusses potential challenges and future paths, primarily focused in the U.S. Pharmacists have positioned themselves as leaders in clinical PGx testing, and will prepare the next generation to utilize PGx testing in their scope of practice. [ABSTRACT FROM AUTHOR]

Psychotropic medications are typically prescribed in a trial-and-error fashion, and some providers are beginning to utilize pharmacogenetic testing (PGx) as a supplemental prescribing tool in treatment decision making. PGx testing shows potential in enhancing provider insights into personalized prescribing for patients by examining genetic information related to drug metabolism. Literature points to providers’ lack of knowledge in PGx interpretation as a main barrier, including psychiatric mental health nurse practitioners (PMHNPs). The aim of this study was to measure a difference, if any, in the knowledge and perceptions of PGx after implementation using a pre-post design. This study implemented an educational intervention on graduate nursing students (n = 15). Data were collected by using a pre- and post-interventional questionnaire. Results demonstrated a significant difference in findings related to students’ knowledge (p < 0.001), students’ skills related to pharmacogenetics, (p < 0.001), as well as students’ perceived ability to implement pharmacogenetics into their practice, (p = 0.028). The authors propose that the knowledge gained from the study demonstrates the importance of introducing PGx education into the PMHNP curricula and to prepare future PMHNPs to confidently utilize PGx in their clinical practice.

Antipsychotic (AP)—induced adverse drug reactions (ADRs) are a current problem of biological and clinical psychiatry. Despite the development of new generations of APs, the problem of AP-induced ADRs has not been solved and continues to be actively studied. One of the important mechanisms for the development of AP-induced ADRs is a genetically-determined impairment of AP efflux across the blood-brain barrier (BBB). We present a narrative review of publications in databases (PubMed, Springer, Scopus, Web of Science E-Library) and online resources: The Human Protein Atlas; GeneCards: The Human Gene Database; US National Library of Medicine; SNPedia; OMIM Online Mendelian Inheritance in Man; The PharmGKB. The role of 15 transport proteins involved in the efflux of drugs and other xenobiotics across cell membranes (P-gp, TAP1, TAP2, MDR3, BSEP, MRP1, MRP2, MRP3, MRP4, MRP5, MRP6, MRP7, MRP8, MRP9, BCRP) was analyzed. The important role of three transporter proteins (P-gp, BCRP, MRP1) in the efflux of APs through the BBB was shown, as well as the association of the functional activity and expression of these transport proteins with low-functional and non-functional single nucleotide variants (SNVs)/polymorphisms of the ABCB1, ABCG2, ABCC1 genes, encoding these transport proteins, respectively, in patients with schizophrenia spectrum disorders (SSDs). The authors propose a new pharmacogenetic panel "Transporter protein (PT)—Antipsychotic (AP) Pharmacogenetic test (PGx)" (PTAP-PGx), which allows the evaluation of the cumulative contribution of the studied genetic biomarkers of the impairment of AP efflux through the BBB. The authors also propose a riskometer for PTAP-PGx and a decision-making algorithm for psychiatrists. Conclusions: Understanding the role of the transportation of impaired APs across the BBB and the use of genetic biomarkers for its disruption may make it possible to reduce the frequency and severity of AP-induced ADRs, since this risk can be partially modified by the personalized selection of APs and their dosing rates, taking into account the genetic predisposition of the patient with SSD. [ABSTRACT FROM AUTHOR]

The collection of family health history (FHH) is an essential component of clinical practice and an important piece of data for patient risk assessment. However, family history data have generally been limited to diseases and have not included medication history. Family history was a key component of early pharmacogenetic research, confirming the role of genes in drug response. With the substantial number of known pharmacogenes, many affecting response to commonly prescribed medications, and the availability of clinical pharmacogenetic (PGx) tests and guidelines for interpretation, the collection of family medication history can inform testing decisions. This paper explores the roots of family-based pharmacogenetic studies to confirm the role of genes in these complex phenotypes and the benefits and challenges of collecting family medication history as part of family health history intake. [ABSTRACT FROM AUTHOR]

Schizophrenia is a serious mental disorder, characterized by a marked impairment in the sphere of thinking, affectivity, perceptions and social relationships, which causes patients to interpret reality in an erroneous way. The variability of response to treatment of patients with psychotic disorders is significantly correlated with metabolic polymorphisms, and patient response to atypical and typical antipsychotic pharmacotherapy shows inter-individual variability. Pharmacogenetic testing helps investigate the effects of genetic variation on medication response, safety, tolerability and efficacy. The aim of the study was to present a case of schizophrenia, from diagnosis to treatment. Initiation of personalized antipsychotic treatment starting from pharmacogenetic evaluation, tracking efficacy, tolerability and response to medication. In order to administer a personalized treatment, appropriate to the patient's profile, pharmacogenetic testing was performed. Treatment with Aripiprazole, Haloperidol and Topiramate was initiated until the 3-month assessment when the result of pharmacogenetic testing was available. The metabolic activity of the CYP2D6 enzyme is reduced in the patient, the pharmacological result identifying the patient as an intermediate metabolizer (IM, *4/wt). Intermediate metabolizers (IM) present allelic variants that encode the production of mutant proteins with reduced enzymatic activity. At the 3-month evaluation, the patient received treatment with Olanzapine, which is predominantly metabolized at the level of CYP1A2 and less at the level of CYP2D6 and CYP3A4. The evolution of the patient after receiving the treatment was followed according to the result of the pharmacogenetic testing. In the conditions of treatment adherence and therapeutic compliance, the patient's evolution is slowly favorable, with the entry into remission, affective normalization, socio-familial reintegration and increased quality of life. [ABSTRACT FROM AUTHOR]

Background: Individualized pharmaceutical care, which consists of therapeutic drug monitoring (TDM), pharmacogenetic (PGx) testing and pharmacist-managed clinic (PMC), is one of the most important trends in clinical pharmacy development in the future. While relevant studies in China were primarily single-center or regional. This study aims to explore the current status of individualized pharmaceutical care in China, find out the existing problems and provide references for its further development. Methods: An electronic questionnaire was used and national hospitals' pharmaceutical administration data from January to December 2019 were collected. The data were sorted into Excel for further statistical analysis. All analyses were descriptive. Results: The proportions of hospitals that performed TDM and PGx testing were 12.83% and 9.48%, respectively. The major responsible departments were the clinical laboratory and pharmacy department. External quality control was carried out in around 70% of hospitals for both TDM and PGx testing. More than half of hospitals provided TDM services for valproate sodium, digoxin, carbamazepine, vancomycin and cyclosporine. And an average of 6.84 drugs were performed TDM in 540 hospitals. Clopidogrel and warfarin were the top two drugs that performed PGx testing. As for the PMC, 10.03% of hospitals opened PMC, of which 60.00% had independent PMC. Approximately 80% of PMC services were free of charge. Conclusion: The development of individualized pharmaceutical care in China is still in the early stage. Different sectors have to coalesce to promote its implementation, including the appropriate education, coverage, reimbursement policies, high-quality evidence, data systems, health system processes and health policies, etc. [ABSTRACT FROM AUTHOR]

Abstract Background Despite the increased demand for pharmacogenetic (PGx) testing to guide antidepressant use, little is known about how to implement testing in clinical practice. Best–worst scaling (BWS) is a stated preferences technique for determining the relative importance of alternative scenarios and is increasingly being used as a healthcare assessment tool, with potential applications in implementation research. We conducted a BWS experiment to evaluate the relative importance of implementation factors for PGx testing to guide antidepressant use. Methods We surveyed 17 healthcare organizations that either had implemented or were in the process of implementing PGx testing for antidepressants. The survey included a BWS experiment to evaluate the relative importance of Consolidated Framework for Implementation Research (CFIR) constructs from the perspective of implementing sites. Results Participating sites varied on their PGx testing platform and methods for returning recommendations to providers and patients, but they were consistent in ranking several CFIR constructs as most important for implementation: patient needs/resources, leadership engagement, intervention knowledge/beliefs, evidence strength and quality, and identification of champions. Conclusions This study demonstrates the feasibility of using choice experiments to systematically evaluate the relative importance of implementation determinants from the perspective of implementing organizations. BWS findings can inform other organizations interested in implementing PGx testing for mental health. Further, this study demonstrates the application of BWS to PGx, the findings of which may be used by other organizations to inform implementation of PGx testing for mental health disorders.

Patient preferences for pharmacogenetic (PGx) counseling, testing and results dissemination are not well-established, especially in medically underserved Black and Latino populations. The aim of this study was to capture the preferences of Black and Latino patients who received PGx testing to ascertain: (1) factors enhancing their willingness to do testing and (2) preferences for the dissemination of results. Using the constant comparative method, we thematically analyzed interviews with 13 patients from medically underserved populations who had undergone PGx testing. The findings describe participants wanting better medication options, receiving a clear explanation about the testing, valuing or having an interest in science or medicine and having misconceptions about testing results as factors affecting one's willingness to undergo PGx testing. Additionally, patients confirmed preferring receiving results of PGx testing in a sharable format and described the significance of discussing results in a clinical appointment. The findings provide insight into what Black and Latino patients may prefer in terms of clinical implementation of PGx testing. These results can be utilized for tailoring future implementation of PGx testing and informing best pre- and post-test patient counseling and education practices. [ABSTRACT FROM AUTHOR]

Studies from various countries have shown that majorities would accept genetic testing for personalization of treatment, but little is known about differences among population subgroups. The present study investigated whether readiness to accept a hypothetical cost-free offer of genetic testing to personalize treatment depends on socio-demographic characteristics, health-related vulnerabilities, personal dispositions, and prior awareness about personalized medicine. The study was based on a cross-sectional survey design. Out of a representative initial sample of 50–80-year-old Danish citizens (n = 15,072), n = 6807 returned a fully answered web-based questionnaire. Socio-demographic data were added from a national registry. Data were analyzed by multivariable logistic regression. A large majority of respondents (78.3%) expressed their readiness to be tested. Rates were higher in men, younger persons, and those with higher income. Additionally, ex-smokers and obese persons as well as those less satisfied with their health and respondents who perceived a personal genetic risk were more interested, as were those with higher internal health control, higher extraversion, higher emotional stability, and those who had not heard about this option before. Further research should investigate the specific concerns among population subgroups which need being addressed by systematic communication efforts in a clinical but also a broader public health context. [ABSTRACT FROM AUTHOR]

Since the rebirth of pharmacogenomics (PGx) in the 1990s and 2000s, with new discoveries of genetic variation underlying adverse drug response and new analytical technologies such as sequencing and microarrays, there has been much interest in the clinical application of PGx testing. The early involvement of pharmacists in clinical studies and the establishment of organizations to support the dissemination of information about PGx variants have naturally resulted in leaders in clinical implementation. This paper presents an overview of the evolving role of pharmacists, and discusses potential challenges and future paths, primarily focused in the U.S. Pharmacists have positioned themselves as leaders in clinical PGx testing, and will prepare the next generation to utilize PGx testing in their scope of practice.

Abstract Background Pharmacogenetic (PGx) testing for germline variants in the DPYD and UGT1A1 genes can be used to guide fluoropyrimidine and irinotecan dosing, respectively. Despite the known association between PGx variants and chemotherapy toxicity, preemptive testing prior to chemotherapy initiation is rarely performed in routine practice. Methods We conducted a qualitative study of oncology clinicians to identify barriers to using preemptive PGx testing to guide chemotherapy dosing in patients with gastrointestinal malignancies. Each participant completed a semi-structured interview informed by the Consolidated Framework for Implementation Research (CFIR). Interviews were analyzed using an inductive content analysis approach. Results Participants included sixteen medical oncologists and nine oncology pharmacists from one academic medical center and two community hospitals in Pennsylvania. Barriers to the use of preemptive PGx testing to guide chemotherapy dosing mapped to four CFIR domains: intervention characteristics, outer setting, inner setting, and characteristics of individuals. The most prominent themes included 1) a limited evidence base, 2) a cumbersome and lengthy testing process, and 3) a lack of insurance coverage for preemptive PGx testing. Additional barriers included clinician lack of knowledge, difficulty remembering to order PGx testing for eligible patients, challenges with PGx test interpretation, a questionable impact of preemptive PGx testing on clinical care, and a lack of alternative therapeutic options for some patients found to have actionable PGx variants. Conclusions Successful adoption of preemptive PGx-guided chemotherapy dosing in patients with gastrointestinal malignancies will require a multifaceted effort to demonstrate clinical effectiveness while addressing the contextual factors identified in this study.

Abstract Background Major depressive disorder (MDD) is a common, chronic, debilitating mood disorder that causes serious functional impairment and significantly decreased quality of life. Pharmacotherapy represents the first-line treatment option; however, only approximately one third of patients respond to the first treatment because of the ineffectiveness or side effects of antidepressants. Precision medicine in psychiatry might offer clinicians the possibility to tailor treatment according to the best possible evidence of efficacy and tolerability for each subject. In this context, our study aims to carry out a clinical validation of a combinatorial pharmacogenomics (PGx) test in an Italian MDD patient cohort with advocacy license independence. Methods Our study is a prospective participant- and rater-blinded, randomized, controlled clinical observational trial enrolling 300 MDD patients who are referred to psychiatric services to receive a new antidepressant due to the failure of their current treatment and/or the onset of adverse effects. Eligible participants are randomized to the TGTG group (Treated with Genetic Test Guide) or TAU group (Treated as Usual). For all subjects, DNA is collected with a buccal brush. The primary outcome is the reduction in depressive symptomatology. The secondary outcomes involve a range of scales that assess MDD symptoms and social functioning outcomes. The assessment is performed at four timepoints: baseline and 4, 8, and 12 weeks. Discussion This project represents the first randomized controlled clinical trial to investigate whether a non-commercial PGx test improves outcomes in an MDD naturalistic cohort. Moreover, the identification of new genetic variants associated with non-response or side effects will improve the efficacy of the test, leading to further cost-saving. Trial registration number ClinicalTrials.gov NCT04615234. Registered on November 4, 2020.

Background: Pharmacogenetic testing enhances patient safety by improving medical treatment and reducing side effects. It has shown potential in both primary and secondary care. However, implementation in healthcare, particularly in primary care, is slow.Objective: The objective was to review articles published on the attitudes towards, and knowledge on pharmacogenetic testing in primary care, among general practitioners, pharmacists, and patients.Methods: The review was performed according to the PRISMA checklist. A systemized literature search was followed by a 2-step screening process. Apart from the content of articles being within the scope of the review, inclusion criteria included: articles in English; primary research articles; qualitative, quantitative, or mixed methods. Content analysis was conducted as a qualitative meta-synthesis. The methodological rigor of included articles was assessed.Results: Fifteen studies were included. The analysis resulted in the following main themes: i) benefits of pharmacogenetic testing, ii) barriers to pharmacogenetic testing, iii) pharmacists' role in pharmacogenetic counselling, and iv) pharmacists' knowledge on pharmacogenetics. Methodological rigor was generally medium/high.Conclusions: More studies are needed in this area, and there is a need for more education on pharmacogenetic testing for healthcare professionals. Issues like patient autonomy, economy, and access to tests also need to be addressed. [ABSTRACT FROM AUTHOR]

Aim: To survey Veterans Health Administration providers who prescribed tramadol or codeine to patients with known genotyping for cytochrome 2D6 ( CYP2D6 ) to ascertain awareness of their patient's pharmacogenetic (PGx) test status, whether these results influenced prescribing, perceived benefit of PGx testing, and resources needed to obtain and deliver PGx testing information. Materials & methods: A provider survey was conducted of those who prescribed tramadol or codeine in a patient genotyped for CYP2D6 . Results: Of 876 eligible providers, 220 completed the survey. Ten percent were aware that their patient received a PGx test, 64% had not ordered any PGx test related to any medication in the prior year, 55% strongly agreed or agreed that PGx testing is or will be valuable to guide pain medication prescriptions, 29% felt that the evidence base for PGx testing is very strong or moderately strong, 22% responded likely or extremely likely to order a future PGx test, and 51% felt that it would be either very important or fairly important to have a local subject matter expert as a resource for PGx testing. Conclusion: There are modifiable factors that the Veterans Health Administration could address to optimize PGx testing for pain management.

Abstract Background Pharmacogenetics targets genetic variations that influence drug response. It is relatively a new science that has not been vastly employed in most developing countries including Syria. Therefore we aimed at evaluating the depth of knowledge in pharmacogenetics and the attitude towards it amongst Syrian pharmacists and physicians. Methods We carried out an internet-based questionnaire consisted of 26 questions, sent through specialized websites and private groups with a large number of pharmacists and physicians members. The survey was available online for a period of 1 month. Results The total number of respondents was 154, mostly female pharmacists. Our statistical analysis showed a strong positive association between profession (in favour of pharmacists) and pharmacogenetics knowledge p = 0.049; however, no correlation with experience p = 0.811 was found. A significant difference was reported between the knowledge of pharmacists and physicians p = 0.001 concerning drugs that need pharmacogenetics testing before being prescribed. The majority of respondents had no information about applying genetic tests in Syria before prescribing medications nor did they possess the knowledge regarding drugs that show differential responses in patients according to their unique genotypes. In our study, the percentage knowledge assessment score was low in general (mean ± Standard deviation, SD) (46% ± 13.9%). The majority of the respondents agreed that pharmacists should provide counselling to patients on the subject of pharmacogenetics. Respondents’ opinions varied concerning making pharmacogenetics learning a priority. Conclusion Lack of pharmacogenetics knowledge was found amongst respondents in general. Our findings raise concerns about the lack of awareness amongst physicians, which may hinder the implementation of this crucial field in Syria. We suggest an emphasis on the role of education, training, and conducting genotyping research on the Syrian population.

Introduction: Pharmacogenomics and personalized medicine are the two rapidly emerging areas in medical field which will determine the drug therapy of the future. It is very important for current medical students to be aware of these medical fields and apply these principles in their medical practice. There is huge scope for research in this area, hence an awareness study was conducted among medical students of college of medicine, Shaqra university, Dawadmi. Methods: A cross sectional questionnaire-based study was conducted among the medical students of Shaqra university, Dawadmi by self-administered questionnaire. 150 students participated in the study. Results: Out of the 150 students participated in the study Pharmacogenomics is relevant to my education 25% strongly agree. 45% agreed to recommend pharmacogenomic testing. Familiarity with genetics is only 16% and only 14% are familiar with interpreting results of pharmacogenomic tests. Knowledge testing showed overall less percentage. Only 16% can identify drugs that require pharmacogenomic testing. But 36% are confident to use the results of pharmacogenomics tests to make an appropriate adjustment to a patient's drug therapy. Knowledge about personalized medicine is 31% with scale of 3 out of 7.40% of students agreed to undergo genetic testing. 52% of the participants agreed to know about their risk for developing genetic based chronic diseases. Conclusion: There is genuine interest and awareness about Pharmacogenomics and Personalized medicine among the medical students but the knowledge is lacking. Hence including these areas in the undergraduate medical curriculum will impart valuable knowledge to the future medical students. [ABSTRACT FROM AUTHOR]

Susanne B Haga, Rachel Mills, Jivan Moaddeb, Yiling Liu, Deepak Voora Center for Applied Genomics & Precision Medicine, Duke University School of Medicine, Durham, NC, 27708, USACorrespondence: Susanne B Haga Email Susanne.haga@duke.eduObjective: The delivery of pharmacogenetic (PGx) testing has primarily been through clinical and hospital settings. We conducted a study to explore the feasibility of delivering PGx testing through community pharmacies, a less-studied setting.Methods: We conducted a cluster randomized trial of community pharmacies in North Carolina through two approaches: the provision of PGx testing alone or PGx testing with medication therapy management (MTM).Results: A total of 150 patient participants were enrolled at 17 pharmacies and reported high satisfaction with their testing experience. Participants in the PGx plus MTM arm were more likely to recall a higher number of results (p=0.04) and more likely to clearly understand their choices for prevention or early detection of side effects (p=0.01). A medication or dose change based on the PGx results was made for 8.7% of participants.Conclusion: Limited differences were observed in the provision of PGx testing as a standalone test or combined with MTM. A limited number of treatment changes were made based on PGx test results. Patient acceptance of PGx testing offered through the community pharmacy was very high, but the addition of MTM did not impact patient-reported perceptions about PGx testing or medication adherence.Keywords: pharmacy, pharmacogenetic testing, feasibility, patient experience

Susanne B Haga, Rachel Mills, Jivan Moaddeb, Yiling Liu, Deepak Voora Center for Applied Genomics & Precision Medicine, Durham, NC, 27708, USACorrespondence: Susanne B HagaCenter for Applied Genomics & Precision Medicine, 101 Science Drive, Box 3382, Durham, NC, 27708 Tel +919-684-0325Email susanne.haga@duke.eduObjective: This study assessed pharmacist experiences with delivering pharmacogenetic (PGx) testing in independent community pharmacies.Methods: We conducted a cluster randomized trial of independent community pharmacies in North Carolina randomized to provide either PGx testing as a standalone service or integrated into medication therapy management (MTM) services. Surveys and pharmacist data about the delivery of PGx testing were collected. Semi-structured interviews were also conducted.Results: A total of 36 pharmacists participated in the study from 22 pharmacies. Sixteen pharmacists completed the pre-study and post-study surveys, and four pharmacists completed the semi-structured interviews. Thirty-one percent (11/36) of pharmacists had had some education in personalized medicine or PGx prior to the study. The only outcome that differed by study arm was the use of educational resources, with significantly higher utilization in the PGx testing only arm (p=0.007). Overall, compared to the pre-study assessment, pharmacists’ knowledge about PGx significantly improved post-study (p=0.018). In the post-study survey, almost all pharmacists indicated that they felt qualified/able to provide PGx testing at their pharmacy. While 75% of pharmacists indicated that they may continue to provide PGx testing at their pharmacy after the study, the major concerns were lack of reimbursement for PGx counseling and consultation given the necessary time required.Conclusion: Our findings demonstrated a positive experience with delivering PGx testing in the community pharmacy setting with little difference in pharmacists’ experiences in providing PGx testing with or without MTM. Pharmacists were confident in their ability to provide PGx testing and were interested in continuing to offer testing, though sustained delivery may be challenged by lack of prescribing provider engagement and reimbursement.Keywords: pharmacy, pharmacogenetic testing, feasibility, pharmacist experience

Background: To describe trends and clinical experiences in applying commercial pharmacogenetic testing among pediatric patients with neuropsychiatric disorders. Methods: Demographic and clinical data of patients receiving GeneSight® testing from January 2015 to November 2016 at an urban pediatric hospital were retrospectively extracted from medical charts. Outcome data included pharmacogenetic test results and medication prescriptions before and after the test. Results: A total of 450 patients (12.1 ± 4.3 years) diagnosed with anxiety disorder, attention deficit hyperactivity disorder, developmental disorders including autism, and/or a mood disorder received testing, and 435 of them were prescribed medications. Comparing data before and after testing, the total number of psychotropic prescriptions were reduced by 27.2% and the number of prescribed medications with severe gene-drug interactions decreased from 165 to 95 (11.4% to 8.9% of total medications prescribed). Approximately 40% of actionable genetic annotation were related to CYP2CD6 and CYP2C19. Patients of Asian descent had significantly higher likelihood than other races of being classified as poor to intermediate metabolizers of antidepressants, mood stabilizers, and antipsychotics (p = 0.008, 0.007, and 0.001, respectively). Diagnoses, including autism spectrum disorder, were not associated with increased risks of severe gene-drug interactions. Conclusions: Pharmacogenetic testing in child and adolescent psychiatry is currently based on few clinically actionable genes validated by CPIC and/or FDA. Although this approach can be moderately utilized to guide psychotropic medication prescribing for pediatric patients with psychiatric disorders, clinicians should cautiously interpret test results while still relying on clinical experience and judgment to direct the final selection of medication.

Shimaa Aboelbaha,1 Monica Zolezzi,2 Hazem Elewa2 1College of Pharmacy, QU Health, Qatar University, Doha, Qatar; 2Clinical Pharmacy and Practice, College of Pharmacy, QU Health, Qatar University, Doha, QatarCorrespondence: Monica ZolezziCollege of Pharmacy, QU Health, Qatar University, Doha, QatarEmail mzolezzi@qu.edu.qaObjective: Evidence supporting the utility of pharmacogenetic (PGX) tests in depression is scarce. The main objectives of this study were to summarize, update, and assess the quality of the available evidence regarding PGX testing in depression as well as estimating the impact of using PGX testing tools in depression outcomes in the Middle East/North Africa (MENA) region.Methodology: Scientific databases were systematically searched from inception to June 30, 2020 for systematic reviews and randomized controlled trials (RCTs) assessing the clinical utility of PGX tests in the treatment of depression. Meta-analyses only and RCTs that were included in eligible systematic reviews were excluded. The quality of the eligible studies was assessed using the Crowe Critical Appraisal Tool (CCAT).Results: Six systematic reviews and three RCTs met the inclusion criteria and were included in this study. The results of the systematic reviews provided weak evidence on the efficacy of PGX testing, especially in patients with moderate–severe depression at 8 weeks. In addition, there was a lack of evidence regarding safety outcomes. Newer RCTs with better quality showed clinical promise regarding efficacy outcomes, especially in patients with gene–drug interactions. No evidence was found regarding PGX testing impact in the MENA region.Conclusion: This systematic review is an update and summary of the available literature on the clinical utility of PGX testing in depression. The findings of this study demonstrate that PGX testing prior to treatment initiation or during the course of therapy may improve efficacy outcomes. Further studies are warranted to assess the impact of PGX testing on safety outcomes.Keywords: pharmacogenetic testing, major depressive disorder, clinical decision support, antidepressant treatment response

Introduction Schizophrenia is socially significant mental disorder characterized by early onset and high time and financial expenditure on treatment. Antipsychotics (APs) are highly effective against positive and negative symptoms, but at same time have a wide range of adverse drug reactions (ADRs). APs efficiency and safety are variable and depend on characteristics of genetically determined mechanisms (transportation, biotransformation, and elimination). Objectives Investigation role of pharmacogenetic testing (PhGT) on example of clinical case of severe ADRs in 47-year-old woman with schizophrenia. Methods Patient’s medical history analysis; clinical observation; biochemical serum analysis; therapeutic drug monitoring; PhGT. Results The clinical case of a woman with schizophrenia who has been noted to be unresponsive to APs for some years after schizophrenia onset. She was found to be homozygous for nonfunctional SNVs CYP2D6*4 and CYP2C9*2, heterozygous for CYP1A1*2A, which was reason for complete shutdown of isoenzymes 2D6, 2C9 and 1A1 activity and development of ADRs in use of initial doses of several APs, as well as for an increase in severity of ADRs with schizophrenia positive symptoms aggravation with an even slower titration of APs daily dose not only with polytherapy, but also with monotherapy. So, not recommented APs for patient: aripiprazole, haloperidol, zuclopenthixol, cariprazine, quetiapine, paliperidone, risperidone, thioridazine, sertindole, asenapine, alimemazine, chlorpromazine, etc. (CYP2D6); haloperidol, clozapine, olanzapine, perphenazine, promazine (CYP2C9); carefully: haloperidol, olanzapine, perospirone (СYP1A1). Conclusions This rare case demonstrates PhGT importance before APs therapy, because the patient had very high risk AP – induced ADRs. She needed PhGt before APs use, but not after severe ADRs during 12 years. Disclosure No significant relationships.

Objectives To assess the perception of pharmacists and physicians towards pharmacogenetic testing. Methods A self-administered questionnaire was developed, validated, tested for reliability and disseminated to pharmacists and physicians in Malta. Key findings The study population consisted of 292 participants; 61% pharmacists (64% female, 38% practicing >10 years) and 39% physicians (50% female, 54% practicing >10 years). Pharmacists and physicians felt they lack sufficient competence in the area (95.0% and 97.4%, respectively; P > 0.05) and agreed that further training is required (92.7% and 91.2%, respectively; P > 0.05). Conclusions The need for further training was identified by the participants to support competency development and sustain confidence on the topic, hence facilitating the clinical implementation of pharmacogenetic testing. [ABSTRACT FROM AUTHOR]

Aim: Patient knowledge and attitudes toward pharmacogenetic (PGx) testing may impact adoption of clinical testing. Methods: Questionnaires regarding knowledge, attitudes and ethics of PGx testing were distributed to 504 patients enrolled in the ADAPT study conducted at two urban hospitals in Philadelphia, Pennsylvania, USA. Responses were assessed using multivariable logistic regression. Results: 311 completed the survey (62% response rate). 74% were unaware of PGx testing, but 79% indicated using PGx results to predict medication efficacy was important. In a multivariable model, higher education level (p = 0.031) and greater genetics knowledge (p < 0.001) were associated with more positive attitudes toward PGx testing. Conclusion: Greater patient knowledge of genetics was associated with a more positive attitude toward PGx testing, indicating that educational strategies aimed at increasing genetics knowledge may enhance adoption of PGx testing in the clinic. Pharmacogenetic (PGx) testing looks for genetic variations that may impact one's ability to respond to certain medications. This has the potential to improve patient care and minimize side effects from medications but is not currently used as standard of care for several reasons including a limited understanding of patient perceptions toward PGx testing. This study aimed to assess patient knowledge, attitudes and ethics of PGx testing. Questionnaires were given to patients enrolled in a clinical trial at two urban hospitals in Philadelphia, Pennsylvania, USA. In the study, patients underwent a nonsurgical procedure to open narrowed blood vessels supplying the heart muscles and were prescribed antiplatelet medications afterward. As part of study participation, some patients had undergone PGx testing to guide antiplatelet therapy following while others received standard of care (no PGx testing). We found that patients were generally not aware of PGx testing but felt it would be important information to have to guide their treatment options. Higher education levels and greater genetics knowledge were factors associated with more positive attitudes toward PGx testing. An understanding of patient perceptions, knowledge and misconceptions of PGx testing can allow healthcare professionals to better address knowledge gaps and increase the use of PGx testing in clinical settings. [ABSTRACT FROM AUTHOR]

Abstract Background Effective communication in support of clinical decision-making is central to the pediatric cancer care experience for families. A new laboratory derived pharmacogenetic test (LDT) that can diagnose difficult-to-treat brain cancers has been developed to stratify children based on their ability to respond to available treatment; however, the potential implementation of the LDT may make effective communication challenging since it can potentially remove the option for curative treatment in those children identified as non-responders, i.e. those with a catastrophic diagnosis. Objective We solicited the perspectives of parents of children with difficult-to-treat brain cancer on communication preferences surrounding the potential implementation of the LDT in standard care using deliberative stakeholder consultations. Methods Eight bereaved parents of children who succumbed to difficult-to-treat brain cancer, and four parents of children currently undergoing treatment for similar cancers attended separate small-group deliberative consultations – a stakeholder engagement method that enables the co-creation of recommendations following the consideration of competing arguments and diverse opinions of parents with different experiences. In the small-group consultations (Phase I), parents discussed four questions about potential communication issues that may arise with the LDT in practice. In Phase II, a total of five parents from both stakeholder groups (4 bereaved and 1 in current treatment) attended a consultation, known as the ‘mixed’ consultation, with the purpose of co-developing concrete recommendations for implementation of the LDT. Results Explaining the risks, benefits, and accuracy of the LDT were considered essential to parents. Once an LDT-based diagnosis/prognosis can be made, parents valued honesty, empathy, and clarity in communication. Parents also requested that all results and treatment options be presented to them in measured doses, and in an unbiased manner over the course of several meetings. This communication strategy allowed sufficient time to understand and accept the diagnosis/prognosis, particularly if it was catastrophic. Continuous access to the appropriate psychological and social support or counselling at and post-diagnosis was also strongly recommended. Conclusions Deliberants co-created family-centered recommendations surrounding communication issues of the LDT, providing guidance to pediatric oncologists that could implement the test in practice.

INTRODUCTION. Antipsychotic-induced parkinsonism (AIP) is an extrapyramidal adverse drug reaction (ADR) associated with antipsychotics (APs). Despite its classification as a non-serious ADR, AIP significantly decreases the quality of life in patients with schizophrenia spectrum disorders, which makes early diagnosis and timely management of AIP an urgent issue.AIM. This study aimed to develop a risk assessment scale and a personalised diagnostic algorithm for AIP as the most common and clinically significant neurological ADR in patients with schizophrenia spectrum disorders.MATERIALS AND METHODS. The authors analysed modifiable and non-modifiable risk factors for AIP, as well as rating scales, questionnaires, and laboratory testing methods to diagnose the condition. The analysis was based on full-text publications in Russian or in English sourced from the eLIBRARY.RU, PubMed, Springer, ClinicalKey, and Google Scholar databases. As a preliminary step, the authors compared the effectiveness of validated AIP risk assessment scales, including the Simpson–Angus Scale (SAS), the Extrapyramidal Symptom Rating Scale (ESRS), the Unified Parkinson’s Disease Rating Scale (UPDRS), the Hoehn and Yahr scale (H&Y Scale), the Webster Rating Scale, and the Mindham Rating Scale. Comparisons were made regarding the duration of testing, the degree of reliability in assessing clinical manifestations of AIP, and the ability to assess risk factors (predictors) of AIP and the rate of AIP development. The results obtained formed the basis for developing an AIP riskometer and a diagnostic algorithm.RESULTS. The authors developed an original risk assessment scale for diagnosing and predicting AIP. Directions for personalised patient management were determined for patients at high and medium risk of AIP. This article presents an algorithm for diagnosing AIP in patients with schizophrenia spectrum disorders in two variants based on pro-reactive (predictive) or reactive pharmacogenetic testing. According to the study results, pro-reactive pharmacogenetic testing can help determine the risk of AIP in a patient before primary therapy.CONCLUSIONS. The risk assessment scale and the personalised diagnostic algorithm developed by the authors may be useful for practising neurologists, psychiatrists, and clinical pharmacologists. The development and clinical implementation of novel tools for risk assessment, prevention, and diagnosis of AIP—the most common AP-associated neurological ADR—can improve the quality of treatment and preventive care for patients with schizophrenia spectrum disorders.

Aim: The aim of the paper is to evaluate the use of pharmacogenetic testing in patients with a psychiatric diagnosis. Methods: In the Faculty Hospital Brno-Bohunice the genotyping and phenotyping of CYP2D6 is available and covered by insurance since 1997. The requests for pharmacogenetic analysis were provided by the Department of Medical Genetics, University Hospital Brno. Results: Between 1997 and 2019 totally 223 requests were collected and pharmacogenetic analyses performed in patients with psychiatric diagnosis. Most of analyses were performed in the first decade. The patients were recruited in studies aiming at exploring the influence of CYP2D6 activity on efficacy and tolerability of treatment with antidepressants. In further years there was a progressive decrease of requests. Discussion: The possible reasons are discussed including absence of interconnection with drug plasma levels measurement. Conclusions: Genotyping and/or phenotyping of drug metabolising enzymes in unresponsive individuals facilitates and accelerates choice of further treatment strategy. Pharmacogenetic testing together with therapeutic drug monitoring should be available at least at university hospitals with cumulation of difficult to treat patients. [ABSTRACT FROM AUTHOR]

Background: Pharmacogenetic (PGx) testing for germline variants in the DPYD and UGT1A1 genes can be used to guide fluoropyrimidine and irinotecan dosing, respectively. Despite the known association between PGx variants and chemotherapy toxicity, preemptive testing prior to chemotherapy initiation is rarely performed in routine practice. Methods: We conducted a qualitative study of oncology clinicians to identify barriers to using preemptive PGx testing to guide chemotherapy dosing in patients with gastrointestinal malignancies. Each participant completed a semi-structured interview informed by the Consolidated Framework for Implementation Research (CFIR). Interviews were analyzed using an inductive content analysis approach. Results: Participants included sixteen medical oncologists and nine oncology pharmacists from one academic medical center and two community hospitals in Pennsylvania. Barriers to the use of preemptive PGx testing to guide chemotherapy dosing mapped to four CFIR domains: intervention characteristics, outer setting, inner setting, and characteristics of individuals. The most prominent themes included 1) a limited evidence base, 2) a cumbersome and lengthy testing process, and 3) a lack of insurance coverage for preemptive PGx testing. Additional barriers included clinician lack of knowledge, difficulty remembering to order PGx testing for eligible patients, challenges with PGx test interpretation, a questionable impact of preemptive PGx testing on clinical care, and a lack of alternative therapeutic options for some patients found to have actionable PGx variants. Conclusions: Successful adoption of preemptive PGx-guided chemotherapy dosing in patients with gastrointestinal malignancies will require a multifaceted effort to demonstrate clinical effectiveness while addressing the contextual factors identified in this study. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is a common, chronic, debilitating mood disorder that causes serious functional impairment and significantly decreased quality of life. Pharmacotherapy represents the first-line treatment option; however, only approximately one third of patients respond to the first treatment because of the ineffectiveness or side effects of antidepressants. Precision medicine in psychiatry might offer clinicians the possibility to tailor treatment according to the best possible evidence of efficacy and tolerability for each subject. In this context, our study aims to carry out a clinical validation of a combinatorial pharmacogenomics (PGx) test in an Italian MDD patient cohort with advocacy license independence.Methods: Our study is a prospective participant- and rater-blinded, randomized, controlled clinical observational trial enrolling 300 MDD patients who are referred to psychiatric services to receive a new antidepressant due to the failure of their current treatment and/or the onset of adverse effects. Eligible participants are randomized to the TGTG group (Treated with Genetic Test Guide) or TAU group (Treated as Usual). For all subjects, DNA is collected with a buccal brush. The primary outcome is the reduction in depressive symptomatology. The secondary outcomes involve a range of scales that assess MDD symptoms and social functioning outcomes. The assessment is performed at four timepoints: baseline and 4, 8, and 12 weeks.Discussion: This project represents the first randomized controlled clinical trial to investigate whether a non-commercial PGx test improves outcomes in an MDD naturalistic cohort. Moreover, the identification of new genetic variants associated with non-response or side effects will improve the efficacy of the test, leading to further cost-saving.Trial Registration Number: ClinicalTrials.gov NCT04615234. Registered on November 4, 2020. [ABSTRACT FROM AUTHOR]