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European Neuropsychopharmacology : the... Jul 2023Selegiline is an irreversible, selective type-B monoamine oxidase inhibitor (MAOI) approved for Parkison's disease-oral and major depressive disorder-transdermal... (Meta-Analysis)
Meta-Analysis
Selegiline is an irreversible, selective type-B monoamine oxidase inhibitor (MAOI) approved for Parkison's disease-oral and major depressive disorder-transdermal formulation) resulting in non-selective MAOI activity at oral doses≥20 mg/day. The present systematic review and meta-analysis appraises the evidence of different formulations/dosages of selegiline across different psychiatric conditions. We inquired PubMed/MEDLINE/Cochrane-Central/WHO-ICTRP/Clarivate-WebOfScience and the Chinese-Electronic-Journal Database from inception to 10/26/2022 for selegiline trials involving psychiatric patients. Random-effects meta-analyses assessed heterogeneity, publication/risk biases, and confidence in the evidence, followed by sensitivity, subgroup, and meta-regression analyses. Co-primary outcomes were: changes in symptom score (standardized mean difference=SMD) and author-defined response (risk ratios=RRs). RRs of adverse events and all-cause discontinuation were secondary and acceptability outcomes, respectively. Systematic-review included 42 studies; meta-analysis, 23. Selegiline outperformed placebo in depressive symptom reduction (SMD=-0.96, 95%C.I.=-1.78, -0.14, k = 10, n = 1,308), depression (RR=1.61, 95%C.I.=1.20, 2.15, k = 9, n = 1,238) and atypical-depression response (RR=2.23, 95%C.I.=1.35, 3.68, k = 3, n = 136). Selegiline failed to outperform the placebo in negative (k = 4) or positive symptoms of schizophrenia (k = 4), attention-deficit-hyperactivity disorder (ADHD) symptoms reduction (k = 2), and smoking abstinence rate (k = 4). Selegiline did not differ from methylphenidate and ADHD scores (k = 2). No significant difference emerged in acceptability, incident diarrhea, headache, dizziness, and nausea RRs, in contrast to xerostomia (RR=1.58, 95%C.I. =1.03, 2.43, k = 6, n = 1,134), insomnia (RR=1.61, 95%C.I.=1.19, 2.17, k = 10, n = 1,768), and application-site reaction for transdermal formulation (RR=1.81, 95%C.I.=1.40, 2.33, k = 6, n = 1,662). Confidence in findings was low/very-low for most outcomes; moderate for depressive symptoms reduction (transdermal). Selegiline proved effective, safe, and well-tolerated for depressive disorders, yet further evidence is warranted about specific psychiatric disorders.
Topics: Humans; Selegiline; Depressive Disorder, Major; Monoamine Oxidase Inhibitors; Attention Deficit Disorder with Hyperactivity; Methylphenidate
PubMed: 37087864
DOI: 10.1016/j.euroneuro.2023.03.012 -
Pharmaceutics Jun 2022This systematic review summarizes the impact of pharmacogenetics on the effect and safety of non-steroidal anti-inflammatory drugs (NSAIDs) and antidepressants when used... (Review)
Review
BACKGROUND
This systematic review summarizes the impact of pharmacogenetics on the effect and safety of non-steroidal anti-inflammatory drugs (NSAIDs) and antidepressants when used for pain treatment.
METHODS
A systematic literature search was performed according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines regarding the human in vivo efficacy and safety of NSAIDs and antidepressants in pain treatment that take pharmacogenetic parameters into consideration. Studies were collected from PubMed, Scopus, and Web of Science up to the cutoff date 18 October 2021.
RESULTS
Twenty-five articles out of the 6547 initially detected publications were identified. Relevant medication-gene interactions were noted for drug safety. Interactions important for pain management were detected for (1) ibuprofen/; (2) celecoxib/; (3) piroxicam/, ; (4) diclofenac/, , , ; (5) meloxicam/; (6) aspirin/, , and ; (7) amitriptyline/ and ; (8) imipramine/; (9) nortriptyline/, , ; and (10) escitalopram/, , and .
CONCLUSIONS
Overall, a lack of well powered human in vivo studies assessing the pharmacogenetics in pain patients treated with NSAIDs or antidepressants is noted. Studies indicate a higher risk for partly severe side effects for the poor metabolizers and NSAIDs. Further in vivo studies are needed to consolidate the relevant polymorphisms in NSAID safety as well as in the efficacy of NSAIDs and antidepressants in pain management.
PubMed: 35745763
DOI: 10.3390/pharmaceutics14061190 -
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 -
Journal of Personalized Medicine Jun 2023This systematic review evaluated the animal and human evidence for pharmacomicrobiomics (PMx) interactions of antidepressant medications. Studies of gut microbiota... (Review)
Review
This systematic review evaluated the animal and human evidence for pharmacomicrobiomics (PMx) interactions of antidepressant medications. Studies of gut microbiota effects on functional and behavioral effects of antidepressants in human and animal models were identified from PubMed up to December 2022. Risk of bias was assessed, and results are presented as a systematic review following PRISMA guidelines. A total of 28 (21 animal, 7 human) studies were included in the review. The reviewed papers converged on three themes: (1) Antidepressants can alter the composition and metabolites of gut microbiota, (2) gut microbiota can alter the bioavailability of certain antidepressants, and (3) gut microbiota may modulate the clinical or modeled mood modifying effects of antidepressants. The majority (n = 22) of studies had at least moderate levels of bias present. While strong evidence is still lacking to understand the clinical role of antidepressant PMx in human health, there is evidence for interactions among antidepressants, microbiota changes, microbiota metabolite changes, and behavior. Well-controlled studies of the mediating and moderating effects of baseline and treatment-emergent changes in microbiota on therapeutic and adverse responses to antidepressants are needed to better establish a potential role of PMx in personalizing antidepressant treatment selection and response prediction.
PubMed: 37511699
DOI: 10.3390/jpm13071086 -
Neuroscience and Biobehavioral Reviews Dec 2023Non-Alzheimer's dementia (NAD) accounts for 30% of all neurodegenerative conditions and is characterized by cognitive decline beyond mere memory dysfunction. Diagnosing... (Meta-Analysis)
Meta-Analysis Review
Non-Alzheimer's dementia (NAD) accounts for 30% of all neurodegenerative conditions and is characterized by cognitive decline beyond mere memory dysfunction. Diagnosing NAD remains challenging due to the lack of established biomarkers. Transcranial magnetic stimulation (TMS) is a non-invasive neurophysiological tool that enables the investigation of cortical excitability in the human brain. Paired-pulse TMS paradigms include short- and long-interval intracortical inhibition (SICI/LICI), intracortical facilitation (ICF), and short-latency afferent inhibition (SAI), which can assess neurophysiological functions of GABAergic, glutamatergic, and cholinergic neural circuits, respectively. We conducted the first systematic review and meta-analysis to compare these TMS indices among patients with NAD and healthy controls. Our meta-analyses indicated that TMS neurophysiological examinations revealed decreased glutamatergic function in patients with frontotemporal dementia (FTD) and decreased GABAergic function in patients with FTD, progressive supranuclear palsy, Huntington's disease, cortico-basal syndrome, and multiple system atrophy-parkinsonian type. In addition, decreased cholinergic function was found in dementia with Lewy body and vascular dementia. These results suggest the potential of TMS as an additional diagnostic tool to differentiate NAD.
Topics: Humans; Transcranial Magnetic Stimulation; Frontotemporal Dementia; Neurodegenerative Diseases; NAD; Alzheimer Disease; Cholinergic Agents; Neural Inhibition; Evoked Potentials, Motor
PubMed: 37926239
DOI: 10.1016/j.neubiorev.2023.105451 -
Research in Social & Administrative... Nov 2023The field of pharmacogenomics is rapidly advancing, but its adoption and implementation remain slow and lacking. Lack of pharmacogenomics knowledge among healthcare... (Review)
Review
BACKGROUND
The field of pharmacogenomics is rapidly advancing, but its adoption and implementation remain slow and lacking. Lack of pharmacogenomics knowledge among healthcare professionals is the most frequently cited barrier to adopting and implementing pharmacogenomics in clinical settings.
OBJECTIVES
This study aimed to critically evaluate and determine the effectiveness of educational interventions in improving pharmacogenomics knowledge and practice.
METHODS
Four electronic databases were searched: MEDLINE, EMBASE, CENTRAL, and PsycINFO. Studies on pharmacogenomics educational interventions for health care professionals and students with pre- and post-intervention assessments and results were included. No restrictions were placed on time, language, or educational contexts. The educational outcomes measured include both objective and subjective outcomes. The pharmacogenomics competency domains used to judge educational interventions are based on the competency domains listed by the American Association of Colleges of Pharmacies (AACP). The National Heart, Lung, and Blood Institute of the National Institutes of Health was used for the quality assessment of pre-post studies with no control group and the controlled intervention studies. No meta-analysis was conducted; the data were synthesized qualitatively. The systematic review was reported in accordance with the PRISMA statement.
RESULTS
Fifty studies were included in this review. All included studies integrated the AACP pharmacogenomics competency domains into their educational interventions. Most of the studies had educational interventions that integrated clinical cases (n = 44; 88%). Knowledge was the most frequently evaluated outcome (n = 34; 68%) and demonstrated significant improvement after the educational intervention that integrated AACP pharmacogenomics competency domains and employed active learning with clinical case inclusion.
CONCLUSION
This review provided evidence of the effectiveness of educational interventions in improving pharmacogenomics knowledge and practice. Incorporating pharmacogenomics competency domains into education and training, with patient cases for healthcare professionals and students, dramatically improved their pharmacogenomics knowledge, attitudes, and confidence in practice.
Topics: Humans; Pharmacogenetics; Students; Health Personnel; Educational Status; Delivery of Health Care
PubMed: 37586945
DOI: 10.1016/j.sapharm.2023.07.012 -
Journal of Child and Adolescent... Feb 2021To systematically review the impact of genetic variation on antipsychotic pharmacokinetics, efficacy, and adverse drug reactions among children and youth. The...
To systematically review the impact of genetic variation on antipsychotic pharmacokinetics, efficacy, and adverse drug reactions among children and youth. The published literature was systematically searched in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations and critically evaluated using standardized tools and consensus criteria. A total of 20 eligible studies comprising 1078 children and youth were evaluated. The included studies were of fair to moderate quality and included mostly males, individuals of European ancestry, and those treated with risperidone. CYP2D6 poor metabolizers (PMs) were consistently shown to have increased concentrations of risperidone relative to normal metabolizers (NMs). PMs were also consistently shown to have a greater propensity to experience antipsychotic (primarily risperidone) associated adverse drug reactions relative to NMs. However, robust evidence for an association between and efficacy was less apparent. The current knowledge base suggests that genetic variation has an appreciable impact on antipsychotic pharmacokinetics and the propensity for adverse drug reactions, particularly among children receiving risperidone treatment. However, several limitations with the current literature (e.g., sample sizes, study design, sample heterogeneity) should be addressed in future studies. Assuming that future studies support the link between genetic variation and antipsychotic outcomes, we would anticipate an increase in the implementation of -guided antipsychotic drug selection and dose optimization in child and adolescent psychiatric services.
Topics: Adolescent; Antipsychotic Agents; Child; Cytochrome P-450 CYP2D6; Drug-Related Side Effects and Adverse Reactions; Humans; Pharmacogenetics; Risperidone; Treatment Outcome
PubMed: 33074724
DOI: 10.1089/cap.2020.0093 -
Cancer Reports (Hoboken, N.J.) Jan 2023Accumulating studies have evaluated the association between MAP3K1 polymorphisms and cancer prognosis. However, the results of these studies are conflicting. Given the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Accumulating studies have evaluated the association between MAP3K1 polymorphisms and cancer prognosis. However, the results of these studies are conflicting. Given the potential impact of MAP3K1 rs889312 SNP on the prognosis of various cancers, this meta-analysis was performed to obtain solid and credible evidence.
METHODS AND MATERIALS
This study was performed according to the PRISMA 2020 statement. A comprehensive article search was conducted to find and select articles from multiple databases, including PubMed, Google Scholar, Web of Science, EMBASE and the Cochrane Library, published up to 15th September 2022. The data analysis was performed with Review Manager v5.2. Pooled HR with its 95% CI and p-value was calculated where HR >1 suggests worse/poor survival and HR <1 suggests better survival of cancer patients.
RESULTS
A total of five articles comprising 24 439 patients were included for both qualitative and quantitative data synthesis. It was found that only the dominant genetic model (AC + CC vs. AA) showed a statistically significant poor overall survival for MAP3K1 rs889312 polymorphism (HR = 1.25, 95% CI = 1.06-1.47, p = .01). In addition, publication bias analysis by the Egger's test and the Begg-Mazumdar test reported no significant bias in the analysis of overall survival (p > .05).
CONCLUSIONS
The present study concludes that MAP3K1 gene rs889312 polymorphism plays a prognostic role in the survival of cancer patients. However, future research is recommended that will analyze more MAP3K SNPs along with rs889312, which may reveal more credible outcomes in terms of cancer prognosis.
Topics: Humans; Neoplasms; Polymorphism, Single Nucleotide; Prognosis; MAP Kinase Kinase Kinase 1
PubMed: 36560873
DOI: 10.1002/cnr2.1773 -
Pharmacogenomics Jul 2023Sirolimus is an antiproliferative and immunosuppressive compound inhibiting the mTOR pathway, which is often activated in congenital low-flow vascular malformations.... (Review)
Review
Sirolimus is an antiproliferative and immunosuppressive compound inhibiting the mTOR pathway, which is often activated in congenital low-flow vascular malformations. Studies have demonstrated the efficacy of sirolimus for this disease. Studies in kidney transplant patients suggest that genetic variants can influence these pharmacokinetic parameters. Therefore, a systematic literature search was performed to gain insight into pharmacogenetic studies with sirolimus. Most studies investigated and , with inconsistent results. No pharmacogenetic studies focusing on sirolimus have been performed for low-flow vascular malformations. We analyzed two common variants of and ( and , respectively) in patients (n = 59) with congenital low-flow vascular malformations treated with sirolimus. No association with treatment outcome was identified in this small cohort of patients.
Topics: Humans; Sirolimus; Cytochrome P-450 CYP3A; Polymorphism, Single Nucleotide; Immunosuppressive Agents; Kidney Transplantation; Tacrolimus; Genotype
PubMed: 37551646
DOI: 10.2217/pgs-2022-0147 -
Clinical Pharmacology and Therapeutics Apr 2022Polygenic scores (PGSs) have emerged as promising tools for complex trait risk prediction. The application of these scores to pharmacogenomics provides new opportunities...
Polygenic scores (PGSs) have emerged as promising tools for complex trait risk prediction. The application of these scores to pharmacogenomics provides new opportunities to improve the prediction of treatment outcomes. To gain insight into this area of research, we conducted a systematic review and accompanying analysis. This review uncovered 51 papers examining the use of PGSs for drug-related outcomes, with the majority of these papers focusing on the treatment of psychiatric disorders (n = 30). Due to difficulties in collecting large cohorts of uniformly treated patients, the majority of pharmacogenomic PGSs were derived from large-scale genome-wide association studies of disease phenotypes that were related to the pharmacogenomic phenotypes under investigation (e.g., schizophrenia-derived PGSs for antipsychotic response prediction). Examination of the research participants included in these studies revealed that the majority of cohort participants were of European descent (78.4%). These biases were also reflected in research affiliations, which were heavily weighted towards institutions located in Europe and North America, with no first or last authors originating from institutions in Africa or South Asia. There was also substantial variability in the methods used to develop PGSs, with between 3 and 6.6 million variants included in the PGSs. Finally, we observed significant inconsistencies in the reporting of PGS analyses and results, particularly in terms of risk model development and application, coupled with a lack of data transparency and availability, with only three pharmacogenomics PGSs deposited on the Polygenic Score Catalog. These findings highlight current gaps and key areas for future pharmacogenomic PGS research.
Topics: Genome-Wide Association Study; Humans; Multifactorial Inheritance; Pharmacogenetics; Phenotype; Schizophrenia
PubMed: 34953075
DOI: 10.1002/cpt.2520