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Pharmacogenomic (PGx) testing is an increasingly utilized technology that offers the potential for precision drug selection to treat depression. Though PGx-guided therapy is associated with increased rates of remission of depression symptoms, for many patients, treatment will not change based on PGx testing results. Lack of consensus guidelines for pre-test counseling may hinder the communication of PGx testing limitations, and patients often have high expectations for test outcomes. To explore this issue, we created and evaluated the impact of a pre-test education video for patients with depression. Individuals in the education group (n = 198) viewed this brief video about PGx testing prior to completing a survey that explored knowledge, perception, and expectations of PGx testing developed using a theoretical framework to measure intention to test. Individuals in the survey-only group (n = 189) completed the same survey but were not provided with any PGx educational materials. Analyses demonstrate efficacy of the video in improving knowledge of PGx. The education group also reported more positive attitudes and greater perceived control over pursuing PGx testing compared to the survey-only group. Further analyses identified significant differences in expectations, attitudes, and intention to pursue PGx testing based on number of previous medication trials. Path analyses identified the best model for predicting PGx testing intention, specifically that social norms and ease of testing have a strong positive association, and knowledge has a strong negative association with patients' intentions to test across the full sample, the education group, and the survey-only group. The findings of this study serve as a foundation for future tailored educational initiatives in the PGx testing space.
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Motivação , Testes Farmacogenômicos , Humanos , Farmacogenética/educação , Farmacogenética/métodos , Antidepressivos/uso terapêutico , Inquéritos e QuestionáriosRESUMO
The gut microbiome is a complex and dynamic community of commensal, symbiotic, and pathogenic microorganisms that exist in a bidirectional relationship with the host. Bacterial functions in the gut play a critical role in healthy host functioning, and its disruption can contribute to many medical conditions. The relationship between gut microbiota and the brain has gained attention in mental health due to the mounting evidence supporting the association of gut bacteria with mood and behavior. Patients with bipolar disorder exhibit an increased frequency of gastrointestinal illnesses such as inflammatory bowel disease, which mechanistically has been linked to microbial community function. While the heterogeneity in microbial communities between individuals might be associated with disease risk, it may also moderate the efficacy or adverse effects associated with the use of medication. The following review highlights published evidence linking the function of gut microbiota both to bipolar disorder risk and to the effect of medications that influence microbiota, inflammation, and mood symptoms.
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Anticonvulsivantes/farmacologia , Antimaníacos/farmacologia , Antipsicóticos/farmacologia , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Animais , HumanosRESUMO
Genetic testing has multiple clinical applications including disease risk assessment, diagnosis, and pharmacogenomics. Pharmacogenomics can be utilized to predict whether a pharmacologic therapy will be effective or to identify patients at risk for treatment-related toxicity. Although genetic tests are typically ordered for a distinct clinical purpose, the genetic variants that are found may have additional implications for either disease or pharmacology. This review will address multiple examples of germline genetic variants that are informative for both disease and pharmacogenomics. The discussed relationships are diverse. Some of the agents are targeted for the disease-causing genetic variant, while others, although not targeted therapies, have implications for the disease they are used to treat. It is also possible that the disease implications of a genetic variant are unrelated to the pharmacogenomic implications. Some of these examples are considered clinically actionable pharmacogenes, with evidence-based, pharmacologic treatment recommendations, while others are still investigative as areas for additional research. It is important that clinicians are aware of both the disease and pharmacogenomic associations of these germline genetic variants to ensure patients are receiving comprehensive personalized care.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Mutação em Linhagem Germinativa , Farmacogenética/métodos , Catecol O-Metiltransferase/genética , Doença de Charcot-Marie-Tooth/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Genes BRCA1 , Genes BRCA2 , Predisposição Genética para Doença , Variação Genética , Glucosefosfato Desidrogenase/genética , Glucuronosiltransferase/genética , Humanos , Interferons , Interleucinas/genética , Terapia de Alvo Molecular/métodos , Receptores Adrenérgicos beta 1/genética , Canal de Liberação de Cálcio do Receptor de Rianodina/genéticaRESUMO
Introduction: Treatment-emergent sexual dysfunction (TESD) is a commonly reported side effect of antidepressant medications in clinical trials. Limited literature exists exploring the role of routine use of the Arizona Sexual Experience Scale (ASEX) in identification of TESD in clinical practice. Therefore, we completed a retrospective study with the primary goal of capturing the rates of sexual dysfunction associated with antidepressant use among adult patients at an outpatient encounter with a psychiatric clinical pharmacist between June 2020 and March 2022. Methods: Rates of identification of sexual dysfunction were compared pre-ASEX survey (June 2020 to June 2021) to post-ASEX survey (July 2021 to March 2022). Results: There was a significant increase in the identification of sexual dysfunction following implementation of the ASEX scale (10% in the pre-ASEX group versus 59% meeting sexual dysfunction criteria with the ASEX scale). Approximately 70% of patients in the post-ASEX group shared they would not have reported symptoms unless directly asked. Discussion: In conclusion, a validated survey (ASEX) in an ambulatory psychiatry clinic improves identification of sexual dysfunction associated with antidepressants. Use of interdisciplinary care teams in the setting of medication follow-up can assist with identifying tolerability concerns between visits with patients' prescribing clinicians.
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Antipsychotics are an important pharmacotherapy option for the treatment of many mental illnesses. Unfortunately, selecting antipsychotics is often a trial-and-error process due to a lack of understanding as to which medications an individual patient will find most effective and best tolerated. Metabolomics, or the study of small molecules in a biosample, is an increasingly used omics platform that has the potential to identify biomarkers for medication efficacy and toxicity. This systematic review was conducted to identify metabolites and metabolomic pathways associated with antipsychotic use in humans. Ultimately, 42 studies were identified for inclusion in this review, with all but three studies being performed in blood sources such as plasma or serum. A total of 14 metabolite classes and 12 lipid classes were assessed across studies. Although the studies were highly heterogeneous in approach and mixed in their findings, increases in phosphatidylcholines, decreases in carboxylic acids, and decreases in acylcarnitines were most consistently noted as perturbed in patients exposed to antipsychotics. Furthermore, for the targeted metabolomic and lipidomic studies, seven metabolites and three lipid species had findings that were replicated. The most consistent finding for targeted studies was an identification of a decrease in aspartate with antipsychotic treatment. Studies varied in depth of detail provided for their study participants and in study design. For example, in some cases, there was a lack of detail on specific antipsychotics used or concomitant medications, and the depth of detail on sample handling and analysis varied widely. The conclusions here demonstrate that there is a large foundation of metabolomic work with antipsychotics that requires more complete reporting so that an objective synthesis such as a meta-analysis can take place. This will then allow for validation and clinical application of the most robust findings to move the field forward. Future studies should be carefully controlled to take advantage of the sensitivity of metabolomics while limiting potential confounders that may result from participant heterogeneity and varied analysis approaches.
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Psychosis spectrum disorders (PSDs), as well as other severe mental illnesses where psychotic features may be present, like bipolar disorder, are associated with intrinsic metabolic abnormalities. Antipsychotics (APs), the cornerstone of treatment for PSDs, incur additional metabolic adversities including weight gain. Currently, major gaps exist in understanding psychosis illness biomarkers, as well as risk factors and mechanisms for AP-induced weight gain. Metabolomic profiles may identify biomarkers and provide insight into the mechanistic underpinnings of PSDs and antipsychotic-induced weight gain. In this 12-week prospective naturalistic study, we compared serum metabolomic profiles of 25 cases within approximately 1 week of starting an AP to 6 healthy controls at baseline to examine biomarkers of intrinsic metabolic dysfunction in PSDs. In 17 of the case participants with baseline and week 12 samples, we then examined changes in metabolomic profiles over 12 weeks of AP treatment to identify metabolites that may associate with AP-induced weight gain. In the cohort with pre-post data (n = 17), we also compared baseline metabolomes of participants who gained ≥5% baseline body weight to those who gained <5% to identify potential biomarkers of antipsychotic-induced weight gain. Minimally AP-exposed cases were distinguished from controls by six fatty acids when compared at baseline, namely reduced levels of palmitoleic acid, lauric acid, and heneicosylic acid, as well as elevated levels of behenic acid, arachidonic acid, and myristoleic acid (FDR < 0.05). Baseline levels of the fatty acid adrenic acid was increased in 11 individuals who experienced a clinically significant body weight gain (≥5%) following 12 weeks of AP exposure as compared to those who did not (FDR = 0.0408). Fatty acids may represent illness biomarkers of PSDs and early predictors of AP-induced weight gain. The findings may hold important clinical implications for early identification of individuals who could benefit from prevention strategies to reduce future cardiometabolic risk, and may lead to novel, targeted treatments to counteract metabolic dysfunction in PSDs.
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There is growing interest in utilizing pharmacogenetic (PGx) testing to guide antidepressant use, but there is lack of clarity on how to implement testing into clinical practice. We administered two surveys at 17 sites that had implemented or were in the process of implementing PGx testing for antidepressants. Survey 1 collected data on the process and logistics of testing. Survey 2 asked sites to rank the importance of Consolidated Framework for Implementation Research (CFIR) constructs using best-worst scaling choice experiments. Of the 17 sites, 13 had implemented testing and four were in the planning stage. Thirteen offered testing in the outpatient setting, and nine in both outpatient/inpatient settings. PGx tests were mainly ordered by psychiatry (92%) and primary care (69%) providers. CYP2C19 and CYP2D6 were the most commonly tested genes. The justification for antidepressants selected for PGx guidance was based on Clinical Pharmacogenetics Implementation Consortium guidelines (94%) and US Food and Drug Administration (FDA; 75.6%) guidance. Both institutional (53%) and commercial laboratories (53%) were used for testing. Sites varied on the methods for returning results to providers and patients. Sites were consistent in ranking CFIR constructs and identified patient needs/resources, leadership engagement, intervention knowledge/beliefs, evidence strength and quality, and the identification of champions as most important for implementation. Sites deployed similar implementation strategies and measured similar outcomes. The process of implementing PGx testing to guide antidepressant therapy varied across sites, but key drivers for successful implementation were similar and may help guide other institutions interested in providing PGx-guided pharmacotherapy for antidepressant management.
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Antidepressivos/uso terapêutico , Farmacogenética , Testes Farmacogenômicos , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2D6/genética , Depressão/tratamento farmacológico , Humanos , Farmacogenética/métodosRESUMO
BACKGROUND: Despite the increased demand for pharmacogenetic (PGx) testing to guide antidepressant use, little is known about how to implement testing in clinical practice. Best-worst scaling (BWS) is a stated preferences technique for determining the relative importance of alternative scenarios and is increasingly being used as a healthcare assessment tool, with potential applications in implementation research. We conducted a BWS experiment to evaluate the relative importance of implementation factors for PGx testing to guide antidepressant use. METHODS: We surveyed 17 healthcare organizations that either had implemented or were in the process of implementing PGx testing for antidepressants. The survey included a BWS experiment to evaluate the relative importance of Consolidated Framework for Implementation Research (CFIR) constructs from the perspective of implementing sites. RESULTS: Participating sites varied on their PGx testing platform and methods for returning recommendations to providers and patients, but they were consistent in ranking several CFIR constructs as most important for implementation: patient needs/resources, leadership engagement, intervention knowledge/beliefs, evidence strength and quality, and identification of champions. CONCLUSIONS: This study demonstrates the feasibility of using choice experiments to systematically evaluate the relative importance of implementation determinants from the perspective of implementing organizations. BWS findings can inform other organizations interested in implementing PGx testing for mental health. Further, this study demonstrates the application of BWS to PGx, the findings of which may be used by other organizations to inform implementation of PGx testing for mental health disorders.
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Aim: Teaching of genetics and pharmacogenetics with personal genotyping (PGT) is becoming commonplace. We aimed to perform a systematic review and meta-analysis to understand the effects of PGT on student outcomes. Methods: A systematic review was performed on studies that reported the effects of PGT on student attitudes, perceptions or knowledge. Extracted data were summarized qualitatively and when possible, quantitatively. Results: Student PGT has a positive effect on student attitude and perceptions survey responses in studies without a control group (p = 0.009) and in studies with a control group (p = 0.025). Knowledge increased after the use of PGT (p < 0.001) in studies without a control group. Conclusion: The findings here suggest that perceptions, attitudes and knowledge increase with PGT in the classroom.
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Genética Médica/educação , Técnicas de Genotipagem , Farmacogenética/educação , Estudantes , Técnicas de Genotipagem/métodos , HumanosRESUMO
Background: Patients with schizophrenia are at high risk of pre-mature mortality due to cardiovascular disease (CVD). Our group has completed studies in pharmacogenomics and metabolomics that have independently identified perturbations in one-carbon metabolism as associated with risk factors for CVD in this patient population. Therefore, this study aimed to use genetic and metabolomic data to determine the relationship between folate pharmacogenomics, one-carbon metabolites, and insulin resistance as measured using the homeostatic model assessment for insulin resistance (HOMA-IR) as a marker of CVD. Methods: Participants in this pilot analysis were on a stable atypical antipsychotic regimen for at least 6 months, with no diabetes diagnosis or use of antidiabetic medications. Participant samples were genotyped for MTHFR variants rs1801131 (MTHFR A1298C) and rs1801133 (MTHFR C677T). Serum metabolite concentrations were obtained with NMR. A least squares regression model was used to predict log(HOMA-IR) values based on the following independent variables: serum glutamate, glycine, betaine, serine, and threonine concentrations, and carrier status of the variant alleles for the selected genotypes. Results: A total of 67 participants were included, with a median age of 47 years old (IQR 42-52), 39% were female, and the median BMI was 30.3 (IQR 26.3-37.1). Overall, the model demonstrated an ability to predict log(HOMA-IR) values with an adjusted R 2 of 0.44 and a p-value of < 0.001. Glutamate, threonine, and carrier status of the MTHFR 1298 C or MTHFR 677 T allele were positively correlated with log(HOMA-IR), whereas glycine, serine, and betaine concentrations trended inversely with log(HOMA-IR). All factors included in this final model were considered as having a possible effect on predicting log(HOMA-IR) as measured with a p-value < 0.1. Conclusions: Presence of pharmacogenomic variants that decrease the functional capacity of the MTHFR enzyme are associated with increased risk for cardiovascular disease, as measured in this instance by log(HOMA-IR). Furthermore, serine, glycine, and betaine concentrations trended inversely with HOMA-IR, suggesting that increased presence of methyl-donating groups is associated with lower measures of insulin resistance. Ultimately, these results will need to be replicated in a significantly larger population.
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Multiple groups have described strategies for clinical implementation of pharmacogenetics (PGx) that often include internal laboratory tests that are specifically developed for their implementation needs. However, many institutions are not able to follow this practice and instead must utilize external laboratories to obtain PGx testing results. As each external laboratory might have different ordering and reporting workflows, consistent reporting and storing of PGx results within the medical record can be a challenge. This might result in patient safety concerns as important PGx information might not be easily identifiable at the point of current or future prescribing. Herein, we describe initial PGx clinical implementation efforts at a large academic medical center, focusing on optimizing three different test ordering workflows and two distinct result reporting strategies. From this, we identified common issues such as variable reporting location and structure of PGx results, as well as duplicate PGx testing. We identified several opportunities to optimize our current processes, including-(1) PGx laboratory stewardship, (2) increasing visibility of PGx tests, and (3) clinician and patient education. Key to the success was the importance of engaging clinician, informatics, and pathology stakeholders, as we developed interventions to improve our PGX implementation processes.
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Antipsychotic (AP) medications are associated with an increased risk of developing metabolic side effects including weight gain, type 2 diabetes (T2D), dyslipidemia, and hypertension. In the majority of clinical studies, females on APs are noted to gain more weight, and are more likely to be diagnosed with metabolic syndrome when compared to males. However, the data is less clear when comparing sex disparities associated with other specific AP-induced metabolic risk factors. Accumulating evidence has demonstrated a role for AP-induced adipose tissue accumulation as well as whole body glucose dysregulation in male models that is independent of changes in body weight. The purpose of this narrative review is to explore the susceptibility of males and females to changes in adiposity and glucose metabolism across clinical and preclinical models of AP treatment. It is important that future research examining AP-induced metabolic side effects analyzes outcomes by sex to help clarify risk and identify the mechanisms of adverse event development to improve safe prescribing of medications.
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STUDY OBJECTIVE: Previous studies identified shifts in gut microbiota associated with atypical antipsychotic (AAP) treatment that may link AAPs to metabolic burden. Dietary prebiotics such as resistant starch may be beneficial in obesity and glucose regulation, but little is known mechanistically about their ability to modify gut microbiota in AAP-treated individuals. This investigation was undertaken to delineate mechanistically the effects of AAP treatment and resistant starch supplementation on gut microbiota in a psychiatric population. DESIGN: Cross-sectional cohort study. SETTING: The study was performed in an outpatient setting. PATIENTS: A total of 37 adults with a diagnosis of bipolar disorder or schizophrenia who were treated with an AAP (clozapine, olanzapine, risperidone, quetiapine, or ziprasidone [21 patients]) or lithium and/or lamotrigine (16 patients) for at least 6 months. INTERVENTION: Patients in the AAP group received raw unmodified potato starch (resistant starch) daily for 14 days. MEASUREMENTS AND MAIN RESULTS: Of the 37 patients, the mean ± SD age was 52.2 ± 12.5 years, and 57% were male. The primary outcome was gut microbiome DNA composition. Microbiome DNA obtained from stool samples from all patients was subject to 16S ribosomal RNA (rRNA) gene sequencing before and during resistant starch supplementation. Inter- and intragroup microbial diversity measures were performed by permutational multivariate analysis of variance and the Inverse Simpson Diversity Index, respectively. Differentially abundant organisms were detected by using linear discriminant analysis effect size. Although no significant difference in overall microbiota composition was detected at baseline between AAP users and nonusers, non-AAP users showed increased fractional representation of Alistipes. AAP-treated women exhibited decreased diversity compared with non-AAP-treated women. Although the microbiome of AAP-treated patients varied with resistant starch administration, an increased abundance of the Actinobacteria phylum was observed. CONCLUSION: These data suggest that AAP treatment is associated with measurable differences in gut microbiota, particularly in female AAP-treated patients in whom reduced species richness was observed. Additionally, variable microbiome responses to resistant starch supplementation were seen, with a significant increase in starch degraders.
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Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Prebióticos , Esquizofrenia/tratamento farmacológico , Antipsicóticos/farmacologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Inquéritos e QuestionáriosRESUMO
Although metabolic syndrome and cognitive inefficiencies are well-described common complications of schizophrenia, their association remains inconsistent, potentially due to poorly understood mechanisms underlying their relationship. Variability in the endothelial nitric oxide synthase (eNOS) gene, specifically the T-786C variant, has been separately associated with cognition and metabolic syndrome, with worse outcomes for eNOS-786C carriers likely occurring via negative effects on blood vessel functioning. However, the interaction between eNOS and metabolic syndrome in cognition among adults with schizophrenia is unknown. This study aimed to test the main and interaction effects of the eNOS-786C allele in cognition using hierarchical regression analyses controlling for age, sex, education, race, and antipsychotic exposure. Metabolic syndrome, eNOS T-786C genotype, and cognitive performance were assessed in 226 community-dwelling participants with chronic schizophrenia-spectrum disorders. Results demonstrated a significant interaction between metabolic syndrome and the eNOS-786C allele. Specifically, among eNOS-786C carriers only, metabolic syndrome was independently associated with lower scores in processing speed and verbal fluency, and predicted 12.5% and 15.8% of variance in performance, respectively. These results suggest that the additive negative effects of eNOS-786C and metabolic syndrome on blood vessel functioning may be severe enough to negatively impact cognition. The finding that metabolic syndrome is associated with worse cognition only in the presence of the eNOS-786C allele may clarify extant inconsistencies in the literature. These findings provide preliminary evidence that may inform interventions to reduce cognitive morbidity among adults with schizophrenia.
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Doenças Cardiovasculares , Disfunção Cognitiva , Síndrome Metabólica , Óxido Nítrico Sintase Tipo III/genética , Transtornos Psicóticos , Esquizofrenia , Adulto , Idoso , Doenças Cardiovasculares/genética , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/genética , Disfunção Cognitiva/fisiopatologia , Feminino , Heterozigoto , Humanos , Masculino , Síndrome Metabólica/genética , Pessoa de Meia-Idade , Transtornos Psicóticos/complicações , Transtornos Psicóticos/genética , Esquizofrenia/complicações , Esquizofrenia/genética , Adulto JovemRESUMO
INTRODUCTION: Drug-induced parkinsonism (DIP) and tardive dyskinesia (TD) are stigmatizing movement disorders associated with exposure to dopamine receptor blocking agents such as antipsychotics, but they differ in their pathophysiology and clinical management. Treatment for one may worsen the other, and there are important diagnostic clues that assist in making an accurate assessment and instituting a rational treatment plan. METHODS: A literature review was executed to identify articles relating to the presentation, pathophysiology, epidemiology, and management of DIP and TD. RESULTS: DIP and TD prevalence estimates range from approximately 20 to 35% among antipsychotic users, but may be higher in select populations. DIP often presents as bradykinesia and rigidity, as well as rhythmic tremor, and the majority of cases appear within hours to weeks of initiation of therapy with an antipsychotic, or if dosage of the antipsychotic is increased. TD onset is delayed, typically appearing after at least 3 months or longer of treatment, and patients will commonly present with involuntary, abnormal facial movements such as lip smacking, puckering, chewing, or tongue protrusion. DIP often resolves with discontinuation of the causative agent, but TD may be permanent. Broadly, proposed mechanisms underlying these adverse events include decreased dopamine concentrations in the nigrostriatal pathway of the striatum and dopamine hypersensitivity, for DIP and TD, respectively. Pharmacologic treatment approaches for DIP have commonly included anticholinergic agents such as benztropine; however, anticholinergic medications can make TD worse. Switching the antipsychotic medication to one with lower propensity for DIP is an option for some patients. Amantadine, a non-anticholinergic agent used for the treatment of DIP, may be preferred in patients with comorbid DIP and TD. In TD, treatment options include the new reversible vesicular monoamine 2 transporter inhibitors, valbenazine and deutetrabenazine. CONCLUSIONS: It is important for clinicians to be able to recognize DIP and TD in patients using antipsychotics so that they can minimize the impact of these adverse events on their patients' quality of life. Accurate diagnosis will drive the selection of the correct treatment. Plain language summary available for this article.
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PURPOSE: To identify the number of medication discrepancies following establishment of a telephone-based, introductory pharmacy practice experience student-driven, medication reconciliation service for new patients in an ambulatory psychiatry clinic. Secondarily, to identify factors impacting medication discrepancies to better target medication profiles to reconcile and to evaluate whether the implementation of a call schedule effected clinic no-show rates. METHODS: This was a retrospective analysis of a telephone-based medication reconciliation service from June 2014 to January 2016. RESULTS: At least 1 medication discrepancy was identified among 84.7% of medication profiles (N = 438), with a total of 1416 medication discrepancies reconciled (3.2 discrepancies per patient). Of the 1416 discrepancies, 38.6% were deletions, 38.9% were additions, and 22.5% were changes in dosage strength or frequency. Discrepancies pertaining to prescription medications totaled 57.8%. Student pharmacists were critical team members in the service. Patient's age, number of medications on the patient's list, and number of days since the last medication reconciliation were not clinically significant determinants for targeting medication profiles. There was a statistically significant reduction in the clinic no-show rates following implementation of a call schedule compared with no-show rates prior to call schedule implementation. CONCLUSION: This student pharmacist-led telephone medication reconciliation service demonstrated the importance of medication reconciliation in ambulatory psychiatry by identifying numerous discrepancies within this population. Further, we demonstrated pharmacy students across various levels of education can assist in this process under the supervision of a pharmacist.
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Instituições de Assistência Ambulatorial , Erros de Medicação/prevenção & controle , Reconciliação de Medicamentos/métodos , Psiquiatria/métodos , Estudantes de Farmácia , Telefone , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Instituições de Assistência Ambulatorial/normas , Feminino , Humanos , Masculino , Reconciliação de Medicamentos/normas , Transtornos Mentais/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Retrospectivos , Telefone/estatística & dados numéricos , Adulto JovemRESUMO
Atypical antipsychotics (AAPs) are a class of medications associated with significant metabolic side effects, including insulin resistance. The aim of this study was to analyze the skeletal muscle lipidome of patients on AAPs, compared to mood stabilizers, to further understand the molecular changes underlying AAP treatment and side effects. Bipolar patients on AAPs or mood stabilizers underwent a fasting muscle biopsy and assessment of insulin sensitivity. A lipidomic analysis of total fatty acids (TFAs), phosphatidylcholines (PCs) and ceramides (CERs) was performed on the muscle biopsies, then lipid species were compared between treatment groups, and correlation analyses were performed with insulin sensitivity. TFAs and PCs were decreased and CERs were increased in the AAP group relative to those in the mood stabilizer group (FDR q-value <0.05). A larger number of TFAs and PCs were positively correlated with insulin sensitivity in the AAP group compared to those in the mood stabilizer group. In contrast, a larger number of CERs were negatively correlated with insulin sensitivity in the AAP group compared to that in the mood stabilizer group. The findings here suggest that AAPs are associated with changes in the lipid profiles of human skeletal muscle when compared to mood stabilizers and that these changes correlate with insulin sensitivity.
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STUDY OBJECTIVE: Patients with schizophrenia are known to have higher rates of metabolic disease than the general population. Contributing factors likely include lifestyle and atypical antipsychotic (AAP) use, but the underlying mechanisms are unknown. The objective of this study was to identify metabolomic variability in adult patients with schizophrenia who were taking AAPs and grouped by fasting insulin concentration, our surrogate marker for metabolic risk. DESIGN: Metabolomics analysis PARTICIPANTS: Ninety-four adult patients with schizophrenia who were taking an AAP for at least 6 months, with no changes in their antipsychotic regimen for the previous 8 weeks, and who did not require treatment with insulin, participated in the study. Twenty age- and sex-matched nonobese (10 subjects) and obese (10 subjects) controls without cardiovascular disease or mental health diagnoses were used to match the body mass index (BMI) range of the patients with schizophrenia to account for metabolite concentration differences attributable to BMI. MEASUREMENTS AND MAIN RESULTS: Existing serum samples were used to identify aqueous metabolites (to differentiate fasting insulin concentration quartiles) and fatty acids with quantitative nuclear magnetic resonance and gas chromatography methods, respectively. To exclude metabolites from our pathway mapping analysis that were due to variability in weight, we also subjected serum samples from the nonobese and obese controls to the same analyses. Patients with schizophrenia had a median age of 47.0 years (interquartile range 41.0-52.0 years). Using a false discovery rate threshold of less than 25%, 10 metabolites, not attributable to weight, differentiated insulin concentration quartiles in patients with schizophrenia and identified variability in one-carbon metabolism between groups. Patients with higher fasting insulin concentrations (quartiles 3 and 4) also trended toward higher levels of saturated fatty acids compared with patients with lower fasting insulin concentrations (quartiles 1 and 2). CONCLUSION: Our results illustrate the utility of metabolomics to identify pathways underlying variable fasting insulin concentration in patients with schizophrenia. Importantly, no significant difference in AAP exposure was observed among groups, suggesting that current antipsychotic use may not be a primary factor that differentiates middle-aged adult patients with schizophrenia by fasting insulin concentration.
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Antipsicóticos/uso terapêutico , Metabolômica , Esquizofrenia/tratamento farmacológico , Adulto , Ácidos Graxos/sangue , Feminino , Humanos , Insulina/sangue , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fenótipo , Esquizofrenia/metabolismoRESUMO
Objectives: A pilot of clinical services provided by psychiatric clinical pharmacists in an outpatient clinic are described and evaluated. The primary objective was to evaluate the difference in change of Patient Health Questionnaire (PHQ)-9 and/or Generalized Anxiety Disorder (GAD) Questionnaire scores between the two groups. Secondary objectives were to assess time patients spent in clinic, time to target psychotropic medication dose, and patient self-reported medication adherence. Experimental Design: Data were collected from January 2014 to November 2015 for patients with depression and/or anxiety who had an appointment within an outpatient psychiatric clinic with either a provider (control) or both a provider and clinical pharmacist (case). Principle Observations: A total of 217 patients were included in the study; 117 patients served as controls and 100 patients received clinical pharmacist intervention. No statistical difference was detected in the primary outcome. However, patients in the case group had higher baseline PHQ-9/GAD scores, and the frequency of measured values was lower than anticipated, limiting power to detect a difference. All secondary outcomes achieved statistical significance. Both time in clinic and time to reach a stabilized psychotropic medication regimen were shorter in the control group. Patient self-reported adherence favored a higher adherence rate in the intervention group. Conclusion: While this study found no significant difference in the change in PHQ-9/GAD scores between groups, it demonstrated the need for enhanced utilization of measurement-based outcomes in the psychiatric setting. Pharmacists provide a range of services to patients and providers and can serve as key partners to enhance measurement-based care.
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Assistência Ambulatorial , Transtornos de Ansiedade/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Serviços de Saúde Mental , Avaliação de Processos e Resultados em Cuidados de Saúde , Questionário de Saúde do Paciente , Assistência Farmacêutica , Escalas de Graduação Psiquiátrica , Psicotrópicos/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos PilotoRESUMO
The adverse metabolic risks associated with second generation antipsychotics (SGAs) are well known, and likely contribute to the high rate of premature mortality due to cardiovascular disease in schizophrenia. Female schizophrenia patients appear to be diagnosed with metabolic diseases at higher rates than males, which may reflect disparate adverse responses to SGAs. However, the relationship between sex, metabolic risk, and drug use is less developed. We aimed to explore this relationship further by identifying rates of metabolic disease in community dwelling schizophrenia patients by sex and SGA risk. Schizophrenia participants (N = 287, 40.4% female) were included in this analysis. Oneway-ANOVA and Fisher's Exact Test were used to compare groups, as appropriate, and Cohen's d was employed to estimate the effect size of sex. In the group as a whole, the rate of metabolic syndrome was higher than previously reported, but did not differ by sex. For females, greater metabolic disturbances across all medication risk groups were seen in BMI and waist circumference (p < 0.005) but most commonly in those receiving high risk medication (clozapine or olanzapine). Additionally, the number of participants receiving medications for these metabolic disturbances was extremely low (<30%). These results suggest that female schizophrenia patients taking clozapine or olanzapine represent a group at uniquely high risk for metabolic dysfunction and future adverse cardiovascular outcomes, and warrant close monitoring by clinicians to prevent worsening of metabolic risk through proper monitoring and interventions.