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Background: Common atypical antipsychotics include risperidone, paliperidone, olanzapine, lurasidone, quetiapine, clozapine, aripiprazole, ziprasidone, asenapine, brexpiprazole, and cariprazine. Previous studies on ocular adverse reactions of antipsychotics were mainly focused on typical antipsychotics. Systematic research on atypical antipsychotics remains limited. Objective: This study aimed to evaluate the potential risks of different atypical antipsychotics causing ocular side effects by mining the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: Extract reports from the FAERS from the first quarter of 2016 to the fourth quarter of 2022 were obtained. Data mining of eye disorders associated with atypical antipsychotics was carried out using The Reporting Odds Ratio (ROR) method and The Medicines and Healthcare Products Regulatory Agency (MHRA) method to determine positive signals. Results: FAERS reports for 9913783 cases were included in these 28 quarters. 64 defined ocular adverse events were classified into 10 categories according to High-Level Group Terms (HLGT). Conclusions: There were differences in the types and severity of ocular-related adverse events associated with atypical antipsychotics. Ocular neuromuscularrelated adverse events were found among all 11 atypical antipsychotics. Olanzapine had the highest signal intensity in oculogyric crisis. Aripiprazole had the highest signal strength in blepharospasm. Cariprazine was associated with cataract-related ocular adverse reactions. In terms of the types of adverse events, our study found that aripiprazole was associated with 28 types of ocular adverse events, followed by quetiapine. Clozapine was only associated with two types of ocular adverse events. [ABSTRACT FROM AUTHOR]

Loss of function (LoF) mutations affecting the histone methyl transferase SETD1A are implicated in the aetiology of a range of neurodevelopmental disorders including schizophrenia. We examined indices of development and adult behaviour in a mouse model of Setd1a haploinsufficiency, revealing a complex pattern of sex-related differences spanning the pre- and post-natal period. Specifically, male Setd1a+/- mice had smaller placentae at E11.5 and females at E18.5 without any apparent changes in foetal size. In contrast, young male Setd1a+/- mice had lower body weight and showed enhanced growth, leading to equivalent weights by adulthood. Embryonic whole brain RNA-seq analysis revealed expression changes that were significantly enriched for mitochondria-related genes in Setd1a+/ samples. In adulthood, we found enhanced acoustic startle responding in male Setd1a+/- mice which was insentitive to the effects of risperidone, but not haloperidol, both commonly used antipsychotic drugs. We also observed reduced pre-pulse inhibition of acoustic startle, a schizophrenia-relevant phenotype, in both male and female Setd1a+/- mice which could not be rescued by either drug. In the open field and elevated plus maze tests of anxiety, Setd1a haplosufficiency led to more anxiogenic behaviour in both sexes, whereas there were no differences in general motoric ability and memory. Thus, we find evidence for changes in a number of phenotypes which strengthen the support for the use of Setd1a haploinsufficient mice as a model for the biological basis of schizophrenia. Furthermore, our data point towards possible underpinning neural and developmental mechanisms that may be subtly different between the sexes. [ABSTRACT FROM AUTHOR]

Objective: This pharmacovigilance study evaluated the profile of clozapine-related adverse events by region using the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: We categorized each case into five regions (America, Europe/West Asia, Oceania, Asia, and Africa) based on the reporting country information in the FAERS database. The number of clozapine-related adverse events reported in each region was aggregated according to the preferred term (PT) and the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ). Results: A total of 101,872 clozapine-related adverse events were registered in the FAERS database. In America and Europe, leukocyte or neutrophil count abnormalities accounted for half of the top 10 PTs by relative reporting rate. However, Asia had higher relative reporting rates of pyrexia and salivary hypersecretion (13.91% and 10.85%, respectively). Regarding the SMQ, the relative reporting rates of infective pneumonia, convulsions, extrapyramidal syndrome, gastrointestinal obstruction, and hyperglycaemia/new onset diabetes mellitus were higher in Asia than in other regions (5.26%, 9.72%, 12.65%, 5.13%, and 8.26%, respectively), with significant differences even after adjusting for confounding factors using multivariate logistic regression analysis. Conclusion: Spontaneous reports of adverse events associated with clozapine show regional disparities, particularly in Asia, where concentration-dependent adverse events are more frequently reported. However, the spontaneous reporting system has several limitations, requiring further research for validation. [ABSTRACT FROM AUTHOR]

Delirium is a distressing condition in terminally ill cancer patients, often treated with antipsychotics. Administering them orally, subcutaneously, or intravenously can be challenging in severely agitated patients. Transdermal antipsychotic patches offer an alternative, but their use for terminal delirium remains underexplored. We present the case of a 73-year-old man with advanced diffuse large B cell lymphoma who developed severe mixed delirium during third-line chemotherapy. Nonpharmacological interventions and oral risperidone plus intravenous haloperidol failed to improve his condition. Subsequently, a transdermal blonanserin patch was applied, resulting in the resolution of hallucinations on day 1 and agitation on day 3, allowing improved communication. The patch was easily applied daily without notable adverse events. However, he deteriorated a week later with an estimated survival of days, ultimately requiring continuous midazolam for refractory agitation. This case underscores the potential of transdermal blonanserin patches for delirium in terminally ill cancer patients, emphasizing the need for future prospective studies. [ABSTRACT FROM AUTHOR]

Deficits in executive functions (EF) are strongly related to real-life functioning and negative symptoms (NS) in schizophrenia. Recently, virtual reality has enabled more ecologically valid approaches to assess EF in simulated "real-life" scenarios among which the virtual cooking task (VCT) has gained attention. However, the clinical implications of the VCT in schizophrenia have not been investigated exhaustively. In this study, clinically stable individuals with schizophrenia (n = 38) and healthy controls (n = 42) completed a novel VCT and a set of computerized standard EF tools (CST) to primarily investigate concurrent and discriminant validity. In addition, the study explored links between EF assessments, functioning, and NS while controlling for antipsychotic intake, clinical stability, and age. This VCT consisted of four tasks with increasing difficulty and time constraints. The most relevant findings indicate that (1) the VCT showed moderate to strong correlations with CST, (2) the VCT discriminated EF performance between both the groups, (3) the VCT predicted interpersonal functioning, and (4) the VCT predicted NS in greater extent than CST. Accordingly, the findings give support to the concurrent and discriminant validity of the VCT to assess EF and indicate its value to deepen the study of collateral functional deficits and NS in schizophrenia. [ABSTRACT FROM AUTHOR]

Objective: This review aimed to address the limited evidence on the efficacy of continuation or maintenance electroconvulsive therapy (C/M-ECT) in schizophrenia, with a focus on international case reports and series due to the scarcity of randomised controlled trials. Materials and Methods: Electronic database searches were conducted to identify case reports or series evaluating the efficacy of C/M-ECT in patients with schizophrenia or schizoaffective disorder. Results: C/M-ECT treatment span varied from 3 months to 36 years (Median = 30 months; M = 43.9 months; SD = 63.0) and was effective in maintaining remission for most patients with schizophrenia in combination with antipsychotic medication. Reporting of adverse events including cognitive adverse effects was infrequent. Conclusions: Collation of case reports and series data indicated that C/M-ECT, when combined with antipsychotics, appears to be a safe and effective strategy for maintaining remission, even over several years. Caution is warranted due to the potential influence of publication bias. [ABSTRACT FROM AUTHOR]

Schizophrenia is a polygenic complex disease with a heritability as high as 80 %, yet the mechanism of polygenic interaction in its pathogenesis remains unclear. Studying the interaction and regulation of schizophrenia susceptibility genes is crucial for unraveling the pathogenesis of schizophrenia and developing antipsychotic drugs. Therefore, we developed a bioinformatics method named GRACI (Gene Regulation Analysis based on Causal Inference) based on the principles of information theory, a causal inference model, and high order chromatin 3D conformation. GRACI captures the interaction and regulatory relationships between schizophrenia susceptibility genes by analyzing genotyping data. Two datasets, comprising 1459 and 2065 samples respectively, were analyzed, and the gene networks from both datasets were constructed. GRACI showcased superior accuracy when compared to widely adopted methods for detecting gene-gene interactions and intergenic regulation. This alignment was further substantiated by its correlation with chromatin high-order conformation patterns. Using GRACI, we identified three potential genes— KCNN3 , KCNH1 , and KCND3 —that are directly associated with schizophrenia pathogenesis. Furthermore, the results of GRACI on the standalone dataset illustrated the method's applicability to other complex diseases. GRACI download: https://github.com/liuliangjie19/GRACI [ABSTRACT FROM AUTHOR]

Certain antipsychotics elevate prolactin levels in patients with schizophrenia spectrum disorders (SSD), potentially affecting cognition, symptoms, and hormone levels. This study examines the association between prolactin, testosterone, and estrogen and cognition and symptoms in men with SSD, considering antipsychotic medication. This cross-sectional study included 128 men with SSD and 44 healthy men from two trials. Patients were divided into a prolactin-sparing (n = 53) and prolactin-raising group (n = 75) based on antipsychotic medication. We examined the association between hormones (testosterone, estrogen and prolactin), and cognition and symptoms using backward linear regression. Three domains of cognition were assessed including: processing speed, verbal fluency, and working memory, while symptoms were measured using the Positive and Negative Syndrome Scale (PANSS). Prolactin levels were highest in the prolactin-raising group, followed by the control group, and lowest in the prolactin-sparing group (H = 45.279, p <.001). Testosterone and estrogen levels did not differ significantly between groups. In the prolactin-raising group, prolactin negatively correlated with testosterone (r (73) = −0.32, p =.005). Higher testosterone predicted better cognitive functioning (working memory: β = 0.20, p =.007, verbal fluency: β = 0.30, p =.001) and lower symptom scores (total: β = −0.21, p =.001; negative: β = −0.24, p =.002) in men with SSD. Conversely, higher estrogen levels related to slower processing speed (β = −0.22, p <.001) and higher symptoms scores (β = 0.23, p =.010) in men with SSD. The results suggest positive associations between testosterone and cognition and symptoms in men with SSD, while suggesting that high prolactin levels could relate to lower testosterone levels, possibly worsening cognition and symptoms in men with SSD. [ABSTRACT FROM AUTHOR]

Clozapine is the only antipsychotic approved for treating treatment-resistant schizophrenia (TRS), characterized by persistent positive symptoms despite adequate antipsychotic treatment. Unfortunately, clozapine demonstrates clinical efficacy in only ~30–60 % of patients with TRS (clozapine-responders; ClzR+), while the remaining ~40–70 % are left with no pharmacological recourse for improvement (clozapine-resistant; ClzR−). Mechanism(s) underlying clozapine's superior efficacy remain unclear. However, in vitro evidence suggests clozapine may mitigate glutamatergic dysregulations observed in TRS, by modulating astrocyte activity in ClzR+, but not ClzR−. A factor that if proven correct, may help the assessment of treatment response and development of more effective antipsychotics. To explore the presence of clozapine-astrocyte interaction and clinical improvement, we used 3 T proton-magnetic resonance spectroscopy to quantify levels of myo-Inositol, surrogate biomarker of astrocyte activity, in regions related to schizophrenia neurobiology: Dorsal-anterior-cingulate-cortex (dACC), left-dorsolateral-prefrontal-cortex (left-DLPFC), and left-striatum (left-striatum) of 157 participants (ClzR− = 30; ClzR+ = 37; responders = 38; controls = 52). Clozapine treatment was assessed using clozapine to norclozapine plasma levels, 11–12 h after last clozapine dose. Measures for symptom severity (i.e., Positive and Negative Symptoms Scale) and cognition (i.e., Mini-Mental State Examination) were also recorded. Higher levels of myo-Inositol were observed in TRS groups versus responders and controls (dACC (p < 0.001); left-striatum (p = 0.036); left-DLPFC (p = 0.023)). In ClzR+, but not ClzR−, clozapine to norclozapine ratios were positively associated with myo-Inositol levels (dACC (p = 0.004); left-DLPFC (p < 0.001)), and lower positive symptom severity (p < 0.001). Our results support growing in vitro evidence of clozapine-astrocyte interaction in clozapine-responders. Further research may determine the viability of clozapine-astrocyte interactions as an early marker of clozapine response. [ABSTRACT FROM AUTHOR]

There is a significant variability in the prevalence of psychotropic medication use among young autistic persons worldwide and this is under-studied in Australia. Apart from risperidone, approved by the Therapeutic Goods Administration to manage challenging behaviour, the appropriateness of other psychotropic medications prescribed to young autistic persons warrants scrutiny. This retrospective study aims to gain initial insight into the magnitude, types and indications of psychotropic medication use in autistic children and adolescents in Western Australia. We analysed de-identified data from 239 autistic children and adolescents (⩽21 years) who participated in the Western Australian Autism Biological Registry between 2011 and 2015 and who completed a questionnaire regarding medication use. One-quarter (n = 66, 28%) of young autistic people reported using a total of 137 medications. Most (n = 46, 70%) of those medicated were under 12 years of age; half (n = 33) were 6–12 years and a fifth (n = 13) were under 6 years. The most used medications were stimulants (n = 35, 53.0%), followed by antidepressants (n = 24, 36.4%), antiepileptics (n = 21, 31.8%), sedatives (n = 15, 22.7%) and antipsychotics (n = 14, 21.2%). These medications were mainly to manage attention deficit hyperactivity disorder, challenging behaviours, seizures, insomnia, undefined anxiety, depression and mood instability. While most autistic young people in the Western Australian Autism Biological Registry did not report using psychotropic medication, over a quarter were prescribed medications, primarily stimulants, to manage symptoms of attention deficit hyperactivity disorder. Various medications, including risperidone, were used to help manage challenging behaviours. Medication use should be studied more comprehensively in a larger cohort of autistic persons to confirm our current preliminary observations. Further, future studies should monitor the effectiveness and safety outcomes of such medications due to a limited understanding of their effectiveness in managing the atypical presentation of co-occurring disorders in young autistic persons. Prescriptions and use of medications to treat mental health conditions in young autistic populations are inconsistent worldwide. This makes it hard to compare findings from international studies to the Australian autistic population, where there are limited relevant studies. Apart from risperidone, there are no other medications specified for direct use in autistic persons. This study aims to gain initial broad understanding of the use of medications, commonly prescribed for mental health conditions, specifically by autistics under the age of 21 years. We analysed data that were previously collected as part of the Western Australian Autism Biological Registry between 2011 and 2015 which amounted to 239 surveys completed on young persons with diagnosed autism. The questionnaires included information on co-occurring conditions, current or previous use of medications and reasons for use of the medications. Only one-quarter of the participants in this study reported using at least one mental health–related medication in their lifetime. The most reported medications were stimulants, antidepressants and antiepileptics. The reasons for using medication included managing attention deficit hyperactivity disorder, challenging behaviours, seizures, sleep difficulties and symptoms of anxiety and depression. The number of individuals reporting medication use in this study was lower compared to other developed countries. Nevertheless, these medications should be monitored due to limited understanding of their use to manage co-occurring symptoms in young autistic persons. The findings highlight the importance of ongoing research to better understand mental health–related medications and inform best practice. [ABSTRACT FROM AUTHOR]

Good adherence to antipsychotic therapy helps prevent relapses in first-episode psychosis (FEP). We used data from the FEP-CAUSAL Collaboration, an international consortium of observational cohorts, to emulate a target trial comparing antipsychotics, with treatment discontinuation as the primary outcome. Other outcomes included all-cause hospitalization. We benchmarked our results to estimates from the European First Episode Schizophrenia Trial, a randomized trial conducted in the 2000s. We included 1097 patients with a psychotic disorder and less than 2 years since psychosis onset. Inverse-probability weighting was used to control for confounding. The estimated 12-month risks of discontinuation for aripiprazole, first-generation agents, olanzapine, paliperidone, quetiapine, and risperidone were 61.5% (95% CI, 52.5-70.6), 73.5% (95% CI, 60.5-84.9), 76.8% (95% CI, 67.2-85.3), 58.4% (95% CI, 40.4-77.4), 76.5% (95% CI, 62.1-88.5), and 74.4% (95% CI, 67.0-81.2), respectively. Compared with aripiprazole, the 12-month risk differences were -15.3% (95% CI, -30.0 to 0.0) for olanzapine, -12.8% (95% CI, -25.7 to -1.0) for risperidone, and 3.0% (95% CI, -21.5 to 30.8) for paliperidone. The 12-month risks of hospitalization were similar between agents. Our estimates support use of aripiprazole and paliperidone as first-line therapies for FEP. Benchmarking yielded similar results for discontinuation and absolute risks of hospitalization as in the original trial, suggesting that data from the FEP-CAUSAL Collaboration sufficed to remove confounding for these clinical questions. This article is part of a Special Collection on Mental Health. [ABSTRACT FROM AUTHOR]

Background: The continuation rates of pharmacotherapy in schizophrenia exhibit variability, a phenomenon influenced by the specific antipsychotic agent prescribed and patient-related factors such as age and duration of illness. In this context, our study aims to elucidate the predictors of medication continuation for asenapine sublingual tablets, characterized by unique formulation properties. Methods: Our investigation leveraged real-world data collected through post-marketing surveillance in Japan, comprising 3236 cases. Utilizing multivariate logistic regression analysis, we identified patient-related factors associated with medication continuation as the primary outcome measure, subsequently employing survival analysis for further evaluation. Additionally, adverse event occurrence was assessed as a secondary outcome measure. Results: Multivariate logistic regression analysis unveiled significant predictors of asenapine continuation, notably including patient-related factors such as a chlorpromazine equivalent dose exceeding 600 mg/day and an illness duration of 25 years or more. While the overall continuation rate stood at 40.6%, patients exhibiting factors such as a chlorpromazine equivalent dose surpassing 600 mg/day or an illness duration exceeding 25 years demonstrated continuation rates of 46.3% and 47.9%, respectively. Remarkably, patients presenting both factors showcased the highest continuation rate at 52.5%. Conclusions: Our findings shed light on distinct patient-related predictors of asenapine continuation, deviating from those observed with other antipsychotic medications. This underscores the necessity of recognizing that predictive factors for antipsychotic medication continuation vary across different agents. Moving forward, elucidating these predictive factors for various antipsychotic medications holds paramount importance in schizophrenia treatment, facilitating the delivery of tailored therapeutic interventions for individual patients. [ABSTRACT FROM AUTHOR]

Background and aim: Bromazolam, a novel designer benzodiazepine (NBD), exhibits potent sedative, hypnotic and anxiolytic effects, raising concerns regarding its potential for misuse and fatal outcomes, particularly when combined with opioids such as fentanyl. Despite limited documented fatalities globally, its use poses a significant threat, exacerbated by under-reporting and a lack of routine testing. This study analysed NBD-related deaths in a major US city over a 4-year period. Methods: Analysis of accidental overdose deaths involving NBDs in San Francisco, CA, USA from 2020 to 2023, was performed utilizing medico-legal death investigations including comprehensive forensic toxicology, pathology and demographic information. San Francisco conducts thorough investigations into all non-natural and sudden unexpected deaths, including routine alcohol and drug testing of decedents under its jurisdiction, including etizolam, flualprazolam, flubromazolam and bromazolam analysis. Results: There was a sudden surge in bromazolam-related deaths, with 44 fatalities documented in 2023, contrasting with relatively fewer deaths related to other NBDs. Bromazolam fatalities frequently involved co-ingestion with opioids, primarily fentanyl, and stimulants such as methamphetamine and cocaine. Demographic characteristics indicated a predominance of males, with a significant proportion lacking fixed addresses. Blood concentrations of bromazolam increased during the study period, suggesting heightened availability and/or purity in the community. Conclusion: There was a surge in bromazolam-related deaths during 2023 in San Francisco, CA, USA, contrasting with relatively stable numbers of deaths associated with other NBDs over the preceding years. The findings underscore the urgency for enhanced death investigation, testing and reporting to facilitate targeted harm reduction strategies for individuals at risk of bromazolam-related morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background: Compared with the general population, adults with an intellectual developmental disorder (IDD) are more likely to develop mental health problems and to receive high levels of psychotropic medication, particularly antipsychotics. The emotional development (ED) approach may help to better understand the nature of challenging behaviour (CB) and tailor treatment and support accordingly. The aim of this retrospective study was to investigate the impact of the ED approach on the prescription of psychotropic medication during inpatient psychiatric treatment. Methods: The clinical data of 1758 patients were analysed within a retrospective study design over a period of 12 years. ED level was assessed (1) for the first time (INITIAL‐SEO), (2) during a previous hospital stay (PAST‐SEO) or (3) not at all (NO‐SEO). The effects of the ED assessment and the respective intervention during the current admission on the number of psychotropics and the number and dosage of antipsychotics were analysed for the total sample, including those with CB, autism spectrum disorders and psychosis. Group differences were analysed by a chi‐square test and a one‐factorial analysis of variance. For analysing the impact of the application of the ED approach on psychotropic medication, a covariance model was applied. Changes between the subsamples were analysed by t‐tests for dependent samples. Results: The ED approach had a significant impact on reducing the overall amount of psychotropic medication and the dosage of antipsychotics in all patients with IDD. These effects were mainly attributable to those showing CB. In patients with autism spectrum disorders, the developmental approach reduced the number of antipsychotics. No effects could be observed in patients with psychosis; in this subsample, both the number and dosage of antipsychotics increased. Conclusions: The application of the ED approach in the current hospital stay reduced the number of psychotropic drugs and the number and dosage of antipsychotics, especially in those patients with IDD and CB, but also in those with autism spectrum disorders. [ABSTRACT FROM AUTHOR]

Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is gaining attention in pharmacovigilance, but its association with antipsychotics, other than clozapine, is still unclear. Methods: We conducted a case/non-case study with disproportionality analysis based on the World Health Organization (WHO) global spontaneous reporting database, VigiBase®. We analyzed individual case safety reports of DRESS syndrome related to antipsychotics compared to (1) all other medications in VigiBase®, (2) carbamazepine (a known positive control), and (3) within classes (typical/atypical) of antipsychotics. We calculated reporting odds ratio (ROR) and Bayesian information component (IC), with 95% confidence intervals (CIs). Disproportionate reporting was prioritized based on clinical importance, according to predefined criteria. Additionally, we compared characteristics of patients reporting with serious/non-serious reactions. Results: A total of 1534 reports describing DRESS syndrome for 19 antipsychotics were identified. The ROR for antipsychotics as a class as compared to all other medications was 1.0 (95% CI 0.9–1.1). We found disproportionate reporting for clozapine (ROR 2.3, 95% CI 2.1–2.5; IC 1.2, 95% CI 1.1–1.3), cyamemazine (ROR 2.3, 95% CI 1.5–3.5; IC 1.2, 95% CI 0.5–1.7), and chlorpromazine (ROR 1.5, 95% CI 1.1–2.1; IC 0.6, 95% CI 0.1–1.0). We found 35.7% of cases with co-reported anticonvulsants, and 25% with multiple concurrent antipsychotics in serious compared to 8.6% in non-serious cases (p = 0.03). Fatal cases were 164 (10.7%). Conclusions: Apart from the expected association with clozapine, chlorpromazine and cyamemazine (sharing an aromatic heteropolycyclic molecular structure) emerged with a higher-than-expected reporting of DRESS. Better knowledge of the antipsychotic-related DRESS syndrome should increase clinicians' awareness leading to safer prescribing of antipsychotics. [ABSTRACT FROM AUTHOR]

Background: Second-generation antipsychotics (SGAs) are commonly prescribed medications used to treat a variety of mental health conditions. Recent data has correlated antipsychotic medications with venous thromboembolism (VTE). SGAs have diverse side effect profiles, which may contribute to differences in incidence of VTE. It is unknown which SGAs confer the most risk, and what the mechanism of increased risk is. Objective: Determine incidence of VTE in Veterans at Veterans Affairs North Texas Health Care System (VA-NTX HCS) between SGAs aripiprazole, olanzapine and risperidone. Methods: Retrospective chart review of adult Veterans at VA-NTX HCS between October 2015 to December 2019 prescribed aripiprazole, olanzapine, or risperidone. Results: Of 823 Veterans, incidence of VTE was lowest in aripiprazole group at.4%, increased to 1.7% in the olanzapine group, and was highest at 2.5% in the risperidone group. However, differences in incidence of VTE between SGAs were not statistically different, indicating no between-group differences. Conclusion: There was no difference in the incidence of VTE between risperidone, olanzapine, or aripiprazole. Given multiple limitations with this study, higher-powered studies should be conducted to investigate the possibility of differences in the incidence of VTE between the SGAs. [ABSTRACT FROM AUTHOR]

Schizophrenia (SCZ) is a severe psychiatric disorder with unclear pathophysiology. Moreover, there is no specific biological marker to help clinicians to define a diagnosis, and medication is decided according to the psychiatrist's experience. In this scenario, microRNAs (miRNAs), which are small noncoding RNA molecules that regulate several genes, emerge as potential peripheral biomarkers to help not only the evaluation of the disease state but also the treatment response. Here, we systematically reviewed indexed literature and evaluated follow-up studies investigating the changes in miRNA expression due to antipsychotic treatment. We also assessed target genes and performed pathway enrichment analysis of miRNAs listed in this systematic review. A total of 11 studies were selected according to research criteria, and we observed that 28 miRNAs play a relevant role in schizophrenia pathogenesis or response to antipsychotic treatment, seven of those of extreme interest as possible biomarkers either for condition or treatment. Predicted targets of the miRNAs reviewed here were previously associated with schizophrenia in genome-wide studies, and pathway analysis showed enrichment for genes related to neural processes. With this review, we expect to highlight the importance of miRNAs in schizophrenia pathogenesis and its treatment and point out interesting miRNAs to future studies. [ABSTRACT FROM AUTHOR]

This study aims to describe the patterns and trends in antipsychotic prescription among Dutch youth before and during the corona virus disease 2019 (COVID-19) pandemic (between 2017 and 2022). The study specifically aims to determine whether there has been an increase or decrease in antipsychotic prescription among this population, and whether there are any differences in prescription patterns among different age and sex groups. The study utilized the IADB database, which is a pharmacy prescription database containing dispensing data from approximately 120 community pharmacies in the Netherlands, to analyze the monthly prevalence and incidence rates of antipsychotic prescription among Dutch youth before and during the pandemic. The study also examined the prescribing patterns of the five most commonly used antipsychotics and conducted an autoregressive integrated moving average (ARIMA) analysis using data prior to the pandemic, to predict the expected prevalence rate during the pandemic. The prescription rate of antipsychotics for Dutch youth was slightly affected by the pandemic, with a monthly prevalence of 4.56 [4.50–4.62] per 1000 youths before COVID-19 pandemic and 4.64 [4.59–4.69] during the pandemic. A significant increase in prevalence was observed among adolescent girls aged 13–19 years. The monthly incidence rate remained stable overall, but rose for adolescent girls aged 13–19 years. Aripiprazole, and Quetiapine had higher monthly prevalence rates during the pandemic, while Risperidone and Pipamperon had lower rates. Similarly, the monthly incidence rates of Aripiprazole and Olanzapine went up, while Risperidone went down. Furthermore, the results from the ARIMA analysis revealed that despite the pandemic, the monthly prevalence rate of antipsychotic prescription was within expectation. The findings of this study suggest that there has been a moderate increase in antipsychotic prescription among Dutch youth during the COVID-19 pandemic, particularly in adolescent females aged 13–19 years. However, the study also suggests that factors beyond the pandemic may be contributing to the rise in antipsychotic prescription in Dutch youth. [ABSTRACT FROM AUTHOR]

BACKGROUND: Postoperative delirium in patients receiving head and neck surgery is a pressing concern, affecting morbidity, mortality, and healthcare costs. With an aging population and about 65,000 new head and neck cancer diagnoses per year in the United States, surgery remains a primary treatment modality, regardless of age. OBJECTIVES: This article offers an educational overview of postoperative delirium management in patients receiving head and neck surgery, summarizing incidence, etiology, pathophysiology, diagnostic tests, treatment, complications, and risk factors. METHODS: A narrative literature review of articles published in the past 10 years was conducted to consolidate information on postoperative delirium in patients receiving head and neck surgery. FINDINGS: Postoperative delirium is characterized by acute, fluctuating cognitive dysfunction within 30 days after surgery, with incidence ranging from 11% to 26%. Pathophysiology is multifactorial, and pharmacologic options are limited because of side effects and varying effectiveness. Nonpharmacologic management focuses on addressing underlying causes and early mobilization. Reducing postoperative delirium risk necessitates interprofessional, systemwide collaboration. [ABSTRACT FROM AUTHOR]

Schizophrenia (SCZ) is a complex neuropsychiatric disorder associated with altered bioenergetic pathways and mitochondrial dysfunction. Antipsychotic medications, both first and second-generation, are commonly prescribed to manage SCZ symptoms, but their direct impact on mitochondrial function remains poorly understood. In this study, we investigated the effects of commonly prescribed antipsychotics on bioenergetic pathways in cultured neurons. We examined the impact of risperidone, aripiprazole, amisulpride, and clozapine on gene expression, mitochondrial bioenergetic profile, and targeted metabolomics after 24-h treatment, using RNA-seq, Seahorse XF24 Flux Analyser, and gas chromatography–mass spectrometry (GC–MS), respectively. Risperidone treatment reduced the expression of genes involved in oxidative phosphorylation, the tricarboxylic acid cycle, and glycolysis pathways, and it showed a tendency to decrease basal mitochondrial respiration. Aripiprazole led to dose-dependent reductions in various mitochondrial function parameters without significantly affecting gene expression. Aripiprazole, amisulpride and clozapine treatment showed an effect on the tricarboxylic acid cycle metabolism, leading to more abundant metabolite levels. Antipsychotic drug effects on mitochondrial function in SCZ are multifaceted. While some drugs have greater effects on gene expression, others appear to exert their effects through enzymatic post-translational or allosteric modification of enzymatic activity. Understanding these effects is crucial for optimising treatment strategies for SCZ. Novel therapeutic interventions targeting energy metabolism by post-transcriptional pathways might be more effective as these can more directly and efficiently regulate energy production. [ABSTRACT FROM AUTHOR]

Accessible Summary: What is known on the subject?: Little is known about how mental health services can cause harm in ways other than medication, talking therapies, diagnosis and detention under the Mental Health Act.The outcomes of people who avoid seeking help from mental health services due to previous experiences of harm are not well known. What this article adds to existing knowledge?: I provide a first‐person perspective of experiences of harm within mental health services, how this impacted my care, the long‐term effects of the harm on my well‐being and my ongoing experiences of avoiding mental health services. What are the implications for mental health nursing?: Healthcare professionals should be aware of the multitude of ways service provision can harm patients, and how, unknown to professionals, patients may create an internal understanding of how to best navigate harmful service environments.Healthcare professionals should have a deeper understanding of the reasons why people may choose not to engage with mental health services, and what impact this may have on them. The recent announcement of the first ever statutory public inquiry into a UK mental health service indicates a growing recognition of iatrogenic harm in mental healthcare. Despite the potential for harm across all services and practices, restrictive practices, psychotherapy, diagnosis and psychiatric medications are often the only areas of mental healthcare given significant attention. While the topic is widely discussed in survivor communities, accounts of harm caused by the everyday workings of services, including team cultures, administrative processes and staff–patient interactions, are missing from academic literature. In this article, I describe my 10‐year journey through mental health services, and how everyday practices, cultures and staff behaviour deeply impacted my ability to receive appropriate care, replicated previously traumatic environments, and damaged my mental health. Taking steps to protect myself from further harm, I self‐discharged and am currently living as a 'service‐avoider'. The ongoing implications of this decision and the long‐term impacts of harm are discussed. [ABSTRACT FROM AUTHOR]

Background: Researchers often conduct small studies on testing a drug's efficacy in off-label indications. If positive results from these exploratory studies are not followed up by larger, randomized, double-blinded trials, physicians cannot be sure of a drug's clinical value. This may lead to off-label prescriptions of ineffective treatments. We aim to describe the way clinical studies fostered off-label prescription of the antipsychotic drug quetiapine (Seroquel). Methods: In this systematic meta-epidemiological analysis, we searched EMBASE, MEDLINE, Cochrane CENTRAL and PsycINFO databases and included clinical studies testing quetiapine for unapproved indications between May 1995 and May 2022. We then assessed the frequency with which publications providing low-level evidence suggesting efficacy of quetiapine for off-label indications was not followed up by large, randomized and double-blinded trials within 5 years. Results: In total, 176 published studies were identified that reported potential efficacy of quetiapine in at least 26 indications. Between 2000 and 2007, publication of exploratory studies suggesting promise for off-label indications rapidly outpaced publication of confirmatory trials. In the 24 indications with a minimum of 5 years of follow-up from the first positive exploratory study, 19 (79%) were not followed up with large confirmatory trials within 5 years. At least nine clinical practice guidelines recommend the use of quetiapine for seven off-label indications in which published confirmatory evidence is lacking. Conclusion: Many small, post-approval studies suggested the promise of quetiapine for numerous off-label indications. These findings generally went unconfirmed in large, blinded, randomized trials years after first being published. The imbalance of exploratory and confirmatory studies likely encourages ineffective off-label treatment. [ABSTRACT FROM AUTHOR]

Objective: Although antipsychotic medications are considered first-line treatment for psychosis, rates of discontinuation and nonadherence are high, and debate persists about their use. This pilot study aimed to explore the usability, feasibility, and potential impact of a shared decision making (SDM) intervention, the Antipsychotic Medication Decision Aid (APM-DA), for decisions about use of antipsychotic medications. Methods: A pilot randomized controlled trial was conducted with 17 participants in a first-episode psychosis program. Nine participants received the APM-DA, and eight received usual care. Results: After their appointments, intervention group participants had less decisional conflict and greater satisfaction with decisions than control group participants had. Use of the APM-DA did not increase appointment length. Comparison of the intervention outcomes with the control outcomes was limited because of the small sample. Conclusions: The results support the feasibility and usability of an SDM process via the use of the APM-DA in routine community psychosis care. [ABSTRACT FROM AUTHOR]

Objective: Previous research has suggested that demographic factors affect the likelihood of a patient with schizophrenia receiving a clozapine prescription. The authors aimed to determine the impact of race, social determinants of health, gender, rurality, and care patterns on clozapine prescription rates. Methods: This cross-sectional observational study used structured electronic health records data from 3,160 adult patients diagnosed as having schizophrenia between October 1, 2015, and November 30, 2021, in a multifacility health system. The social vulnerability index (SVI) was used to quantify social determinants of health. Descriptive data analysis, logistic regression, and sensitivity analysis were conducted to identify differences between patients with schizophrenia who received a clozapine prescription and those who received antipsychotic medications other than clozapine. Results: Overall, 401 patients with schizophrenia were given a clozapine prescription during the study period, and 2,456 received antipsychotics other than clozapine. Results of the logistic regression indicated that White race (OR=1.71, compared with Black race), community minority status and language SVI score (OR=2.97), and increased treatment duration (OR=1.36) were significantly associated with a higher likelihood of clozapine prescription; gender, rurality, age at first diagnosis, and ethnicity did not influence the likelihood of receiving clozapine. Conclusions: Black patients with schizophrenia had a lower likelihood of receiving a clozapine prescription compared with White patients, even after analyses accounted for demographic variables, social determinants of health, and care access patterns. Given the effectiveness of clozapine in managing treatment-resistant schizophrenia, it is crucial for future research to better understand the factors contributing to this treatment disparity. [ABSTRACT FROM AUTHOR]

Background: Sexual dysfunction is the most frequent health problem among psychiatric patients. This could be the result of both the nature of the illness itself and the side effects of prescribed psychotropic medications. It also significantly affects an individual's general well-being, interpersonal relationships, self-esteem, and treatment outcomes. Therefore, the current systematic review and meta-analysis was conducted to determine the combined prevalence of sexual dysfunction and its correlated factors among people with mental illness. Methods: We retrieved eligible primary studies using various search databases like PubMed, EMBASE, Science Direct, African Journal Online, Google Scholar, and Psychiatry Online. The report of this systematic review was reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. We used standardized data extraction checklists and STATA version 14 for data extraction and analysis, respectively. The I-squared statistics test was used to check statistical heterogeneity within the included articles. Publication bias was assessed using a funnel plot and the Egger test. To estimate the overall prevalence and correlated factors of sexual dysfunction, a random effects model meta-analysis was employed. Results: In this meta-analysis, a total of 15 primary studies with 2849 psychiatric patients were included. The overall pooled prevalence of sexual dysfunction among psychiatric patients in Africa was 58.42% (95% CI: 49.55, 67.28). Having older age (OR = 1.92, 95% CI: 1.28, 2.87), longer duration of illness (OR = 2.60, 95% CI: 1.14, 5.93), history of relapse (OR = 3.51, 95% CI: 1.47, 8.43), poor quality of life (OR = 3.89, 95% CI: 2.15, 7.05), and antipsychotic medications (OR = 2.99, 95% CI: 1.84, 4.86) were significantly associated with sexual dysfunction. Conclusion: This meta-analysis revealed that approximately two-thirds of psychiatric patients in Africa are affected by sexual dysfunction. Therefore, the findings of this study recommend that when evaluating psychiatric patients, health professionals should focus more on sexual dysfunction. It is also essential to promote awareness and incorporate sexual health assessment and intervention into mental health services to reduce the overall burden of the problem. [ABSTRACT FROM AUTHOR]

Background: Stevens–Johnson syndrome-toxic epidermal necrolysis (SJS-TNE) overlap is a rare skin disorder characterized by erythema, blisters, extensive exfoliation, epidermal detachment, the involvement of multiple mucosae, and positive Nikolsky's sign. SJS-TEN has a high mortality rate. Our case involves a rare occurrence of drug-induced Stevens–Johnson syndrome-toxic epidermal necrolysis overlap with a delayed onset in the setting of quetiapine and famotidine therapy. Case presentation: An 82-year-old Taiwanese female was admitted to our hospital for decreased urine output, generalized edema, and multiple skin blisters and bedsores. With further spread of the lesions, multiple ruptured bullae with shallow erosions on the face, trunk, and limbs and mucosal involvement affected 20% of the total body surface area. Nikolsky's sign was positive. A diagnosis of Steven–Johnson syndrome was highly suspected. One month prior, she had started famotidine and quetiapine. Intravenous methylprednisolone treatment was initiated, which ameliorated the skin lesions after 3 days. However, new lesions developed after only 1 day of methylprednisolone tapering. The patient died 12 days after admission. Conclusion: Stevens–Johnson syndrome-toxic epidermal necrolysis is a rare skin disorder. Although it is mainly acute and has a high mortality rate, delayed onset can still occur. Quetiapine and famotidine are generally safe and effective for treating geriatric and gastrointestinal problems, but rare drug hypersensitivity reactions can lead to debilitating consequences. Therefore, increased clinical awareness and the initiation of supportive care are imperative. Optimal management guidelines are still lacking, and confirmation of developed guidelines through randomized controlled trials is needed. Collaboration for better management strategies is warranted. [ABSTRACT FROM AUTHOR]

A novel antipsychotic medication named brexpiprazole (BRX) is currently employed for the treatment of schizophrenia and other psychotic disorders. Because BRX's molecular structure includes a benzothiophene ring, it natively fluoresces. To detect BRX with precision and speed, a flow injection-fluorometric method, which is both sensitive and selective, is recommended. The fluorescence detection was conducted at 364 nm following excitation at 326 nm to capture the strong intrinsic fluorescence of BRX. The carrier solution employed was a mixture of phosphate buffer (pH 4, 10 mM) and acetonitrile (50: 50, v/v), with a flow rate of 0.5 mL min− 1. The calibration curve, based on peak areas, exhibited linearity within the concentration range of 20–350 ng mL− 1, with a remarkable correlation coefficient (r2) of 0.9999. The limit of quantitation was 9.7 ng mL− 1, and the limit of detection was found to be 3.2 ng mL− 1. This method was applied to quantify BRX in Neopression® tablets, achieving recovery within an acceptable range without interference from the tablet's additives. Additionally, the proposed approach was successfully utilised to quantify the drug in spiked human plasma. The approach underwent validation following ICH requirements. [ABSTRACT FROM AUTHOR]

Background: Atypical antipsychotics (AAPs)-induced sexual dysfunction (SD) is a frequent issue in clinical practice, often underestimated by clinicians and not extensively researched. The current study aimed to quantify the strength of association between the use of different AAPs and SD using real-world data from the FDA Adverse Event Reporting System (FAERS), as well as investigate the receptor mechanisms that are involved. Methods: Data from the FAERS database from the first quarter of 2004 to the third quarter of 2023 were queried through OpenVigil 2.1. Disproportionality analysis was estimated using the reporting odds ratio (ROR) and information component (IC) methods, and linear regression was used to investigate the relationship between ROR and receptor occupancy which was estimated using in vitro receptor binding profiles. Results: Our analysis yielded 4839 reports that co-mentioned AAP and SD events, and the findings revealed statistical associations between 12 AAPs and SD. The highest signal value was identified for iloperidone reporting retrograde ejaculation with iloperidone (ROR = 832.09, ROR025 = 552.77; IC = 9.58, IC025 = 6.36), followed by compulsive sexual behavior with aripiprazole (ROR = 533.02, ROR025 = 435.90; IC = 7.30, IC025 = 5.97), and psychosexual disorder for aripiprazole (ROR = 145.80, ROR025 = 109.57; IC025 = 6.47, IC025 = 4.86). Different characteristics of the SD side effects in each AAPs were discovered after further data mining. Regression analysis revealed potential effects for receptor occupancy of D2, D3, and 5-HT1A receptors on ROR. However, no significant correlation persisted following sensitivity analyses. Conclusion: This is the first study to investigate the AAP-SD associations by using FAERS. In this study, we report for the first time a significant association between aripiprazole and SD based on real-world data. The study suggests that different AAPs have varying levels of association with SD, and the D2, D3, and 5-HT1A receptor occupancy may contribute to potential mechanisms. The findings of this study warrant further validation of more studies and clinical causality assessment. [ABSTRACT FROM AUTHOR]

Background and Objectives: The aim of this analysis was to evaluate the long-term safety and effectiveness of lurasidone in the treatment of schizophrenia in adolescents and young adults (13–25). Methods: The 2 pooled studies used similar designs and outcome measures. Patients (13–25) with schizophrenia completed an initial double-blind 6-week trial of lurasidone (40 and 80 mg/day) in the adolescent trial and (80 and 160 mg/day) in the young adult trial. In open-label long-term trials, adolescent patients were treated with 20–80 mg/day lurasidone, and adults were treated with 40–160 mg/day lurasidone. Efficacy was evaluated based on the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity Scale (CGI-S). Results: The safety population consisted of 306 patients (mean age, 16.2 years; 208 patients (68.0%) who completed 12 months of treatment; 8.2% who discontinued treatment by 12 months due to an adverse event). The mean (SD) changes in the PANSS total score from the extension baseline to months 6 and 12 were − 11.8 (13.9) and – 15.3 (15.0), respectively (OC), and the mean (SD) changes in the CGI-S score were − 0.8 (1.0) and − 1.0 (1.1), respectively (OC). The most frequent adverse events were headache (17.6%), anxiety (11.4%), schizophrenia (9.8%), and nausea (9.8%). No clinically meaningful changes were observed in weight, metabolic parameters, or prolactin. Conclusions: In adolescents and young adults with schizophrenia, treatment with lurasidone was generally well tolerated and effective. Long-term treatment was associated with a continued reduction in symptoms of schizophrenia. Long-term treatment was associated with minimal effects on weight, metabolic parameters, and prolactin. Clinicaltrials.gov identifiers D1050234, D1050302. [ABSTRACT FROM AUTHOR]

Background: Aripiprazole is the most frequently recommended antipsychotic for the treatment of tics in children and adolescents with Tourette's disorder (TD). However, to date, a randomized controlled trial for aripiprazole oral solution has not been conducted despite being widely preferred by children. Therefore, we examined whether aripiprazole oral solution is effective for treating tics. Methods: All patients received a flexible dose of aripiprazole oral solution (1 mg/mL, range: 2–20 mg) with a starting dose of 2 mg. The target dose for patients weighing < 50 kg was 2, 5, and 10 mg/day, and that for patients weighing ≥ 50 kg was 5, 10, 15, and 20 mg/day. The primary efficacy endpoint was the mean change in the Yale Global Tic Severity Scale-total tic score (YGTSS-TTS) from baseline to week 8. Results: Of the 121 patients enrolled, 59 patients (96.7%) in the aripiprazole group and 53 patients (88.3%) in the placebo group completed the study. The aripiprazole group showed significantly greater improvement in the YGTSS-TTS from baseline to week 8 than the placebo group (least squares mean difference [95% confidence interval (CI)] −5.5 [95% CI − 8.4 to − 2.6]). At week 8, the response rate (i.e., percentage of patients with a Tourette's Syndrome Clinical Global Impression-Improvement score of 1 or 2) of the aripiprazole group (86.4%) was significantly higher than that of the placebo group (56.6%; odds ratio: 3.6, p < 0.001). The incidence of treatment-emergent adverse events (TEAEs) reported in at least one patient was 86.9% in the aripiprazole group and 65.5% in the placebo group. All TEAEs were mild or moderate in severity. No serious adverse events or deaths occurred during the study. Conclusions: Our findings suggest that aripiprazole oral solution is an effective, well-tolerated, and safe treatment for children and adolescents with TD. Trial registration: ClinicalTrials.gov Identifier: NCT03487783. Registered 4 April 2018. [ABSTRACT FROM AUTHOR]

Background: Antipsychotics are widely used in the elderly due to the high prevalence of neuropsychiatric associated with dementia. Objective: To analyze potential disparities in antipsychotic use in the general population of Gipuzkoa by socioeconomic status (SES) and diagnosis of Alzheimer's disease and related dementia (ADRD) adjusting for somatic and psychiatric comorbidities, age, and sex. Methods: A retrospective observational study was carried out in all the 221,777 individuals over 60 years of age (Gipuzkoa, Spain) to collect diagnosis of ADRD, the Charlson Comorbidity Index, and psychiatric comorbidities considering all primary, outpatient, emergency and inpatient care episodes and first- and second-generation antipsychotics, and sociodemographic variables, namely, age, sex, SES and living in a nursing home. Logistic regression was used for multivariate statisticalanalysis. Results: Use of any antipsychotic was greater in women, individuals over 80 years old, living in a nursing home, with a diagnosis of dementia, somatic and psychiatric comorbidities, and low SES. Quetiapine was the most used drug. The likelihood of any antipsychotic use was significantly associated with low SES (odds ratio [OR]: 1.60; confidence interval [CI]: 1.52–1.68), age over 80 years (OR: 1.56; CI: 1.47–1.65), institutionalization (OR: 12.61; CI: 11.64–13.65), diagnosis of dementia (OR: 10.18; CI: 9.55–10.85) and the comorbidities of depression (OR: 3.79; CI: 3.58–4.01) and psychosis (OR: 4.96; CI: 4.64–5.30). Conclusions: The greater levels of antipsychotic use and institutionalization in people of low SES indicate inequity in the management of neuropsychiatric symptoms. Increasing the offer of non-pharmacological treatments in the health system might help reduce inequity. [ABSTRACT FROM AUTHOR]

Background: The risk of arrhythmia is usually assessed by the length of the corrected QT interval (QTc) when patients use antipsychotics. Prolonged QTc intervals are thought to increase the probability of malignant ventricular arrhythmias, and if we focus only on the QTc interval, we may be influenced by a single factor and make decisions that are not conducive to effective treatment. The index of cardiac electrophysiological balance (iCEB) is considered more valuable than the QTc for predicting drug-induced arrhythmias. It has been used in clinical practice, but no studies have observed changes in this index after the use of antipsychotics. Objective: To investigate the changes in ventricular repolarization indices and the occurrence of arrhythmias in patients who have been using antipsychotic drugs for a long time, to compare the changes in iCEBc and QTc and to predict abnormal iCEBc values. Methods: Patients with schizophrenia who had been hospitalized for more than 4 years and who were receiving atypical antipsychotics underwent a 12-lead synchronized electrocardiogram (ECG) every 2–4 weeks. The baseline data were measured at admission, defined as the baseline (time0), and the most obvious abnormal changes in ventricular depolarization and repolarization measured every 12 months were one-year follow-up (time1), two-year follow-up (time2), three-year follow-up (time3), and four-year follow-up (time4). Repeated measures analysis of variance was used for comparisons. The types and doses of drugs taken at 5 time points were recorded and converted into chlorpromazine equivalents for comparison. The incidence of arrhythmia during the observation cycle was recorded. Results: The patients had been treated with antipsychotic medication for 4 years, and the duration of the QRS wave was longer in males than in females. TpTe, TpTe/QRS, TpTe/QT, TpTe/QTc, iCEB, and iCEBc increased significantly with hospital stay, while TpTe, TpTe/QRS, TpTe/QT, and TpTe/QTc exhibited more obvious changes in these indicators in female patients (P < 0.01). The changes in iCEB and iCEBc were more significant in males (P < 0.01). The incidences of arrhythmia (arrhythmic events included premature ventricular beats and premature atrial beats) within 5 time points were 2.5%, 6.25%, 6.25%, 6.25% and 5%, respectively. More than 90% of patients treated with antipsychotics did not have any arrhythmias. No TdP syncope or other cardiovascular symptoms were found in any of the patients. Conclusion: After long-term use of antipsychotics, the ventricular repolarization index gradually increased with time. The new ventricular repolarization indices iCEB and iCEBc were more sensitive than the QTc at predicting arrhythmia. According to the abnormal QTc values in men and women, we predict that the abnormal value of the iCEBc in males is 4.528 and that in females is 5.315. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a lifelong metabolic disorder that impacts people's well-being and biopsychosocial status. Psychiatric problems and diabetes mellitus have a complex, reciprocal interaction in which one condition affects the other. In this narrative review, we provide an overview of the literature on the psychological effects of diabetes, expound on the evaluation of emotional disorders in the setting of diabetes, and suggest interventions aimed at enhancing both mental and physical health. Diabetes can make daily life complicated and stressful. Frequent blood glucose testing, taking medications on a regular basis, adhering to a tight diet plan, and exercising are some examples of the suggested daily routine of subjects with diabetes. Furthermore, comorbid diseases and typical diabetic complications can have a detrimental impact on quality of life. When mental health conditions coexist with diabetes mellitus, there is a greater likelihood of medication noncompliance, a decreased commitment to diabetes-related self-care, increased functional impairment, inadequate glycemic control, a higher risk of complications, and overall higher healthcare expenses. Thus, evaluation of the mental health status of patients with diabetes is crucial. When treating psychological issues and psychiatric disorders, a comprehensive biopsychosocial approach should be taken, and where appropriate, psychopharmacological therapies or psychotherapy should be applied. The goal of continuous education and assistance for self-care is to give individuals with the disease the information and abilities they need to control their condition over time. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions Prescribing of antidepressant and antipsychotic drugs in general populations has increased in the United Kingdom, but prescribing trends in people with type 2 diabetes (T2D) have not previously been investigated. The aim of this study was to describe time trends in annual prevalence of antidepressant and antipsychotic drug prescribing in adult patients with T2D.We conducted repeated annual cross‐sectional analysesof a population‐based diabetes registry with 99% coverage, derived from primary and secondary care data in Scotland, from 2004 to 2021. For each cross‐sectional calendar year time period, we calculated the prevalence of antidepressant and antipsychotic drug prescribing, overall and by sociodemographic characteristics and drug subtype.The number of patients with a T2D diagnosis in Scotland increased from 161 915 in 2004 to 309 288 in 2021. Prevalence of antidepressant and antipsychotic prescribing in patients with T2D increased markedly between 2004 and 2021 (from 20.0 per 100 person‐years to 33.3 per 100 person‐years and from 2.8 per 100 person‐years to 4.7 per 100 person‐years, respectively). We observed this pattern for all drug subtypes except for first‐generation antipsychotics, prescribing of which remained largely stable. The degree of increase, as well as the overall prevalence of prescribing, differed by age, sex, socioeconomic status and subtype of drug class.There has been a marked increase in the prevalence of antidepressant and antipsychotic prescribing in patients with T2D in Scotland. Further research should identify the reasons for this increase, including indication for use and the extent to which this reflects increases in incident prescribing rather than increased duration. [ABSTRACT FROM AUTHOR]

Introduction: Psychiatric patients suffer from oral diseases and side effects of antipsychotic medication. In particular, the typical antipsychotic drugs may cause severe hyposalivation with subsequent oral symptoms. We therefore aimed to compare oral health behavior and oral side effects of in-hospital patients taking typical vs. atypical antipsychotic drugs with the hypothesis that the former drugs cause more oral pain than the newer drugs. Methods: This cross-sectional questionnaire and interview study investigated subjective oral symptoms and their health behavior in 170 hospitalized psychiatric patients, comparing those taking typical vs. atypical antipsychotic drugs. Cross-tabulations and chi-square tests were used for analyses. Results: Persistent oral pain lasting throughout the day was reported by 46% in the typical, and 5% in the atypical antipsychotic group patients, respectively. In both groups, the pain was mainly in the tongue and buccal mucosa and was described as a burning sensation. A significantly higher prevalence of xerostomia was reported in the typical antipsychotic medication group (66%) compared with the atypical antipsychotic medication group (53%, p<0.01). Self-assessed dental health was assessed as poor by two-thirds of the patients of whom 69% reported toothbrushing once daily. Approximately half of them reported having had a visit to a dentist within the previous year. Of the women 28%, and of the men 17%, respectively, had received professional consultations for oral symptoms. Conclusion: The current results on psychiatrically hospitalized patients emphasize the need for awareness of oral discomfort and its subsequent effects on the quality of life in this challenging patient group. Focus should also be placed on a wide range of support encouraging the patients to maintain good daily oral hygiene and seek professional dental help when needed. [ABSTRACT FROM AUTHOR]

Background: Rash is one of common adverse drug reaction and which have been reported in typical and atypical antipsychotics. Reports of lurasidone induced skin reactions are sparse. In this study, we report a case of rash caused by lurasidone. Case presentation: A 63-year-old man with bipolar disorder (BD) who is treated by lurasidone. However, the patient presents a rash all over after lurasidone dose increasing from 40 mg/day to 60 mg/day. With the diagnosis of drug induced rash, lurasidone was discontinued, and the rash complete disappears within 2 weeks. In addition, all case reports about antipsychotics associated rash were reviewed by searching English and Chinese database including Pubmed, Embase, Cochrane Library, CNKI and Wanfang database. A total of 139 articles contained 172 patients were included in our study. The literature review and our case suggest that the cutaneous adverse events caused by antipsychotic drugs should not be ignored, particularly for the patient who was first use or at dose increasing of antipsychotic. Conclusions: In conclusion, we report a case of lurasidone related rash and review rash caused by antipsychotics. Psychiatrists should be alert to the possibility of the rash caused by antipsychotics, especially the patient was first use of antipsychotics or the antipsychotic dose was increasing. [ABSTRACT FROM AUTHOR]

Background: Delirium is a common disorder affecting patients' psychiatric illness, characterized by a high rate of underdiagnosis, misdiagnosis, and high risks. However, previous studies frequently excluded patients with psychiatric illness, leading to limited knowledge about risk factors and optimal assessment tools for delirium in psychiatric settings. Objectives: The scoping review was carried out to (1) identify the risk factors associated with delirium in patients with psychiatric illness; (2) synthesize the performance of assessment tools for detecting delirium in patients with psychiatric illness in psychiatric settings. Design: Scoping review. Data sources: PubMed, Web of Science, and Embase were searched to identify primary studies on delirium in psychiatric settings from inception to Dec 2023 inclusive. Two independent reviewers screened eligible studies against inclusion criteria. A narrative synthesis of the included studies was conducted. Results: A final set of 36 articles meeting the inclusion criteria, two main themes were extracted: risk factors associated with delirium in patients with psychiatric illness and assessment tools for detecting delirium in psychiatric settings. The risk factors associated with delirium primarily included advanced age, physical comorbid, types of psychiatric illness, antipsychotics, anticholinergic drug, Electroconvulsive therapy, and the combination of lithium and Electroconvulsive therapy. Delirium Rating Scale-Revised-98, Memorial Delirium Assessment Scale, and Delirium Diagnostic Tool-Provisional might be valuable for delirium assessment in patients with psychiatric illness in psychiatric settings. Conclusions: Delirium diagnosis in psychiatric settings is complex due to the overlapping clinical manifestations between psychiatric illness and delirium, as well as their potential co-occurrence. It is imperative to understand the risk factors and assessment methods related to delirium in this population to address diagnostic delays, establish effective prevention and screening strategies. Future research should focus on designing, implementing, and evaluating interventions that target modifiable risk factors, to prevent and manage delirium in patients with psychiatric illness. What is already known about the topic?: • Delirium is common among individuals living in psychiatric settings and remains clinically under-detected, and it is associated with the length of hospital stay and poor prognoses. • Dementia with behavioral and psychological symptoms of dementia (BPSD) and other psychiatric illnesses has been shown to make delirium more likely. However, despite extensive research on factors associated with delirium, there is a notable lack of studies conducted in psychiatric settings. • Early detection and identification of delirium are crucial in psychiatric settings; however, literature regarding the assessment and identification of delirium has not been synthesized, particularly in the context of comorbid psychiatric illness. What this paper adds?: • Risk factors associated with delirium in patients with psychiatric illness primarily include advanced age, physical comorbid, types of psychiatric illness, antipsychotics, anticholinergic drug, Electroconvulsive therapy (ECT), and the combination of lithium and ECT. • Delirium Rating Scale-Revised-98, Memorial Delirium Assessment Scale, and Delirium Diagnostic Tool-Provisional might hold promising value as assessment tools for delirium in patients with psychiatric illness in psychiatric settings. [ABSTRACT FROM AUTHOR]

Predictive processing is a computational framework that aims to explain how the brain processes sensory information by making predictions about the environment and minimizing prediction errors. It can also be used to explain some of the key symptoms of psychotic disorders such as schizophrenia. In recent years, substantial advances have been made in our understanding of the neuronal circuitry that underlies predictive processing in cortex. In this review, we summarize these findings and how they might relate to psychosis and to observed cell type–specific effects of antipsychotic drugs. We argue that quantifying the effects of antipsychotic drugs on specific neuronal circuit elements is a promising approach to understanding not only the mechanism of action of antipsychotic drugs but also psychosis. Finally, we outline some of the key experiments that should be done. The aims of this review are to provide an overview of the current circuit-based approaches to psychosis and to encourage further research in this direction. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of lurasidone on a new, patient Life Engagement scale in schizophrenia. Patients and Methods: This post-hoc analysis included participants (ages 18 to 74) diagnosed with schizophrenia who were randomized to lurasidone (40 mg/day) or placebo in a 6-week double-blind efficacy study and those who continued in a subsequent 12-week open-label extension study during which patients received either 40 or 80/mg day lurasidone (flexibly dosed). Change in life engagement was measured using the Positive and Negative Syndrome Scale (PANSS) 11-item Life Engagement subscale score, and individual subscale items, at week 6 during the double-blind phase and extension phase week 12 during the open-label extension phase. Results: Analysis focused on 478 subjects randomized to lurasidone or placebo during the 6-week trial, and 146 who received lurasidone during the extension phase. During the 6-week trial, there was a significantly greater change on the PANSS11 Life Engagement subscale score from baseline to week 6 in the lurasidone group compared to the placebo group (mean changes of − 6.4 and − 4.8, respectively, p = 0.006; effect size = 0.27). Further improvement was evident during the extension phase for patients who received lurasidone in both phases, with a mean change from double-blind baseline to week 12 of the open-label treatment phase of − 10.1 on in PANSS11 Life Engagement subscale. Conclusion: This post-hoc analysis suggests that lurasidone may improve life engagement in patients with schizophrenia, a meaningful outcome from patients' perspective. Further studies are needed to confirm this effect. Eudract Number: Trial registration: EudraCT Numbers: 2016-000060-42; 2016-000061-23. [ABSTRACT FROM AUTHOR]

Clozapine is an antipsychotic drug whose accumulation in white cells can sometimes prove toxic; understanding the transporters and alleles responsible is thus highly desirable. We used a strategy in which a yeast (Saccharomyces cerevisiae) CRISPR-Cas9 knock-out library was exposed to cytotoxic concentrations of clozapine to determine those transporters whose absence made it more resistant; we also recognised the structural similarity of the fluorescent dye safranin O (also known as safranin T) to clozapine, allowing it to be used as a surrogate marker. Strains lacking the mitochondrial ABC transporter MDL1 (encoded by YLR188W) showed substantial resistance to clozapine. MDL1 overexpression also conferred extra sensitivity to clozapine and admitted a massive increase in the cellular and mitochondrial uptake of safranin O, as determined using flow cytometry and microscopically. Yeast lacking mitochondria showed no such unusual accumulation. Mitochondrial MDL1 is thus the main means of accumulation of clozapine in S. cerevisiae. The closest human homologue of S. cerevisiae MDL1 is ABCB10. [ABSTRACT FROM AUTHOR]