Therapeutic Advances in Psychopharmacology最新文献

{"title":"Plasma levels of interleukin-6 and 3-methoxy-4-hydroxyphenylglycol and treatment with milnacipran in major depression.","authors":"Reiji Yoshimura, Naomichi Okamoto, Atsuko Ikenouchi","doi":"10.1177/20451253221116238","DOIUrl":"https://doi.org/10.1177/20451253221116238","url":null,"abstract":"Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). TherapeuTic advances in psychopharmacology","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":" ","pages":"20451253221116238"},"PeriodicalIF":4.2,"publicationDate":"2022-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7a/dd/10.1177_20451253221116238.PMC9364219.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40708755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dose-response analysis of aripiprazole in patients with schizophrenia in Taiwan.","authors":"Yun Tien,&nbsp;Hsiang-Ping Huang,&nbsp;Ding-Lieh Liao,&nbsp;Shang-Chien Huang","doi":"10.1177/20451253221113238","DOIUrl":"https://doi.org/10.1177/20451253221113238","url":null,"abstract":"<p><strong>Background: </strong>Aripiprazole is a third-generation antipsychotic agent with acceptable efficacy and a good safety profile. Previous studies have indicated the therapeutic serum concentration of aripiprazole to be 100 to 350 ng/ml; however, most of these studies examined a Western population. Patients with schizophrenia from Tungs' Taichung MetroHarbor Hospital in central Taiwan were recruited to analyze the dose-response relationship of aripiprazole in the Chinese population.</p><p><strong>Objective: </strong>We aimed to investigate whether a serum concentration of aripiprazole higher than the current suggested range leads to higher response rates.</p><p><strong>Design: </strong>A prospective cohort study was designed to investigate the response rates in different studied cohorts grouped by serum concentration of aripiprazole.</p><p><strong>Data sources and methods: </strong>Data of 64 patients who presented to a single medical center in central Taiwan and who received therapeutic drug monitoring (TDM) were obtained. Serum concentrations of aripiprazole were correlated with the clinical response of patients by using the Clinical Global Impressions (CGI) scores.</p><p><strong>Results: </strong>The mean concentration of aripiprazole was 432.1 ± 275.1 ng/ml in the study cohort. Among the much-improved patients, the mean serum concentration of aripiprazole was 494 ± 273 ng/ml (25th-75th percentiles 264-666 ng/ml), which was higher than the current recommended therapeutic target of 100-350 ng/ml for aripiprazole. The response rate in the severe group (baseline CGI score of 6 or 7) was significantly higher than in the moderate group (baseline CGI score of 4 or 5; 86.7% <i>versus</i> 55.9%, <i>p</i> = 0.007).</p><p><strong>Conclusion: </strong>A significantly higher response rate was observed in the study cohort with serum aripiprazole concentrations over 300 ng/ml. Therefore, dosing higher than the current recommended range may potentially improve the treatment efficacy in the Chinese population. Because the serum concentration varies among patients due to multiple intrinsic and extrinsic factors, TDM, especially in outpatients, is recommended if the clinical response is limited.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":" ","pages":"20451253221113238"},"PeriodicalIF":4.2,"publicationDate":"2022-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2b/52/10.1177_20451253221113238.PMC9340887.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40667676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on: Treatment strategies for clozapine-induced hypotension: A systematic review.","authors":"Patrick M Wieruszewski,&nbsp;Erica D Wittwer,&nbsp;Sarah B Leung,&nbsp;Jonathan G Leung","doi":"10.1177/20451253221111682","DOIUrl":"https://doi.org/10.1177/20451253221111682","url":null,"abstract":"Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). TherapeuTic advances in psychopharmacology","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":" ","pages":"20451253221111682"},"PeriodicalIF":4.2,"publicationDate":"2022-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b9/4c/10.1177_20451253221111682.PMC9301097.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40644863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Olanzapine long-acting injection, discontinuation rates and reasons for discontinuation: 10 years' experience at a UK high-secure hospital.","authors":"Azizah Attard, John Wakelam, Josephine Broyd, David Taylor, Jonathan Hafferty","doi":"10.1177/20451253221113093","DOIUrl":"10.1177/20451253221113093","url":null,"abstract":"<p><strong>Background: </strong>Olanzapine pamoate has been shown to be an effective second-generation long-acting injection. Its popularity has possibly been adversely affected by the rare incidence of post-injection syndrome (PIS) and the associated requirement to monitor for 3 h after each injection.</p><p><strong>Objective: </strong>This study aimed to collect and present data on the use of olanzapine long-acting injection (OLAI) over a 10-year period in a high-security forensic hospital in South East England.</p><p><strong>Design: </strong>This was a non-interventional retrospective study collecting information from anonymised electronic patient and prescription records. As per hospital Trust guidelines, patient consent to access of hospital records was presumed unless explicitly withdrawn.</p><p><strong>Method: </strong>All patients prescribed OLAI between the years 2009 and 2019 were identified. Data collected included date that OLAI was started, stopped, dose range, side effects and concomitant medication.</p><p><strong>Results: </strong>Of 88 patients who were started OLAI, 45 (51%) continued at month 24. At 60 months, 22 of 70 (31%) patients for whom data were available continued with OLAI. Over 60% of continuers were on higher than recommended doses. Of almost 5000 injections administered, there was 1 episode of PIS.</p><p><strong>Conclusion: </strong>OLAI is an effective treatment for schizophrenia and schizoaffective disorder, especially when used in patients have been able to tolerate the drug and were stabilised on it for 24 months. In over half the patients who continued OLAI, the doses were higher than that recommended by the manufacturer. The incidence of PIS in this study was very low in comparison with other studies.</p><p><strong>Registration code: </strong>2049.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":"12 ","pages":"20451253221113093"},"PeriodicalIF":3.4,"publicationDate":"2022-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1c/bf/10.1177_20451253221113093.PMC9301109.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9955904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise interventions to reduce anxiety in mid-life and late-life anxiety disorders and subthreshold anxiety disorder: a systematic review.","authors":"Terence W H Chong,&nbsp;Scherazad Kootar,&nbsp;Helen Wilding,&nbsp;Sarah Berriman,&nbsp;Eleanor Curran,&nbsp;Kay L Cox,&nbsp;Alex Bahar-Fuchs,&nbsp;Ruth Peters,&nbsp;Kaarin J Anstey,&nbsp;Christina Bryant,&nbsp;Nicola T Lautenschlager","doi":"10.1177/20451253221104958","DOIUrl":"https://doi.org/10.1177/20451253221104958","url":null,"abstract":"<p><strong>Background: </strong>Anxiety disorders are highly prevalent and cause significant distress, disability, and cost. Medication adverse effects and interactions increase in mid-life and late-life, highlighting the need for effective non-pharmacological interventions.</p><p><strong>Objectives: </strong>We aimed to evaluate the extent of evidence supporting exercise interventions for anxiety and subthreshold anxiety disorders in mid-life and late-life.</p><p><strong>Design: </strong>Systematic review.</p><p><strong>Data sources and methods: </strong>We searched MEDLINE, PsycINFO, Embase, Emcare, Ovid Nursing, CINAHL Plus, Cochrane Library, Health Collection, Humanities & Social Sciences Collection, and https://clinicaltrials.gov databases for trials published January 1994-May 2019. Randomised controlled trials of exercise interventions involving aerobic exercise or resistance training for adults aged 40 years and above with anxiety or subthreshold anxiety disorders in residential or health settings were identified. The primary outcome was change in anxiety. We excluded trials including participants aged below 40 years, participants with diagnosis of separation anxiety, selective mutism, obsessive-compulsive disorder, acute stress disorder and post-traumatic stress disorder, and head-to-head comparisons of interventions. Trial quality was assessed using the Cochrane Risk of Bias Tool and evidence synthesised in narrative form.</p><p><strong>Results: </strong>Four trials totalling 132 participants met inclusion criteria, although some had methodological limitations. Interventions included a home-based resistance training intervention, supervised group-based aerobic intervention, Tai Chi intervention, and supervised group-based aerobic and strength intervention. Three trials included late-life participants and the fourth mid-life. Three trials demonstrated greater reductions in anxiety in the intervention group compared with control. The fourth trial showed pre-post reductions in anxiety in both groups, with between-group difference not reaching statistical significance.</p><p><strong>Conclusion: </strong>There is limited supportive evidence suggesting that exercise interventions have potential to be effective, feasible and safe non-pharmacological interventions for anxiety and subthreshold anxiety disorders in mid-life and late-life. The heterogeneity, limited number and high risk of bias of some trials meant that we were not able to conduct a meta-analysis. Tailoring of interventions may improve uptake and reduce dropout. The paucity of research in this area with only four included trials demonstrates the urgent need for future and larger trials to provide proof of concept, data about effective types and doses of exercise interventions, and guidance to community, clinical, and public health services.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":" ","pages":"20451253221104958"},"PeriodicalIF":4.2,"publicationDate":"2022-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/24/7a/10.1177_20451253221104958.PMC9272174.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40504008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vortioxetine as adjunctive therapy in the treatment of schizophrenia.","authors":"Sofia Redaelli, Lilla Porffy, Ebenezer Oloyede, Olubanke Dzahini, Gabriella Lewis, Maria Lobo, Eromona Whiskey, Sukhi S Shergill","doi":"10.1177/20451253221110014","DOIUrl":"10.1177/20451253221110014","url":null,"abstract":"<p><strong>Background: </strong>The evidence for safe and effective interventions to treat the negative and cognitive symptoms of schizophrenia is lacking.</p><p><strong>Objectives: </strong>Vortioxetine is a novel antidepressant that has been used as adjunctive therapy for the treatment of psychosis; however, its effectiveness in clinical practice is relatively unknown. In this study, we aimed to determine the potential clinical effectiveness and safety and tolerability of vortioxetine in psychosis.</p><p><strong>Design: </strong>This is a non-interventional, retrospective study on the add-on use of vortioxetine in a group of people with schizophrenia-spectrum disorders in a large UK NHS mental health trust.</p><p><strong>Methods: </strong>Clinical effectiveness of vortioxetine was retrospectively assessed through the Clinical Global Impression - Severity (CGI-S) scale at 3 months. Safety and tolerability were evaluated through treatment discontinuation rates at 3, 6, and 12 months, and clinical reasons were evaluated at the primary endpoint of 3 months.</p><p><strong>Results: </strong>Data were available for 40 subjects with a diagnosis of schizophrenia or schizoaffective disorder-prescribed vortioxetine treatment; 30 (75%) remained on treatment at 3 months. At CGI-S assessment, 15 of the 35 evaluated subjects reported at least a 1-point improvement, from 5 at baseline to 4 after 3 months of treatment. Twenty-six (65%) remained on treatment at 1-year follow-up. The main reasons for those discontinuing treatment were inadequate response (10%) and manic switch (7.5%), while one subject refused treatment. Tolerability to treatment was good, and 36 subjects (90%) reported no adverse events specific to vortioxetine treatment.</p><p><strong>Conclusion: </strong>Schizophrenia is a complex illness, and there is insufficient treatment response in many individuals. A significant proportion of whom may require adjunctive treatments depending on the nature of the residual symptoms. Vortioxetine could be a potentially safe and effective option in such people, but further controlled studies are required.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":" ","pages":"20451253221110014"},"PeriodicalIF":3.4,"publicationDate":"2022-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a2/45/10.1177_20451253221110014.PMC9272178.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40504007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Agomelatine for the treatment of generalized anxiety disorder: focus on its distinctive mechanism of action.","authors":"Mark J Millan","doi":"10.1177/20451253221105128","DOIUrl":"https://doi.org/10.1177/20451253221105128","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Generalized anxiety disorder (GAD), the most frequently diagnosed form of anxiety, is usually treated by cognitive-behavioural approaches or medication; in particular, benzodiazepines (acutely) and serotonin or serotonin/noradrenaline reuptake inhibitors (long term). Efficacy, compliance, and acceptability are, however, far from ideal, reinforcing interest in alternative options. Agomelatine, clinically employed in the treatment of major depression, expresses anxiolytic properties in rodents and was effective in the treatment of GAD (including severely ill patients) in several double-blind, short-term (12 weeks) and relapse-prevention (6 months) studies. At active doses, the incidence of adverse effects was no higher than for placebo. Agomelatine possesses a unique binding profile, behaving as a melatonin (MT&lt;sub&gt;1&lt;/sub&gt;/MT&lt;sub&gt;2&lt;/sub&gt;) receptor agonist and 5-HT&lt;sub&gt;2C&lt;/sub&gt; receptor antagonist, yet recognizing neither monoamine transporters nor GABA&lt;sub&gt;A&lt;/sub&gt; receptors. Extensive evidence supports a role for 5-HT&lt;sub&gt;2C&lt;/sub&gt; receptors in the induction of anxious states, and their blockade likely plays a primary role in mediating the anxiolytic actions of agomelatine, including populations in the amygdala and bed nucleus of stria terminalis, as well as the hippocampus. Recruitment of MT receptors in the suprachiasmatic nucleus, thalamic reticular nucleus, and hippocampus appears to fulfil a complimentary role. Downstream of 5-HT&lt;sub&gt;2C&lt;/sub&gt; and MT receptors, modulation of stress-sensitive glutamatergic circuits and altered release of the anxiogenic neuropeptides, corticotrophin-releasing factor, and vasopressin, may be implicated in the actions of agomelatine. To summarize, agomelatine exerts its anxiolytic actions by mechanisms clearly distinct from those of other agents currently employed for the management of GAD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Plain language summary: &lt;/strong&gt;&lt;b&gt;How agomelatine helps in the treatment of anxiety disorders&lt;/b&gt;.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;• Anxiety disorders have a significant negative impact on quality of life.• The most common type of anxiety disorder, called generalized anxiety disorder (GAD), is associated with nervousness and excessive worry.• These symptoms can lead to additional symptoms like tiredness, sleeplessness, irritability, and poor attention.• GAD is generally treated through either cognitive-behavioural therapy or medication. However, widely used drugs like benzodiazepines and serotonin reuptake inhibitors have adverse effects.• Agomelatine, a well-established antidepressant drug, has shown anxiety-lowering ('anxiolytic') properties in rats and has been shown to effectively treat GAD with minimal side effects.• However, exactly how it acts on the brain to manage GAD is not yet clear.• Thus, this review aims to shed light on agomelatine's mechanism of action in treating GAD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;• The authors reviewed studies on how agomelatine treats anxiety in animals.• They also ","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":" ","pages":"20451253221105128"},"PeriodicalIF":4.2,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40487819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of antipsychotics on heart rate in treatment of schizophrenia: a systematic review and meta-analysis.","authors":"Maximilian Huhn,&nbsp;Thomas Arndt,&nbsp;Johannes Schneider-Thoma,&nbsp;Stefan Leucht","doi":"10.1177/20451253221097261","DOIUrl":"https://doi.org/10.1177/20451253221097261","url":null,"abstract":"<p><strong>Background: </strong>Antipsychotics are the treatment of choice in the therapy of schizophrenia. These drugs can be associated with changes in heart rate, but this question has never been examined systematically.</p><p><strong>Objective: </strong>We aimed to analyse changes in heart rate during treatment with antipsychotics using the frequency of tachycardia and bradycardia events.</p><p><strong>Design: </strong>For this systematic review and meta-analysis, we included all randomized controlled trials for the acute treatment of schizophrenia comparing antipsychotics head-to-head or with placebo.</p><p><strong>Data sources and methods: </strong>We searched Embase, MEDLINE, PsycINFO, PubMed, BIOSIS, Cochrane Central Register of Controlled Trials (CENTRAL), WHO International Clinical Trials Registry Platform and ClinicalTrials.gov (last search June 2021). Two authors independently selected studies and extracted data. We conducted pairwise meta-analyses using a random-effects model. Outcomes were tachycardia and bradycardia events.</p><p><strong>Results: </strong>We found 469 trials meeting the inclusion criteria. Seventy-seven studies with 16,907 participants provided data on tachycardia or bradycardia events. We found no significant differences between antipsychotics and placebo or between antipsychotics for bradycardia events based on sparse data. Antipsychotics had a higher risk for tachycardia events compared with placebo [<i>N</i> = 37, <i>n</i> = 7827, risk ratio (RR) = 1.83, 95% confidence interval (CI) = 1.40-2.41], with large differences between the individual substances (iloperidone RR = 14.05, chlorpromazine RR = 4.84, loxapine RR = 4.52, risperidone RR = 3.38, quetiapine RR = 2.64, paliperidone RR = 1.65). Some head-to-head comparisons were also significantly different: olanzapine <i>versus</i> haloperidol RR = 2.87, chlorpromazine <i>versus</i> thiothixene RR = 2.92, quetiapine <i>versus</i> lurasidone RR = 3.22, risperidone <i>versus</i> aripiprazole RR = 4.37, iloperidone <i>versus</i> ziprasidone RR = 4.65).</p><p><strong>Conclusion: </strong>Many studies do not report data for cardiac outcomes, but the available evidence indicates that treatment with antipsychotics raises the risk for tachycardia. Therefore, especially patients with cardiac risk factors should be monitored closely during antipsychotic treatment.</p><p><strong>Registration: </strong>PROSPERO: CRD42014014919.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":" ","pages":"20451253221097261"},"PeriodicalIF":4.2,"publicationDate":"2022-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/68/99/10.1177_20451253221097261.PMC9237927.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40573548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone Deacetylase 6 Inhibitor JS28 Prevents Pathological Gene Expression in Cardiac Myocytes.","authors":"Vivien Ngo, Bernd K Fleischmann, Manfred Jung, Lutz Hein, Achim Lother","doi":"10.1161/JAHA.122.025857","DOIUrl":"10.1161/JAHA.122.025857","url":null,"abstract":"<p><p>Background Epigenetic modulators have been proposed as promising new drug targets to treat adverse remodeling in heart failure. Here, we evaluated the potential of 4 epigenetic drugs, including the recently developed histone deacetylase 6 (HDAC6) inhibitor JS28, to prevent endothelin-1 induced pathological gene expression in cardiac myocytes and analyzed the chromatin binding profile of the respective inhibitor targets. Methods and Results Cardiac myocytes were differentiated and puromycin-selected from mouse embryonic stem cells and treated with endothelin-1 to induce pathological gene expression (938 differentially expressed genes, q<0.05). Dysregulation of gene expression was at least in part prevented by epigenetic inhibitors, including the pan-BRD (bromodomain-containing protein) inhibitor bromosporine (290/938 genes), the BET (bromodomain and extraterminal) inhibitor JQ1 (288/938), the broad-spectrum HDAC inhibitor suberoylanilide hydroxamic acid (227/938), and the HDAC6 inhibitor JS28 (210/938). Although the 4 compounds were similarly effective toward pathological gene expression, JS28 demonstrated the least adverse effects on physiological gene expression. Genome-wide chromatin binding profiles revealed that HDAC6 binding sites were preferentially associated with promoters of genes involved in RNA processing. In contrast, BRD4 binding was associated with genes involved in core cardiac myocyte functions, for example, myocyte contractility, and showed enrichment at enhancers and intronic regions. These distinct chromatin binding profiles of HDAC6 and BRD4 might explain the different effects of their inhibitors on pathological versus physiological gene expression. Conclusions In summary, we demonstrated, that the HDAC6 inhibitor JS28 effectively prevented the adverse effects of endothelin-1 on gene expression with minor impact on physiological gene expression in cardiac myocytes. Selective HDAC6 inhibition by JS28 appears to be a promising strategy for future evaluation in vivo and potential translation into clinical application.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":"6 1","pages":"e025857"},"PeriodicalIF":0.0,"publicationDate":"2022-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87521326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimation of cardiac QTc intervals in people prescribed antipsychotics: a comparison of correction factors.","authors":"Teodora Andric,&nbsp;Karl Winckel,&nbsp;Timothy David Tanzer,&nbsp;Samantha Hollingworth,&nbsp;Lesley Smith,&nbsp;Katherine Isoardi,&nbsp;Olivier Tan,&nbsp;Dan Siskind","doi":"10.1177/20451253221104947","DOIUrl":"https://doi.org/10.1177/20451253221104947","url":null,"abstract":"<p><strong>Background: </strong>A prolonged electrocardiogram (ECG) QT interval is associated with cardiac events and increased mortality. Antipsychotics can prolong the QT interval. The QT interval requires correction (QTc) for heart rate using a formula or QT-nomogram. The QT and QTc can be calculated automatically by the ECG machine or manually; however, machine-measured QT(c) intervals may be inaccurate.</p><p><strong>Objective: </strong>We aimed to investigate the mean QTc and proportion of prolonged QTc intervals in people taking antipsychotic medicines.</p><p><strong>Methods: </strong>We conducted an observational retrospective chart review and data analysis of all consecutive patients taking antipsychotics, with an ECG record, admitted to the psychiatric unit of a large tertiary hospital in Brisbane, Australia, between 1 January 2017 and 30 January 2019. We investigated the mean QTc of people taking antipsychotics to determine differences using (a) machine <i>versus</i> manual QT interval measurement and (b) QTc correction formulae (Bazett, Fridericia, Framingham, Hodges and Rautaharju) and the QT-nomogram. We also determined the number of people with a prolonged QTc using different methods and compared rates of prolonged QTc with antipsychotic monotherapy and polypharmacy.</p><p><strong>Results: </strong>Of 920 included people, the mean (±SD) machine-measured, Bazett-corrected QT interval (recorded from the ECG) was 435 ms (±27), significantly longer (<i>p</i> < 0.001) than the mean manually measured corrected QT intervals with Fridericia 394 ms (±24), Framingham 395 ms (±22), Hodges 398 ms (±22) and Rautaharju 400 ms (±24) formulae. There were significantly more people with a prolonged QTc using machine-measured QT and the Bazett formula (12.0%, 110/920) when compared with manually measured QT and the Fridericia formula (2.2%, 20/920) or QT-nomogram (0.7%, 6/920). Rates of QTc prolongation did not differ between people taking antipsychotic polypharmacy compared with monotherapy.</p><p><strong>Conclusion: </strong>Machine-measured QTc using the Bazett formula overestimates the QTc interval length and number of people with a prolonged QTc, compared with other formulae and the QT-nomogram. We recommend manually measuring the QT and correcting with the Fridericia formula or QT-nomogram prior to modifying antipsychotic therapies.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":" ","pages":"20451253221104947"},"PeriodicalIF":4.2,"publicationDate":"2022-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b0/bb/10.1177_20451253221104947.PMC9210090.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40391772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}