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Background and Purpose: Despite the wide use of dopamine receptor blocking agents (DRBAs) in Huntington disease (HD), neuroleptic malignant syndrome (NMS) is rarely described in this population. The aim of this study was to assess NMS prevalence in a large cohort of HD patients and explore the main associated risk factors. Methods: In 2023, an HD patient was admitted to our neurology department due to NMS. Starting from the case description, we performed a narrative review of the literature of NMS cases in HD, reviewed data from the fifth dataset of the Enroll‐HD (a longitudinal, observational, global study of families with HD) study (PDS5) selecting HD patients treated with DRBAs and/or tetrabenazine (TBZ) who presented at least one of the core symptoms of NMS (rigidity and hyperthermia), and collected data to investigate prevalence of NMS and identify risk factors. Results: In the Enroll‐HD PDS5 dataset, we identified 5108 of 11,569 HD patients who were undergoing DRBA and/or TBZ treatment. Only one patient, a Caucasian man of 46 years, undergoing clozapine and valproate treatment, had a registered diagnosis of NMS. Conclusions: NMS in HD patients is seldom described. This could be due to an underestimation of this condition. There are no available objective NMS diagnostic criteria at present, and the existence of atypical forms of NMS further complicates diagnosis. Advanced disease stage, rigid–akinetic phenotype, abrupt therapy changes, polytherapy, and dehydration are key risk factors, most of which are preventable through awareness and caution in managing medications in the HD population. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion Psychopharmacotherapy plays an important role in the treatment of mentally disordered offenders (MDOs) with schizophrenia spectrum disorders. However, there have been few large‐scale reports from multiple forensic psychiatric wards. This study aimed to clarify the current state of antipsychotic medications for MDOs with schizophrenia spectrum disorders in Japanese forensic psychiatric wards.Medical information, including age, sex, psychiatric diagnosis, index offense, seclusion or restraint experience during hospitalization, and medication for patients discharged from 32 forensic wards nationwide between September 1, 2019 and December 31, 2021 was provided by the Database Scientific Utilization Project of Japanese forensic psychiatric wards. We analyzed the data of MDOs with schizophrenia spectrum disorders who were prescribed psychotropic medications at the time of discharge, especially focusing on comparing differences between the three groups (clozapine, long‐acting injection (LAI), and other medications).A total of 362 MDOs with schizophrenia spectrum disorders were prescribed psychotropic medications at discharge. The prescription rates of clozapine and LAI were 23.2% and 24.9%, respectively. Additionally, the rate of antipsychotic polypharmacy was 37.8%. Among the three groups, the clozapine group had the highest rate of seclusion experience (46.4%), a long mean length of hospitalization (1758 days), and the lowest rate of antipsychotic polypharmacy (4.8%). Olanzapine was the most commonly prescribed antipsychotic medication.This study revealed the current state of antipsychotic medications for MDOs admitted to forensic psychiatric wards in Japan. Future studies are needed to clarify the relevance of antipsychotic medications in the prognosis of MDOs. [ABSTRACT FROM AUTHOR]

Objective: This study aims to summarize and critically evaluate the effects of traditional Chinese exercises, both in isolation and in combination with medical treatments, on cognitive impairment. Methods: A systematic search of academic databases, including PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP, was conducted to identify the randomized controlled trials (RCTs) that evaluated traditional Chinese exercises and their integration with medical treatments for addressing cognitive impairment. Study quality was assessed using the Cochrane Handbook's Risk of Bias tool. A total of 24 RCTs involving 1,808 participants were included. The primary outcome measures were the Montreal Cognitive Assessment (MOCA) and the Mini-Mental State Examination (MMSE). Subgroup analyses were performed to compare the intervention effects. Results: The network meta-analysis revealed that acupuncture combined with Tai Chi (Aandtaiji) showed the most significant improvement in MOCA scores, followed by Qigong. Tai Chi soft ball exercise (Taijiball) demonstrated the greatest improvement in MMSE scores. Conclusion: The combination of traditional Chinese exercises with medical treatment is more effective in improving MOCA scores, while traditional exercises alone yield better results to enhance MMSE scores. The extended practice of Tai Chi and Qigong enhances cognitive function in patients with cognitive impairment. [ABSTRACT FROM AUTHOR]

Delirium can result in undesirable outcomes including increased length of stays and mortality in patients admitted to the intensive care unit (ICU). Dexmedetomidine has emerged for delirium prevention in these patients; however, optimal dosing is challenging. A reinforcement learning-based Artificial Intelligence model for Delirium prevention (AID) is proposed to optimize dexmedetomidine dosing. The model was developed and internally validated using 2416 patients (2531 ICU admissions) and externally validated on 270 patients (274 ICU admissions). The estimated performance return of the AID policy was higher than that of the clinicians' policy in both derivation (0.390 95% confidence interval [CI] 0.361 to 0.420 vs. −0.051 95% CI −0.077 to −0.025) and external validation (0.186 95% CI 0.139 to 0.236 vs. −0.436 95% CI −0.474 to −0.402) cohorts. Our finding indicates that AID might support clinicians' decision-making regarding dexmedetomidine dosing to prevent delirium in ICU patients, but further off-policy evaluation is required. [ABSTRACT FROM AUTHOR]

Background: Immune dysregulation has been identified as a contributing factor in the pathophysiology of schizophrenia. This study aimed to investigate variations in specific immune regulators and their correlation with psychopathology and cognitive functions in male patients with chronic schizophrenia. Methods: Employing a cross-sectional design, this study included 72 male patients with chronic schizophrenia. The Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status were utilized to assess psychopathology and cognitive functions, respectively. Results: Serum levels of interleukin (IL)-4, IL-10, IL-12p40, IL-13, and monocyte chemoattractant protein-1 (MCP-1) were measured. There were significantly increased levels of IL-4, IL-13, and MCP-1, alongside decreased levels of IL-10 in patients compared to controls (all P < 0.05). IL-4 levels showed a significant negative association with PANSS positive symptoms (beta=-0.222, P = 0.042). After controlling for antipsychotic medication, BMI, and smoking, this correlation was no longer significant (r=-0.232, P = 0.055). Additionally, positive correlations of IL-4 (beta = 0.297, P = 0.008), IL-13 (beta = 0.371, P = 0.001), and MCP-1 (beta = 0.280, P = 0.013) with language scores were observed. Increased levels of IL-4 (P = 0.044, OR = 1.994), IL-13 (P = 0.019, OR = 2.245), as well as IL-4 and MCP-1 interactions (P = 0.043, OR = 2.000) were positively associated with the risk of chronic schizophrenia, while lower levels of IL-10 (P = 0.003, OR = 0.2.867) were also linked to an increased risk. Conclusion: The identified associations between specific immune markers and the clinical and cognitive features of chronic schizophrenia in males underscored the potential immune-mediated mechanisms underlying schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia (SCZ) is a chronic, disabling mental illness with a high disease burden and is often comorbid with metabolic syndrome (MetS). The aim of this study was to determine the prevalence of MetS in young, clinically stable, olanzapine-exposed patients with SCZ and to explore predictive factors affecting the development and severity of MetS. Methods: A total of 274 patients with SCZ who met the inclusion criteria were enrolled in this study, and their demographic data and general clinical information were collected. Concurrently, patients were assessed for psychopathology, illness severity, and antipsychotic drug–related adverse effects. Results: The prevalence of MetS in the target population was 35.77%, and the MetS subtype of abdominal obesity + high triglycerides + low level of high-density lipoprotein cholesterol accounted for the majority of patients in the MetS subgroup. Binary logistic regression showed that body mass index (BMI), uric acid (UA), thyroid-stimulating hormone, and QT-c interval could significantly and positively predict the development of MetS. Multiple linear regression showed that olanzapine concentration, BMI, and UA could significantly and positively predict higher MetS scores. Conclusion: This study reports the clinical patterns of MetS in young, clinically stable, olanzapine-exposed patients with SCZ and identifies the correlations influencing the development and severity of MetS. These findings could potentially be applied toward the prevention of and intervention in MetS. [ABSTRACT FROM AUTHOR]

Understanding the relationship between the concentration of a drug and its therapeutic efficacy or side effects is crucial in drug development, especially to understand therapeutic efficacy in central nervous system drug, quantifying drug-induced site-specific changes in the levels of endogenous metabolites, such as neurotransmitters. In recent times, evaluation of quantitative distribution of drugs and endogenous metabolites using matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry imaging (MSI) has attracted much attention in drug discovery research. However, MALDI-MSI quantification (quantitative mass spectrometry imaging, QMSI) is an emerging technique, and needs to be further developed for practicable and convenient use in drug discovery research. In this study, we developed a reliable QMSI method for quantification of clozapine (antipsychotic drug) and dopamine and its metabolites in the rat brain using MALDI-MSI. An improved mimetic tissue model using powdered frozen tissue for QMSI was established as an alternative method, enabling the accurate quantification of clozapine levels in the rat brain. Furthermore, we used the improved method to evaluate drug-induced fluctuations in the concentrations of dopamine and its metabolites. This method can quantitatively evaluate drug localization in the brain and drug-induced changes in the concentration of endogenous metabolites, demonstrating the usefulness of QMSI. [ABSTRACT FROM AUTHOR]

In an online, survey-based experiment, musculoskeletal surgeon members of the science of variation group (n = 243) and a group of consult-liaison psychiatrists (n = 18) read 5 hypothetical scenarios of patients recovering from musculoskeletal trauma, each containing 5 randomized patient variables, and indicated their recommendation for psychiatry consultation or not. Factors associated with recommendation for psychiatry consultation included younger age, history of a psychiatric disorder, and pre-injury use of antipsychotic medications, and scenarios involving psychosis, suicidality, hallucinations in the setting of substance withdrawal, and questionable capacity for informed consent, but not with sadness alone. Musculoskeletal surgeons can collaborate with psychiatrists to develop comprehensive care for inpatients with musculoskeletal trauma starting with relatively pressing mental health needs and perhaps expanding into treatment of sadness or worry that can manifest as greater symptom intensity and a delayed recovery trajectory. [ABSTRACT FROM AUTHOR]

In this study, we aimed to investigate the nationwide utilization of antipsychotic drugs (APDs) during radiotherapy and evaluate their association with survival in patients with breast cancer. This retrospective cohort study used the National Health Insurance Service database in Korea and included patients diagnosed with breast cancer from 2010 to 2020 who received radiotherapy. The APDs included in the analysis were aripiprazole, quetiapine, olanzapine, risperidone, haloperidol, and chlorpromazine, and the APD prescription details included prescription time, dosage, and duration. Among 170,226 patients with breast cancer treated with radiotherapy, 3361 (1.97%) received APD during radiotherapy. Use of APDs was significantly associated with higher mortality in all patients and in a subgroup of patients excluding those with metastasis or other cancers. Among patients taking APD during radiotherapy, those with accompanied psychiatric history and long-term APD use for ≥ 3 months were associated with lower mortality, whereas patients who started APD during radiotherapy had higher mortality than those who started APD before radiotherapy. The high mortality observed in breast cancer patients using APDs during radiotherapy could be influenced by the underlying conditions that necessitated APD use. Further studies are needed to determine the effects of APDs during radiotherapy in patients with breast cancer. [ABSTRACT FROM AUTHOR]

Background: Although second-generation antipsychotics (SGAs) have proven to be effective therapeutic options for patients with schizophrenia, there is a notable lack of evidence on patients' subjective perspectives regarding their well-being, quality of life, and satisfaction with these medications. This study aimed to evaluate the treatment satisfaction and effectiveness of lurasidone on quality of life and functioning in adult patients with schizophrenia in real-world Italian clinical practice. Methods: This was a multicentre, national, non-interventional, single-arm, 3-month prospective study. Patients who were naive to lurasidone treatment and whose treating physician had decided to start them on this medication were enrolled and evaluated over a 3-month period. Eligible patients were adults (≥ 18 years of age) with a primary diagnosis of schizophrenia who were being treated with lurasidone (for the first time [i.e., they were lurasidone naive]) as part of routine clinical practice. Efficacy endpoints were changes in patient/caregiver treatment satisfaction (seven-point Likert scale from the Treatment Satisfaction Questionnaire for Medication), patient quality of life and functioning (QLS), investigator-rated global assessment of functioning (CGI-S, IAQ) after 6 weeks and 3 months of lurasidone, and number of relapses and hospitalizations. Results: Sixty-one patients were enrolled and 59 completed the study. The median dosage of lurasidone at baseline was 37.00 mg/day. The median duration of titration was 86.0 days (Min 28; Max 115 days); the median number of dosage changes was 1.0. At the end of 3-month observation period, the median dose of lurasidone was 74.00 mg/day. QoL and Functioning Score showed a trend of improvement over time, reaching a mean change from baseline of 9.8 at the end of the study. According to the CGI-S, the percentage of patients who were "markedly or severely ill" showed a continuous decrease from baseline to 3 months, from 62.29% to 8.20%. Patient satisfaction increased over time, with 80.32% of patients reporting that they were somewhat, fairly, or very satisfied (including 63.93% who were completely or very satisfied) at the end of the study. No relapses/hospitalizations for psychiatric reasons were reported. Lurasidone was well tolerated with no safety concerns or discontinuations due to AEs. Conclusions: Lurasidone represents a valid option for the treatment of schizophrenia and positively affects subjective well-being, quality of life and satisfaction. Trial registration: NCT06527885 retrospectively registered (01/08/2024). [ABSTRACT FROM AUTHOR]

Background/objectives: The blood–brain barrier (BBB) significantly limits the treatment of central nervous system disorders, such as schizophrenia, by restricting drug delivery to the brain. This study explores the potential of intranasal clozapine-loaded lipid nanocapsules (IN LNCsClo) as a targeted and effective delivery system to the brain. Methods: LNCsClo were prepared using the phase inversion technique and characterized in terms of size, zeta potential, entrapment efficiency (EE%), and in vitro drug release. The pharmacokinetic, safety, and pharmacodynamic effects of LNCsClo were then evaluated in a rat model through intranasal (IN) administration and compared with those of oral and intravenous (IV) Clo solutions. Results: LNCsClo were prepared using a phase inversion technique, resulting in a nanocarrier with a particle size of 28.6 ± 3.6 nm, homogenous dispersion, and high EE% (84.66 ± 5.66%). Pharmacokinetic analysis demonstrated that IN LNCsClo provided enhanced Clo brain bioavailability, rapid CNS targeting, and prolonged drug retention compared to oral and intravenous routes. Notably, the area under the curve (AUC) for brain concentration showed more than two-fold and eight-fold increases with LNCsClo, compared to IV and oral solutions, respectively, indicating improved brain-targeting efficiency. Safety assessments indicated that LNCsClo administration mitigated Clo-associated metabolic side effects, such as hyperglycemia, insulin imbalance, and liver enzyme alterations. Additionally, pharmacodynamic studies showed that LNCsClo significantly improved antipsychotic efficacy and reduced schizophrenia-induced hyperactivity, while preserving motor function. Conclusions: These results highlight the potential of IN LNCsClo as a novel drug delivery system, offering improved therapeutic efficacy, reduced systemic side effects, and better patient compliance in the treatment of schizophrenia and potentially other CNS disorders. [ABSTRACT FROM AUTHOR]

Psychiatric disorders are common in patients on hemodialysis. To the best of our knowledge there are no reported cases of psychosis developing in hemodialysis patients in the context of nephrectomy, and there is limited data on the use of long-acting antipsychotics in hemodialysis, which are generally not recommended in chronic kidney disease. We present the case of a 40-year-old lady with bilateral nephrectomy receiving hemodialysis who developed psychosis that resulted in her refusing to continue hemodialysis and was irregularly compliant with oral antipsychotics, necessitating the use of a long-acting injection. We report on the approach to clinical reasoning in the choice of aripiprazole and the need for a long-acting injection. Based on its pharmacological and pharmacokinetic properties oral aripiprazole 20 mg was commenced and after establishing tolerability and response, the patient was switched to long-acting aripiprazole 400 mg monthly achieving full remission of psychotic symptoms after 6 months with maintained improvement after 12 months. Based on its properties, aripiprazole may be a reasonable option in the treatment of psychosis in patients on hemodialysis with nephrectomy and can be considered even as a long-acting injection in these patients. [ABSTRACT FROM AUTHOR]

Objective: Schizophrenia is a severe and chronic mental disorder that significantly impacts cognitive, social, and occupational functions, leading to substantial economic burdens. Long-acting injectable (LAI) antipsychotics have been introduced to improve treatment adherence and outcomes, yet their economic impact remains debated. We aim to analyze the impact of LAIs on the medical costs of Korean schizophrenia patients. Methods: A retrospective analysis of 164 schizophrenia patients treated with LAI antipsychotics, paliperidone palmitate, and aripiprazole monohydrate at Korea University Guro Hospital between January 2017 and July 2022 was performed. Comparisons of inpatient department (IPD) and outpatient department (OPD) healthcare expenditures one year before and after LAI initiation were conducted. Results: LAIs led to an increase in annual OPD costs (1,437.44 ± 1,127.60 to 4,015.42 ± 1,204.59; units: 1,000 KRW) but significantly reduced IPD admission associated costs (3,826.06 ± 5,500.63 to 698.06 ± 3,619.38; units: 1,000 KRW). After LAI administration, there was an overall reduction in total annual healthcare costs (5,263.49 ± 5,333.11 to 4,713.48 ± 3,625.89; units: 1,000 KRW), but it was not statistically significant. Conclusion: Although the use of LAIs did not significantly lower the first-year medical costs of schizophrenia patients, they offer beneficial economic impacts over time by reducing hospitalization-associated costs. Future research should focus on long-term cost analyses and the impacts of newer LAI formulations. [ABSTRACT FROM AUTHOR]

Aims: 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. Methods: 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. Results: 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. Conclusions: 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]

Background/Objectives: In psychiatric disorders, antipsychotics and antidepressant medication are often administered together. Aripiprazole, a third-generation antipsychotic drug, is extensively metabolized by CYP2D6 and CYP3A4 isoenzymes, while bupropion, used in depressive disorders, is known as a moderate or strong CYP2D6 enzyme inhibitor. This in vivo experiment aimed to assess the presence of a pharmacokinetic drug interaction between aripiprazole and bupropion and its magnitude on the systemic exposure of aripiprazole. Methods: 24 healthy Wistar albino male rats were included in two study groups. A single dose of 8 mg/kg aripiprazole was given to rats in the reference group, while the test group received repeated doses of bupropion for 6 days, followed by a single dose of aripiprazole. An LC-MS/MS method was developed for the concomitant quantification of aripiprazole and its active metabolite, dehydroaripiprazole, and non-compartmental analysis was employed to assess their pharmacokinetic parameters. Results: The mean AUC0-∞ of aripiprazole increased 5.65-fold (1117.34 ± 931.41 vs. 6311.66 ± 2978.71 hr·ng/mL), the mean Cmax increased by 96.76% and the apparent systemic clearance decreased over 9-fold after bupropion repeated doses. The exposure to aripiprazole's active metabolite increased as well, having a 4-fold increase in the mean AUC0–∞ (from 461.13 ± 339.82 to 1878.66 ± 1446.91 hr·ng/mL) and a 2-fold increase in the mean Cmax. Conclusions: The total exposure to the aripiprazole parent compound and active moiety significantly increased after bupropion pretreatment in this preclinical in vivo experiment. Clinical studies should further establish the significance of this interaction in humans. [ABSTRACT FROM AUTHOR]

Background/Objectives: Treatment-resistant schizophrenia (TRS) may be considered as a neuro-immune disorder. Electroconvulsive therapy (ECT) remains an important therapeutic option for patients with TRS, however, its impact on cytokine profile is barely investigated. Therefore, this study attempts to establish associations between serum cytokines IL-6, IL-12, IL-5, IL-10 and TGF-β1 changes (pre- and post-ECT) and the effectiveness of ECT in TRS patients. The second aim is to search for correlations between serum concentrations of the above specified cytokines and psychometric assessments of clinical schizophrenia symptoms. Methods: The cytokine concentrations were measured in eight TRS patients on psychopharmacological treatment prior to and following ECT and in 13 control subjects. Psychopathology assessment was based on the Positive and Negative Syndrome Scale (PANSS). Results: Prior to ECT, IL-10 concentration was significantly higher in TRS patients, while IL-5 was decreased in comparison to the controls. A significant concentration decrease in the pro-inflammatory cytokines IL-6 (p = 0.012), IL-12 (p = 0.049) and anti-inflammatory IL-10 (p = 0.012) post-ECT vs. pre-ECT was observed, whereas concentrations of IL-5 and TGF-β1 did not significantly change. Also, a significant decrease in schizophrenia symptoms measured by the PANSS post-ECT was found. Furthermore, the pattern of correlations between PANSS scores and cytokine concentrations was different when comparing levels pre- and post-ECT. Additionally, correlations between changes in PANSS scores and cytokine concentrations were found. Conclusions: These results may indicate the probable impact of electroconvulsive therapy on the balance between pro- and anti-inflammatory cytokines, which may correspond to a neurobiological therapeutic effect of ECT in TRS patients. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) and its related complications are associated with schizophrenia. However, the relationship between antipsychotic medications (APs) and T2DM risk remains unclear. In this population-based, retrospective cohort study across the country, we investigated schizophrenia and the effect of APs on the risk of T2DM, and glucose homeostasis-related gene expression. Methods: We used information from the Longitudinal Health Insurance Database of Taiwan for individuals newly diagnosed with schizophrenia (N = 4,606) and a disease-free control cohort (N = 4,606). The differences in rates of development of T2DM between the two cohorts were assessed using a Cox proportional hazards regression model. The effects of APs on the expression of glucose homeostasis-related genes in liver and muscle cell lines were assessed using quantitative real-time PCR. Results: After controlling potential associated confounding factors, the risk of T2DM was higher in the case group than that in the control group [adjusted hazard ratio (aHR), 1.80, p < 0.001]. Moreover, the likelihood of T2DM incidence in patients with schizophrenia without AP treatment (aHR, 2.83) was significantly higher than that in non-schizophrenia controls and those treated with APs (aHR ≤ 0.60). In an in vitro model, most APs did not affect the expression of hepatic gluconeogenesis genes but upregulated those beneficial for glucose homeostasis in muscle cells. Conclusion: This study demonstrates the impact of schizophrenia and APs and the risk of developing T2DM in Asian populations. Unmeasured confounding risk factors for T2DM may not have been included in the study. These findings may help psychiatric practitioners identify patients at risk of developing T2DM. [ABSTRACT FROM AUTHOR]

Introduction: Antipsychotic psychopharmacotherapy is associated with the risk of drug-induced liver injury (DILI). However, understanding specific risk factors remains challenging due to limited data. This study investigates the relationship between receptor binding affinities and occupancies of antipsychotics and their associated hepatotoxic risks. Methods: A disproportionality analysis with calculation of the Reporting Odds Ratio (ROR) and the Information Component (IC) was conducted using data from the FDA Adverse Event Reporting System (FAERS) to identify signals related to the Standardised MedDRA Query "drug-related hepatic disorders", which served as a proxy for drug-induced hepatotoxicity. This was followed by a pharmacoepidemiologic-pharmacodynamic approach to investigate the relationship between the ROR and substance-related receptor binding affinities and occupancy, which was estimated based on in vitro receptor-binding profiles. Results: Significant signals were identified for several antipsychotics, including chlorpromazine, loxapine, olanzapine, and quetiapine, with chlorpromazine and loxapine showing the highest RORs for DILI. Gender-specific analysis revealed a higher frequency of signals in female patients. Statistically significant negative correlations were identified between the ROR for drug-related hepatic disorders and the affinity for serotonin receptor 5-HT1A (r (17) = -0.68, p = 0.0012), while a positive correlation was observed for cholinergic receptors (r (17) = 0.46, p = 0.048). No significant correlations were found related to other receptors or drug properties. Conclusion: Our findings suggest that the serotonin and probably the cholinergic system may play a role in the development of DILI related to antipsychotic medications. The identification of antipsychotics with a higher association with DILI, such as chlorpromazine, underscores the need for careful monitoring in clinical practice. However, our findings need further longitudinal studies to confirm causality. A better understanding of the associations may inform clinical decision-making, particularly in patients with an increased susceptibility to liver damage. [ABSTRACT FROM AUTHOR]

Individuals with epilepsy are at risk of developing preictal, ictal, postictal and interictal psychoses. Antipsychotic drugs (APDs) are the main class of drugs used to treat psychosis and schizophrenia. The efficacy and safety of APDs as a treatment for epileptic psychosis is not well understood. This systematic review aimed to assess the effectiveness and adverse effects of APDs for treating psychosis in people with epilepsy. We adhered to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) guidelines. We searched MEDLINE, Embase, PsycInfo, and AMED (Allied and Complementary Medicine) from database inception to June 20, 2023. We contacted experts in the field and performed citation searches to identify additional records. Title, abstract, full‐text review, and data analysis were conducted in duplicate, with conflicts resolved by discussion among authors. Given the considerable heterogeneity of study designs, meta‐analysis was not deemed appropriate; instead, the results were tabulated in a narrative synthesis. The Joanna Briggs Institute Risk of Bias tool and GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework were used to assess study quality. We identified 13 studies with a total of 1180 participants. In the four case series included, the psychotic symptoms of 25 of 28 patients treated with APDs partially improved or fully resolved. Three of the four cohort studies reported an association between antipsychotic use and longer duration of psychotic episodes, two found similar results in both APD and non‐APD groups, and two did not report control psychosis outcomes. When reported, seizure frequency was observed to remain unchanged or decrease following APD treatment. The evidence on the effectiveness of antipsychotics in the treatment of psychosis in epilepsy is inconclusive and may reflect confounding by indication. However, most studies suggest that antipsychotics were not associated with a marked worsening in seizure frequency. It remains unclear whether antipsychotics should be used in epilepsy, and well‐controlled cohort studies and randomized controlled trials are necessary to draw definitive conclusions. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the study was to assess the efficacy of In-Dex sedation in comparison to oral melatonin and hydroxyzine in individuals with Autism Spectrum Disorder (ASD) undergoing EEG recording and 15 determine which categories of patients exhibit the most favorable response to In-Dex sedation. Methods: This retrospective observational study involved pediatric patients with ASD who underwent sleep-EEG recording across two periods, before (biennium 2018-19) and after (biennium 2021-22) the routine implementation of In-Dex sedation. Clinical, EEG, and sedation data were stored in a database. A logistic multiple regression model was employed, with the failure of EEG serving as the dependent variable. Results: In the first period 203 EEGs were performed with a rate of failure of 10.8%, while in the second one 177 EEGs were recorded with a percentage of failure of 7.3% (8.3% with MH 23 sedation and 5.8% with In-Dex sedation). No significant adverse events were reported in either period. Multivariate logistic analysis demonstrated that In-Dex decreased the probability of failure (OR=0.25, 25 (0.61-0.88)), while the presence of behavioral disturbances (OR=3.65((1.54-8.85)) and the use of antipsychotic drugs (OR=2.76, (1.09-6.95)) increased it. Discussion: In the light of these results, we can state that In-Dex sedation is safe and reduce EEG failure rate compared to the use of melatonin and hydroxyzine alone, particularly in patients with severe behavioral issues. [ABSTRACT FROM AUTHOR]

Background: The relationship between mental disorders and oral health is complex, involving behavioral, biological, and psychosocial factors. This review aims to investigate the impact of mental disorders, including autism spectrum disorder (ASD), depression, bipolar disorder, and schizophrenia, on oral health outcomes. Methods: A comprehensive review of existing literature was conducted to analyze the oral health outcomes associated with each mental disorder. The focus was on examining dietary habits, oral hygiene behaviors, physiological changes, and medication side effects that contribute to oral health issues. Results: The findings indicate that individuals with ASD often exhibit unique dietary habits and reduced oral hygiene capabilities due to sensory sensitivities, leading to a higher prevalence of dental caries and periodontal diseases. Depression and bipolar disorder are associated with physiological changes such as reduced saliva production and poor oral hygiene behaviors, increasing the risk of oral health problems. Medications used for these conditions exacerbate issues like xerostomia, further elevating the risk of dental diseases. Schizophrenia poses additional challenges, including cognitive impairments and medication side effects that hinder effective oral care, heightening susceptibility to oral diseases. Conclusions: This review highlights the specific oral health challenges associated with different mental disorders and emphasizes the need for tailored dental care strategies that integrate mental health considerations. The study contributes to the literature by demonstrating the unique oral health impacts of these disorders. However, the findings are limited by the scope of available cross-sectional data and the absence of longitudinal studies. Future research should focus on longitudinal and intervention-based studies to explore causal relationships and develop effective treatments. [ABSTRACT FROM AUTHOR]

Background: Pharmacogenomic (PGx) factors significantly influence how patients respond to antipsychotic medications This systematic review was performed to synthesize the clinical utility of PGx-assisted treatment versus standard of care in schizophrenia. Methods: PubMed, Embase, and Cochrane CENTRAL databases were searched for randomized controlled trials (RCTs) from inception till June 2024 that had compared the clinical utility of PGx-assisted intervention as compared to the standard of care in schizophrenia. The primary outcome was safety, and the secondary outcomes were efficacy and medication adherence. Pooled standardized mean differences (SMD) along with a 95% confidence interval (CI) were calculated (random-effects model) wherever feasible. Results: A total of 18,821 studies were screened, and five were included for review. All the RCTs had a high risk of bias. Four studies included the commonly used antipsychotics. Three studies reported negative outcomes (safety, efficacy, and medication adherence) and two reported positive outcomes (safety) using different scales. In the meta-analysis, there were significant differences in the total Udvalg for Kliniske Undersogelser Side-Effect Rating scale score [SMD 0.95 (95% CI: 0.76–1.13), p < 0.001); I2 = 0%] and the total Positive and Negative Syndrome Scale score [SMD 10.65 (95% CI: 2.37–18.93), p = 0.01); I2 = 100%] between the PGx-assisted treatment and standard of care arms. However, the results were inconsistent, and the certainty of evidence (GRADE criteria) was very low. Conclusion: Current evidence on the clinical utility of PGx-assisted treatment in schizophrenia is limited and inconsistent and further evidence is required in this regard. [ABSTRACT FROM AUTHOR]

Background: QT prolongation is a potential serious adverse drug reaction, and assessing the risk of QT-prolonging drugs is routinely included in psychotropic medication reviews. However, the actual clinical benefits of such assessments are unknown. We investigate whether QT prolongation (QTc value > 480 ms) manifests in psychiatric inpatients at risk of QT prolongation as identified by assessing drug regimens. Secondly, we test the predictive value of well-known risk factors for QT prolongation. Results: The median patient age was 49 years (IQR 34–64) for patients treated with a median of nine drugs (IQR 6–12) and a median QT-prolonging drug sum of three daily defined dosages (IQR 1.88–4.76). We extracted 290 ECGs for patients where pharmacist-led-medication reviews (PMRs) identified an increased risk of QT prolongation and 190 ECGs for patients with no such risk, identifying 33 cases of verified QT prolongation equally distributed between groups. Unadjusted regression analysis revealed that advanced age (OR 3.27 CI 95% 1.60–6.84) and cardiovascular comorbidity (OR 3.53 CI 95% 1.71–7.29) were associated with manifest QT prolongation, while the QT-prolonging drug load was not. Methods: We reviewed electronic health records (EHRs) of 799 psychiatric inpatients exposed to PMRs made from 1 September 2016 to 31 December 2018 in Region Zealand Denmark. Conclusions: Patients at risk of QT prolongation as identified by drug reviews rarely manifests with actual QT prolongation. Non-pharmacological risk factors seem to be better predictors for identifying patients with QT prolongation. [ABSTRACT FROM AUTHOR]

The article discusses three randomized controlled trials (RCT) which focused on the use of brexpiprazole to treat the behavioral and psychological symptoms of dementia (BPSD). Topics explored include the brexpiprazole dosage administered which demonstrated improvement in symptoms, the treatment-emergent adverse events recorded following treatment, and a comparison between brexpiprazole and other antipsychotic medications in terms of effectiveness in managing BPSD.

Clinical outcomes after a first-episode of psychosis (FEP) are heterogeneous. Many patient-related factors such as gender and comorbidity have been studied to predict symptomatic outcomes. However, psychiatrist-related factors such as prescription behaviour and gender have received little attention. We assessed the relationship between patients' psychiatrists, psychosis severity and daily functioning in 201 patients remitted from an FEP for a duration of one year, treated by 18 different psychiatrists. We controlled for baseline severity, dose and type of antipsychotic medication, frequency of visits, and patients' education. Symptom severity, daily functioning, and antipsychotic drug use were assessed at baseline and at 3, 6, and, 12 months follow-up. We found that psychiatrists accounted for 9.1% of the explained variance in patients' symptom severity and 10.1% of the explained variance in daily functioning.These effects persisted even when controlling for factors such as baseline severity and the prescribed dose. The effect of prescribed dose on symptom severity and daily functioning differed between psychiatrists. Treatment centre, session frequency, and medication nonadherence were not related to symptom severity. Our results emphasize the importance of individual psychiatrist factors in symptomatic outcomes after an FEP. Further identification of psychiatrist-related factors such as the quality of therapeutic alliances and shared decision-making, may optimize psychiatrists' training with the goal of improving patient outcomes. [ABSTRACT FROM AUTHOR]

Objective: This research aims to evaluate patterns of prescription of medications used to manage acute agitation in adult Iranian patients at the emergency department (ED) of Roozbeh Psychiatric Hospital in Tehran. Method: The study analyzed data from the medical records of 252 patients who received pharmacotherapy for agitation. Results: The findings revealed that 181 patients (71.82%) were given typical antipsychotics, with haloperidol being the most commonly prescribed medication. Atypical antipsychotics were administered to 24 participants (9.52%), primarily olanzapine, and 52 patients (20.63%) received benzodiazepines, predominantly lorazepam. The treatment response was also assessed as appropriate in 224 patients (88.89%) and inappropriate in 28 patients (11.11%). Conclusion: The study recommends providing new-generation medications to developing countries and underscores the importance of updating student educational programs. [ABSTRACT FROM AUTHOR]

Background and Aims: Antipsychotic drugs are critical in managing psychosis but they also carry risks when misused, leading to toxicity. Case Presentation: A patient overdosed on olanzapine, resulting in anticholinergic toxidrome with symptoms like tachycardia and altered mental status. Immediate recognition and management of antipsychotic toxicity-induced toxidromes in emergency settings are crucial. Treatment strategy includes maintaining airway, breathing and circulation along with decontamination. There is no specific antidote. Conclusion: This case underscores the need for emergency physicians to remain vigilant and proactive in identifying and addressing such toxicity by identification of toxidromes to prevent complications and missed diagnosis in emergency department. [ABSTRACT FROM AUTHOR]

Background. This study assessed the potential efficacy of donepezil in treating autism spectrum disorder (ASD), a neurodevelopmental condition characterized by social communication difficulties and repetitive behaviors. Donepezil, primarily used to treat Alzheimer’s disease as an acetylcholinesterase inhibitor, has gained attention as a potential treatment for ASD symptoms. Methods. Following PRISMA guidelines, a systematic review was conducted to investigate the effects of donepezil on individuals with ASD. Outcome measures assessed various aspects of ASD, including language skills, executive function, behavior, and core symptoms. Nine studies were identified, including four randomized controlled trials (RCTs), three retrospective studies, one open-label trial, and one case report. Results. One RCT reported significant improvements in expressive and receptive language skills, especially in younger children. Another study combining donepezil with choline supplementation showed enhanced receptive language skills, particularly in younger participants. An open-label trial indicated improved rapid eye movement sleep patterns in autistic children treated with donepezil. Several retrospective studies reported improvements in behavioral symptoms, such as aggression and hyperactivity. However, other RCTs did not find statistically significant improvements in executive functioning. Conclusion. In general, donepezil use in ASD demonstrates promise in specific areas, notably language development and behavioral symptom management. However, the results are contradictory, requiring further research to clarify its role, optimal dosing, long-term effects, and potential side effects in individuals with ASD. Practical Implications. Donepezil can be used to improve the clinical global impression and language skills of people with ASD. [ABSTRACT FROM AUTHOR]

Background/Objectives: Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with an increased risk of obesity and disordered eating behaviors. This study compared weight status and eating behaviors among drug-naïve ADHD children, those on stimulant monotherapy, those on combined stimulant and antipsychotic treatment, and healthy controls. Methods: This cross-sectional study included 547 children aged 6–12 years from four Turkish provinces: 361 with ADHD (152 drug-naïve, 156 on stimulants, and 53 on combined therapy), and 186 healthy controls. Anthropometric measurements, psychiatric assessments, and eating behavior evaluations were conducted using standardized tools. Results: Drug-naïve ADHD children had the highest obesity rate (13.8%), while those on stimulant monotherapy had the lowest (4.5%) compared to controls. Combined treatment group obesity rates were similar to controls (7.5% vs. 8.6%). The drug-naïve and combined treatment groups showed increased food approach behavior and desire to drink, with the combined treatment group also showing increased emotional overeating. Conclusions: This study reveals a complex relationship between ADHD, its pharmacological management, and the risk of obesity. Stimulant monotherapy may mitigate the risk of obesity, while combined stimulant and antipsychotic treatment may lead to problematic eating behaviors. These findings emphasize the importance of monitoring weight status and eating behaviors in ADHD children, especially those receiving pharmacological interventions. [ABSTRACT FROM AUTHOR]

Objectives: Parkinson's disease psychosis (PDP) is a prevalent non-motor symptom associated with Parkinson's disease. The treatment options for PDP are limited, and its pharmacological management remains ambiguous. This study aimed to evaluate the existing evidence in relation to clinical practice. Methods: This multi-methods study consisted of a systematic review of reviews, adhering to the PRISMA guidelines. The review was registered with PROSPERO. Following data extraction and assessment using the AMSTAR 2 tool, a narrative synthesis was performed. In the second phase of the study, a questionnaire was developed, validated, piloted, and distributed to the heads of specialized PD clinics in Germany and Austria. Results: The search resulted in the inclusion of eleven reviews. The quality of eight of these reviews was rated as high (n = 7) or moderate (n = 1). The reviews indicated that clozapine and pimavanserin demonstrated the highest efficacy and tolerability. Other antipsychotic medications either failed to alleviate PDP symptoms or resulted in distinct motor complications. The survey findings also favored clozapine for its efficacy in managing PDP and improving quality of life, although quetiapine was regarded as effective and pimavanserin was not available. Clinicians reported initiating antipsychotic treatment at various stages of PDP, with a tendency to reduce the dosage or discontinue D2 agonists or anticholinergics. Conclusions: The reviewed literature and the survey results consistently favored clozapine for its efficacy and tolerability in treating PDP. It may be considered the first-line treatment, with pimavanserin as an alternative option. [ABSTRACT FROM AUTHOR]

Schizophrenia is a chronic, severe, and disabling mental disorder that significantly impacts individuals’ lives. Long-term treatment with antipsychotic drugs, coupled with the complications of the disease itself, increases the risk of dysphagia in patients. These disorders further heighten the likelihood of choking and asphyxia death among this population. This project aims to comprehensively review the pathological mechanisms behind dysphagia in schizophrenia, alongside proposing early screening and evaluation methods. It also suggests treatment recommendations to mitigate the risks and complications associated with dysphagia in these patients. [ABSTRACT FROM AUTHOR]

Abstract Clinical outcomes after a first-episode of psychosis (FEP) are heterogeneous. Many patient-related factors such as gender and comorbidity have been studied to predict symptomatic outcomes. However, psychiatrist-related factors such as prescription behaviour and gender have received little attention. We assessed the relationship between patients’ psychiatrists, psychosis severity and daily functioning in 201 patients remitted from an FEP for a duration of one year, treated by 18 different psychiatrists. We controlled for baseline severity, dose and type of antipsychotic medication, frequency of visits, and patients’ education. Symptom severity, daily functioning, and antipsychotic drug use were assessed at baseline and at 3, 6, and, 12 months follow-up. We found that psychiatrists accounted for 9.1% of the explained variance in patients’ symptom severity and 10.1% of the explained variance in daily functioning.These effects persisted even when controlling for factors such as baseline severity and the prescribed dose. The effect of prescribed dose on symptom severity and daily functioning differed between psychiatrists. Treatment centre, session frequency, and medication nonadherence were not related to symptom severity. Our results emphasize the importance of individual psychiatrist factors in symptomatic outcomes after an FEP. Further identification of psychiatrist-related factors such as the quality of therapeutic alliances and shared decision-making, may optimize psychiatrists’ training with the goal of improving patient outcomes.

BACKGROUND: Psychotic disorders are a leading cause of disability in young adults. Antipsychotics have been the primary intervention for psychosis for over 60 years, and yet, we have made little progress in treating negative symptoms, neurocognition, and functional disability. There is growing evidence that cannabidiol (CBD) is effective in treating positive psychotic symptoms, possibly also negative and neurocognitive symptoms, and moreover is well tolerated compared to other psychotropic medications. Anecdotally, patients participating in the Cognitive Assessment and Risk Evaluation (CARE) Early Psychosis Treatment Program at the University of California, San Diego, are self-administering CBD and report subjective improvement in stress, anxiety, and ability to cope with symptoms. The overarching aim of the trial is to explore the effectiveness of CBD augmentation on symptoms and neurocognition in early psychosis while also exploring the mechanism of action of CBD and predictors of response to treatment. The mechanism by which cannabidiol has a therapeutic effect on psychosis is poorly understood. Recent evidence has suggested that CBD may reduce stress and pro-inflammatory biomarker levels. Endocannabinoids also have powerful roles in eating behavior, reward, and mood, indicating these neurotransmitters may play a role in reducing hyperphagia and metabolic abnormalities that are present early in the course of psychotic illness and exacerbated by antipsychotic medication. The neurophysiological effects of CBD have been studied in animal models of psychosis that show improvements in information processing in response to CBD, but there are no studies in individuals with early psychosis. METHOD: A total of 120 individuals in the early stages of psychosis will be randomized to 1000 mg of CBD versus placebo as an adjunct to existing treatment in a 8-week, double-blind superiority randomized control trial. The primary outcome measures are symptoms and neurocognition. DISCUSSION: We hypothesized that CBD will improve symptoms and neurocognition as well as secondary outcome measures of neurohormones, inflammation, eating behaviors, and information processing. Importantly, predictors, moderators, and mediators of the CBD effects will be examined. A better understanding of which individuals are likely to respond to CBD can inform treatment planning and personalize treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT04411225. Registered on June 2, 2020.

BackgroundSecond-generation antipsychotics (SGAs) are frontline treatments for serious mental illness. Often, individual patients benefit only from some SGAs and not others. The mechanisms underlying this unpredictability in treatment efficacy remain unclear. All SGAs bind the dopamine D3 receptor (D3R) and are traditionally considered antagonists for dopamine receptor signaling.MethodsHere, we used a combination of two-photon calcium imaging, in vitro signaling assays, and mouse behavior to assess signaling by SGAs at D3R.ResultsWe report that some clinically important SGAs function as arrestin-3 agonists at D3R, resulting in modulation of calcium channels localized to the site of action potential initiation in prefrontal cortex pyramidal neurons. We further show that chronic treatment with an arrestin-3 agonist SGA, but not an antagonist SGA, abolishes D3R function through postendocytic receptor degradation by GASP1 (G protein-coupled receptor-associated sorting protein-1).ConclusionsThese results implicate D3R-arrestin-3 signaling as a source of SGA variability, highlighting the importance of including arrestin-3 signaling in characterizations of drug action. Furthermore, they suggest that postendocytic receptor trafficking that occurs during chronic SGA treatment may contribute to treatment efficacy.