ORCID Profile
0000-0001-6303-8696
Current Organisation
University of Calgary
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Wiley
Date: 11-10-2022
DOI: 10.1002/CPT.2748
Abstract: 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.
Publisher: Elsevier BV
Date: 08-2014
DOI: 10.1016/J.JAD.2014.04.044
Abstract: Genetic variation in the G-protein β3 subunit (GNB3) has previously been associated with gene splicing that has been further linked to increased signal transduction and major depressive disorder. However, the effect of GNB3 genetic variation on depressive symptom trajectories is currently unknown. The aim of the present study is to examine whether genetic variation in GNB3 moderates depressive symptom trajectories among 301 primary care attendees enrolled in the Diagnosis, Management and Outcomes of Depression in Primary Care (diamond) prospective cohort study. Depressive symptoms were assessed using three measures: (1) DSM-IV criteria, (2) Primary Care Evaluation of Mental Disorders Patient Health Questionnaire-9 (PHQ-9), and (3) Center for Epidemiologic Studies Depression Scale (CESD). DSM-IV criteria were measured at baseline, 24, 36, 48, and 60 months post-baseline, whereas, PHQ-9 and CESD measurements were taken at baseline, 12, 24, 36, 48, and 60 months post-baseline. Two haplotype-tagging single nucleotide polymorphisms [rs5443 (C825T) and rs5440] spanning the GNB3 gene including ~1Kb upstream and downstream of the gene boundaries were genotyped. Five-year PHQ-9 and CESD depressive symptom trajectories were moderated by rs5440. Carriers of the rs5440 GG genotype had more favourable depressive symptom trajectories compared to AG or AA genotype carriers. The rs5443 polymorphism did not moderate depressive symptom trajectories, regardless of the measure used. Generalizability to depressed populations outside of the primary care setting may be limited. These results provide novel evidence suggesting genetic variation in the 5-prime region of GNB3 moderates depressive symptom trajectories among primary care attendees.
Publisher: Springer Science and Business Media LLC
Date: 19-05-2023
DOI: 10.1186/S13063-023-07361-6
Abstract: The evidence for the clinical utility of pharmacogenomic (PGx) testing is growing, and guidelines exist for the use of PGx testing to inform prescribing of 13 antidepressants. Although previous randomised controlled trials of PGx testing for antidepressant prescribing have shown an association with remission of depression in clinical psychiatric settings, few trials have focused on the primary care setting, where most antidepressant prescribing occurs. The PRESIDE Trial is a stratified double-blinded randomised controlled superiority trial that aims to evaluate the impact of a PGx-informed antidepressant prescribing report (compared with standard prescribing using the Australian Therapeutic Guidelines) on depressive symptoms after 12 weeks, when delivered in primary care. Six hundred seventy-two patients aged 18–65 years of general practitioners (GPs) in Victoria with moderate to severe depressive symptoms, measured using the Patient Health Questionnaire-9 (PHQ-9), will be randomly allocated 1:1 to each arm using a computer-generated sequence. Participants and GPs will be blinded to the study arm. The primary outcome is a difference between arms in the change of depressive symptoms, measured using the PHQ-9 after 12 weeks. Secondary outcomes include a difference between the arms in change in PHQ-9 score at 4, 8 and 26 weeks, proportion in remission at 12 weeks, a change in side effect profile of antidepressant medications, adherence to antidepressant medications, change in quality of life and cost-effectiveness of the intervention. This trial will provide evidence as to whether PGx-informed antidepressant prescribing is clinically efficacious and cost-effective. It will inform national and international policy and guidelines about the use of PGx to select antidepressants for people with moderate to severe depressive symptoms presenting in primary care. Australian and New Zealand Clinical Trial Registry ACTRN12621000181808. Registered on 22 February 2021.
Publisher: Wiley
Date: 09-2013
DOI: 10.1002/HUP.2340
Abstract: The objective of this study is to investigate the influence of the 5-HTTLPR (serotonin transporter-linked promoter region), cytochrome P450 2C19, and cytochrome P450 2D6 polymorphisms on escitalopram (ESC) and venlafaxine (VEN) responses in major depressive disorder. A prospective multi-site study of 106 patients (Caucasian and Han Chinese ethnicities) with major depressive disorder treated with either ESC or VEN was conducted. The 17-item Hamilton Depression scale (HDRS), Clinical Global Impression Scale, and an adverse events scale (UKU) were assessed over 8 weeks, blind to genotype. At the 8-week end point, a significant HDRS reduction for both ESC and VEN occurred (p < 0.0001). The 5-HTTLPR l/l genotype was associated with significantly greater score reductions on the HDRS compared with s/s carriers (p = 0.016) among Caucasian subjects receiving ESC (n = 47). Response rates were significantly higher for l/l (92%) compared with l/s (61%) and s/s (46%) variants (p = 0.042). For every l allele a participant carried, there was a 3.33 (95% confidence interval 1.25, 8.84 p = 0.02) times greater odds of ESC response. No significant associations between any of the genotypes and adverse effects were found. Ethnicity may have differential effects on the 5-HTTLPR genotype-efficacy relationship. Results suggest that l/l allele for 5-HTTLPR is associated with a robust treatment response to ESC in Caucasian subjects only.
Publisher: Cambridge University Press (CUP)
Date: 25-08-2010
DOI: 10.1017/S1355617710000846
Abstract: Neuropsychological disturbances have been reported in association with use of the recreational drug “ecstasy,” or 3,4-methylenedioxymeth hetamine (MDMA), but findings have been inconsistent. We performed comprehensive neuropsychological testing examining seven ability domains in 21 MDMA users (MDMA+) and 21 matched control participants (MDMA−). Among MDMA+ participants, median [interquartile range] lifetime MDMA use was 186 [111, 516] doses, with 120 [35–365] days of abstinence. There were no significant group differences in neuropsychological performance, with the exception of the motor speed/dexterity domain in which 43% of MDMA+ were impaired compared with 5% of MDMA− participants ( p = .004). Motor impairment differences were not explained by use of other substances and were unrelated to length of abstinence or lifetime number of MDMA doses. Findings provide limited evidence for neuropsychological differences between MDMA+ and MDMA− participants with the exception of motor impairments observed in the MDMA+ group. However, replication of this finding in a larger s le is warranted. ( JINS , 2010, 16 , 1047–1055.)
Publisher: Hindawi Limited
Date: 2010
DOI: 10.1155/2010/678648
Abstract: Catechol-O-methyltransferease ( COMT ) metabolizes prefrontal cortex dopamine (DA), a neurotransmitter involved in executive behavior the Val158Met genotype has been linked to executive dysfunction, which might increase sexual risk behaviors favoring HIV transmission. Main and interaction effects of COMT genotype and executive functioning on sexual risk behavior were examined. 192 sexually active nonmonogamous men completed a sexual behavior questionnaire, executive functioning tests, and were genotyped using blood-derived DNA. Main effects for executive dysfunction but not COMT on number of sexual partners were observed. A COMT x executive dysfunction interaction was found for number of sexual partners and insertive anal sex, significant for carriers of the Met/Met and to a lesser extent Val/Met genotypes but not Val/Val carriers. In the context of HIV and meth hetamine dependence, dopaminergic overactivity in prefrontal cortex conferred by the Met/Met genotype appears to result in a liability for executive dysfunction and potentially associated risky sexual behavior.
Publisher: Springer Science and Business Media LLC
Date: 10-2010
Publisher: SAGE Publications
Date: 16-11-2022
Publisher: Elsevier BV
Date: 07-2005
DOI: 10.1016/J.ADDBEH.2004.10.006
Abstract: This study examined the frequency of substance use among 14- to 24-year-old homeless youth (N=113) recruited from two community drop-in centers and explored the relationship between substance use and hypothesized psychosocial predictors. Audio-computer-assisted self-interviewing (A-CASI) was used for assessment. Including alcohol and tobacco, the mean number of different drugs used was 3.55 for lifetime and 2.34 for the last 3 months. A three-block hierarchical multiple regression was conducted to determine potential predictors of overall drug use (the sum of all different drugs used) during the last 3 months. Block 1 included demographic variables, Block 2 included a parental monitoring variable, and Block 3 included peer and environmental variables derived from learning theories. Parental monitoring (-) and peer variables (+) predicted overall 3-month drug use. The final model explained 36% of the variance in overall drug use. Results suggest that homeless adolescent drug use exists at high levels and is related to parental monitoring and peer modeling of other risk behaviors. These results may inform future prevention strategies for homeless youth and other high-risk populations.
Publisher: Informa UK Limited
Date: 29-05-2017
Publisher: Georg Thieme Verlag KG
Date: 15-12-2021
DOI: 10.1055/A-1625-6388
Abstract: This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300-600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2013
Publisher: Informa UK Limited
Date: 2010
DOI: 10.2147/NBHIV.S8245
Publisher: Wiley
Date: 30-05-2023
DOI: 10.1002/CPT.2903
Abstract: Serotonin reuptake inhibitor antidepressants, including selective serotonin reuptake inhibitors (SSRIs i.e., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline), serotonin and norepinephrine reuptake inhibitors (i.e., desvenlafaxine, duloxetine, levomilnacipran, milnacipran, and venlafaxine), and serotonin modulators with SSRI‐like properties (i.e., vilazodone and vortioxetine) are primary pharmacologic treatments for major depressive and anxiety disorders. Genetic variation in CYP2D6 , CYP2C19 , and CYP2B6 influences the metabolism of many of these antidepressants, which may potentially affect dosing, efficacy, and tolerability. In addition, the pharmacodynamic genes SLC6A4 (serotonin transporter) and HTR2A (serotonin‐2A receptor) have been examined in relation to efficacy and side effect profiles of these drugs. This guideline updates and expands the 2015 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and SSRI dosing and summarizes the impact of CYP2D6 , CYP2C19 , CYP2B6 , SLC6A4 , and HTR2A genotypes on antidepressant dosing, efficacy, and tolerability. We provide recommendations for using CYP2D6 , CYP2C19 , and CYP2B6 genotype results to help inform prescribing these antidepressants and describe the existing data for SLC6A4 and HTR2A , which do not support their clinical use in antidepressant prescribing.
Publisher: EDITORA SCIENTIFIC
Date: 04-2020
Publisher: Wiley
Date: 15-06-2010
DOI: 10.1002/AJMG.B.31106
Publisher: Research Square Platform LLC
Date: 18-11-2022
DOI: 10.21203/RS.3.RS-2241794/V1
Abstract: Despite loss of grey matter volume and emergence of distinct cognitive deficits in young adults diagnosed with schizophrenia, current treatments for schizophrenia do not target disruptions in late maturational reshaping of the prefrontal cortex. Iron, the most abundant transition metal in the brain, is essential to brain development and function, but in excess, it can impair major neurotransmission systems and lead to lipid peroxidation, neuroinflammation and accelerated aging. However, analysis of cortical iron biology in schizophrenia has not been reported in modern literature. Using a combination of inductively coupled plasma-mass spectrometry and western blots, we quantified iron and its major-storage protein, ferritin, in post-mortem prefrontal cortex specimens obtained from three independent, well-characterised brain tissue resources. Compared to matched controls (n=85), among schizophrenia cases (n=86) we found elevated tissue iron, unlikely to be confounded by demographic and lifestyle variables, by duration, dose and type of antipsychotic medications used or by copper levels. We further observed a loss of physiologic age-dependent iron accumulation among people with schizophrenia, in that iron level among cases was already high in young adulthood. Ferritin, which stores iron in a redox-inactive form, was paradoxically decreased in in iduals with the disorder. Such iron-ferritin uncoupling would lead to more free, chemically reactive, tissue iron in key reasoning and planning areas of the young-adult schizophrenia cortex. Using a prediction model based on iron and ferritin, our data provide a pathophysiologic link between perturbed cortical iron biology and schizophrenia and indicate that achievement of optimal cortical iron homeostasis could offer a new therapeutic target.
Publisher: Wiley
Date: 06-03-2023
DOI: 10.1002/CPT.2854
Abstract: The P‐glycoprotein efflux pump, encoded by the ABCB1 gene, has been shown to alter concentrations of various antidepressants in the brain. In this study, we conducted a systematic review and meta‐analysis to investigate the association between six ABCB1 single‐nucleotide polymorphisms (SNPs rs1045642, rs2032582, rs1128503, rs2032583, rs2235015, and rs2235040) and antidepressant treatment outcomes in in iduals with major depressive disorder (MDD), including new data from the Canadian Biomarker and Integration Network for Depression (CAN‐BIND‐1) cohort. For the CAN‐BIND‐1 s le, we applied regression models to investigate the association between ABCB1 SNPs and antidepressant treatment response, remission, tolerability, and antidepressant serum levels. For the meta‐analysis, we systematically summarized pharmacogenetic evidence of the association between ABCB1 SNPs and antidepressant treatment outcomes. Studies were included in the meta‐analysis if they investigated at least one ABCB1 SNP in in iduals with MDD treated with at least one antidepressant. We did not find a significant association between ABCB1 SNPs and antidepressant treatment outcomes in the CAN‐BIND‐1 s le. A total of 39 studies were included in the systematic review. In the meta‐analysis, we observed a significant association between rs1128503 and treatment response (T vs. C‐allele, odds ratio = 1.30, 95% confidence interval = 1.15–1.48, P value (adjusted) = 0.024, n = 2,526). We did not find associations among the six SNPs and treatment remission nor tolerability. Our findings provide limited evidence for an association between common ABCB1 SNPs and antidepressant outcomes, which do not support the implementation of ABCB1 genotyping to inform antidepressant treatment at this time. Future research, especially on rs1128503, is recommended.
Publisher: Wiley
Date: 13-02-2009
DOI: 10.1002/AJMG.B.30936
Abstract: Efforts to understand the biological processes that increase susceptibility to meth hetamine (METH) use disorders (i.e., abuse, dependence, and psychosis) have uncovered several putative genotypic variants. However, to date a synthesis of this information has not been conducted. Thus, systematic searches of the current literature were undertaken for genetic-association studies of METH use disorders. Each gene's chromosomal location, function, and examined polymorphic markers were extracted. Frequencies, odds ratios and 95% confidence intervals for risk alleles, as well as s le size and power, were calculated. We uncovered 38 studies examining 39 genes, of which 18 were found to have a significant genotypic, allelic, and/or haplotypic association with METH use disorders. Three genes (COMT, DRD4, and GABRA1) were associated with METH abuse, nine (ARRB2, BDNF, CYP2D6, GLYT1, GSTM1, GSTP1, PDYN, PICK1, and SLC22A3) with METH dependence, two (AKT1 and GABRG2) with METH abuse/dependence, and four (DTNBP1, OPRM1, SNCA, and SOD2) with METH psychosis. Limitations related to phenotypic classification, statistical power, and potential publication bias in the current literature were noted. Similar to other behavioral, psychiatric, and substance use disorders, the genetic epidemiology of METH use disorders is complex and likely polygenic. National and international collaborative efforts are needed to increase the availability of large population-based s les and improve upon the power to detect genetic associations of small magnitude. Further, replication of the findings reviewed here along with further development of more rigorous methodologies and reporting protocols will aid in delineating the complex genetic epidemiology of METH use disorders.
Publisher: MDPI AG
Date: 22-01-2023
Abstract: Caffeine is the most consumed drug in the world, and it is commonly used by children. Despite being considered relatively safe, caffeine can have marked effects on sleep. Studies in adults suggest that genetic variants in the adenosine A2A receptor (ADORA2A, rs5751876) and cytochrome P450 1A (CYP1A, rs2472297, rs762551) loci are correlated with caffeine-associated sleep disturbances and caffeine intake (dose), but these associations have not been assessed in children. We examined the independent and interaction effects of daily caffeine dose and candidate variants in ADORA2A and CYP1A on the sleep quality and duration in 6112 children aged 9–10 years who used caffeine and were enrolled in the Adolescent Brain Cognitive Development (ABCD) study. We found that children with higher daily caffeine doses had lower odds of reporting 9 h of sleep per night (OR = 0.81, 95% CI = 0.74–0.88, and p = 1.2 × 10−6). For every mg/kg/day of caffeine consumed, there was a 19% (95% CI = 12–26%) decrease in the odds of children reporting 9 h of sleep. However, neither ADORA2A nor CYP1A genetic variants were associated with sleep quality, duration, or caffeine dose. Likewise, genotype by caffeine dose interactions were not detected. Our findings suggest that a daily caffeine dose has a clear negative correlation with sleep duration in children, but this association is not moderated by the ADORA2A or CYP1A genetic variation.
Publisher: Springer Science and Business Media LLC
Date: 07-04-2022
DOI: 10.1038/S41398-022-01884-3
Abstract: Clozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia. However, response is highly variable and possible genetic underpinnings of this variability remain unknown. Here, we performed polygenic risk score (PRS) analyses to estimate the amount of variance in symptom severity among clozapine-treated patients explained by PRSs (R2) and examined the association between symptom severity and genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activity. Genome-wide association (GWA) analyses were performed to explore loci associated with symptom severity. A multicenter cohort of 804 patients (after quality control N = 684) with schizophrenia spectrum disorder treated with clozapine were cross-sectionally assessed using the Positive and Negative Syndrome Scale and/or the Clinical Global Impression-Severity (CGI-S) scale. GWA and PRS regression analyses were conducted. Genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activities were calculated. Schizophrenia-PRS was most significantly and positively associated with low symptom severity ( p = 1.03 × 10 −3 R2 = 1.85). Cross-disorder-PRS was also positively associated with lower CGI-S score ( p = 0.01 R2 = 0.81). Compared to the lowest tertile, patients in the highest schizophrenia-PRS tertile had 1.94 times ( p = 6.84×10 −4 ) increased probability of low symptom severity. Higher genotype-predicted CYP2C19 enzyme activity was independently associated with lower symptom severity ( p = 8.44×10 −3 ). While no locus surpassed the genome-wide significance threshold, rs1923778 within NFIB showed a suggestive association ( p = 3.78×10 −7 ) with symptom severity. We show that high schizophrenia-PRS and genotype-predicted CYP2C19 enzyme activity are independently associated with lower symptom severity among in iduals treated with clozapine. Our findings open avenues for future pharmacogenomic projects investigating the potential of PRS and genotype-predicted CYP - activity in schizophrenia.
Publisher: Elsevier BV
Date: 06-2021
Publisher: Springer Science and Business Media LLC
Date: 07-02-2023
DOI: 10.1038/S41380-023-01979-3
Abstract: Despite loss of grey matter volume and emergence of distinct cognitive deficits in young adults diagnosed with schizophrenia, current treatments for schizophrenia do not target disruptions in late maturational reshaping of the prefrontal cortex. Iron, the most abundant transition metal in the brain, is essential to brain development and function, but in excess, it can impair major neurotransmission systems and lead to lipid peroxidation, neuroinflammation and accelerated aging. However, analysis of cortical iron biology in schizophrenia has not been reported in modern literature. Using a combination of inductively coupled plasma-mass spectrometry and western blots, we quantified iron and its major-storage protein, ferritin, in post-mortem prefrontal cortex specimens obtained from three independent, well-characterised brain tissue resources. Compared to matched controls ( n = 85), among schizophrenia cases ( n = 86) we found elevated tissue iron, unlikely to be confounded by demographic and lifestyle variables, by duration, dose and type of antipsychotic medications used or by copper and zinc levels. We further observed a loss of physiologic age-dependent iron accumulation among people with schizophrenia, in that the iron level among cases was already high in young adulthood. Ferritin, which stores iron in a redox-inactive form, was paradoxically decreased in in iduals with the disorder. Such iron-ferritin uncoupling could alter free, chemically reactive, tissue iron in key reasoning and planning areas of the young-adult schizophrenia cortex. Using a prediction model based on iron and ferritin, our data provide a pathophysiologic link between perturbed cortical iron biology and schizophrenia and indicate that achievement of optimal cortical iron homeostasis could offer a new therapeutic target.
Publisher: MDPI AG
Date: 16-10-2023
Publisher: Bentham Science Publishers Ltd.
Date: 14-05-2010
DOI: 10.2174/1874613601004030105
Abstract: Meth hetamine is a major contributor to HIV transmission among men who have sex with men (MSM). Recent studies show that up to one-third of meth hetamine-using MSM (MUMSM) inject the drug. We developed a behavioral intervention for MUMSM to decrease unprotected anal intercourse and increase awareness of parenteral HIV transmission risk. This 6-session (3 in-person, 3 by telephone) modular intervention was designed to be tailored to participants’ HIV (+/-) and injection drug user ([IDU] yes/no) status. We present results of formative research used to evaluate the content and to assess feasibility and acceptability of this in idual-level HIV risk-reduction intervention. HIV research clinic in a high MSM and meth hetamine prevalence neighborhood. Avoiding Risks from Meth hetamine-Use (ARM-U) is a brief toolbox intervention that allows counselors to select modules that suit a client’s in idual risk profile and intervention needs employing motivational interviewing and cognitive behavioral theory. We evaluated the format and content of the intervention through focus groups and pre-testing of the entire intervention using volunteers from the target population stratified into four groups (HIV+/IDU, HIV-/IDU, HIV+/non-IDU, HIV-/non-IDU). Four in iduals in each stratum were recruited to undergo the intervention and complete a satisfaction survey at the end of each in-person session. In total, 25 MUMSM attended one of five focus groups. Participants thought all proposed intervention topics were important and could aid in reducing sexual risk behaviors among MUMSM. However, the neurocognitive effects of meth hetamine were reported to be a barrier to practicing safer sex, condom use negotiation or HIV status disclosure. Fifteen (94%) of 16 participants completed all 6 sessions and the satisfaction survey. On average, participants felt the intervention was useful for MUMSM, made them contemplate and move toward behavior change, and would recommend the program to their peers. Based on our formative research, we revised the ARM-U intervention to emphasize pre-planning to avoid combining meth hetamine use and sex or develop strategies to avoid sex risk following meth hetamine use. We also increased emphasis on referrals for care and other requested services. Future efficacy trials are needed to evaluate the intervention’s ability to reduce HIV-associated risk behaviors.
Publisher: Springer Science and Business Media LLC
Date: 14-04-2011
Publisher: Wiley
Date: 15-12-2011
Publisher: SAGE Publications
Date: 19-05-2020
Publisher: Springer Science and Business Media LLC
Date: 27-11-2012
DOI: 10.1038/TP.2012.115
Publisher: Informa UK Limited
Date: 07-2010
DOI: 10.2147/NBHIV.S12354
Publisher: Cambridge University Press (CUP)
Date: 29-09-2023
Publisher: Frontiers Media SA
Date: 2013
Publisher: Elsevier BV
Date: 07-2010
Publisher: Wiley
Date: 06-0011
DOI: 10.1002/PCN5.26
Abstract: Pharmacogenetic (PGx) testing has emerged as a tool for predicting a person's ability to process and react to drugs. Despite the growing evidence‐base, enthusiasm, and successful efforts to implement PGx testing in psychiatry, a consensus on how best to implement PGx testing into practice has not been established and numerous hurdles to widespread adoption remain to be overcome. In this article, we summarize the most used approaches and commonly encountered hurdles when implementing PGx testing into routine psychiatric care. We also highlight effective strategies that have been used to overcome hurdles. These strategies include the development of user‐friendly clinical workflows for test ordering, use, and communication of results, establishment of test standardization and reimbursement policies, and development of tailored curriculums for educating health‐care providers and the public. Although knowledge and awareness of these approaches and strategies to overcome hurdles alone may not be sufficient for successful implementation, they are necessary to ensure the effective spread, scale, and sustainability of PGx testing in psychiatry and other areas of medicine.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2010
Publisher: SAGE Publications
Date: 23-10-2023
Abstract: Services for homeless youth traditionally provided shelter and nourishment but do little to break the cycle of homelessness. A more comprehensive approach to serve homeless youth is the drop-in center model that provides safe and easy-to-find facilities within communities to bridge the gap between the streets and transitional ermanent housing. Research describing homeless youth who utilize drop-in centers is lacking. This study examines characteristics/ preferences of 96 homeless adolescents attending one of two drop-in centers in Southern California. Homeless youth reported high prevalence of risk behaviors regardless of the center of attendance. Furthermore, our analyses revealed significant differences related to demographics, sexual risk behaviors, and substance use between homeless youth at the two drop-in centers. These findings illuminate the specific characteristics and preferences of homeless youth who attend drop-in centers and can be used to inform providers, advocates, and policy makers.
Publisher: Wiley
Date: 04-10-2014
DOI: 10.1002/AJMG.B.32206
Abstract: A better understanding of the factors associated with psychotic symptoms could aid early identification and treatment of psychotic disorders. Previous studies have typically utilized cross-sectional study designs and have focused on in iduals with psychotic disorders. Thus, examination of promising correlates of psychotic symptoms using longitudinal designs among more broadly defined populations is warranted. Two such correlates are neuregulin-1 (NRG1) genotypic variation and depression symptom severity. Both NRG1 and depression symptom severity have cross-sectional evidence for an association with psychosis but their affect on longitudinal patterns of psychotic symptoms and their potential interaction effects are less clear. Using repeated measures analysis of variance and covariance we modeled the main and interaction effects of NRG1 genotypic variation and depressive symptom severity on longitudinal psychotic symptom patterns in 301 primary care attendees assessed annually over 4 years. One-fifth (19.9%) of the participants reported one or more psychotic symptoms over the 4-year assessment period. We observed a curvilinear (i.e., cubic) association between depression symptom severity at baseline and longitudinal patterns of psychotic symptoms but did not observe a main effect for NRG1 genotypic variation on psychotic symptom patterns. However, NRG1 rs6994992 genotype moderated the curvilinear association between depression symptom severity and psychotic symptom patterns. Specifically, depression symptom severity had less of an effect on longitudinal psychotic symptoms among carriers of the rs6994992 TT genotype compared to CC and CT carriers. Our findings suggest a curvilinear association between depression symptom severity and longitudinal patterns of psychotic symptoms that is moderated by NRG1 genotype.
Publisher: MDPI AG
Date: 22-09-2023
Publisher: Wiley
Date: 04-10-2014
DOI: 10.1002/AJMG.B.32209
Abstract: Methylenetetrahydrofolate reductase (MTHFR) genetic variation has been associated with the diagnosis of major depressive disorder (MDD) but no study to date has examined the effect MTHFR variation has on MDD prognosis. We sought to examine the prospective effects of two common MTHFR variants (C677T and A1298C) as well as seven haplotype-tagging single nucleotide polymorphisms (htSNPs) on MDD prognosis over a 5-year (60-month) period. Participants were 147 depressed primary care attendees enrolled in the Diagnosis, Management and Outcomes of Depression in Primary Care (diamond) prospective cohort study. Prognosis of MDD was measured using three methods: (1) DSM-IV criteria, (2) Primary Care Evaluation of Mental Disorders Patient Health Questionnaire-9 (PHQ-9), and (3) Center for Epidemiologic Studies Depression Scale (CESD). DSM-IV criteria for MDD was assessed using the Composite International Diagnostic Interview at baseline and 24, 36, 48, and 60 months post-baseline whereas, PHQ-9 and CESD measures were employed at baseline and 12, 24, 36, 48, and 60 months post-baseline. Repeated measures analysis of variance showed that PHQ-9 symptom severity trajectories differed by C677T genotype (F = 3.34, df = 2,144, P = 0.038), with 677CC genotype showing the most severe symptom severity course over the 60 months of observation. Neither the A1298C polymorphism nor any of the htSNPs were associated with MDD prognosis regardless of measure used. Our results suggest that the MTHFR C677T polymorphism may serve as a marker for MDD prognosis pending independent replication.
Publisher: Elsevier BV
Date: 12-2011
Publisher: Research Square Platform LLC
Date: 17-08-2021
DOI: 10.21203/RS.3.RS-123677/V1
Abstract: There are some data associating variants in the CYP2D6 and/or CYP2C19 genes with concentration-to-dose ratios, efficacy, and retention in treatments. However, much of the above arises from relatively small studies or large datasets with limited genotyping methodologies. Our aim was to develop and validate comprehensive and accurate genotyping methodology for these two genes to facilitate regenotyping in large datasets and hence the generation of more accurate clinical associations. TaqMan copy number variant (CNV) assays for CYP2D6 were used to identify s les from a relevant large dataset (GENDEP study, N = 853) with particularly challenging genotypes to call. These and those representing as broad a range of CYP2D6 and CYP2C19 genotypes as possible by prior available data (AmpliChip CYP450 and TaqMan CYP2C19*17 ) were chosen for further analysis (N = 96). Genotyping techniques employed were: Luminex CYP2D6 xTAGv3 and Luminex CYP2C19 xTAGv3, PharmacoScan, the Ion S5 AmpliSeq Pharmacogenomics Panel, TaqMan single nucleotide variant (SNV) assays, and, for the CYP2D6 hybrids, long-range polymerase chain reactions (L-PCRs) with Sanger sequencing. Agena was also used for CYP2C19 . The TaqMan SNV assays were able to assist with identifying which gene was duplicated or in tandem for multiple copy variants. A multiplex assay was adaptable for analysis of CYP2D6 hybrid genes, with Sanger sequencing data being consistent with the data arising we provide these data for efficient genotyping of such CYP2D6 hybrid genes with adaptable multiplex methods. Consensus genotypes generated to date resulted in revision of assigned enzyme activity score for 28/96(29%) and 2/93 s les (2.2%) for CYP2D6 and CYP2C19, respectively.
Publisher: S. Karger AG
Date: 2012
DOI: 10.1159/000341879
Abstract: b i Objective: /i /b To prospectively examine the influence of the oestrogen-α receptor i (ESR1) /i i Pvu /i II polymorphism on changes in memory performance over a 2-year period among 80 midlife postmenopausal Australian women. b i Methods: /i /b Healthy women aged 56–67 years were administered a battery of four memory (verbal and non-verbal) tasks at baseline and 2 years later. b i Results: /i /b Carriers of the i ESR1 /i p allele had significantly greater declines in logical memory compared to participants with the PP genotype, independent of demographic characteristics (e.g. age), chronic illness (e.g. hypertension), sleep aid usage, hormone levels, apolipoprotein E e4 status and prospective changes in mood, smoking and alcohol consumption. b i Conclusion: /i /b These findings provide preliminary evidence for larger and longer prospective trials that will be able to determine if the p allele of the i ESR1 /i i Pvu /i II polymorphism is a potential biomarker of logical memory decline among aging women.
Publisher: Future Medicine Ltd
Date: 10-2022
Abstract: Pharmacogenomic (PGx) testing of cytochrome P450 (CYP) enzymes may improve the efficacy and/or safety of some medications. This is facilitated by increased availability and affordability of genotyping, the development of clinical practice PGx guidelines and regulatory support. However, the common occurrence of CYP phenoconversion, a mismatch between genotype-predicted CYP phenotype and the actual CYP phenotype, currently limits the application of PGx testing for precision dosing in psychiatry. This review proposes a stepwise approach to assist precision dosing in psychiatry via the introduction of PGx stewardship programs and innovative PGx education strategies. A future perspective on delivering precision dosing for psychiatrists is discussed that involves innovative clinical decision support systems powered by model-informed precision dosing.
Publisher: SAGE Publications
Date: 26-11-2013
Abstract: Concerns have emerged that initiation of an antidepressant can lead to or exacerbate suicidality. If those more at risk could be identified prior to treatment, treatment risk benefit analysis and patient risk management could be assisted. This study investigated the role of child abuse and ongoing emotional impact from abuse on the risk of suicidality during the first week of treatment with an antidepressant. The patient s le for this study was drawn from one site of a larger pharmacogenetic study. The hypothesis was that subjects with high impact child abuse would have greater elevation of suicidality during the first week of antidepressant treatment. Fifty-one subjects were initiated on either venlafaxine (VEN) or escitalopram (ESC) for major depressive disorder (MDD) and had pre-treatment suicidality assayed with the reasons for living scale (RFLS), which was repeated after one week of treatment. Several clinical, demographic and genotype variables were controlled for. The 15-item Impact of Event Scale (IES-15) was administered to subjects reporting abuse to dichotomise the abuse group into low and high (IES-15 ≥ 26) impact groups for sub-analysis as per the scales validated rating guidelines. Subjects reporting no child abuse exposure were less likely to have increased suicidality during the first week of antidepressant treatment (7.6%) compared to subjects with low impact abuse (38.5%, p = 0.041) and high impact abuse (58.3%, p = 0.009). Only high impact abuse predicted increased suicidality after adjustment for potential confounders such as depression severity (OR = 31.5, 95% CI = 1.3 to 748.7, p = 0.03). If these findings are replicated in larger s les, child abuse history could become an important element of assessing risk benefit balance when initiating antidepressants and may help guide the level of patient review needed during antidepressant initiation.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2014
Publisher: SAGE Publications
Date: 17-02-2020
Abstract: To identify and assess pharmacogenetic testing options relevant to psychiatry in Canada. Searches of published literature, websites, and Standard Council of Canada’s Laboratory Directory were conducted to identify pharmacogenetic tests available in Canada. Identified tests were assessed on 8 key questions related to analytical validity, accessibility, test ordering, delivery of test results, turnaround time, cost, clinical trial evidence, and gene/allele content. A total of 13 pharmacogenetic tests relevant to psychiatry in Canada were identified. All tests were highly accessible, and most were conducted in accredited laboratories. Both direct-to-consumer and clinician-gated testing were identified, with turnaround times and cost ranging from 2 to 40 days and CAD$199 to CAD$2310, respectively. Two tests were supported by randomized controlled trials. All tests met minimum gene and allele panel recommendations for psychiatry, but no 2 panels were identical. No test was unequivocally superior to all other tests. Pharmacogenetic testing in Canada is readily available but highly variable in terms of ordering procedures, delivery of results, turnaround times, cost, and gene/allele content. As such, it is important for psychiatrists and other health-care providers to understand the differences between the available tests to ensure appropriate selection and implementation within their practice.
Publisher: MDPI AG
Date: 30-06-2023
DOI: 10.3390/JPM13071086
Abstract: 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.
Publisher: Elsevier BV
Date: 07-2021
DOI: 10.1016/J.BBI.2021.04.002
Abstract: Deficits in brain morphology are one of the most widely replicated neuropathological features in schizophrenia-spectrum disorder (SSD), although their biological underpinnings remain unclear. Despite the existence of hypotheses by which peripheral inflammation may impact brain structure, few studies have examined this relationship in SSD. This study aimed to establish the relationship between peripheral markers of inflammation and brain morphology and determine whether such relationships differed across healthy controls and in iduals with first episode psychosis (FEP) and chronic schizophrenia. A panel of 13 pro- and anti-inflammatory cytokines were quantified from serum in 175 participants [n = 84 Healthy Controls (HC), n = 40 FEP, n = 51 Chronic SCZ]. We first performed a series of permutation tests to identify the cytokines most consistently associated with brain structural regions. Using moderation analysis, we then determined the extent to which in idual variation in select cytokines, and their interaction with diagnostic status, predicted variation in brain structure. We found significant interactions between cytokine level and diagnosis on brain structure. Diagnostic status significantly moderated the relationship of IFNγ, IL4, IL5 and IL13 with frontal thickness, and of IFNγ and IL5 and total cortical volume. Specifically, frontal thickness was positively associated with IFNγ, IL4, IL5 and IL13 cytokine levels in the healthy control group, whereas pro-inflammatory cytokines IFNγ and IL5 were associated with lower total cortical volume in the FEP group. Our findings suggest that while there were no relationships detected in chronic schizophrenia, the relationship between peripheral inflammatory markers and select brain regions are differentially impacted in FEP and healthy controls. Longitudinal investigations are required to determine whether the relationship between brain structure and peripheral inflammation changes over time.
Publisher: Springer Science and Business Media LLC
Date: 30-04-2013
DOI: 10.1038/TP.2013.23
Publisher: Hindawi Limited
Date: 2013
DOI: 10.1155/2013/852930
Abstract: Genes in the Wnt (wingless)/ β -catenin signaling pathway have been implicated in schizophrenia pathogenesis. No study has examined this pathway in the broader context of psychosis symptom severity. We investigated the association between symptom severity scores and expression of 25 Wnt pathway genes in blood from 19 psychotic patients. Significant correlations between negative symptom scores and deshivelled 2 (DVL2) ( r adj = − 0 .70 P = 0 .0008 ) and glycogen synthase kinase 3 beta (GSK3B) ( r adj = 0 .48 P = 0 .039 ) were observed. No gene expression levels were associated with positive symptoms. Our findings suggest that the Wnt signaling pathway may harbor biomarkers for severity of negative but not positive symptoms.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2013
Publisher: OMICS Publishing Group
Date: 2011
Publisher: MDPI AG
Date: 28-10-2023
DOI: 10.3390/NU15214586
Publisher: Springer Science and Business Media LLC
Date: 25-01-2011
Publisher: Wiley
Date: 18-02-2010
DOI: 10.1002/AJMG.B.31006
Publisher: Wiley
Date: 05-01-2012
DOI: 10.1002/AJMG.B.32019
Publisher: Cambridge University Press (CUP)
Date: 23-08-2010
DOI: 10.1017/S1355617710000779
Abstract: While neuropsychological deficits are evident among meth hetamine (meth) addicts, they are often unrelated to meth exposure parameters such as lifetime consumption and length of abstinence. The notion that some meth users develop neuropsychological impairments while others with similar drug exposure do not, suggests that there may be in idual differences in vulnerability to the neurotoxic effects of meth. One source of differential vulnerability could come from genotypic variability in metabolic clearance of meth, dependent on the activity of cytochrome P450-2D6 (CYP2D6). We compared neuropsychological performance in 52 in iduals with a history of meth dependence according with their CYP2D6 phenotype. All were free of HIV or hepatitis C infection and did not meet dependence criteria for other substances. Extensive metabolizers showed worse overall neuropsychological performance and were three times as likely to be cognitively impaired as intermediate oor metabolizers. Groups did not differ in their demographic or meth use characteristics, nor did they evidence differences in mood disorder or other substance use. This preliminary study is the first to suggest that efficient meth metabolism is associated with worse neurocognitive outcomes in humans, and implicates the products of oxidative metabolism of meth as a possible source of brain injury. ( JINS , 2010, 16 , 890–901.)
Publisher: Elsevier BV
Date: 10-2007
Publisher: Cold Spring Harbor Laboratory
Date: 29-07-2021
DOI: 10.1101/2021.07.26.21261157
Abstract: One of the concerns limiting the use of clozapine in schizophrenia treatment is the risk of rare but potentially fatal myocarditis. Our previous genome-wide association study and human leucocyte antigen analyses identified putative loci associated with clozapine-induced myocarditis. However, the contribution of DNA variation in cytochrome P450 genes, copy number variants and rare deleterious variants have not been investigated. We explored these unexplored classes of DNA variation using whole-genome sequencing data from 25 cases with clozapine-induced myocarditis and 25 demographically-matched clozapine-tolerant control subjects. We identified 15 genes based on rare variant gene-burden analysis ( MLLT6, CADPS, TACC2, L3MBTL4, NPY, SLC25A21, PARVB, GPR179, ACAD9, NOL8, C5orf33, FAM127A, AFDN, SLC6A11, PXDN) nominally associated (p .05) with clozapine-induced myocarditis. Of these genes, 13 were expressed in human myocardial tissue. Although independent replication of these findings is required, our study provides preliminary insights into the potential role of rare genetic variants in susceptibility to clozapine-induced myocarditis.
Publisher: Wiley
Date: 24-01-2013
DOI: 10.1002/PTR.4916
Abstract: Presently, little is known about a number issues concerning kava (Piper methysticum), including (i) whether kava has any withdrawal or addictive effects (ii) if genetic polymorphisms of the cytochrome (CYP) P450 2D6 liver enzyme moderates any potential adverse effects and (iii) if medicinal application of kava has any negative or beneficial effect on sexual function and experience. The study design was a 6-week, double-blind, randomized controlled trial (n = 75) involving chronic administration of kava (one tablet of kava twice per day 120 mg of kavalactones per day, titrated in non-response to two tablets of kava twice per day 240 mg of kavalactones) or placebo for participants with generalized anxiety disorder. Results showed no significant differences across groups for liver function tests, nor were there any significant adverse reactions that could be attributed to kava. No differences in withdrawal or addiction were found between groups. Interesting, kava significantly increased female's sexual drive compared to placebo (p = 0.040) on a sub-domain of the Arizona Sexual Experience Scale (ASEX), with no negative effects seen in males. Further, it was found that there was a highly significant correlation between ASEX reduction (improved sexual function and performance) and anxiety reduction in the whole s le.
Publisher: Wiley
Date: 28-09-2023
DOI: 10.1002/CPT.3044
Publisher: MDPI AG
Date: 26-10-2022
Abstract: Background: Despite evidence of clinical utility and the availability of prescription guidelines, pharmacogenomics (PGx) is not broadly used in institutional settings in Canada. To inform future implementation, this study aimed to identify healthcare provider knowledge, experience, and perceptions of PGx in Alberta, Canada. Methods: An online 44-item survey was distributed to pharmacists, nurse practitioners, and physicians employed or contracted with Alberta Health Services from January to May 2022. Questions included: demographics, professional history, PGx education and exposure, knowledge, and ability to use PGx, and attitudes towards, feasibility, clinical utility, education, and implementation. Results: Ninety-one pharmacists, 37 nurse practitioners, and 6 physicians completed the survey. Fifty-nine percent had 10 or more years of experience, and 71% practiced in urban settings. Only one-third had training in PGx, and one-quarter had used PGx. Most respondents (63%) had no knowledge of PGx resources, including the Pharmacogenomics Knowledge Base (75%), or the Clinical Pharmacogenetics Implementation Consortium guidelines (85%). While participants agreed that they understood genetic (75%) and PGx (63%) concepts, most disagreed with their ability regarding practical applications of PGx such as translating genotype to phenotype (74%) or counselling patients on results (66%). Participants agreed on the clinical utility of PGx in preventing adverse drug reactions (80%) and enhancing medication efficacy (77%), and identified oncology (62%), cardiovascular/stroke (60%), and psychiatry (56%) as therapeutic areas to consider implementation. At present, healthcare provider knowledge (87%), cost (81%), and limited guidelines/evidence (70%) are seen as the greatest barriers to implementation. Conclusion: Alberta healthcare providers have limited training, experience, or knowledge in PGx. However, most appear to have a positive outlook regarding clinical utility, especially within oncology, cardiology, and psychiatry. More effort is required to socialize the availability and quality of evidence and guidelines for the interpretation of PGx test results, address other knowledge gaps, and improve financial limitations.
Publisher: Georg Thieme Verlag KG
Date: 20-01-2022
DOI: 10.1055/A-1737-1527
Publisher: Wiley
Date: 07-02-2012
DOI: 10.1002/HUP.2216
Abstract: Kava (Piper methysticum) is a psychotropic plant medicine with history of cultural and medicinal use. We conducted a study comparing the acute neurocognitive, anxiolytic, and thymoleptic effects of a medicinal dose of kava to a benzodiazepine and explored for the first time specific genetic polymorphisms, which may affect the psychotropic activity of phytomedicines or benzodiazepines. Twenty-two moderately anxious adults aged between 18 and 65 years were randomized to receive an acute dose of kava (180 mg of kavalactones), oxazepam (30 mg), and placebo 1 week apart in a crossover design trial. After exposure to cognitive tasks, a significant interaction was revealed between conditions on State-Trait Anxiety Inventory-State anxiety (p = 0.046, partial ŋ² = 0.14). In the oxazepam condition, there was a significant reduction in anxiety (p = 0.035), whereas there was no change in anxiety in the kava condition, and there was an increase in anxiety in the placebo condition. An increase in Bond-Lader "calmness" (p = 0.002) also occurred for the oxazepam condition. Kava was found to have no negative effect on cognition, whereas a reduction in alertness (p < 0.001) occurred in the oxazepam condition. Genetic analyses provide tentative evidence that noradrenaline (SLC6A2) transporter polymorphisms may have an effect on response to kava. Acute "medicinal level" doses of this particular kava cultivar in naive users do not provide anxiolytic activity, although the phytomedicine also appears to have no negative effects on cognition.
Publisher: Springer Netherlands
Date: 2011
Publisher: SAGE Publications
Date: 03-05-2023
DOI: 10.1177/00912174221084818
Abstract: The COVID-19 pandemic has negatively impacted the general population in all aspects of life. Estimates of mental health medication dispensing in Alberta were investigated to elucidate areas of need within mental health and pharmacy practice during the pandemic. We employed an interrupted time series analysis using linear regression models to estimate community and outpatient medication dispensing trends of 46 medications used to treat mental health disorders. Three parameters were examined. The first was the medication dispensing slope before COVID-19. The second was the immediate effect of COVID-19 on dispensing (i.e., the difference in dispensing rate between the month before and after the first case of COVID-19) and the third was the medication dispensing slope during COVID-19. Dispensing rates of 61% ( n = 34) of the examined medications remained similar before and during the COVID-19 pandemic. However, eight medications (i.e., amitriptyline, escitalopram, fluoxetine, paroxetine, bupropion, desvenlafaxine, venlafaxine, and oxazepam) showed an immediate and significant increase in dispensing rate following the onset of the pandemic that was sustained over the first 13-months of the pandemic. Initial increases in dispensing patterns of antidepressants may be attributed to a “stockpiling phenomenon” but the sustained higher levels of dispensing suggest an unfavorable shift in the population’s mental health. Monitoring of medication dispensing patterns during COVID-19 may serve as a useful indicator of the population’s mental health during the current pandemic and better prepare community pharmacists in future pandemic planning, medication dispensing strategies, and care of chronic medical conditions.
Publisher: Springer Science and Business Media LLC
Date: 14-09-2023
Publisher: Springer Science and Business Media LLC
Date: 23-04-2022
DOI: 10.1038/S41397-022-00271-X
Abstract: One of the concerns limiting the use of clozapine in schizophrenia treatment is the risk of rare but potentially fatal myocarditis. Our previous genome-wide association study and human leucocyte antigen analyses identified putative loci associated with clozapine-induced myocarditis. However, the contribution of DNA variation in cytochrome P450 genes, copy number variants and rare deleterious variants have not been investigated. We explored these unexplored classes of DNA variation using whole-genome sequencing data from 25 cases with clozapine-induced myocarditis and 25 demographically-matched clozapine-tolerant control subjects. We identified 15 genes based on rare variant gene-burden analysis (MLLT6, CADPS, TACC2, L3MBTL4, NPY, SLC25A21, PARVB, GPR179, ACAD9, NOL8, C5orf33, FAM127A, AFDN, SLC6A11, PXDN) nominally associated (p < 0.05) with clozapine-induced myocarditis. Of these genes, 13 were expressed in human myocardial tissue. Although independent replication of these findings is required, our study provides preliminary insights into the potential role of rare genetic variants in susceptibility to clozapine-induced myocarditis.
Publisher: Springer Science and Business Media LLC
Date: 13-03-2018
DOI: 10.1038/S41380-021-01340-6
Abstract: Substantial inter-in idual discrepancies exist in both therapeutic effectiveness and adverse effects of antidepressant and antipsychotic medications, which can, in part, be explained by genetic variation. Here, we searched the Pharmacogenomics Knowledge Base for gene-antidepressant and gene-antipsychotic pairs with the highest level of evidence. We then extracted and compared the associated prescribing recommendations for these pairs developed by the Clinical Pharmacogenomics Implementation Consortium, the Dutch Pharmacogenetics Working Group or approved product labels in the US, Canada, Europe, and Asia. Finally, we highlight key economical, educational, regulatory, and ethical issues that, if not appropriately considered, can hinder the implementation of these recommendations in clinical practice. Our review indicates that evidence-based guidelines are available to assist with the implementation of pharmacogenetic-guided antidepressant and antipsychotic prescribing, although the maximum impact of these guidelines on patient care will not be realized until key barriers are minimized or eliminated.
Location: United States of America
No related grants have been discovered for Chad Bousman.