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Annals of Internal Medicine Oct 2022In February 2022, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved a joint clinical practice guideline (CPG) for the management...
DESCRIPTION
In February 2022, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved a joint clinical practice guideline (CPG) for the management of major depressive disorder (MDD). This synopsis summarizes key recommendations.
METHODS
Senior leaders within the VA and the DoD assembled a team to update the 2016 CPG for the management of MDD that included clinical stakeholders and conformed to the National Academy of Medicine's tenets for trustworthy CPGs. The guideline panel developed key questions, systematically searched and evaluated the literature, created two 1-page algorithms, and distilled 36 recommendations for care using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Select recommendations that were identified by the authors to represent key changes from the prior CPG are presented in this synopsis.
RECOMMENDATIONS
The scope of the CPG is diverse; however, this synopsis focuses on key recommendations that the authors identified as important new evidence and changes to prior recommendations on pharmacologic management, pharmacogenomics, psychotherapy, complementary and alternative therapies, and the use of telemedicine.
Topics: Depressive Disorder, Major; Humans; United States; United States Department of Veterans Affairs; Veterans
PubMed: 36122380
DOI: 10.7326/M22-1603 -
Clinical Pharmacology and Therapeutics Dec 2022Pharmacogenomic (PGx) testing has emerged as a compelling strategy that clinicians can use to inform antidepressant medication selection and dosing, but the clinical... (Meta-Analysis)
Meta-Analysis
Pharmacogenomic (PGx) testing has emerged as a compelling strategy that clinicians can use to inform antidepressant medication selection and dosing, but the clinical efficacy of this strategy has been questioned. We systematically reviewed and meta-analyzed clinical trials for an association between the use of PGx-guided antidepressant therapy and depressive symptom remission in patients with major depressive disorder (MDD). We included prospective, controlled clinical trials published in English up to July 12, 2022. Data extraction and synthesis adhered to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Each trial was assessed for risk of bias and a random-effects model was used to estimate pooled risk ratios. Thirteen trials comprising 4,767 patients were analyzed, including 10 randomized controlled trials, and three open label trials. Across all included trials, those that received PGx-guided antidepressant therapy (n = 2,395) were 1.41 (95% confidence interval (CI) = 1.15-1.74, P = 0.001) more likely to achieve remission compared with those that received unguided antidepressant therapy (n = 2,372). Pooled risk ratios for randomized controlled trials and open label trials were 1.46 (95% CI: 1.13-1.88) and 1.26 (95% CI = 0.84-1.88), respectively. These results suggest that PGx-guided antidepressant therapy is associated with a modest but significant increase in depressive symptom remission in adults with MDD. Efforts to address the heterogeneity in PGx test composition (i.e., genes and alleles tested) and accompanying prescribing recommendations across trials will likely reduce the uncertainty about the efficacy of PGx-guided antidepressant therapy in the literature.
Topics: Adult; Humans; Antidepressive Agents; Depression; Depressive Disorder, Major; Pharmacogenomic Testing; Prospective Studies; Randomized Controlled Trials as Topic
PubMed: 36111494
DOI: 10.1002/cpt.2748 -
Biomedicine & Pharmacotherapy =... Sep 2022Multiple sclerosis is a chronic inflammatory neurological disease, and siponimod (Mayzent) is the first oral treatment option for adult patients with secondary... (Review)
Review
Multiple sclerosis is a chronic inflammatory neurological disease, and siponimod (Mayzent) is the first oral treatment option for adult patients with secondary progressive multiple sclerosis. We performed a systematic review of the pharmacogenetics of Siponimod, and we found that (430 C>T; rs1799853) and CYP2C9 * 3 (1075 A>C; rs1057910), both translated no-function alleles, have been related to a lower metabolism of siponimod by CYP2C9 enzyme. The FDA-approved drug label and EMA risk management plan for siponimod require testing patients for CYP2C9 genotype before treatment starts. The FDA drug label states that siponimod is contraindicated in patients carrying a CYP2C9 * 3/* 3 genotype, and a daily maintenance dose of 1 mg in patients with CYP2C9 * 1/* 3 and * 2/* 3 genotypes. The EMA reported the potential long-term safety implications in CYP2C9 poor metabolizer patients treated with this drug. Based on this systematic review we concluded that CYP2C9 SNPs influence on siponimod response might be stated by assessing not only CYP2C9 * 2 and CYP2C9 * 3 but other genetic variants resulting in CYP2C9 IM/PM status. CYP2C9 IM phenotype translated from the CYP2C9 * 2 genotype should be revised since it is contradictory compared to other CYP2C9 no-function alleles, and CYP2C9 * 2 might be excluded from PGx testing recommendation before treatment starts with siponimod since it is not translated into a therapeutic recommendation.
Topics: Azetidines; Benzyl Compounds; Cytochrome P-450 CYP2C9; Genotype; Pharmacogenetics
PubMed: 36076616
DOI: 10.1016/j.biopha.2022.113536 -
Frontiers in Medicine 2022Several healthcare organizations have developed pre-emptive pharmacogenetic testing programs, where testing is undertaken prior to the prescription of a medicine. This...
Several healthcare organizations have developed pre-emptive pharmacogenetic testing programs, where testing is undertaken prior to the prescription of a medicine. This review characterizes the barriers and facilitators which influenced the development of these programs. A bidirectional citation searching strategy identified relevant publications before a standardized data extraction approach was applied. Publications were grouped by program and data synthesis was undertaken using the Consolidated Framework for Implementation Research (CFIR). 104 publications were identified from 40 programs and 4 multi-center initiatives. 26 (66%) of the programs were based in the United States and 95% in high-income countries. The programs were heterogeneous in their design and scale. The Characteristics of the Intervention, Inner Setting, and Process domains were referenced by 92.5, 80, and 77.5% of programs, respectively. A positive institutional culture, leadership engagement, engaging stakeholders, and the use of clinical champions were frequently described as facilitators to implementation. Clinician self-efficacy, lack of stakeholder knowledge, and the cost of the intervention were commonly cited barriers. Despite variation between the programs, there were several similarities in approach which could be categorized the CFIR. These form a resource for organizations planning the development of pharmacogenetic programs, highlighting key facilitators which can be leveraged to promote successful implementation.
PubMed: 36059837
DOI: 10.3389/fmed.2022.945352 -
Clinical Pharmacology and Therapeutics May 2023Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with development of acute hemolytic anemia in the setting of oxidative stress, which can be caused by... (Review)
Review
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with development of acute hemolytic anemia in the setting of oxidative stress, which can be caused by medication exposure. Regulatory agencies worldwide warn against the use of certain medications in persons with G6PD deficiency, but in many cases, this information is conflicting, and the clinical evidence is sparse. This guideline provides information on using G6PD genotype as part of the diagnosis of G6PD deficiency and classifies medications that have been previously implicated as unsafe in individuals with G6PD deficiency by one or more sources. We classify these medications as high, medium, or low to no risk based on a systematic review of the published evidence of the gene-drug associations and regulatory warnings. In patients with G6PD deficiency, high-risk medications should be avoided, medium-risk medications should be used with caution, and low-to-no risk medications can be used with standard precautions, without regard to G6PD phenotype. This new document replaces the prior Clinical Pharmacogenetics Implementation Consortium guideline for rasburicase therapy in the context of G6PD genotype (updates at: www.cpicpgx.org).
Topics: Humans; Glucosephosphate Dehydrogenase; Glucosephosphate Dehydrogenase Deficiency; Pharmacogenetics; Hemolysis; Genotype
PubMed: 36049896
DOI: 10.1002/cpt.2735 -
BMC Psychiatry Aug 2022The main goal of this work was to identify, describe, characterize, and classify the scientific evidence regarding the use of pharmacogenomic biomarkers in...
OBJECTIVE
The main goal of this work was to identify, describe, characterize, and classify the scientific evidence regarding the use of pharmacogenomic biomarkers in antidepressant treatment.
METHODS
The work was developed in two phases: i) a search for pharmacogenomic biomarkers in summaries of antidepressant drugs with marketing authorization in Portugal; and ii) a systematic literature review based on the data obtained in the first phase, with the main objective of finding international literature that could describe and characterize previously reported biomarkers and identify other relevant biomarkers. Finally, the levels of evidence and recommendation grades were classified.
RESULTS
Among the 26 drugs with marketing authorization in Portugal, only 16 had pharmacogenomic information. The most widely studied pharmacogenomic biomarker was CYP2D6. These results were mostly supported by the systematic literature review, which yielded 103 papers, 63 of which were ultimately included in the review. The systematic literature review also revealed the existence of other relevant biomarkers. Most of the included studies show a good level of evidence, which guarantees reliability and good recommendation grades. For the database (built during phase i), the results were informative but resulted in no specific recommendations.
CONCLUSIONS
Most pharmacogenomic variants are not studied or acknowledged by genetic tests, and more scientific research is needed to confirm their usefulness. Therefore, only a small number of variants are considered when prescribing antidepressant drugs. In addition, genotyping of patients is not common in clinical practice.
Topics: Antidepressive Agents; Biomarkers; Genetic Testing; Humans; Pharmacogenetics; Reproducibility of Results
PubMed: 36042420
DOI: 10.1186/s12888-022-04225-2 -
Antioxidants (Basel, Switzerland) Aug 2022The coronavirus disease (COVID-19) pandemic is a leading global health and economic challenge. What defines the disease's progression is not entirely understood, but... (Review)
Review
The coronavirus disease (COVID-19) pandemic is a leading global health and economic challenge. What defines the disease's progression is not entirely understood, but there are strong indications that oxidative stress and the defense against reactive oxygen species are crucial players. A big influx of immune cells to the site of infection is marked by the increase in reactive oxygen and nitrogen species. Our article aims to highlight the critical role of oxidative stress in the emergence and severity of COVID-19 and, more importantly, to shed light on the underlying molecular and genetic mechanisms. We have reviewed the available literature and clinical trials to extract the relevant genetic variants within the oxidative stress pathway associated with COVID-19 and the anti-oxidative therapies currently evaluated in the clinical trials for COVID-19 treatment, in particular clinical trials on glutathione and N-acetylcysteine.
PubMed: 36009328
DOI: 10.3390/antiox11081609 -
Health Science Reports Sep 2022COVID-19 is not only limited to a defined array but also has expanded with several secondary infections. Two uncommon opportunistic fungal infections, COVID-19...
COVID-19 is not only limited to a defined array but also has expanded with several secondary infections. Two uncommon opportunistic fungal infections, COVID-19 associated mucormycosis (CAM) and aspergillosis (CAA), have recently been highly acquainted by many worldwide cases. Two immune response deteriorating factors are considered to be responsible for immunosuppression: comorbidities and medication. Due to unlike infection sites and patterns, CAM and CAA-associated factors deflect a few degrees of proximity, and the present study is for its assessment. The study evaluated 351 CAM cases and 191 CAA cases retrieved from 65 and 53 articles based on inclusion criteria, respectively. Most of the CAM reported from India and CAA were from four South-European and West-European neighbor countries. The mean ages of CAM and CAA were 52.72 ± 13.74 and 64.81 ± 11.14, correspondingly. Mortality of CAA (56.28%) was two times greater than CAM (26.02%). Nevertheless, the count of diabetes cases was very high in CAM compared to CAA. The main comorbidities of CAM were diabetes (nearly 80%) and hypertension (more than 38%). All noticeable complications were higher in CAA except diabetes, and these were diabetes (34.55%), hypertension (45.03%), and obesity (18.32%). Moreover, pre-existing respiratory complications like asthma and chronic obstructive pulmonary disease are visible in CAA. The uses of steroids in CAM and CAA were nearly 70% and 66%, respectively. Almost one-fourth of CAA cases were reported using immunosuppressant monoclonal antibodies, whereas only 7.69% were for CAM. The overall finding highlights diabetes, hypertension, and steroids as the risk factors for CAM, whereas obesity, chronic pulmonary disease, and immunosuppressants for CAA.
PubMed: 36000078
DOI: 10.1002/hsr2.789 -
Expert Review of Clinical Pharmacology Jul 2022Clopidogrel is an antiplatelet agent recommended for secondary prevention of ischemic stroke (IS) and transient ischemic attack (TIA). Conversion of clopidogrel to its...
INTRODUCTION
Clopidogrel is an antiplatelet agent recommended for secondary prevention of ischemic stroke (IS) and transient ischemic attack (TIA). Conversion of clopidogrel to its active metabolite by hepatic cytochrome P450-2C19 (CYP2C19) is essential for the inhibition of the P2Y12 receptor and subsequent platelet aggregation to prevent thrombotic events. is highly polymorphic, with over 30 loss of function (LoF) alleles. This review considers whether there is sufficient data to support genotype guided antiplatelet therapy after stroke.
AREAS COVERED
A systematic literature review retrieved articles, which describe the interaction between genotype and clinical outcomes following IS or TIA when treated with clopidogrel. The review documents efforts to identify optimal antiplatelet regimens and explores the value genotype guided antiplatelet therapy. The work outlines the contemporary understanding of clopidogrel metabolism and appraises evidence linking LoF variants with attenuated platelet inhibition and poorer outcomes.
EXPERT OPINION
There is good evidence that LoF allele carriers of Han-Chinese ancestry have increased risk for further vascular events following TIA or IS when treated with clopidogrel. The evidence base is less certain in other populations. The expansion of pharmacogenetics into routine clinical practice will facilitate further research and help tailor other aspects of secondary prevention.
Topics: Clopidogrel; Cytochrome P-450 CYP2C19; Genotype; Humans; Ischemic Attack, Transient; Ischemic Stroke; Platelet Aggregation Inhibitors; Stroke; Ticlopidine; Treatment Outcome
PubMed: 35912831
DOI: 10.1080/17512433.2022.2108401 -
Health Science Reports Jul 2022Abnormalities in hematological and biochemical markers are assumed to be associated with the progression of COVID-19 disease. This meta-analysis was performed to assess...
BACKGROUND AND AIMS
Abnormalities in hematological and biochemical markers are assumed to be associated with the progression of COVID-19 disease. This meta-analysis was performed to assess the consequences of abnormalities of biomarkers (D-dimers, C-reactive protein [CRP], serum ferritin, lactate dehydrogenase [LDH], random blood sugar [RBS], absolute neutrophil count [ANC], neutrophil to lymphocyte ratio (NLR), serum creatinine, and hemoglobin) in the Bangladeshi COVID-19 patients.
METHODS
The data of biomarker levels in Bangladeshi COVID-19 patients were gathered from five databases: PubMed, ScienceDirect, Web of Science, Google Scholar and Bangladesh Journals Online between January 2020 to March 2022. Review Manager 5.4 was used for the meta-analysis, and Egger's test and Begg-Mazumdar's rank correlation were used to investigate publication bias.
RESULTS
This study included 1542 patients with 567 severe and 975 nonsevere statuses. Based on the accumulated data synthesis, there is a strong correlation between disease severity and different biomarkers, including D-dimer, CRP, ferritin, LDH, RBS, NLR, and serum creatinine (MD = 1.16, = 0.0004; MD = 22.97, = 0.003; MD = 419.26, < 0.00001; MD = 118.37, = 0.004; MD = 1.96, = 0.02; MD = 1.26, = 0.02; and MD = 0.31, = 0.008, respectively). A significantly decreased correlation was observed for hemoglobin levels in severe COVID-19 patients (MD = -0.73, = 0.10).
CONCLUSION
The elevated biomarkers level was noticed in severe cases compared to nonsevere patients, revealing that D-dimer, CRP, ferritin, LDH, RBS, NLR, and serum creatinine are significantly correlated to COVID-19 severity. Only lower hemoglobin level was found to be associated with COVID-19 severity.
PubMed: 35899180
DOI: 10.1002/hsr2.728