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Background: Antipsychotic medications are the primary treatment for schizophrenia, with olanzapine being an effective medication for schizophrenia. The economic cost for each individual with schizophrenia is high, with antipsychotic medication being a major expense. This study aims to develop an economic decision model that compares different treatment options for schizophrenia patients, including olanzapine Orally Dispersible Tablets (ODT), olanzapine [ODT + Standard Oral Tablet (SOT)], risperidone (ODT + SOT), and aripiprazole (ODT + SOT), to determine their cost-effectiveness with an objective to optimize healthcare resource allocation in Morocco. Methods: The study used published medical literature and a clinical expert panel to develop a decision analytic model. This model was designed to capture parameters such as adherence levels, treatment discontinuation, relapse with and without hospitalization, quality-adjusted life years (QALYs), treatment-related adverse events, healthcare resource utilization, and associated costs. The main outcomes of interest included the total annual direct cost per treatment, QALYs, and incremental cost-effectiveness ratio (ICER) per 1 QALY gained. One-way and probabilistic sensitivity analyses were employed to account for parameter uncertainty. Results: According to the simulation model, the ODT and ODT + SOT as a group form of olanzapine was the most effective treatment option in terms of the lowest percentages of inpatient relapse, and patients who remained stable (11% and 79% respectively) than risperidone (19% and 62% respectively) and aripiprazole ODT (26% and 50% respectively) and ODT + SOT formulation groups. Olanzapine (ODT + SOT) therapy group was cost-effective when compared to the combined group of ODT + SOT forms of risperidone [ICER: Moroccan Dirham (MAD) 103,907], and aripiprazole (ICER: MAD 65,047). Additionally, olanzapine ODT was found to be cost-effective compared to olanzapine SOT with an ICER of MAD 3921, risperidone ODT with an ICER of MAD 1,02,298, risperidone SOT with an ICER of MAD 31,088, and aripiprazole ODT or SOT formulations. All the above ICERs fall under the willingness-to-pay threshold in Morocco of MAD 250,832.40. Sensitivity analyses confirmed the reliability of the findings. Conclusions: The model concluded that olanzapine ODT is the most cost-effective first-line treatment option for schizophrenia in Morocco when compared to other atypical antipsychotic medications in ODT and SOT formulations. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the effect of aripiprazole on prolactin levels in patients with schizophrenia and analyze whether varying baseline prolactin levels affect the effectiveness and safety of aripiprazole, in a real-life diagnostic and therapeutic setting in a post-hoc analysis. Methods: In this post-hoc analysis, patients with schizophrenia in the acute phase were divided into an elevated-prolactin group and a normal-prolactin group. After 8 weeks of aripiprazole treatment, changes in the proportion of patients with an abnormal prolactin level were analyzed in both groups, and the efficacy and safety of aripiprazole were compared between the two groups. Results: The elevated-prolactin group had more women, a longer duration of disease, and lower Positive and Negative Syndrome Scale (PANSS) total and subscale scores at baseline compared with the normal-prolactin group (all P < 0.05), and there was no significant difference in the proportion of patients with prior use of antipsychotic medication between the two groups. Regardless of previous antipsychotic use, patients in both groups developed hyperprolactinemia (23/168 [13.7%] in those who had taken antipsychotics vs. 43/375 [11.4%] in those who had not). After 8 weeks of aripiprazole treatment, the proportion of patients with abnormal prolactin in the elevated-prolactin group significantly decreased with prolonged treatment (P < 0.001), and aripiprazole had no significant effect on the normal-prolactin group (P = 0.250). Normalprolactin group showed better efficacy than the elevated-prolactin group, and the differences in efficacy between the two groups was observed from week 4 to the endpoint (all p<0.05). In total, 87.2% (68/78) patients experienced mild to moderate adverse events in the elevated-prolactin group, which was significantly more frequent compared with the normal-prolactin group 71.0% (365/514). Conclusions: In this real-world study, for patients with acute schizophrenia, aripiprazole was effective in lowering the proportion of patients with abnormal prolactin levels, while it had no significant effect on patients with normal baseline prolactin. After adjusting for factors such as sex, age, prior antipsychotic drugs use history and disease severity, effectiveness and safety of aripiprazole in patients with normal baseline prolactin was significantly better than that in patients with elevated baseline prolactin. [ABSTRACT FROM AUTHOR]

Introduction Little is known about the interplay between genetics and epigenetics on antidepressant treatment (1) response and remission, (2) side effects, and (3) serum levels. This study explored the relationship among single nucleotide polymorphisms (SNPs), DNA methylation (DNAm), and mRNA levels of four pharmacokinetic genes, CYP2C19 , CYP2D6 , CYP3A4 , and ABCB1 , and its effect on these outcomes. Methods The Canadian Biomarker Integration Network for Depression-1 dataset consisted of 177 individuals with major depressive disorder treated for 8 weeks with escitalopram (ESC) followed by 8 weeks with ESC monotherapy or augmentation with aripiprazole. DNAm quantitative trait loci (mQTL), identified by SNP-CpG associations between 20 SNPs and 60 CpG sites in whole blood, were tested for associations with our outcomes, followed by causal inference tests (CITs) to identify methylation-mediated genetic effects. Results Eleven cis- SNP-CpG pairs (q<0.05) constituting four unique SNPs were identified. Although no significant associations were observed between mQTLs and response/remission, CYP2C19 rs4244285 was associated with treatment-related weight gain (q =0.027) and serum concentrations of ESCadj (q <0.001). Between weeks 2-4, 6.7% and 14.9% of those with *1/*1 (normal metabolizers) and *1/*2 (intermediate metabolizers) genotypes, respectively, reported ≥2 lbs of weight gain. In contrast, the *2/*2 genotype (poor metabolizers) did not report weight gain during this period and demonstrated the highest ESCadj concentrations. CITs did not indicate that these effects were epigenetically mediated. Discussion These results elucidate functional mechanisms underlying the established associations between CYP2C19 rs4244285 and ESC pharmacokinetics. This mQTL SNP as a marker for antidepressant-related weight gain needs to be further explored. [ABSTRACT FROM AUTHOR]

Binge eating disorder (BED) is the most common specific eating disorder (ED). It is frequently associated with attention deficit hyperactivity disorder (ADHD), depression, bipolar disorder (BD), anxiety disorders, alcohol and nicotine use disorder, and obesity. The aim of this narrative review was to summarize the evidence for the pharmacological treatment of BED and its comorbid disorders. We recommend the ADHD medication lisdexamfetamine (LDX) and the antiepileptic and antimigraine drug topiramate for the pharmacological treatment of BED. However, only LDX is approved for the treatment of BED in some countries. Medications to treat diseases frequently comorbid with BED include atomoxetine and LDX for ADHD; citalopram, fluoxetine, sertraline, duloxetine, and venlafaxine for anxiety disorders and depression; aripiprazole for manic episodes of BD; lamotrigine, lirasidone and lumateperone for depressive episodes of BD; naltrexone for alcohol use disorder; bupropion for nicotine use disorder; and liraglutide, semaglutide, and the combination of bupropion and naltrexone for obesity. As obesity is a frequent health consequence of BED, weight gain-inducing medications, such as the atypical antipsychotics olanzapine or clozapine, the novel antidepressant mirtazapine and tricyclic antidepressants, and the mood stabilizer valproate should be avoided where possible. It is currently unclear whether the novel and promising glucagon, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide 1 (GLP-1) receptor agonists like tirzepatide and retatrutide help with BED and its comorbidities. However, these compounds have been reported to reduce binge eating in individuals with obesity or overweight. [ABSTRACT FROM AUTHOR]

Identifying stable and consistent resting-state functional connectivity patterns across illness trajectories has the potential to be considered fundamental to the pathophysiology of schizophrenia. We aimed to identify consistent resting-state functional connectivity patterns across heterogeneous schizophrenia groups defined based on treatment response. In phase 1, we used a cross-sectional case-control design to characterize and compare stable independent component networks from resting-state functional magnetic resonance imaging scans of antipsychotic-naïve participants with first-episode schizophrenia (n = 54) and healthy participants (n = 43); we also examined associations with symptoms, cognition, and disability. In phase 2, we examined the stability (and replicability) of our phase 1 results in 4 groups (N = 105) representing a cross-sequential gradation of schizophrenia based on treatment response: risperidone responders, clozapine responders, clozapine nonresponders, and clozapine nonresponders following electroconvulsive therapy. Hypothesis-free whole-brain within- and between-network connectivity were examined. Phase 1 identified posterior and anterior cerebellar hypoconnectivity and limbic hyperconnectivity in schizophrenia at a familywise error rate–corrected cluster significance threshold of p <.01. These network aberrations had unique associations with positive symptoms, cognition, and disability. During phase 2, we replicated the phase 1 results while comparing each of the 4 schizophrenia groups to the healthy participants. The participants in 2 longitudinal subdatasets did not demonstrate a significant change in these network aberrations following risperidone or electroconvulsive therapy. Posterior cerebellar hypoconnectivity (with thalamus and cingulate) emerged as the most consistent finding; it was replicated across different stages of treatment response (Cohen's d range −0.95 to −1.44), reproduced using different preprocessing techniques, and not confounded by educational attainment. Posterior cerebellar-thalamo-cingulate hypoconnectivity is a consistent and stable state-independent neural marker of schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Reducing falls and fractures remains an important clinical goal in managing older residents with Parkinson's disease psychosis (PDP) in long-term care/nursing home (LTC/NH) settings. Objectives: This analysis examined risk of all-cause falls or fractures among PDP residents on continuous monotherapy with pimavanserin (PIM) versus (i) other atypical antipsychotics (AAPs) [quetiapine (QUE), risperidone (RIS), olanzapine (OLA), aripiprazole (ARI)] and (ii) QUE. Methods: A retrospective analysis of parts A, B, and D claims from a 100% Medicare sample (2013–2019) in LTC/NH settings was conducted. LTC/NH residents in the USA initiating continuous monotherapy (PIM versus other AAPs; PIM versus QUE) for ≥ 6 months between 01 January 2014 and 31 December 2018 were 1:1 propensity score matched (PSM) on 31 variables (age, sex, race, region, and 27 Elixhauser comorbidities). Outcomes included three measures: risks of falls only, fractures only, and falls/fractures during 6-months follow-up. Demographic characteristics were described using chi-square and t-tests. Generalized linear models were used to assess difference in risks of falls/fractures. Results: Of 7187 residents, 47.59% (n = 3420) were female and mean age was 78.8 (± 7.75) years. In total, 14% (n = 1005) were on PIM and 86% (n = 6182) were on other AAPs. After PSM, falls only among PIM residents (n = 1005) was 4.58% (n = 46) versus 7.66% (n = 77) for other AAPs (n = 1005) [relative risk (RR) = 0.63 (0.46, 0.86), p < 0.05] and 8.26% (n = 83) for QUE (n = 1005) residents (p < 0.05). Fractures only among PIM residents was 1.39% (n = 14) compared with 2.09% (n = 21) for other AAPs (p = 0.31) and 1.89% (n = 19) for QUE (p = 0.49), respectively. Taken together, falls/fractures among PIM residents were 5.67% (n = 57) versus 9.05% (n = 91) for other AAPs [RR = 0.63 (0.46, 0.86), p < 0.05] and 9.55% (n = 96) for QUE (p < 0.05), respectively. Conclusions: In this analysis of LTC/NH residents with PDP, PIM had a 37% and 41% lower risk of all-cause falls/fractures versus other AAPs and versus QUE, respectively. [ABSTRACT FROM AUTHOR]

Background Aim Method Results Conclusion Pharmacotherapy treatment is used to manage women with schizophrenia and bipolar affective disorder admitted to a mother–baby unit (MBU).The aims of this study were (1) to examine prescribing practices for women with schizophrenia and bipolar affective disorder in an MBU, (2) to assess alignment with the Mental health care in the perinatal period: Australian clinical practice guideline and (3) to examine the classes of typical and atypical antipsychotics prescribed to mothers with schizophrenia.A retrospective audit of women with schizophrenia and bipolar affective disorder admitted to a psychiatric MBU, located in Queensland, Australia, was conducted from March 2017–July 2019. The exclusion criteria included women admitted with depression, anxiety, personality disorders, and postpartum psychosis. Pharmacotherapy treatment details were extracted at commencement of admission, mid‐way through admission, and discharge. Descriptive statistics were completed. This project was exempt due to the local policy requirements that constitute research by the Gold Coast Hospital and Health Service Human Research Ethics Committee (Reference no: EX/2023/QGC/102306). The justification for this exemption was as follows: the study was deemed a quality improvement activity and complied with Chapter 2.3 of the National Statement of Ethical Conduct in Research and involved only routinely collected data.Of the 53 mothers included in the study, 29 (55%) had schizophrenia and 24 (45%) had bipolar affective disorder. In addition, 97% of women with schizophrenia received atypical antipsychotics. Five women (21%) with bipolar affective disorder (mean age = 31.60 years, standard deviation = 6.19 years) were prescribed sodium valproate, with four women given contraception. Sodium valproate or lamotrigine were prescribed to four women (67%) with bipolar affective disorder whilst breastfeeding. Of mothers prescribed lithium, 92% did not breastfeed. Overall, 44% of women involuntarily admitted received antipsychotic depot medication compared with 38% of voluntary patients. Results are discussed in relation to the national guidelines.This is the first naturalistic study to examine the pharmacotherapy management of postpartum women admitted to a psychiatric MBU with schizophrenia and bipolar affective disorder. The study highlights that prescribing patterns across three time points during admission were generally in alignment with Australian national guidelines. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown that liver enzyme abnormalities were not only seen with typical antipsychotics (APs) but also with atypical antipsychotics (AAPs). During the last 20 years, the hepatotoxicity of various antipsychotics received much attention. However, systematic evaluations of hepatotoxicity associated with APs are limited. Methods: All drug related hepatic disorders cases were retrieved from the FDA Adverse Event Reporting System (FAERS) database using standardized MedDRA queries (SMQ) from the first quarter of 2017 to the first quarter of 2022. Patient characteristics and prognosis were assessed. In this study, a case/non-case approach was used to calculate reporting odds ratio (RORs) and 95% confidence intervals (CIs). We calculated the drug-induced liver injury (DILI) RORs for each AAPs. Results: A total of 408 DILI cases were attributed to AAPs during the study period. 18.6% of these were designated as serious adverse event (SAE), which include death (19.74%), hospitalization (68.42%), disability (2.63%), and life-threatening (9.21%) outcomes. The RORs values in descending order were: quetiapine (ROR = 0.782), clozapine (ROR = 0.665), aripiprazole (ROR = 0.507), amisulpride (ROR = 0.308), paliperidone (ROR = 0.212), risperidone (ROR = 0.198), ziprasidone (0.131). Conclusion: The result found in our study was that all AAPs didn't have a significant correlation with increased hepatotoxicity. Future analysis of the FAERS database in conjunction with other data sources will be essential for continuous monitoring of DILI. [ABSTRACT FROM AUTHOR]

Introduction: Cardiovascular morbidity and mortality are high in people with serious mental illness (SMI). This problem is mediated, at least in part, by metabolic side effects of second-generation antipsychotics (SGAs) and by unhealthy lifestyle behaviors. We asked whether oral glucose tolerance testing (oGTT) or hemoglobin A1c (HbA1c) is superior in identifying people with SMI at high cardiometabolic risk and whether this risk is shaped by mood, cognition, or lifestyle habits. Methods: We evaluated 40 patients with schizophrenia, schizoaffective, or bipolar disorder receiving SGAs by oGTT, HbA1c, comprehensive metabolic and lipid panels, and CRP. Mood was assessed using the Patient Health Questionnaire (PHQ-9), and cognition was assessed using the Saint Louis University Mental Status examination. Diet was assessed using the UK Diabetes and Diet Questionnaire (UKDDQ), and physical activity was assessed using daily step counts. Results: Most patients had prediabetes (preDM) or diabetes mellitus (DM), 72.5% by oGTT, and 52.5% by HbA1c criteria. Pulse rates and insulin resistance indices (Homeostatic Model Assessment of Insulin Resistance, HOMA IR; Matsuda) were significantly different between patients classified as normal or with preDM/DM, using either oGTT or HbA1c criteria. Patients with preDM/DM by HbA1c but not oGTT criteria also had higher waist/hip ratios, triglyceride, and CRP levels (p<0.05). A strong negative correlation was found between average daily step counts and CRP levels (rho = -0.62, p<0.001). Higher UKDDQ scores, or unhealthier diet habits, were associated with higher fasting plasma glucose (rho = 0.28, p = 0.08), triglyceride levels (rho = 0.31, p = 0.05), and insulin resistance (HOMA IR: rho = 0.31, p = 0.06). Higher PHQ-9 scores correlated with lower 2h-oGTT glucose levels (rho = -0.37, p<0.05). Conclusions: OGTT screening is superior to HbA1c screening in detecting preDM and DM early. Patients identified with preDM/DM by oGTT or HbA1c screening are insulin-resistant and have higher pulse rates. Abdominal obesity, unfavorable lipid profiles, and higher CRP levels were noted in patients screened by HbA1c, but not by oGTT. Low physical activity, low depression scores, and unhealthy diet habits were associated with higher CRP and higher glucose and triglyceride levels, respectively. Future studies should assess the impact of specifically tailored individual lifestyle counseling and medical management interventions in this high-risk population. [ABSTRACT FROM AUTHOR]

Background: Oral aripiprazole exhibits favorable clinical efficacy and safety in the suppression of tics in children and adolescents with tic disorders. This study aims to evaluate and compare the cost-effectiveness of high-dose and low-dose aripiprazole in children and adolescents with tic disorders from the perspective of the Chinese healthcare system. Methods: A questionnaire survey was conducted on 146 patients with tic disorders, of whom 144 completed EQ-5D-Y and YGTSS. Four models were built to convert YGTSS onto EQ-5D-Y utility using two mapping algorithms. We constructed a decision tree model containing efficacy and safety to compare the cost-effectiveness of high-dose and low-dose aripiprazole based on our mapping function. Results: The GLM with model 1 (YGTSS total tic scores) was selected as the preferred function in our decision tree model. The base case cost-effectiveness analysis showed that compared to low-dose aripiprazole, high-dose aripiprazole improves effectiveness by 0.001QALYs and increases the overall cost by $197.99, resulting in an ICER of $174339.22 per QALY, which exceeds three times the gross domestic product per capita. Hence, high-dose aripiprazole is not likely to be a cost-effective option for child patients with tic disorders. One-way sensitivity analysis and probabilistic sensitivity analysis showed that these results is robust. Conclusion: On the basis of currently available data, low-dose aripiprazole may be a safe, effective, and economical dosage for children and adolescents with tic disorders. Limitations: The main limitation of our study is the lack of utility directly used for cost-effectiveness analysis. We obtained the utility of patients with tic disorders indirectly by the mapping function. This may introduce some bias and uncertainty. And it is a limitation to use the direct medical costs of Germany in our model. Although we converted it to the equivalent value of China using purchasing power parities, caution should be exercised when interpreting the results of this study. [ABSTRACT FROM AUTHOR]

Aripiprazole is an atypical antipsychotic medication indicated for the treatment of schizophrenia and bipolar disorders. The drug has been shown to exhibit acceptable efficacy and is often preferred as a first‐line psychiatric treatment option owing to its lower incidence of adverse effects. While first‐generation antipsychotics are associated with extrapyramidal syndrome (EPS), atypical antipsychotics such as aripiprazole are generally associated with a lower frequency of EPS. In this case, we present a 31‐year‐old woman with a history of bipolar disorder who developed EPS after ingesting 200 mg of aripiprazole. Fortunately, her symptoms improved with the administration of biperiden, and she was discharged five days after ingestion. This case highlights the potential for significant consequences associated with aripiprazole, even within its therapeutic index. [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]

Gummy formulations are defined as gradually or slowly released solid oral dosage forms. Risperidone is an atypical antipsychotic medication used to treat schizophrenia and autism-related irritability. This study presents the development of visually appealing, patient-tailored medicated gummies that act as a novel pharmaceutical form of Risperidone for pediatrics. In this study, two gummy bases were used, one containing Glucomannan and the other containing Gelatin as a gelling agent, where these gummy bases were loaded with coated Risperidone pellets with a controlled release layer. The final products were evaluated for their pH, viscosity, content uniformity, drug content, and dissolution profile. Both formulas showed proper rheology and met content and weight uniformity standards. The release rates for F1 and F2 in the acidic media were 25% and 11%, respectively, after 2 h. At the same time, a full-release profile for Risperidone was noticed in both formulae at pH 6.8 where the release lasts for 24 h. It can be concluded that the chewable semi-solid dosages (gummies) filled with coated pellets are suitable for pediatric patients since pediatrics have drug-related problems which can be solved using high gastro-resistance coated pellets, which also shows a proper release profile for the drug. [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]

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]

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]

Rationale: The efficacy and safety of antidepressant augmentation therapy with aripiprazole (AATA) has been established; however, the ongoing effects of continuing aripiprazole after remission remain unclear because no studies have examined this issue. Objectives: We aimed to explore the effect of AATA discontinuation on the major depressive disorder (MDD) recurrence risk in patients with remitted MDD after AATA. Methods: This 24-week, multicenter, placebo-controlled, double-blind, randomized trial evaluated recurrence risk in patients with MDD who achieved remission with AATA. Differences in MDD recurrence, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, between the two groups were compared using survival analysis. The differences in depressive symptom severity and social functioning between the two groups were compared using a mixed model with repeated measures. Extrapyramidal symptoms and akathisia were also assessed. Results: Twenty-three participants were randomized and treated. Two patients in each group experienced recurrence during the study. Kaplan–Meier analysis with Log-rank comparison showed no difference in recurrence between groups (p = 0.642). No significant difference in interactions between group and period was observed in the 17-item Hamilton depression rating scale (p = 0.492) or the Social and Occupational Functioning Assessment Scale (p = 0.638). No patients developed extrapyramidal symptoms or akathisia. Conclusions: Definitive conclusions could not be drawn owing to the small sample size. This study represents a starting point for investigating the safety of aripiprazole discontinuation on recurrence in patients with MDD who have achieved remission with AATA. Future studies with appropriate sample sizes calculated based on this study are needed. [ABSTRACT FROM AUTHOR]

Intrinsic brain network connectivity is already altered in first-episode psychosis (FEP), but the longitudinal trajectories of network connectivity, especially in response to antipsychotic treatment, remain poorly understood. The goal of this study was to investigate how antipsychotic medications affect higher-order intrinsic brain network connectivity in FEP. Data from 87 antipsychotic medication-naïve patients with FEP and 87 healthy control participants were used. Medication-naïve patients received antipsychotic treatment for 16 weeks. Resting-state functional connectivity (FC) of the default mode, salience, dorsal attention, and executive control networks were assessed prior to treatment and at 6 and 16 weeks after treatment. We evaluated baseline and FC changes using linear mixed models to test group × time interactions within each network. Associations between FC changes after 16 weeks and response to treatment were also evaluated. Prior to treatment, significant group differences in all networks were found. However, significant trajectory changes in FC were found only in the default mode and executive control networks. Changes in FC in these networks were associated with treatment response. Several sensitivity analyses showed a consistent normalization of executive control network FC in response to antipsychotic treatment. Here, we found that alterations in intrinsic brain network FC were not only alleviated with antipsychotic treatment, but the extent of this normalization was also associated with the degree of reduction in symptom severity. Taken together, our data suggest modulation of intrinsic brain network connectivity (mainly frontoparietal connectivity) as a mechanism underlying antipsychotic treatment response in FEP. [ABSTRACT FROM AUTHOR]

Antipsychotic drugs (APDs) are used to treat many psychiatric illnesses as schizophrenia. Typical antipsychotic drugs (TAPDs) are being used; however, they have many side effects. Atypical antipsychotic drugs (AAPDs) are newer medications with known fewer side effects. Aripiprazole (ARI) is an AAPD, recommended by healthcare providers, even during pregnancy. It can cross the placental barrier and enter fetal circulation, so it might be possible that ARI can adversely impair normal placental development and growth, if it is given prenatally. ARI was applied orally to pregnant female rats in two doses (3& 6 mg/kg body weight). On gestation day 20, the mothers were sacrificed, and the placentas were removed and processed for general histological and electron microscopic evaluations. Immunohistochemistry was done using anti-PCNA (proliferating cell nuclear antigen), anti-Bax (for apoptosis) and anti-vascular endothelial growth factor alpha (VEGFA). Morphological evaluation revealed degenerative changes in the placenta as dark nuclei, vacuolization, and cyst formation. Ultra-structurally, there was degeneration of cellular components including organelles and nuclei. These changes were found in different cells of the basal and labyrinth zones and were dose dependent. Immunohistochemistry revealed upregulation of Bax and VEGFA and downregulation of PCNA. Prenatal administration of the AAPD, ARI to pregnant female rats resulted in histological changes in the placenta. Additionally, there was a decrease in cellular proliferation and increase in apoptosis, and vascular impairment. This indicates placental atrophy and dysgenesis and might suggest possible teratogenic effects to ARI, which needs further evaluation. [ABSTRACT FROM AUTHOR]

Background: Anxiety is one of the common mental disorders. Non-fatal health loss is one of the consequences of anxiety disorders. Oxidative stress may also play a role in anxiety disorders. As an antioxidant, Vitamin C can create stable ascorbate free radicals and lower reactive oxygen species. In addition, Vitamin C can prevent damage caused by free radicals. Oxidative stress can also lead to depression, schizophrenia, and bipolar disorder. Aim and Objectives: The aim and objectives of the study are to compare the antianxiety effects of Vitamin C, buspirone, and diazepam in albino rats using elevated plus maze and hole board apparatus. Materials and Methods: 36 albino rats of either sex were divided into 6 groups of 6 rats each and drugs were administered orally. Group 1 received distilled water 10 ml/kg, Group 2 received Vitamin C 200 mg/kg, Group 3 received buspirone 10 mg/kg, Group 4 received diazepam 1 mg/kg, Group 5 received buspirone 10 mg/kg + Vitamin C 200 mg/kg, and Group 6 received diazepam 1 mg/kg + Vitamin C 200 mg/kg. Antianxiety effects of these drugs were tested after 14 days of drug administration using hole board apparatus and elevated plus maze. The methods used for statistical analysis were mean, standard deviation, confidence interval, median, interquartile range (IQR), frequency and percentage, ANOVA, Kruskal-Wallis test, and Fisher's exact test. Results: On average time spent in open arms by Group 5 was 98.00 sec (IQR: 19.75-138.00) which was higher than other groups, but it was not statistically significant (P = 0.845). The time spent in closed arms in seconds by Group 4 was 245 ± 28.863, which was higher than other groups, but it was not statistically significant (P = 0. 805). On average head dip by Group 5 was 9.83 ± 4.708, which was higher than other groups, but it was not statistically significant (P = 0.141). Conclusion: Group 5 rats that received buspirone and Vitamin C, followed by Group 6 rats that received diazepam and Vitamin C had spent more time and had more entries into the open arms. Furthermore, Groups 5 and 6 animals had a greater number of head dips in the hole board apparatus compared to the behavior of all animals in other groups. Buspirone and diazepam are known anxiolytics. When these drugs were given in combination with Vitamin C, the antianxiety behaviors in rats were more compared to the drugs given alone in the present study but it was not statistically significant. [ABSTRACT FROM AUTHOR]

Background and Purpose Experimental Approach Key Results Conclusion and Implications Antipsychotics such as olanzapine are associated with significant metabolic dysfunction, attributed to gut microbiome dysbiosis. A recent notion that most psychotropics are detrimental to the gut microbiome has arisen from consistent findings of metabolic adverse effects. However, unlike olanzapine, the metabolic effects of lurasidone are conflicting. Thus, this study investigates the contrasting effects of olanzapine and lurasidone on the gut microbiome to explore the hypothesis of ‘gut neutrality’ for lurasidone exposure.Using Sprague–Dawley rats, the effects of olanzapine and lurasidone on the gut microbiome were explored. Faecal and blood samples were collected weekly over a 21‐day period to analyse changes to the gut microbiome and related metabolic markers.Lurasidone triggered no significant weight gain or metabolic alterations, instead positively modulating the gut microbiome through increases in mean operational taxonomical units (OTUs) and alpha diversity. This novel finding suggests an underlying mechanism for lurasidone's metabolic inertia. In contrast, olanzapine triggered a statistically significant decrease in mean OTUs, substantial compositional variation and a depletion in short‐chain fatty acid abundance. Microbiome depletion correlated with metabolic dysfunction, producing a 30% increase in weight gain, increased pro‐inflammatory cytokine expression, and increased blood glycaemic and triglyceride levels.Our results challenge the notion that all antipsychotics disrupt the gut microbiome similarly and highlights the potential benefits of gut‐neutral antipsychotics, such as lurasidone, in managing metabolic side effects. Further research is warranted to validate these findings in humans to guide personalised pharmacological treatment regimens for schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Shared decision-making (SDM) has yet to be successfully adopted into routine use in psychiatric settings amongst people living with severe mental illnesses. Suboptimal rates of SDM are particularly prominent amongst patients with psychotic illnesses during antipsychotic treatment choices. Many interventions have been assessed for their efficacy in improving SDM within this context, although results have been variable and inconsistent. Aims: To generate an in-depth understanding of how, why, for whom, and to what extent interventions facilitating the application of SDM during antipsychotic treatment choices work and the impact of contextual factors on intervention effectiveness. Methods: This review will use realist review methodology to provide a causal understanding of how and why interventions work when implementing SDM during antipsychotic treatment choices. The cohort of interest will be those experiencing psychosis where ongoing treatment with an antipsychotic is clinically indicated. The review will take place over five stages; (1) Locating existing theories, (2) Searching for evidence, (3) Selecting articles, (4) Extracting and organising data and (5) Synthesizing evidence and drawing conclusions. An understanding of how and why interventions work will be achieved by developing realist programme theories on intervention effectiveness through iterative literature reviews and engaging with various stakeholder groups, including patient, clinician and carer representatives. Discussion: This is the first realist review aiming to identify generative mechanisms explaining how and why successful interventions aimed at improving SDM within the parameters outlined work and in which contexts desired outcomes are most likely to be achieved. Review findings will include suggestions for clinicians, policy and decision-makers about the most promising interventions to pursue and their ideal attributes. [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: Weight gain and metabolic disorders are commonly induced by antipsychotics. Orlistat is a lipase inhibitor used for weight control. The effect of orlistat on weight gain and metabolic disturbances in people (especially women) treated with antipsychotics has not been sufficiently studied. This study aimed to investigate the efficacy of orlistat in mitigating antipsychotic-induced weight gain and abnormal glycolipid metabolism. Methods: Patients with schizophrenia or bipolar disorder with a weight gain ≥ 7% after taking antipsychotics were recruited. Participants were randomly allocated to two groups: one received eight weeks of orlistat (360 mg/day) and the other received a placebo. Anthropometric and fasting serum biochemical parameters were measured at baseline, week 4 and week 8. Results: Sixty individuals (orlistat:placebo = 32:28) participated in the study. After controlling for the study center, the eight-week changes in body mass index (BMI), cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-CH) and low-density lipoprotein cholesterol (LDL-CH) were significantly different between the groups. According to the mixed linear models, CHOL and LDL-CH were significantly lower in the orlistat group than in the control group at week 8. The week 0-to-8 slopes of BMI, CHOL and LDL-CH were also significantly lower in the orlistat group. Conclusions: These findings suggested that orlistat is an effective intervention for attenuating weight gain and serum lipid disturbances in antipsychotic-treated patients. Trial registration: ClinicalTrials.gov NCT03451734. [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: 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]

The prevalence of obesity is increasing worldwide, resulting in various health issues such as hypertension, dyslipidemia, diabetes mellitus, heart disease, and a lower life expectancy. Importantly, several psychiatric disorders and the use of psychotropic medications have been linked to obesity, and the possible risk factors need further investigation. This study examined the prevalence of obesity and its associated factors using a self‐administered questionnaire. Participants were recruited from three outpatient clinics and individuals who met one or more of the ICD‐10 F0‐F9, G4 diagnoses were included. In total, 1384 participants completed the questionnaire about their lifestyle. Statistical analysis compared the demographic and clinical characteristics of the individuals who were obese (Body Mass Index: BMI ≥25) and those who were non‐obese (BMI <25). The results revealed that the factors associated with obesity in psychiatric outpatients were being male, prolonged treatment duration, eating out frequently, and use of both second‐ and first‐generation antipsychotics. The study emphasized the importance of closely monitoring BMI in individuals with multiple obesity‐related factors. [ABSTRACT FROM AUTHOR]

In order to accelerate drug development and avoid unnecessary drug trials in vulnerable pediatric populations, the US Food and Drug Administration (FDA) released a general advice letter to sponsors permitting the effectiveness of atypical antipsychotics for the treatment of schizophrenia in adults to be extrapolated to adolescents. Extrapolation is based on the evidence‐based assumptions that (1) disease characteristics and (2) response to therapy, are similar in adults and adolescents. Whereas the FDA validated the extrapolation approach using data from multiple drug development programs, aripiprazole data are the most relevant to confirm the validity of the extrapolation approach for brexpiprazole, since aripiprazole and brexpiprazole both modulate dopaminergic and serotonergic signaling in the brain. The aims of this analysis were (1) to quantitatively assess the aripiprazole exposure (average steady‐state concentration)–response (Positive and Negative Syndrome Scale total score change from baseline) similarity between adults and adolescents with schizophrenia, (2) to extend the aripiprazole exposure–response modeling to brexpiprazole using adult data, and (3) to use the brexpiprazole model to predict schizophrenia symptom response in adolescents. Disease–drug–dropout models were developed using patient‐level data from clinical studies of aripiprazole (1007 adults, 294 adolescents) and brexpiprazole (1235 adults) in schizophrenia. The aripiprazole model demonstrated similar exposure–response between adults and adolescents with schizophrenia, validating the extrapolation approach. Extrapolation of the brexpiprazole adult exposure–response model to adolescents predicted the efficacy of brexpiprazole in adolescents aged 13–17 years with schizophrenia. [ABSTRACT FROM AUTHOR]

Many children with autism spectrum disorder (ASD) also have attention-deficit/hyperactivity disorder (ADHD). ADHD in children is associated with increased risk of negative outcomes, and early intervention is critical. Current guidelines recommend psychosocial interventions such as behavioral training as the first line of therapy in managing ADHD symptoms in children with or without ASD. Where symptoms are refractory to these interventions, medications such as stimulants, α2-adrenergic agonist inhibitors, selective norepinephrine reuptake inhibitors, and second-generation antipsychotics are recommended. However, these pharmacotherapies do not have regulatory approval for use in children of preschool age, and evidence on their safety and efficacy in this population has historically been very limited. Since publication of the current guidelines in 2020, several new randomized controlled trials and real-world studies have been published that have investigated the efficacy and tolerability of these medications in preschool children with ADHD, with or without comorbid ASD. Here, we provide a review of the key findings of these studies, which suggest that there is growing evidence to support the use of pharmacological interventions in the management of ADHD in preschool children with comorbid ASD. [ABSTRACT FROM AUTHOR]

Background Case Presentation Conclusion In patients with schizophrenia, violent behavior is a clinically important factor that prevents their discharge. Clozapine is an effective antipsychotic medication for treatment‐resistant schizophrenia, and its usefulness for aggressive behavior has also been suggested.We present the case of a 38‐year‐old male patient diagnosed with schizophrenia who was successfully treated with clozapine after recurrent violent behavior. He was diagnosed with schizophrenia during his adolescence. He was hospitalized for treatment in his teens, but his hallucinations and delusions persisted even after discharge. In his 30s, he became noticeably emotionally unstable, and despite being treated for an adequate period with sufficient doses of several antipsychotics, his symptoms did not improve. This led to repeated hospitalizations triggered by violent behavior toward his parents and siblings within the home. During his fourth hospitalization, clozapine was initiated due to multiple incidents of violence toward nursing staff secondary to hallucinations and delusions. As the dose of clozapine was gradually increased with therapeutic drug monitoring, the patient's hostility, uncooperativeness, and suspiciousness markedly improved, and his aggressive behavior disappeared. He was discharged to a facility on day 194 after starting clozapine and has continued outpatient visits.Clozapine was suggested to be effective for aggressive behavior in patients with treatment‐resistant schizophrenia and should be actively considered. In such cases, regular measurement of blood concentration is useful for adjusting the dosage of clozapine. [ABSTRACT FROM AUTHOR]

Antipsychotic drug efficacy may vary in placebo-controlled and active-controlled trials. The study aims to investigate the performance of antipsychotics in these two different study designs using single-arm meta-analysis. We included randomized controlled trials (RCTs) comparing second-generation antipsychotics with placebo or other antipsychotics from our previous systematic reviews and updated the results with the search on Cochrane Schizophrenia Group register until March 06, 2022. The outcomes were the differences in the change of overall, positive and negative symptoms of schizophrenia, and the difference in study discontinuation between placebo-controlled and head-to-head trials. Random-effects single-arm meta-analysis and subgroup test were conducted to examine the differences in each outcome. A total of 208 RCTs (n = 42,159) were included in the analysis. Of these, 85 trials with 17,056 participants were placebo-controlled, while the remaining were head-to-head trials. Antipsychotics in head-to-head trials demonstrated a significantly greater improvement in overall symptoms (MC −23.58; 95 % CI −25.33, −21.83) compared to antipsychotics in placebo-controlled trials (MC −16.74; 95 % CI −17.80, −15.69; p < 0.0001). Similar findings were observed for positive symptoms, negative symptoms, study discontinuation and sensitivity analyses. Notably, when assessing antipsychotics individually, the same antipsychotic consistently demonstrated superior performance in head-to-head trials compared to placebo-controlled trials. In conclusion, antipsychotics in head-to-head trials presented a considerable efficacy superiority compared to those in placebo-controlled trials. Moreover, the efficacy of the same antipsychotics varied depending on the study design. Future trials should carefully consider the methodology and employ strategies to mitigate the potential for overestimation or underestimation of treatment efficacy. [ABSTRACT FROM AUTHOR]

Aims: Norway and Sweden had different early pandemic responses that may have impacted mental health management. The aim was to assess the impact of the early COVID‐19 pandemic on mental health‐related care. Methods: We used national registries in Norway and Sweden (1 January 2018–31 December 2020) to define 2 cohorts: (i) general adult population; and (ii) mental health adult population. Interrupted times series regression analyses evaluated step and slope changes compared to prepandemic levels for monthly rates of medications (antidepressants, antipsychotics, anxiolytics, hypnotics/sedatives, lithium, opioid analgesics, psychostimulants), hospitalizations (for anxiety, bipolar, depressive/mood, eating and schizophrenia/delusional disorders) and specialist outpatient visits. Results: In Norway, immediate reductions occurred in the general population for medications (−12% antidepressants to −7% hypnotics/sedatives) except for antipsychotics; and hospitalizations (−33% anxiety disorders to −17% bipolar disorders). Increasing slope change occurred for all medications except psychostimulants (+1.1%/month hypnotics/sedatives to +1.7%/month antidepressants); and hospitalization for anxiety disorders (+5.5%/month), depressive/mood disorders (+1.7%/month) and schizophrenia/delusional disorders (+2%/month). In Sweden, immediate reductions occurred for antidepressants (−7%) and opioids (−10%) and depressive/mood disorder hospitalizations (−11%) only with increasing slope change in psychostimulant prescribing of (0.9%/month). In contrast to Norway, increasing slope changes occurred in specialist outpatient visits for depressive/mood disorders, eating disorders and schizophrenia/delusional disorders (+1.5, +1.9 and +2.3%/month, respectively). Similar changes occurred in the pre‐existing mental health cohorts. Conclusion: Differences in early COVID‐19 policy response may have contributed to differences in adult mental healthcare provision in Norway and Sweden. [ABSTRACT FROM AUTHOR]

Background and Objective: Antipsychotics are core treatments for people living with psychotic disorders. Understanding individualised factors that influence both efficacy and adverse responses will improve outcomes. The objective of this study was to examine sex differences in antipsychotic-related efficacy and tolerability. Methods: This was a secondary analysis of data from phase 1 and 1a of Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE); participants with schizophrenia were randomly assigned to double-blinded treatment with oral olanzapine, quetiapine, risperidone, ziprasidone or perphenazine. Measures included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions (CGI) scale and Calgary Depression Rating Scale, as well as self-reported side effects, medication compliance, dosage, weight measurements and various blood parameters. Results: There were 1460 participants including 380 female and 1080 male individuals. Very few differences existed between male and female participants in response, adverse reactions, compliance or antipsychotic dosage. However, significantly more female participants than male participants reported constipation (28% vs 16%), dry mouth (50% vs 38%), gynecomastia/galactorrhea (11% vs 3%), incontinence/nocturia (16% vs 8%) and self reported weight gain (37% vs 24%) [all p < 0.001]. Within the risperidone treatment group, there was a significantly greater increase in prolactin levels (p < 0.001) among female participants (n = 61) than male participants (n = 159). No overall differences in clinician-rated measures, weight gain or other laboratory indicators were found. Conclusions: While overall sex differences were limited across efficacy and tolerability for antipsychotic treatment, there were some specific findings with risperidone. Further examination of sex differences within antipsychotic trials will be important to improve efficacy and reduce adverse responses across as well as individualising care for people with schizophrenia. [ABSTRACT FROM AUTHOR]

Worldwide, acute antipsychotic poisoning results in high morbidities and mortalities. Though extrapyramidal syndromes are commonly associated, the extent of extrapyramidal syndromes in relation to the severity of antipsychotic poisoning has not been addressed yet. Thus, this study aimed to assess the Global Dystonia Rating Scale (GDRS) as an unfavorable outcomes predictive tool in acute antipsychotic poisoning. A cross-sectional study included 506 antipsychotic-poisoned patients admitted to Tanta University Poison Control Center, Egypt, over three years was conducted. The mean GDRS was 9.1 ± 16.7 in typical antipsychotic poisoning, which was significantly higher than that of atypical antipsychotics (4.2 ± 11.5) (p = 0.003). Patients with GDRS> 20 showed significantly higher liability for all adverse outcomes (p < 0.05). However, poisoning with typical antipsychotics was associated with significantly more cardiotoxicity (p = 0.042), particularly prolonged QRS (p = 0.005), and intensive care unit (ICU) admission (p = 0.000). In contrary to the PSS, which failed to predict the studied adverse outcomes, GDRS significantly predicted all adverse outcomes (p < 0.000) for all antipsychotic generations. In atypical antipsychotics, GDRS above three accurately predicted cardiotoxicities, prolonged QTc interval, and respiratory failure with Area under curves (AUC) of 0.937, 0.963, and 0.941, respectively. In typical antipsychotic poisoning, at higher cutoffs (7.5, 27.5, 18, and 7.5), cardiotoxicities, prolonged QTc interval, and respiratory failure were accurately predicted (AUC were 0.974, 0.961, and 0.960, respectively). GDRS is an objective, substantially useful tool that quantifies dystonia and can be used as an early reliable predictor of potential toxicity in acute antipsychotic poisoning. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 24-year-old female diagnosed with familial encephalopathy with neuroserpin inclusion bodies (FENIB) who initially presented with catatonia, a rare manifestation of the condition. Topics discussed include the diagnostic challenges of distinguishing FENIB from other psychiatric disorders, the role of electroconvulsive therapy (ECT) in managing catatonic symptoms, and the impact of genetic findings on treatment and prognosis.

Introduction Cariprazine is an atypical dopamine receptor partial agonist antipsychotic available in the form of capsules. Although capsules are one of the most desirable routes of administration, there are certain situations (e. g., in an acute psychiatric setting, or when swallowing difficulties, or liquid shortages are present) when they cannot be administered. Therefore, alternative solutions like orodispersible tablets are needed. This study aimed to investigate the bioequivalence of a newly developed orodispersible tablet to the commercially available hard gelatine capsule of cariprazine 1.5 mg. Methods This was a phase I, open-label, randomized, single-dose bioequivalence study. It had a 2-period, 2-sequence, cross-over design, where each subject received one test and one reference product in a randomized sequence, separated by a wash-out period of 55 days. Blood sampling was performed over 72 h after dosing. Cariprazine concentrations were analyzed by a validated HPLC-MS/MS method. Standard bioequivalence statistics was applied to PK parameters calculated by non-compartmental analysis. Safety measures were analyzed descriptively. Result Pharmacokinetic data of 43 healthy volunteers and safety data of 54 subjects was analyzed. Cariprazine AUC0–72h and Cmax geometric mean ratios were 117.76% and 100.88%, respectively. The 90% confidence intervals were within the pre-defined bioequivalence acceptance limits of 80.00% – 125.00%. Safety data was in line with the Summary of Product Characteristics of Cariprazine. Discussion The result of this clinical trial proved the bioequivalence of the new orodispersible tablet formulation when compared to hard gelatine capsules, enabling an alternative option for treatment of those suffering from schizophrenia. [ABSTRACT FROM AUTHOR]