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Long‐term sample stability of five atypical antipsychoticdrugs risperidone, paliperidone, clozapine, quetiapine and olanzapine and the antidepressant drug mirtazapine in serum was studied by use of a newly developed and validated analytical method based on solid‐phase extraction and liquid chromatography–tandem mass spectrometry. Ascorbic acid was used as an antioxidative agent to stabilize olanzapine during storage and sample preparation. We assessed analyte stability on long‐term storage in serum samples at 25°C, 5°C, −20°C and −80°C, and during five freeze–thaw cycles. Analytes were stable for 23 days at room temperature except for olanzapine and mirtazapine (17 days). All analytes were stable for at least 30 days at 5°C. All analytes were stable for 270 days at −20°C, except for paliperidone and mirtazapine with 60 days and 180 days, respectively. All analytes were stable for 270 days at −80°C. Furthermore, all analytes were stable for five freeze–thaw cycles. We recommend storage at −80°C when samples drawn for analysis of antipsychotic drugs are stored for more than 60 days, whereas a temperature of −20°C is sufficient for storage less than 60 days. [ABSTRACT FROM AUTHOR]

Risperidone extended‐release injectable suspension (R‐ERIS; marketed as RYKINDO) is a novel immediate‐release version of risperidone formulated as extended‐release microspheres for biweekly intramuscular injection to treat schizophrenia in adults. The pharmacokinetics (PK) and safety of R‐ERIS were evaluated in a multicenter, randomized, open‐label, multiple‐dose study in patients with stable schizophrenia or schizoaffective disorder. Eligible patients (N = 108) 18 to 65 years old were randomized (1:1) to receive IM injections of R‐ERIS 25 mg or the comparator, a biweekly risperidone long‐acting injectable (BW‐RLAI; marketed as RISPERDAL CONSTA) 25 mg for a total of 5 injections. The primary objective was to evaluate the relative bioavailability of active moiety (risperidone plus 9‐hydroxyrisperidone) at steady state. Blood samples were analyzed for risperidone and 9‐hydroxyrisperidone using a validated, specific, and sensitive liquid chromatography with tandem mass spectrometry method. Plasma concentration–time data were analyzed using non‐compartmental methods. Pharmacokinetic parameters were calculated based on individual patient PK profiles. Safety was assessed using standard measures. At steady state, mean plasma concentrations of the active moiety were similar for R‐ERIS and BW‐RLAI. R‐ERIS rapidly released risperidone after the injection without apparent lag time. Plasma active moiety levels reached steady state after the second injection of R‐ERIS. The elimination of the drug was completed approximately 2 weeks earlier for R‐ERIS as compared to that for BW‐RLAI. R‐ERIS was safe and well tolerated. Overall, R‐ERIS exhibited a faster onset and offset than BW‐RLAI and statistical analysis of exposure parameters demonstrated bioequivalence at steady state. [ABSTRACT FROM AUTHOR]

The rare psychiatric phenomenon of catatonia has recently been decoupled from schizophrenia in the ICD‐11 and DSM‐V and is now a stand‐alone syndrome. This article explores a complex case of catatonia in intellectual disability, considering a broad array of differential diagnoses for the underlying pathology. The authors also explore evolutionary theories of catatonia and consider the compounding factors resulting in delayed diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Purpose: The administration of sedatives to critically ill patients is a common practice in intensive care units (ICU) and has been associated with negative outcomes. To mitigate this, atypical antipsychotics are utilized as adjunctive therapy. This study aims to review and quantify overall effectiveness of the atypical antipsychotics quetiapine, risperidone, and olanzapine on reduction in the amount of continuous infusion propofol utilized in the ICU. Methods: This was an observational study that took place from February 27, 2021 to December 31, 2022. The primary outcome of this study was the percentage change in average propofol infusion rate (mcg/kg/min) from baseline to the greater than 24 to 48 hours period after atypical antipsychotic initiation. Secondary outcomes included ICU length of stay, duration of mechanical ventilation, QTc interval monitoring, and continuation of the antipsychotic without a valid indication. Descriptive statistics were utilized for the statistical analysis. Results: A total of 47 patients were included in the study. The average baseline propofol rate was 31 mcg/kg/min, which reduced 8.6% to 28.35 mcg/kg/min over the 0 to 24 hours period, was reduced by 19.4% compared to baseline to a rate of 25 mcg/kg/min during the greater than 24 to 48 hours period, and finally a percent reduction of 54.2% seen during the greater than 48 to 72 hours period to a rate of 14 mcg/kg/min. Conclusions: Patients who received an adjunctive antipsychotic saw resulting propofol rate reductions of 8.6% at 24 hours, 19.4% at 48 hours, and 54.2% at 72 hours. However, research on this topic should not end here, as further investigation with higher-level study design is needed to determine the true impact of these agents for this indication. [ABSTRACT FROM AUTHOR]

Purpose: The CYP2D6 gene exhibits significant polymorphism, contributing to variability in responses to drugs metabolized by CYP2D6. While CYP2D6*2 and CYP2D6*35 are presently designated as alleles encoding normal metabolism, this classification is based on moderate level evidence. Additionally, the role of the formerly called "enhancer" single nucleotide polymorphism (SNP) rs5758550 is unclear. In this study, the impacts of CYP2D6*2, CYP2D6*35 and rs5758550 on CYP2D6 activity were investigated using risperidone clearance as CYP2D6 activity marker. Methods: A joint parent-metabolite population pharmacokinetic model was used to describe 1,565 serum concentration measurements of risperidone and 9-hydroxyrisperidone in 512 subjects. Risperidone population clearance was modeled as the sum of a CYP2D6-independent clearance term and the partial clearances contributed from each individually expressed CYP2D6 allele or haplotype. In addition to the well-characterized CYP2D6 alleles (*3-*6, *9, *10 and *41), *2, *35 and two haplotypes assigned as CYP2D6*2-rs5758550G and CYP2D6*2-rs5758550A were evaluated. Results: Each evaluated CYP2D6 allele was associated with significantly lower risperidone clearance than the reference normal function allele CYP2D6*1 (p < 0.001). Further, rs5758550 differentiated the effect of CYP2D6*2 (p = 0.005). The haplotype-specific clearances for CYP2D6*2-rs5758550A, CYP2D6*2-rs5758550G and CYP2D6*35 were estimated to 30%, 66% and 57%, respectively, relative to the clearance for CYP2D6*1. Notably, rs5758550 is in high linkage disequilibrium (R2 > 0.85) with at least 24 other SNPs and cannot be assigned as a functional SNP. Conclusion: CYP2D6*2 and CYP2D6*35 encode reduced risperidone clearance, and the extent of reduction for CYP2D6*2 is differentiated by rs5758550. Genotyping of these haplotypes might improve the precision of genotype-guided prediction of CYP2D6-mediated clearance. [ABSTRACT FROM AUTHOR]

Schizophrenia is a complex neuropsychiatric disorder with positive, negative, and cognitive symptoms. In rats, sub-chronic administration of ketamine is used for the induction of schizophrenia model. Increased locomotor activity is one of the most important features of psychotic-like symptoms in rodents. On the other hand, risperidone is a potent antipsychotic medication that is approved for the treatment of schizophrenia and bipolar disorder. In the present research, we aimed to investigate the effect of sub-chronic treatment of ketamine on cognitive and behavioral functions, and brain-derived neurotrophic factor (BDNF) expression level in the prefrontal cortex. Also, we assessed the efficacy of risperidone on cognitive and behavioral impairments induced by ketamine. Possible sex differences were also measured. Ketamine was intraperitoneally injected at the dose of 30 mg/kg for five consecutive days. Risperidone was also intraperitoneally injected at the dose of 2 mg/kg. Novel object recognition memory, pain threshold, locomotor activity, rearing behavior, and BDNF level were evaluated. The results showed that ketamine injection for five consecutive days impaired the acquisition of long-term recognition memory and decreased BDNF level in the prefrontal cortex in both sexes. Also, it decreased pain threshold in females, increased rearing behavior in males, and induced hyperlocomotion with greater effect in females. On the other hand, risperidone restored or attenuated the effect of ketamine on all the behavioral effects and BDNF level. In conclusion, we suggested that there were sex differences in the effects of ketamine on pain perception, locomotion, and rearing behavior in a rat model of schizophrenia. [Display omitted] • Ketamine impaired novel object recognition memory and decreased BDNF in both sexes. • Ketamine decreased pain threshold in females and increased rearing in males. • Ketamine induced hyperlocomotion with greater effect in females. • Risperidone restored ketamine-induced behavioral changes and increased BDNF. • Sex differences were seen in the effects of ketamine on pain, locomotion, rearing. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that is significantly increasing, resulting in severe distress. The approved treatment for ASD only partially improves the sympoms, but it does not entirely reverse the symptoms. Developing novel disease-modifying drugs is essential for the continuous improvement of ASD. Because of its pleiotropic effect, atorvastatin has been garnered attention for treating neuronal degeneration. The present study aimed to investigate the therapeutic effects of atorvastatin in autism and compare it with an approved autism drug (risperidone) through the impact of these drugs on TLR4/NF-κB/NOX-2 and the apoptotic pathway in a valproic acid (VPA) induced rat model of autism. Methods: On gestational day 12.5, pregnant rats received a single IP injection of VPA (500 mg/kg), for VPA induced autism, risperidone and atorvastatin groups, or saline for control normal group. At postnatal day 21, male offsprings were randomly divided into four groups (n = 6): control, VPA induced autism, risperidone, and atorvastatin. Risperidone and atorvastatin were administered from postnatal day 21 to day 51. The study evaluated autism-like behaviors using the three-chamber test, the dark light test, and the open field test at the end of the study. Biochemical analysis of TLR4, NF-κB, NOX-2, and ROS using ELISA, RT-PCR, WB, histological examination with hematoxylin and eosin and immunohistochemical study of CAS-3 were performed. Results: Male offspring of prenatal VPA-exposed female rats exhibited significant autism-like behaviors and elevated TLR4, NF-κB, NOX-2, ROS, and caspase-3 expression. Histological analysis revealed structural alterations. Both risperidone and atorvastatin effectively mitigated the behavioral, biochemical, and structural changes associated with VPA-induced rat model of autism. Notably, atorvastatin group showed a more significant improvement than risperidone group. Conclusions: The research results unequivocally demonstrated that atorvastatin can modulate VPA-induced autism by suppressing inflammation, oxidative stress, and apoptosis through TLR4/NF-κB/NOX-2 signaling pathway. Atorvastatin could be a potential treatment for ASD. [ABSTRACT FROM AUTHOR]

Introduction: Risperidone is one of the atypical antipsychotics that has been used for the treatment of dementia-related psychosis (DRP). However, the findings concerning its efficacy and safety in DRP are contradictory. Methods: We conducted a systematic review and meta-analysis to address the effects of risperidone on the alleviation of DRP. We searched Medline via PubMed, Scopus, Web of Science, Google Scholar, and PsychINFO from the inception until May 2024. Appropriate statistical tests were used to test the study hypothesis. Results: The study included 17 articles and 2,311 patients with DRP. Risperidone alleviated DRP with a standardized mean difference (SMD) of 0.355 (95% CI: 0.170–0.541, p = 0.000). The impact of treatment was positively associated with treatment duration (slope p = 0.038) and dose (slope p = 0.000). Six studies (n = 354) reported the data for the effects of risperidone on cognitive function. Analysis showed that risperidone treatment deteriorated cognitive function in DRP patients with an SMD of −0.185 (95% CI: −0.349 to −0.020, p = 0.028). The mean effect size was 0.36 with a 95% CI of 0.17–0.54. However, the true effect size in 95% of all comparable populations fell in the interval of −0.37 to 1.08. This revealed a high heterogeneity among the included publications as the prediction interval showed a wider range of expected treatment effects than CI. Conclusion: Our meta-analysis provides evidence for the effectiveness of risperidone in the management of DRP. However, because of safety concerns and high data heterogeneity, risperidone use should be individualized for each patient. [ABSTRACT FROM AUTHOR]

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]

Background/Objectives: Risperidone-related metabolic side effects in children have been primarily linked to variations between guideline-recommended and clinical treatment procedures. We explored the metabolic effects of risperidone administration in pediatric patients diagnosed with neurological disorders, thus evaluating its influence on metabolic indicators. Methods: This prospective cohort study gathered data from electronic health records, medical databases, and clinical reports. These data included patient demographics (e.g., age, sex, and body mass index) and information on risperidone use, including dosage, dosing frequency, and treatment duration. Additionally, laboratory tests were conducted at baseline and during treatment, along with other pertinent clinical variables. Result: A total of 52 eligible children (male; 73.1%) with neurological disorders treated with risperidone were included. The mean age was 13.4 ± 2.2 years. Risperidone was administered to 32.7% of patients for <2 years, 40.4% for 2–5 years, and 26.9% for 6–9 years, with a mean duration of 3.6 years. Most (53.8%) of the children experienced at least one metabolic side effect, with hyperlipidemia being the most common (34.6%). The median prolactin level increased slightly from 448.5 ng/mL at baseline to 479 ng/mL after 6–8 weeks. No significant associations were found between age, sex, duration of treatment, dosage form, dosing frequency, and hemoglobin A1c levels. Conclusion: Monitoring metabolic and anthropometric parameters in children receiving risperidone for neurological disorders is cardinal. Clinicians should consider individualized treatment plans, closely monitor metabolic markers, and address potential risks associated with long-term risperidone use in this vulnerable population. [ABSTRACT FROM AUTHOR]

Background: Risperidone is one of the most reliable and effective antipsychotics for schizophrenia treatment. However, the mechanism of action of risperidone is not yet fully understood. Traf2 and Nck-interacting protein kinase (TNIK), a schizophrenia susceptibility gene, is associated with risperidone treatment response. Our previous in vitro experiments confirmed that downregulated TNIK affected the effect of risperidone on downstream targets. However, the effect of downregulated TNIK on risperidone-induced molecular expression remains to be further explored. Methods: Transcriptome analysis was performed on U251 cells subjected to risperidone, TNIK siRNA, and no treatment, respectively. Compared to the notreatment group, two groups of DEGs were screened out and then intersected with the schizophrenia-related genes to screen the cross-talk genes. Those DEGs were analyzed using GO and KEGG. STRING and Cytoscape were used to construct a protein-protein interaction (PPI) network for the cross-talk gene. Results: The results showed that the parathyroid hormone synthesis, secretion, and action were significantly enriched after risperidone treatment. Downregulated TNIK could have an impact on the collagen-containing extracellular matrix, signaling receptor activator activity, and PI3K-Akt signaling pathway. Interestingly, bone mineralization function and calcium signaling pathway were enriched in the cross-talk genes. Additionally, FGFR2, FGF1, and FGFR might be the potential targets for TNIK affecting the effects of risperidone. Conclusion: The study indicated that risperidone primarily influences functions and/or pathways associated with bone metabolism, potentially contributing to the adverse effect of osteoporosis. Our study may offer a novel perspective on investigating the mechanisms underlying the adverse effects of risperidone. [ABSTRACT FROM AUTHOR]

Recent studies have highlighted the potential involvement of reactive oxygen species (ROS) and microglia, a major source of ROS, in the pathophysiology of schizophrenia. In our study, we explored how the second‐generation antipsychotic risperidone (RIS) affects ROS regulation and microglial activation in the hippocampus using a mouse ketamine (KET) model of schizophrenia. KET administration resulted in schizophrenia‐like behaviors in male C57BL/6J mice, such as impaired prepulse inhibition (PPI) of the acoustic startle response and hyper‐locomotion. These behaviors were mitigated by RIS. We found that the gene expression level of an enzyme responsible for ROS production (Nox2), which is primarily associated with activated microglia, was lower in KET/RIS‐treated mice than in KET‐treated mice. Conversely, the levels of antioxidant enzymes (Ho‐1 and Gclc) were higher in KET/RIS‐treated mice. The microglial density in the hippocampus was increased in KET‐treated mice, which was counteracted by RIS. Hierarchical cluster analysis revealed three morphological subtypes of microglia. In control mice, most microglia were resting‐ramified (type I, 89.7%). KET administration shifted the microglial composition to moderately ramified (type II, 44.4%) and hyper‐ramified (type III, 25.0%). In KET/RIS‐treated mice, type II decreased to 32.0%, while type III increased to 34.0%. An in vitro ROS assay showed that KET increased ROS production in dissociated hippocampal microglia, and this effect was mitigated by RIS. Furthermore, we discovered that a NOX2 inhibitor could counteract KET‐induced behavioral deficits. These findings suggest that pharmacological inhibition of ROS production by RIS may play a crucial role in ameliorating schizophrenia‐related symptoms. Moreover, modulating microglial activation to regulate ROS production has emerged as a novel avenue for developing innovative treatments for schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Chinese hamster ovarian (CHO) cells are widely employed in biotechnology for the production of recombinant proteins. Extending the life span of CHO cells and inhibiting the loss of producing cell population through the inhibition of apoptosis can benefit the productivity of those cells. In this study, we aimed to screen and evaluate the impact of some caspase-7 inhibitor candidates on the lifespan of CHO cells. Results: Through virtual screening and molecular docking, risperidone was screened and selected as a potential inhibitor of caspase-7 in CHO cells. The results of MTT assay revealed that the cytotoxicity of risperidone at all concentrations was lower than 50%, and thus it can be suggested as a safe treatment for CHO cells. Annexin V apoptosis and flow cytometry assays revealed that risperidone at 1, 25, and 50 lM concentrations inhibited apoptosis 72 h post-treatment through caspase-7 inhibition. Although gene expression analysis through qRT-PCR demonstrates that risperidone did not affect caspase-7 gene expression. Conclusions: This bioinformatics and experimental study suggests risperidone as a caspase-7 inhibitor with the potential to extend the lifespan of CHO cells and offers possible opportunities in biotechnology. [ABSTRACT FROM AUTHOR]

Many articles suggest that clozapine was strongly associated with a higher incidence of new-onset diabetes mellitus, and the issue has remained unsettled. Many articles have compared clozapine with FGAs, but few have compared clozapine with SGAs. We aimed to compare the risk of new-onset diabetes mellitus in adults with schizophrenia treated with clozapine and other SGAs. We conducted a comprehensive search of databases from their inception up until August 26, 2023. The specific databases include PubMed, Embase and others. We included non-randomized controlled trials involving the use of SGAs such as clozapine, olanzapine, risperidone, quetiapine, amisulpride, and zotepine, with a focus on new-onset diabetes mellitus as an outcome. We utilized odds ratio with 95 % credible intervals (95 % CI) as our effect size measures. The study protocol is registered with PROSPERO, number CRD42024511280. We included 7 studies with sufficient data to include in the meta-analysis. A total of eight studies with 641,48 participants met the eligibility criteria. The OR of the incidence rates of new-onset diabetes between clozapine and olanzapine was 0.95 (95 % CI:[0.82–1.09]), between clozapine and risperidone was 1.25 (95 % CI: [1.09–1.44]), between clozapine and quetiapine was 1.44 (95 % CI: [0.92–2.25]). In patients with schizophrenia, clozapine has been found to have a higher rate of new-onset diabetes mellitus compared to risperidone. However, there was no significant difference in incidence rate between clozapine versus olanzapine and quetiapine. These findings can assist clinicians in balancing the risks and benefits of those drugs. • Differences in the incidence of new-onset diabetes caused by second-generation antipsychotics were compared. • Clozapine and olanzapine cause a similar incidence of new-onset diabetes. • Clozapine is more likely to cause new-onset diabetes than risperidone. • Explored relationship between therapy duration and incidence [ABSTRACT FROM AUTHOR]

Introduction Conventional antipsychotic drugs that attenuate dopaminergic neural transmission are ineffective in approximately one-third of patients with schizophrenia. This necessitates the development of non-dopaminergic agents. Methods A systematic search was conducted for completed phase II and III trials of compounds for schizophrenia treatment using the US Clinical Trials Registry and the EU Clinical Trials Register. Compounds demonstrating significant superiority over placebo in the primary outcome measure in the latest phase II and III trials were identified. Collateral information on the included compounds was gathered through manual searches in PubMed and press releases. Results Sixteen compounds were identified; four compounds (ulotaront, xanomeline/trospium chloride, vabicaserin, and roluperidone) were investigated as monotherapy and the remaining 12 (pimavanserin, bitopertin, BI 425809, encenicline, tropisetron, pregnenolone, D-serine, estradiol, tolcapone, valacyclovir, cannabidiol, and rimonabant) were examined as add-on therapy. Compared to the placebo, ulotaront, xanomeline/trospium chloride, vabicaserin, bitopertin, estradiol, cannabidiol, rimonabant, and D-serine showed efficacy for positive symptoms; roluperidone and pimavanserin were effective for negative symptoms; and encenicline, tropisetron, pregnenolone, tolcapone, BI 425809, and valacyclovir improved cognitive function. Discussion Compounds that function differently from existing antipsychotics may offer novel symptom-specific therapeutic strategies for patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Aims: The aims of this study were to develop a population pharmacokinetic (PK) model for risperidone ISM® and to investigate the relationships between active moiety exposure, as described by apparent clearance (CL40), and several covariates using all data from five clinical studies. Methods: A population PK model was developed using active moiety concentrations from a study in healthy volunteers and two studies in patients with schizophrenia. Data from a comparative bioavailability study in medically stable patients and a Phase III study in patients with acute exacerbation of schizophrenia were then incorporated, using empirical Bayesian feedback and model refinement in NONMEM. Finally, covariate analysis was performed on CL40. Results: The final model adequately described the pharmacokinetics of 6288 active moiety concentrations in 17 healthy volunteers and 430 patients with schizophrenia. This one‐compartment disposition model had a complex absorption process, combining a small amount immediately entering the central active moiety compartment, two first‐order absorption processes and a combined zero‐order and first order process, with first‐order elimination from the central compartment. Significant covariates on CL40 were BMI and sex. Goodness‐of‐fit (GOF) plots and visual predictive checks (VPC) confirmed acceptable description of the data. Conclusions: The population PK model adequately described active moiety concentrations from five clinical studies after risperidone ISM® administration. Relationships between active moiety exposure and covariates were defined in order to facilitate simulations for future studies. The model showed that risperidone ISM® rapidly achieves therapeutic plasma levels within the first hours after the first injection that are maintained sustainedly throughout the whole dosing interval following once‐monthly gluteal injections of 100 mg and 75 mg. [ABSTRACT FROM AUTHOR]

Purpose: Drug-induced gynecomastia significantly affects patient health and quality of life. This study aimed to perform an exploratory analysis of gynecomastia reports and the most commonly associated medications within the FAERS database. Patients and Methods: A comprehensive analysis of the FAERS from January 2004 to December 2023 was conducted. Disproportionality analysis and subsequent sensitivity analysis were performed to identify drugs potentially associated with gynecomastia, utilizing the reported odds ratio (ROR). Logistic regression analysis was employed to assess potential risk factors. The Weibull shape parameter (WSP) test was used to assess the time-to-onset characteristics of the top drugs associated with gynecomastia. Results: The study identified 30,265 cases of gynecomastia, primarily associated with nervous system drugs, accounting for 85.50% of cases. Notably, risperidone accounted for 80.81% of the total cases. Among the 165 agents with ≥ 5 cases of gynecomastia, the strongest signals were exhibited by risperidone (ROR 602.38, 95% CI 585.07– 620.20), dutasteride (ROR 17.18, 95% CI 15.55– 18.89), spironolactone (ROR 15.8, 95% CI 13.99– 17.83), and paliperidone (ROR 7.16, 95% CI 6.55– 7.84). In the sensitivity analysis of disproportionality, unexpected associations were observed, such as montelukast (n = 21, ROR 1.94, 95% CI 1.26– 2.98). The logistic regression analysis indicated that the risk of risperidone-induced gynecomastia was significantly lower in adults compared to pediatric patients (OR 0.12, 95% CI 0.09– 0.15) and in patients with higher body weight than in those with lower body weight (OR 5.24, 95% CI 3.62– 7.76). The WSP test showed that gynecomastia induced by most of the top 10 common agents tends to occur in an early failure mode. Conclusion: The rankings and signal strengths of drugs associated with gynecomastia were extracted from the FAERS. The age distribution and time-to-onset distribution of the top 10 drugs linked to gynecomastia were investigated, which can facilitate accurate clinical recognition of drug-induced gynecomastia. [ABSTRACT FROM AUTHOR]

According to certain findings, heroin addiction represents a significant medical as well as social problem. It is known that with opioid substitution treatment this disease can be overcome or alleviated. However, the application of this treatment does not always give the expected results, so it is necessary to apply additional neuroleptic therapy until the patients are fully stabilized. But the joint application of substitution and neuroleptic therapy can lead to a series of side effects, one of which is the appearance of hyperpolactinemia. The aim of this study is to observe the prevalence of symptoms of hyperprolactinemia in patients with poor response to methadone treatment, treated with neuroleptic therapy. Material and methods: The cross-sectional study evaluated 20 male patients with a mean age of ±24.13 years treated at the Skopje Psychiatric Hospital with high doses of Sol methadone 80-120 mg/day. All patients had a bad agreement on the methadone treatment, so additional therapy was included, tab. Risperidone with an average dose of 2 mg/day. Participants signed an informed consent to participate. Patients were assessed using a semi-structured questionnaire specifically designed for the study. Data consisted of age, sex, and symptoms of hyperprolactinemia: amenorrhea, loss of libido, erectile dysfunction, and gynecomastia. The results of this study were analyzed using descriptive methods, t-test and Pearson's correlation coefficient. The p value of statistical significance was set at p<0.05. Results: The results obtained in our study showed that a certain percentage of methadone patients who were on Risperidone therapy had symptoms of hyperprolactinemia, but the results were without statistical significance p>0.05. Conclusion: although in our study we obtained a small percentage of patients with symptoms of hyperprolactinemia, care must be taken in patients on methadone treatment who are also treated with neuroleptic therapy due to their synergistic effect, we should always keep in mind the possibility of developing hyperprolactinemia. [ABSTRACT FROM AUTHOR]

Leslie Citrome,1 Mark Suett,2 Kelli R Franzenburg,3 Roy Eshet,4 Anna Elgart,4 Glen L Davis 3rd,5 Eran Harary,4 Orna Tohami,4 Marko A Mychaskiw,6 John M Kane7– 9 1Department of Psychiatry and Behavioral Sciences, New York Medical College, Valhalla, NY, USA; 2Global Medical Affairs, Teva UK Limited, Harlow, UK; 3Global Medical Affairs, Teva Branded Pharmaceutical Products R&D, Inc., West Chester, PA, USA; 4Innovative Medicines, Global Clinical Development, Teva Pharmaceutical Industries Ltd, Netanya, Israel; 5Global Clinical Operations, Teva Branded Pharmaceutical Products R&D, Inc., West Chester, PA, USA; 6Global Health Economics and Outcomes Research, Teva Branded Pharmaceutical Products R&D, Inc, West Chester, PA, USA; 7Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA; 8Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA; 9Institute of Behavioral Science, Feinstein Institutes for Medical Research, Manhasset, NY, USACorrespondence: Leslie Citrome, Department of Psychiatry and Behavioral Sciences, New York Medical College, 40 Sunshine Cottage Road, Valhalla, NY, 10595, USA, Email nntman@gmail.comBackground: TV46000 is a long-acting subcutaneous antipsychotic (LASCA) formulation of risperidone approved for the treatment of schizophrenia in adults.Methods: The RISE study (NCT03503318) compared TV-46000 once monthly (q1m) and once every 2 months (q2m) with placebo (1:1:1) in patients with schizophrenia who underwent stabilization on oral risperidone. The SHINE study (NCT03893825) evaluated the long-term safety, tolerability, and effectiveness of TV-46000 in patients who completed RISE without relapse (rollover; placebo rollover randomized [1:1] to q1m or q2m; TV-46000 rollover continued assigned treatment) or who were newly recruited (de novo; randomized [1:1] to q1m or q2m after oral stabilization). Patient-centered outcomes included the Schizophrenia Quality of Life Scale (SQLS), the 5-Level EuroQoL 5-Dimensions Questionnaire (EQ-5D-5L), the Personal and Social Performance Scale (PSP), and the Drug Attitudes Inventory 10-item version (DAI-10).Results: In RISE, SQLS least-squares mean changes (SE) improved to last assessment (LA) for TV-46000 q1m (– 4.15 [1.03]) and q2m (– 3.28 [1.06]) but worsened for placebo (1.75 [1.07]; P< 0.001 for both). PSP, EQ5D-5L, and DAI-10 showed similar trends. In SHINE, SQLS decreased (improved) at LA for both TV-46000 q1m (− 0.43 [0.98]) and q2m (− 2.16 [0.98]); reductions were observed in the de novo (q2m only) and placebo rollover (q1m and q2m) cohorts, but not for the TV46000 rollover cohort. Results for PSP, EQ5D-5L, and DAI-10 were consistent with those reported in the RISE study.Conclusion: Improvements in patient-centered outcomes were observed across cohorts, with the largest improvements observed for patients who began TV-46000 during SHINE (ie, de novo and placebo rollover cohorts), while gains made during RISE were minimally improved or maintained in the TV-46000 rollover cohort, indicating the benefit of uninterrupted TV-46000 treatment. These data support the effectiveness of TV-46000 to improve patient-centered outcomes in patients with schizophrenia.Plain Language Summary: RISE and SHINE were clinical studies where patients with schizophrenia received TV-46000. TV-46000 is injected under the skin once monthly or once every 2 months to treat schizophrenia in adults. In RISE, patients took pills for the first 3 months, and then received injections under the skin. Some patients received inactive (placebo) injections. Comparing results among groups showed the effectiveness and side effects of TV-46000. Patients who completed RISE could continue into SHINE. SHINE included patients who had not been part of RISE as well. All patients received TV-46000 in SHINE to see if results were the same long term. This report summarizes the results of patient-centered outcomes. These included measures of quality of life and attitudes toward the medicine. In RISE, quality of life and attitudes toward the medicine improved with TV-46000, but worsened with placebo. In SHINE, the patient-centered outcomes also improved. The largest improvements were for patients who began taking TV-46000 during SHINE. This analysis showed that there is a benefit in taking TV-46000 for longer times without breaks. It also showed that TV-46000 improves quality of life and attitudes toward the medicine.Keywords: schizophrenia, long-acting injectable, risperidone, patient-centered outcomes

Abstract Background Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that is significantly increasing, resulting in severe distress. The approved treatment for ASD only partially improves the sympoms, but it does not entirely reverse the symptoms. Developing novel disease-modifying drugs is essential for the continuous improvement of ASD. Because of its pleiotropic effect, atorvastatin has been garnered attention for treating neuronal degeneration. The present study aimed to investigate the therapeutic effects of atorvastatin in autism and compare it with an approved autism drug (risperidone) through the impact of these drugs on TLR4/NF-κB/NOX-2 and the apoptotic pathway in a valproic acid (VPA) induced rat model of autism. Methods On gestational day 12.5, pregnant rats received a single IP injection of VPA (500 mg/kg), for VPA induced autism, risperidone and atorvastatin groups, or saline for control normal group. At postnatal day 21, male offsprings were randomly divided into four groups (n = 6): control, VPA induced autism, risperidone, and atorvastatin. Risperidone and atorvastatin were administered from postnatal day 21 to day 51. The study evaluated autism-like behaviors using the three-chamber test, the dark light test, and the open field test at the end of the study. Biochemical analysis of TLR4, NF-κB, NOX-2, and ROS using ELISA, RT-PCR, WB, histological examination with hematoxylin and eosin and immunohistochemical study of CAS-3 were performed. Results Male offspring of prenatal VPA-exposed female rats exhibited significant autism-like behaviors and elevated TLR4, NF-κB, NOX-2, ROS, and caspase-3 expression. Histological analysis revealed structural alterations. Both risperidone and atorvastatin effectively mitigated the behavioral, biochemical, and structural changes associated with VPA-induced rat model of autism. Notably, atorvastatin group showed a more significant improvement than risperidone group. Conclusions The research results unequivocally demonstrated that atorvastatin can modulate VPA-induced autism by suppressing inflammation, oxidative stress, and apoptosis through TLR4/NF-κB/NOX-2 signaling pathway. Atorvastatin could be a potential treatment for ASD. Graphical Abstract