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The current research aims to develop thermosensitive polymeric micelles loaded with risperidone for nasal administration, emphasizing the added benefits of their thermosensitive behavior under nasal conditions. An initial risk assessment facilitated the advanced development process, confirming that the key indicators of thermosensitivity were suitable for nasal application. The polymeric micelles exhibited an average size of 118.4 ± 3.1 nm at ambient temperature and a size of 20.47 ± 1.2 nm at 36.5 °C, in both cases in monodisperse distribution. Factors such as pH and viscosity did not significantly impact these parameters, demonstrating appropriate nasal applicability. The model formulations showed a rapid, burst-like drug release profile in vitro, accompanied by a quick and high permeation rate at nasal conditions. Overall, the Quality by Design-based risk assessment process led to the development of an advanced drug delivery system capable of administering risperidone through the nasal cavity. [ABSTRACT FROM AUTHOR]

Microglia are the primary innate immune cells of the central nervous system and extensively contribute to brain homeostasis. Dysfunctional or excessive activity of microglia may be associated with several neuropsychiatric disorders, including schizophrenia. Therefore, we examined whether aripiprazole and risperidone could influence the expression of the Cd200–Cd200r and Cx3cl1–Cx3cr1 axes, which are crucial for the regulation of microglial activity and interactions of these cells with neurons. Additionally, we evaluated the impact of these drugs on microglial pro- and anti-inflammatory markers (Cd40, Il-1β, Il-6, Cebpb, Cd206, Arg1, Il-10 and Tgf-β) and cytokine release (IL-6, IL-10). The research was executed in organotypic cortical cultures (OCCs) prepared from the offspring of control rats (control OCCs) or those exposed to maternal immune activation (MIA OCCs), which allows for the exploration of schizophrenia-like disturbances in animals. All experiments were performed under basal conditions and after additional stimulation with lipopolysaccharide (LPS), following the "two-hit" hypothesis of schizophrenia. We found that MIA diminished the mRNA level of Cd200r and affected the OCCs' response to additional LPS exposure in terms of this parameter. LPS downregulated the Cx3cr1 expression and profoundly changed the mRNA levels of pro- and anti-inflammatory microglial markers in both types of OCCs. Risperidone increased Cd200 expression in MIA OCCs, while aripiprazole treatment elevated the gene levels of the Cx3cl1–Cx3cr1 dyad in control OCCs. The antipsychotics limited the LPS-generated increase in the expression of proinflammatory factors (Il-1β and Il-6) and enhanced the mRNA levels of anti-inflammatory components (Cd206 and Tgf-β) of microglial polarization, mostly in the absence of the MIA procedure. Finally, we observed a more pronounced modulating impact of aripiprazole on the expression of pro- and anti-inflammatory cytokines when compared to risperidone in MIA OCCs. In conclusion, our data suggest that MIA might influence microglial activation and crosstalk of microglial cells with neurons, whereas aripiprazole and risperidone could beneficially affect these changes in OCCs. [ABSTRACT FROM AUTHOR]

Background: Antipsychotics, including risperidone (RIS), are frequently indicated for various autism spectrum disorder (ASD) manifestations; however, "actionable" PGx testing in psychiatry regarding antipsychotic dosing and selection has limited applications in routine clinical practice because of the lack of standard guidelines, mostly due to the inconsistency and scarcity of genetic variant data. The current study is aimed at examining the association of RIS effectiveness, according to ABC-CV and CGI indexes, with relevant pharmacokinetics (PK) and pharmacodynamics (PD) genes. Methods: Eighty-nine ASD children who received a consistent RIS-based regimen for at least 8 weeks were included. The Axiom PharmacoFocus Array technique was employed to generate accurate star allele-predicted phenotypes of 3 PK genes (CYP3A4, CYP3A5, and CYP2D6). Genotype calls for 5 candidate PD receptor genes (DRD1, DRD2, DRD3, HTR2C, and HTR2A) were obtained and reported as wild type, heterozygous, or homozygous for 11 variants. Results: Based on the ABC total score, 42 (47.2%) children were classified as responders, while 47 (52.8%) were classified as nonresponders. Multivariate logistic regression analyses, adjusted for nongenetic factors, suggested nonsignificant impacts of the star allele-predicted phenotypes of all 3 PK genes on improvement in ASD symptoms or CGI scores. However, significant positive or negative associations of certain PD variants involved in dopaminergic and serotonergic pathways were observed with specific ASD core and noncore symptom subdomains. Our significant polymorphism findings, mainly those in DRD2 (rs1800497, rs1799978, and rs2734841), HTR2C (rs3813929), and HTR2A (rs6311), were largely consistent with earlier findings (predictors of RIS effectiveness in adult schizophrenia patients), confirming their validity for identifying ASD children with a greater likelihood of core symptom improvement compared to noncarriers/wild types. Other novel findings of this study, such as significant improvements in DRD3 rs167771 carriers, particularly in ABC total and lethargy/social withdrawal scores, and DRD1 rs1875964 homozygotes and DRD2 rs1079598 wild types in stereotypic behavior, warrant further verification in biochemical and clinical studies to confirm their feasibility for inclusion in a PGx panel. Conclusion: In conclusion, we provide evidence of potential genetic markers involved in clinical response variability to RIS therapy in ASD children. However, replication in prospective samples with greater ethnic diversity and sample sizes is necessary. [ABSTRACT FROM AUTHOR]

• We provide the first network meta-analysis comparing long-acting injectable antipsychotics and their oral counterparts for the acute treatment of schizophrenia. • The efficacy of long-acting injectable and oral antipsychotics for acute schizophrenia is similar. • Some side-effects may be less frequent under LAIs, although this pattern is not consistent across outcomes and drugs. Long-acting injectable antipsychotics (LAIs) are primarily used for relapse prevention, but in some settings and situations, they may also be useful for acute treatment of schizophrenia. We conducted a systematic review and frequentist network meta-analysis of randomized-controlled trials (RCTs), focusing on adult patients in the acute phase of schizophrenia. Interventions were risperidone, paliperidone, aripiprazole, olanzapine, and placebo, administered either orally or as LAI. We synthesized data on overall symptoms, complemented by 17 other efficacy and tolerability outcomes. Confidence in the evidence was assessed with the Confidence-in-Network-Meta-Analysis-framework (CINeMA). We included 115 RCTs with 25,550 participants. All drugs were significantly more efficacious than placebo with the following standardized mean differences and their 95 % confidence intervals: olanzapine LAI -0.66 [-1.00; -0.33], risperidone LAI -0.59[-0.73;-0.46], olanzapine oral -0.55[-0.62;-0.48], aripiprazole LAI -0.54[-0.71; -0.37], risperidone oral -0.48[-0.55;-0.41], paliperidone oral -0.47[-0.58;-0.37], paliperidone LAI -0.45[-0.57;-0.33], aripiprazole oral -0.40[-0.50; -0.31]. There were no significant efficacy differences between LAIs and oral formulations. Sensitivity analyses of the primary outcome overall symptoms largely confirmed these findings. Moreover, some side effects were less frequent under LAIs than under their oral counterparts. Confidence in the evidence was moderate for most comparisons. LAIs are efficacious for acute schizophrenia and may have some benefits compared to oral formulations in terms of side effects. These findings assist clinicians with insights to weigh the risks and benefits between oral and injectable agents when treating patients in the acute phase. [ABSTRACT FROM AUTHOR]

Dopamine β-hydroxylase (DBH) is a copper-containing enzyme that has an important role in maintaining the cellular homeostasis between the two neurotransmitters, dopamine (DA) and nor-adrenaline (NA). DBH functional polymorphisms are associated with multiple neuro-psychiatric conditions and are found to alter the DBH protein levels in serum affecting DBH enzymatic activity. The current study was conducted to determine the genetic and serum levels association of DBH rs1611115 functional polymorphism with major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SHZ) in the Pakistani population. In total n = 1097 subjects including MDD (n = 427), BD (n = 204), SHZ (n = 134) and healthy controls (n = 332), were screened for the functional polymorphism by polymerase chain reaction-restriction fragment length polymorphism. Univariate logistic regression analysis was applied and the results were adjusted for age and sex. The DBH levels in serum were determined through enzyme-linked immunosorbent assay (ELISA) and the Mann Whitney U test was applied. The minor allele (-1021 C > T) was found to be significantly associated with a higher risk of developing BD and SHZ in both univariable and multivariable analyses. The overall total serum concentration of DBH was comparatively raised in MDD, however, in cross-comparison DBH serum levels were found markedly higher in CC homozygotes compared to TT homozygotes within the BD group. The present study suggested a significant association of DBH rs1611115 with BD and SHZ and also the effect of rs1611115 on DBH serum levels in MDD and BD for the first time in the Pakistani population. [ABSTRACT FROM AUTHOR]

Variability in hepatic cytochrome P450 (CYP) enzymes such as 2C19 and 2D6 may influence side-effect and efficacy outcomes for antipsychotics. Aripiprazole and risperidone are two commonly prescribed antipsychotics, metabolized primarily through CYP2D6. Here, we aimed to provide an overview of the effect of CYP2C19 and CYP2D6 on side-effects of aripiprazole and risperidone, and expand on existing literature by critically examining methodological issues associated with pharmacogenetic studies. A PRISMA compliant search of six electronic databases (Pubmed, PsychInfo, Embase, Central, Web of Science, and Google Scholar) identified pharmacogenetic studies on aripiprazole and risperidone. 2007 publications were first identified, of which 34 were included. Quality of literature was estimated using Newcastle-Ottowa Quality Assessment Scale (NOS) and revised Cochrane Risk of Bias tool. The average NOS score was 5.8 (range: 3–8) for risperidone literature and 5 for aripiprazole (range: 4–6). All RCTs on aripiprazole were rated as high risk of bias, and four out of six for risperidone literature. Study populations ranged from healthy volunteers to inpatient individuals in psychiatric units and included adult and pediatric samples. All n = 34 studies examined CYP2D6. Only one study genotyped for CYP2C19 and found a positive association with neurological side-effects of risperidone. Most studies did not report any relationship between CYP2D6 and any side-effect outcome. Heterogeneity between and within studies limited the ability to synthesize data and draw definitive conclusions. Studies lacked statistical power due to small sample size, selective genotyping methods, and study design. Large-scale randomized trials with multiple measurements, providing robust evidence on this topic, are suggested. • Personalizing psychiatric medication may be achieved through pharmacogenetics. • Metabolic enzymes CYP2C19 and CYP2D6 are of interest for psychopharmacology. • Combining all available data suggests that empirical evidence remains mixed. • Some evidence exists for a link between CYP2D6 and side-effects of risperidone. • Research on CYP2C19 and antipsychotic medication is lacking. [ABSTRACT FROM AUTHOR]

Background: International guidelines discourage antipsychotic use for delirium; however, concerns persist about their continued use in clinical practice. Objectives: We aimed to describe the prevalence and patterns of antipsychotic use in delirium management with regard to best-practice recommendations. Primary outcomes investigated were prevalence of use, antipsychotic type, dosage and clinical indication. Methods: Eligibility criteria: studies of any design that examined antipsychotic use to manage delirium in adults in critical care, acute care, palliative care, rehabilitation, and aged care were included. Studies of patients in acute psychiatric care, with psychiatric illness or pre-existing antipsychotic use were excluded. Information sources: we searched five health databases on 16 August, 2023 (PubMed, CINAHL, Embase, APA PsycInfo, ProQuest Health and Medical Collection) using MeSH terms and relevant keywords, including 'delirium' and 'antipsychotic'. Risk of bias: as no included studies were randomised controlled trials, all studies were assessed for methodological quality using the Mixed Methods Appraisal Tool. Synthesis of results: descriptive data were extracted in Covidence and synthesised in Microsoft Excel. Results: Included studies: 39 studies published between March 2004 and August 2023 from 13 countries (n = 1,359,519 patients). Most study designs were retrospective medical record audits (n = 16). Synthesis of results: in 18 studies, participants' mean age was ≥65 years (77.79, ±5.20). Palliative care had the highest average proportion of patients with delirium managed with antipsychotics (70.87%, ±33.81%); it was lower and varied little between intensive care unit (53.53%, ±19.73%) and non-intensive care unit settings [medical, surgical and any acute care wards] (56.93%, ±26.44%) and was lowest in in-patient rehabilitation (17.8%). Seventeen different antipsychotics were reported on. In patients aged ≥65 years, haloperidol was the most frequently used and at higher than recommended mean daily doses (2.75 mg, ±2.21 mg). Other antipsychotics commonly administered were olanzapine (mean 11 mg, ±8.54 mg), quetiapine (mean 64.23 mg, ±43.20 mg) and risperidone (mean 0.97 mg, ±0.64 mg). Conclusions: The use of antipsychotics to manage delirium is strongly discouraged in international guidelines. Antipsychotic use in delirium care is a risk for adverse health outcomes and a longer duration of delirium, especially in older people. However, this study has provided evidence that clinicians continue to use antipsychotics for delirium management, the dose, frequency and duration of which are often outside evidence-based guideline recommendations. Clinicians continue to choose antipsychotics to manage delirium symptoms to settle agitation and maintain patient and staff safety, particularly in situations where workload pressures are high. Sustained efforts are needed at the individual, team and organisational levels to educate, train and support clinicians to prioritise non-pharmacological interventions early before deciding to use antipsychotics. This could prevent delirium and avert escalation in behavioural symptoms that often lead to antipsychotic use. [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]

Hypofunctioning of NMDA receptors, and the resulting shift in the balance between excitation and inhibition, is considered a key process in the pathophysiology of schizophrenia. One important manifestation of this phenomenon is changes in neural oscillations, those above 30 Hz (i.e., gamma-band oscillations), in particular. Although both preclinical and clinical studies observed increased gamma activity following acute administration of NMDA receptor antagonists, the relevance of this phenomenon has been recently questioned given the reduced gamma oscillations typically observed during sensory and cognitive tasks in schizophrenia. However, there is emerging, yet contradictory, evidence for increased spontaneous gamma-band activity (i.e., at rest or under baseline conditions). Here, we use the sub-chronic phencyclidine (PCP) rat model for schizophrenia, which has been argued to model the pathophysiology of schizophrenia more closely than acute NMDA antagonism, to investigate gamma oscillations (30–100 Hz) in the medial prefrontal cortex of anesthetized animals. While baseline gamma oscillations were not affected, oscillations induced by train stimulation of the posterior dorsal CA1 (pdCA1) field of the hippocampus were enhanced in PCP-treated animals (5 mg/kg, twice daily for 7 days, followed by a 7-day washout period). This effect was reversed by pharmacological enhancement of endocannabinoid levels via systemic administration of URB597 (0.3 mg/kg), an inhibitor of the catabolic enzyme of the endocannabinoid anandamide. Intriguingly, the pharmacological blockade of CB1 receptors by AM251 unmasked a reduced gamma oscillatory activity in PCP-treated animals. The findings are consistent with the observed effects of URB597 and AM251 on behavioral deficits reminiscent of the symptoms of schizophrenia and further validate the potential for cannabinoid-based drugs as a treatment for schizophrenia. [ABSTRACT FROM AUTHOR]

Endothelial inflammation may be involved in the pathogenesis of schizophrenia, and cellular adhesion molecules (CAMs) on endothelial cells may facilitate leukocyte binding and transendothelial migration of cells and inflammatory factors. The aim of the present study was to assess levels of soluble cellular adhesion molecules, including intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, mucosal addressin cell adhesion molecule (MADCAM), junctional adhesion molecule (JAM-A) and neural cadherin (N-CAD) in patients with schizophrenia compared to healthy controls. The study population consists of 138 patients with schizophrenia-spectrum disorder, of whom 54 were drug-naïve, compared to 317 general population controls. The potential confounders age, gender, smoking and body mass index (BMI) were adjusted for in linear regression models. The total patient group showed significantly higher levels of ICAM-1 (p < 0.001) and VCAM-1 (p < 0.001) compared to controls. Previously medicated patients showed higher ICAM-1 levels compared to drug-naïve patients (p = 0.042) and controls (p < 0.001), and elevated VCAM-1 levels compared to controls (p < 0.001). Drug-naive patients had elevated levels of VCAM-1 (p = 0.031) compared to controls. In our study, patients with schizophrenia – including the drug-naïve – have higher levels of soluble CAMs compared to healthy controls. These findings suggest activation of the endothelial system as in inflammation. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have suggested that the suicide rate of patients with schizophrenia is high. This study investigates factors influencing suicidal ideation in first‐episode schizophrenia patients, focusing on cognitive function, brain‐derived neurotrophic factor (BDNF), triglyceride (TG), and total cholesterol (TC) in patients with first‐episode schizophrenia. Methods: A total of 123 patients with first‐episode schizophrenia and 38 healthy controls were included in the study. The patients were divided into suicidal and nonsuicidal ideation groups based on the Beck Scale for Suicidal Ideation, and they were assessed with Positive and Negative Syndrome Scale (PANSS). Cognitive function was assessed using the Chinese version of the MATRICS consensus cognitive battery (MCCB) and the serum BDNF, TG, and TC were detected. The main statistical methods include t‐test, χ2 test, multivariate logistic regression analysis, receiver operating characteristic (ROC) curve analysis, and the DeLong test. Results: 26.02% of patients exhibited suicidal ideation. Higher PANSS and TC levels were risk factors, while higher MCCB scores and BDNF levels were protective factors. ROC analysis indicated AUCs of 0.630, 0.724, and 0.762 for serum BDNF, PANSS, and MCCB, respectively, with a combined AUC of 0.870. Conclusion: Serum BDNF level, PANSS score, and MCCB score can be used as auxiliary predictors of suicidal ideation in schizophrenic patients. Combining these three indicators can effectively predict suicidal ideation in schizophrenic patients. [ABSTRACT FROM AUTHOR]

Background: Sudden unexplained death in individuals with mental health problems was described in 1960 and a link with antipsychotic drugs was postulated over 40 years ago. Down the years, a clear relation between electrocardiography (ECG) abnormalities and antipsychotic use was observed with special emphasis on QT prolongation. Various factors modulate the risk of QT prolongation including gender, age, race, and drug choice. An evaluation of antipsychotic use-induced QT changes in Eastern Indian population is the dire need of the hour. Aims and Objectives: The aim and objective are to study the effects of risperidone, olanzapine, and aripiprazole on QT interval after a period of 4 weeks of usage in previously drug-naïve Eastern Indian psychotic patients. Materials and Methods: A total of 78 drug-naïve patients fulfilling inclusion and exclusion criteria were randomly assigned to receive risperidone, olanzapine, and aripiprazole after a baseline ECG. A repeat ECG after 4 weeks of drug usage was done and compared using standard protocols with respect to QT interval. Findings were tabulated and statistical analysis was done using SPSS 25.0 to test for statistical significance at P<0.05. Results: Our study found significant rise in QT values after 4 weeks of using olanzapine and aripiprazole, but not with risperidone. However, none of the patients from either of the groups experienced any incidence of QT prolongation. Rise with olanzapine was significantly higher than that with risperidone. Conclusion: Caution is suggested in patients with risk factors for QT prolongation or a high value of QT during prescribing olanzapine. Studies with larger sample size can be carried out to find genetic predisposition of Indian population to anti-psychotic induced QT interval rise/prolongation. [ABSTRACT FROM AUTHOR]

Background and Objective: Long-acting injectable antipsychotics have shown benefits over oral medications with reduced hospitalization rates and improved health-related quality of life. RBP-7000 (PERSERIS®) is a monthly risperidone formulation (90 or 120 mg) for the treatment of schizophrenia administered by subcutaneous abdominal injection. The objective of this study was to assess a higher dose of 180 mg RBP-7000 and an alternate injection site. Methods: Following stabilization on 6 mg/day (3 mg twice daily) oral risperidone, clinically stable schizophrenic participants received 3 monthly doses of 180 mg RBP-7000 in the abdomen followed by a fourth monthly dose of 180 mg RBP-7000 in the upper arm (each dose administered as two 90-mg injections). The primary endpoint was the steady-state average plasma concentration (Cavg(ss)) of risperidone and total active moiety after oral and RBP-7000 administration. Secondary endpoints included measures of clinical efficacy (Positive and Negative Syndrome Scale, Clinical Global Impression Scale for Severity of Illness), safety, and local injection-site tolerability to assess the switch from oral risperidone and compare injection sites. Results: In all, 23 participants received at least one dose of RBP-7000, 16 received all four doses, and 15 completed the study. Monthly doses of 180 mg RBP-7000 provided similar Cavg(ss) of total active moiety compared with 6 mg/day oral risperidone. The pharmacokinetics of RBP-7000 were similar after injection in the abdomen versus upper arm. Clinical efficacy measures remained stable throughout the study. All RBP-7000 injections were well tolerated with no unexpected safety findings. Conclusions: The results support the use of 180 mg RBP-7000 in schizophrenic patients stable on 6 mg/day oral risperidone and a second injection site in the upper arm. Trial Registration: ClinicalTrials.gov identifier: NCT03978832. [ABSTRACT FROM AUTHOR]

Aims: We aimed to evaluate the potential of a novel selective α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole‐propionic acid receptor (AMPAR) potentiator, LT‐102, in treating cognitive impairments associated with schizophrenia (CIAS) and elucidating its mechanism of action. Methods: The activity of LT‐102 was examined by Ca2+ influx assays and patch‐clamp in rat primary hippocampal neurons. The structure of the complex was determined by X‐ray crystallography. The selectivity of LT‐102 was evaluated by hERG tail current recording and kinase‐inhibition assays. The electrophysiological characterization of LT‐102 was characterized by patch‐clamp recording in mouse hippocampal slices. The expression and phosphorylation levels of proteins were examined by Western blotting. Cognitive function was assessed using the Morris water maze and novel object recognition tests. Results: LT‐102 is a novel and selective AMPAR potentiator with little agonistic effect, which binds to the allosteric site formed by the intradimer interface of AMPAR's GluA2 subunit. Treatment with LT‐102 facilitated long‐term potentiation in mouse hippocampal slices and reversed cognitive deficits in a phencyclidine‐induced mouse model. Additionally, LT‐102 treatment increased the protein level of brain‐derived neurotrophic factor and the phosphorylation of GluA1 in primary neurons and hippocampal tissues. Conclusion: We conclude that LT‐102 ameliorates cognitive impairments in a phencyclidine‐induced model of schizophrenia by enhancing synaptic function, which could make it a potential therapeutic candidate for CIAS. [ABSTRACT FROM AUTHOR]

Introduction: RYKINDO® (Rykindo) is a novel, long-acting injectable risperidone formulation administered biweekly (Q2W) through intramuscular gluteal injection for the treatment of schizophrenia in adult patients. This analysis was conducted to demonstrate that the clinical outcomes of Rykindo are equivalent to those of RISPERDAL CONSTA® (Consta; Q2W), and to establish a dosing methodology to switch from Consta to Rykindo, as well as to introduce Rykindo to patients who are currently on oral RISPERDAL® (Risperdal). Methods: Population pharmacokinetic (PK) models for Rykindo and Consta were developed using a nonlinear mixed-effects model with the data from phase 1 studies. A model-based simulation was also conducted using NONMEM. Results: The PK profiles of Rykindo and Consta were adequately represented by a one-compartment model with an immediate release followed by an intermediate and third main release. Drug release of Rykindo was faster than for Consta, reaching steady state approximately 2–3 weeks earlier. The exposures of the active moiety of Rykindo and Consta were comparable at steady state. Model-based simulation indicated that switching from Consta to Rykindo requires administration of the first Rykindo injection within 4–5 weeks following the last Consta injection. For patients taking Risperdal, introducing Rykindo with 1 week of Risperdal supplemental for once-daily dosing (QD) can achieve comparable or superior exposure to that of Consta with 3 weeks of oral QD supplements. A dosing window of ± 3 days for Rykindo was recommended. Conclusions: This established approach provides guidance to physicians to initiate Rykindo therapy in adult patients with schizophrenia. Trial Registration: ClinicalTrials.gov identifier, NCT02055287, NCT02186769 and NCT02091388. [ABSTRACT FROM AUTHOR]

Background Patients with delusional infestation (DI) frequently refuse to be treated with psychoactive drugs. In the past, pimozide was commonly used as a first-line agent but is now prescribed more rarely. Risperidone was first used to treat DI in 1995. A recent review identified 12 studies that evaluated the use of risperidone in 43 patients with DI. Objectives To study the characteristics of and therapeutic results in patients with DI treated with risperidone at a university medical centre in São Paulo, Brazil. Methods We performed a retrospective study of patients with DI treated with risperidone at a dermatological university clinic since 2016. Records were reviewed for personal data and findings related to treatment. Results Twenty-seven patients were studied (20 women and 7 men). The maintenance dose of risperidone varied from 1 mg three times weekly to 8 mg daily. Control of symptoms was achieved in the majority of patients. A reduction in dosage due to side-effects was seen in four patients; risperidone had to be switched to another antipsychotic in three cases, despite a good response. Only one patient did not respond to risperidone. Conclusions Risperidone is an effective, well-tolerated and safe treatment for delusional parasitosis. Adequate follow-up is mandatory in order to obtain long-term control of symptoms. [ABSTRACT FROM AUTHOR]

Antipsychotics can cause hematologic disorders, and they can have life-threatening consequences. Risperidone, less commonly associated with hematologic adverse effects, is an atypical antipsychotic medication used to treat conditions such as schizophrenia, bipolar disorder and irritability associated with autism. While risperidone primarily affects the central nervous system, it can have some hematologic adverse effects, although these are relatively rare. It is crucial to note that these side effects are not common, and most people taking risperidone do not experience hematologic disorders. The reporting of such disorders may be more frequent with clozapine compared to other atypical antipsychotics because clozapine treatment necessitates regular hematological monitoring 1. [ABSTRACT FROM AUTHOR]

Aims: The extensive variability in cytochrome P450 2D6 (CYP2D6) metabolism is mainly caused by genetic polymorphisms. However, there is large, unexplained variability in CYP2D6 metabolism within CYP2D6 genotype subgroups. Solanidine, a dietary compound found in potatoes, is a promising phenotype biomarker predicting individual CYP2D6 metabolism. The aim of this study was to investigate the correlation between solanidine metabolism and the CYP2D6‐mediated metabolism of risperidone in patients with known CYP2D6 genotypes. Methods: The study included therapeutic drug monitoring (TDM) data from CYP2D6‐genotyped patients treated with risperidone. Risperidone and 9‐hydroxyrisperidone levels were determined during TDM, and reprocessing of the respective TDM full‐scan high‐resolution mass spectrometry files was applied for semi‐quantitative measurements of solanidine and five metabolites (M402, M414, M416, M440 and M444). Spearman's tests determined the correlations between solanidine metabolic ratios (MRs) and the 9‐hydroxyrisperidone‐to‐risperidone ratio. Results: A total of 229 patients were included. Highly significant, positive correlationswere observed between all solanidine MRs and the 9‐hydroxyrisperidone‐to‐risperidone ratio (ρ > 0.6, P <.0001). The strongest correlation was observed for the M444‐to‐solanidine MR in patients with functional CYP2D6 metabolism, i.e., genotype activity scores of 1 and 1.5 (ρ 0.72–0.77, P <.0001). Conclusion: The present study shows strong, positive correlations between solanidine metabolism and CYP2D6‐mediated risperidone metabolism. The strong correlation within patients carrying CYP2D6 genotypes encoding functional CYP2D6 metabolism suggests that solanidine metabolism may predict individual CYP2D6 metabolism, and hence potentially improve personalized dosing of drugs metabolized by CYP2D6. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the role of Brain derived neurotrophic factor (BDNF) in the psychotic symptoms in first‐episode patients with schizophrenia and whether BDNF levels were associated with the improvement of psychotic symptoms after risperidone treatment. Methods: 89 schizophrenia patients and 90 healthy controls were recruited, the schizophrenia patients were assigned into early response or early non‐response groups at 2 weeks based on improvement in the positive and negative symptoms scale (PANSS) total score. All patients were treated with risperidone for 2 weeks, their serum BDNF levels were compared at baseline and after 2 weeks treatment. Results: We found that patients had lower BDNF levels, compared to controls at baseline. After 2 weeks of treatment of risperidone, BDNF levels were significantly increased and psychotic symptoms were decreased in early response group. Correlation analysis showed that the change of BDNF levels after treatment was correlated with the change of PANSS total score. Further regression analysis showed that the change in BDNF levels was an independent predictor for the improvement in psychotic symptoms. Conclusions: Our findings reveal that the level of BDNF was lower in first‐episode schizophrenic patients, moreover, the changes in serum BDNF levels may have a predictive effect on the early improvement in psychotic symptoms in the first 2 weeks. [ABSTRACT FROM AUTHOR]

Background: Quetiapine is commonly prescribed off-label to manage delirium in intensive care unit (ICU) patients. However, limited studies comparing its efficacy and safety to those of other antipsychotics exist in the literature. Method: A retrospective, single-center chart review study was conducted on adults admitted to the ICU between January 2017 and August 2022, who were diagnosed with delirium and treated with a single antipsychotic and had no neurological medical conditions, active alcohol withdrawal, or prior use of antipsychotics. Data were analyzed using SPSS software version 28, with p-values of <0.05 indicating statistical significance. Results: In total, 47 patients were included, of whom 22 (46.8%), 19 (40.4%), 4 (8.5%), and 2 (4.3%) were on quetiapine, haloperidol, risperidone, and olanzapine, respectively. The median number of hours needed to resolve delirium were 12 (21.5), 23 (28), 13 (13.75), and 36 (10) (p = 0.115) for quetiapine, haloperidol, risperidone, and olanzapine, respectively, with haloperidol being used for a significantly shorter median number of days than quetiapine (3 (2.5) days vs. 7.5 (11.5) days; p = 0.007). Of the medication groups, only quetiapine-treated patients received a significantly higher median maintenance compared to the initiation dose (50 (50) mg vs. 50 (43.75) mg; p = 0.039). For the length of stay in the ICU and hospital, delirium-free days, % of ICU time spent in delirium, ventilator-free days, the difference between the highest and baseline QTc intervals, and ICU and hospital mortalities, no significant difference was observed between the groups. Conclusions: Overall, the use of quetiapine in our retrospective study seems to not be advantageous over the other drugs in terms of efficacy and safety outcomes. [ABSTRACT FROM AUTHOR]

Dopamine and serotonin receptors and transporters play an essential role in the pathophysiology of schizophrenia; changes in their expression have been reported in neurons and leukocytes. Each antipsychotic induces a unique pattern in leukocyte function and phenotype. However, the use of polytherapy to treat schizophrenia makes it challenging to determine the specific effects of risperidone on peripheral blood mononuclear cells (PBMCs). The aim of this study was to evaluate the changes in the expression of D3, D5, DAT, 5-HT2A, and SERT in PBMCs from healthy volunteers (HV), drug-naive patients with schizophrenia (PWS), drug-free PWS, and PWS treated with risperidone for up to 40 weeks using quantitative PCR. Our study revealed elevated mRNA levels of D3, DAT, 5-HT2A, and SERT in unmedicated PWS. Treatment with risperidone led to a reduction only in the expression of 5-HT2A and SERT. Furthermore, we observed a moderate correlation between 5-HT2A expression and the positive and negative syndrome scale (PANSS), as well as SERT expression and PANSS scale. We also found a moderate correlation between 5-HT2A and SERT expression and the positive subscale. The duration of risperidone consumption had a significant negative correlation with the expression of 5-HT2A and SERT. Our study introduces the measurement of 5-HT2A and SERT expression in PBMCs as a useful parameter for assessing the response to risperidone in PWS. [ABSTRACT FROM AUTHOR]

Currently, research predominantly focuses on evaluating clinical effects at specific time points while neglecting underlying patterns within the treatment process. This study aims to analyze the dynamic alterations in PANSS total scores and prolactin levels in patients with schizophrenia treated with risperidone, along with the influencing covariates. Using data from an 8-week randomized, double-blind, multicenter clinical trial, a population pharmacodynamic model was established for the PANSS total scores of and prolactin levels in patients treated with risperidone. The base model employed was the Emax model. Covariate selection was conducted using a stepwise forward inclusion and backward elimination approach. A total of 144 patients were included in this analysis, with 807 PANSS total scores and 531 prolactin concentration values. The PANSS total scores of the patients treated with risperidone decreased over time, fitting a proportionally parameterized sigmoid Emax model with covariates including baseline score, course of the disease, gender, plasma calcium ions, and lactate dehydrogenase levels. The increase in prolactin levels conformed to the ordinary Emax model, with covariates encompassing course of the disease, gender, weight, red blood cell count, and triglyceride levels. The impacts of the baseline scores and the course of the disease on the reduction of the PANSS scores, as well as the influence of gender on the elevation of prolactin levels, each exceeded 20%. This study provides valuable quantitative data regarding PANSS total scores and prolactin levels among patients undergoing risperidone treatment across various physiological conditions. [ABSTRACT FROM AUTHOR]

This article discusses the molecular pharmacology of trace amine-associated receptor 1 (TAAR1) and its potential role in advancing antipsychotic drug discovery. Schizophrenia, a chronic mental disorder, is characterized by negative symptoms, positive symptoms, and cognitive impairment. Current antipsychotic drugs have limited efficacy and are associated with side effects. TAAR1 has emerged as a potential therapeutic target for psychiatric disorders, and recent studies have provided insights into the molecular mechanisms and activation characteristics of TAAR1. These findings could contribute to the development of new antipsychotic drugs. [Extracted from the article]

Several studies have indicated that the plasma concentration of risperidone increases 3–5-fold during the acute-phase reaction (APR) of inflammation or infection. Psychiatric symptoms are present or deteriorate when the dose is lowered; thus, the complex effects of inflammation on the pharmacokinetics of risperidone need to be examined. We established a APR model in rabbits induced by lipopolysaccharide (LPS) and studied the effect of APR on pharmacokinetics, distribution and disposition of risperidone in vivo and in vitro. Following intramuscular administration, the plasma exposures for risperidone and its active metabolite (9-hydroxyrisperidone) were increased approximately 6-fold on day 2 of inflammation. The exposure values did not change between day 2 and 5 of inflammation, nor did the metabolite-to-parent ratio before and during inflammation. Following oral administration, the increase of risperidone exposure was twice as high as that following intramuscular administration during APR. However, the concentration of risperidone and 9-hydroxyrisperidone in brain tissue was similar between the inflammatory and control groups. Moreover, the plasma protein binding (PPB) of risperidone and 9-hydroxyrisperidone associated with inflammation were all increased to >99 %. In addition, risperidone and 9-hydroxyrisperidone were not substrates of the key transporters, OATP1B3, OCT2, OAT3, MATE-1, or MATE-2 K. The expression of progesterone X receptor and P-glycoprotein was inhibited by LPS. During APR, reduced expression of P-glycoprotein and increased PPB were responsible for increased exposure in plasma, while maintaining stable concentrations in the brain, and risperidone does not need to be dose-adjusted so as to achieve psychopharmacological outcomes. [ABSTRACT FROM AUTHOR]

Background: Risperidone and, to a lesser extent, paliperidone are metabolized by CYP2D6; however, there are limited data related to variation in CYP2D6 phenotypes and the tolerability of these medications in children and adolescents. Furthermore, the impact of CYP2D6 on the association of risperidone and paliperidone with hyperprolactinemia in youth is not well understood. Methods: A retrospective chart review was performed in psychiatrically hospitalized children and adolescents prescribed risperidone (n = 263, age = 3–18 years, mean age = 13 ± 3 years, 49% female) or paliperidone (n = 124, age = 5–18 years, mean age = 15 ± 2 years, 44% female) who had CYP2D6 genotyping performed as part of routine care. CYP2D6 phenotypes were determined based on Clinical Pharmacogenetics Implementation Consortium guidelines and CYP2D6 inhibitors causing phenoconversion. Adverse effects were obtained from a review of the electronic health record, and patients were selected, in part, to enrich non-normal metabolizers. Results: Among risperidone-treated patients, 45% experienced an adverse effect, whereas 36% of paliperidone-treated patients experienced adverse effects. Discontinuation of risperidone due to lack of efficacy was more frequent in the CYP2D6 normal metabolizers and ultrarapid metabolizers compared with intermediate metabolizers (IMs) and phenoconverted poor metabolizers (pPMs) (54.5% vs. 32.7%, p < 0.001). Discontinuation due to weight gain was more common among risperidone- than paliperidone-treated patients (17% vs. 7%, p = 0.011). Among those taking paliperidone, CYP2D6 was associated with discontinuation due to side effects (p = 0.008), and youth with slower CYP2D6 metabolism (i.e., pPMs and IMs) were more likely to discontinue. Hyperprolactinemia was found in 10% of paliperidone-treated patients and 5% of risperidone-treated patients, and slower CYP2D6 metabolizers required higher risperidone doses to cause hyperprolactinemia (p = 0.011). Conclusions: CYP2D6 phenotype is associated with discontinuation of risperidone due to lack of efficacy and the dose of risperidone that induced hyperprolactinemia, as well as discontinuation of paliperidone due to adverse effects. Future studies should evaluate exposure-response and toxicity relationships in risperidone- and paliperidone-treated youth. [ABSTRACT FROM AUTHOR]

Background: Hydroxyzine hydrochloride is a piperazine derivative antihistamine that is used in the treatment of anxiety. Its tendency to cause somnolence makes it an attractive option for patients with anxiety-induced insomnia. Despite its antihistamine activity, hydroxyzine is noted to have alpha-adrenergic antagonism activity. Other alpha-adrenergic inhibitors have been implicated in medication-induced priapism, including risperidone. Risperidone is a second-generation antipsychotic that primarily blocks serotonin and dopamine receptors, while also inhibiting alpha-1 and alpha-2 receptors with high affinity. Objective: We report a case of a first-of-its-kind case report of a patient who was stable on risperidone and presented with priapism after taking hydroxyzine nightly for the previous 10 days. Results: A 35-year-old male with a past psychiatric history of depression, generalized anxiety disorder, schizoaffective disorder, presented to the emergency department with priapism for 15 hours that required intracaveronsal phenylephrine hydrochloride and manual drainage to achieve detumescence. The patient was on a stable dose risperidone but reported taking hydroxyzine 50 mg nightly for anxiety and insomnia 10 days prior to emergency department admission. Upon resolution of the priapism, the patient stopped hydroxyzine, but continued risperidone. The patient had another prolonged erection 10 days after stopping hydroxyzine; however, he reported that it resolved spontaneously without intervention after 4 hours. Conclusion: This case report demonstrates the risk of addition of hydroxyzine to antipsychotics which can result in an increased risk of priapism or prolonged episodes. [ABSTRACT FROM AUTHOR]

Background: To explore the influence of CYP2D6 genetic polymorphism on risperidone metabolism, thereby affecting risperidone's effects and safeties in patients with chronic schizophrenia. Methods: Sixty-nine subjects with chronic schizophrenia treated with risperidone were recruited. CYP2D6 genotypes was determined using targeted sequencing and translated into phenotype using activity system. Risperidone plasma concentrations were measured using HPLC. Positive and Negative Symptom Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) were used to evaluate the existence and severity of psychiatric symptoms, Barnes Akathisia Scale (BAS) and Extrapyramidal Symptom Rating Scale (ESRS) for neurological side effects. Metabolic and endocrine status assess were also included. Results: The plasma drug concentrations varied hugely among individuals. Intermediate metabolizer (IM) group had higher plasma levels of RIP and dose corrected RIP concentration, RIP/9-OH-RIP ratio and C/D ratio than normal metabolizer (NM) group (p < 0.01). There was no statistic difference between responders and non-responders in dose-adjusted plasma concentrations and ratios of RIP/9-OH-RIP and C/D. The occurrence of EPS was related to active moiety levels in 4th week (p < 0.05). The prolactin (PRL) levels in two follow-ups were both significantly higher than baseline (p < 0.01). PRL change from baseline to week 4 and week 8 were both positively associated with active moiety concentration detected in week 4 (p < 0.05). Conclusions: The risperidone plasma levels have great inter- and intraindividual variations, and are associated with the CYP2D6 phenotypes, as well as the changes in serum prolactin in patients diagnosed with chronic schizophrenia. [ABSTRACT FROM AUTHOR]

Objective: Recent evidence suggests that oxidative stress contributes to the pathophysiology of schizophrenia. This study aimed to compare thiol-disulphide homeostasis in acute and stable phases of schizophrenia for the first time. Methods: Among the patients with schizophrenia, 61 in the acute-phase and 61 in the stable phase of their illness were enrolled in the study. Native thiol (NT), total thiol (TT), disulphide (SS), disulphide/native thiol, disulphide/total thiol, and native thiol/total thiol for thiol-disulphide homeostasis were compared between the groups. The Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive/Negative Symptoms (SAPS/SANS), Clinical Global ImpressionSeverity Scale (CGI-S), Barnes Akathisia Rating Scale, and Simpson-Angus Scale were used to assess symptoms. Results: After controlling for age, sex, body mass index, and smoking status there were significant differences in NT, TT, SS/NT, SS/TT, and NT/TT, but not SS. Thiol/disulphide homeostasis has shifted in favour of the oxidative side in patients with acute-phase compared to that in stable schizophrenia. BPRS, SAPS, and CGI-S scores were significantly correlated with all six thiol-disulphide parameters, but not SANS, when controlling for age and sex. Significant receiver operating characteristic (ROC) curves were obtained for all thiol-disulphide homeostasis parameters. Discriminant analysis was found to be statistically significant in discriminating between groups. Conclusion: These results show that oxidative status increases thiol-disulphide homeostasis in patients with acute-phase schizophrenia compared to those with stable schizophrenia. These findings suggest that thiol-disulphide parameters can be used as biomarkers for the acute exacerbation of schizophrenia. [ABSTRACT FROM AUTHOR]

Posterior cortical atrophy, also called Benson's syndrome or visual variant of Alzheimer's disease, refers to a constellation of neurodegenerative features associated with Alzheimer's disease. The authors describe an unusual case of a patient diagnosed with this condition in addition to paranoid schizophrenia, in a forensic low secure unit. The focus of the article is on the distinctiveness of the presentation, the heterogeneity of symptoms and difficulties encountered in the diagnostic formulation process. [ABSTRACT FROM AUTHOR]

Aim: Clomipramine (tricyclic antidepressant), Risperidone (a non-typical antidepressant), and Escitalopram (selective serotonin reuptake inhibitor antidepressant) might be good candidates for investigating the anti-colitis activity. Background: The incidence of depression with ulcerative colitis in patients has led to the use of antidepressants in their treatment. In addition to the antidepressant effect of these drugs, anti-inflammatory effects have also been reported. Methods: In this study, 36 rats were used 2 ml of 3% acetic acid solution rectally to show the colitis. Then, Clomipramine (25 mg/kg), Escitalopram (10 mg/kg), Prednisolone (5 mg/kg), Risperidone (2 mg/kg), and normal saline as the control was administered orally for six days. The levels of Tumor Necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6), and myeloperoxidase (MPO) were measured by Enzyme-linked immune sorbent assay (ELISA), and changes in the tissue pathology were investigated. Results: IL-6 level was significantly reduced after the administration of clomipramine and Prednisolone (p=0.025). Risperidone has significantly reduced MPO activity in colonic tissue (P=0.006). We did find no statistical decrease in MPO activity and TNF-α and IL-6 levels after consumption of Escitalopram (p>0.05). Conclusion: Clomipramine showed the best anti-inflammatory effect compared to Escitalopram and Risperidone. Therefore, clomipramine showed the best relieving effect on inflammation of ulcerative colitis in rats. [ABSTRACT FROM AUTHOR]

The retention profile of six serotonin receptor ligands such as arylpiperazines (aripiprazole, ziprasidone, risperidone), and benzothiazepine derivatives (olanzapine, mianserin, quetiapine), was investigated on C8 alkyl and pentafluorophenylpropyl stationary phases. The experimental design methodology was used to define their retention behavior and achieve acceptable separation results. Both phases showed satisfactory selectivity for all compounds. The optimal separation among the structurally related arylpiperazines and benzothiazepines was found with the C8 phase at 25°C, using acetonitrile (40%, v/v) and 20 mM ammonium acetate as a mobile phase modifier. The selectivity and sensitivity performances of the selected C8 system were discussed considering the separation of aripiprazole and its related compounds. In addition, the specified conditions were validated for determining aripiprazole in pharmaceutical dosage forms. The developed reversed-phase high-performance liquid chromatography method can be successfully used for the rapid chromatographic profiling of serotonin receptor ligands and related analogs, providing increased selectivity during pharmaceutical analysis. [ABSTRACT FROM AUTHOR]

Mental and behavioural disorders are prevalent worldwide. These conditions account for 12% of the global burden of disease 4. It is estimated that, they will account for the loss of 15% of the disability-adjusted life-years (DALYs). Globally, these illnesses have a point prevalence of about 10% for adults. After obtaining approval and clearance from the Institutional Ethical Committee, 320 cases were included for the present study. After obtaining the informed Consent from the patients/guardians, relevant data was recorded from patient's medical records and prescription orders. Among all the psychotropic drugs used, Risperidone had shown good improvement (n=88, 49.7%), Satisfactory improvement (n=39, 36.8%). Escitalopram showed good, satisfactory and best improvement in (25.4%), (41.5%) and (54.5%) of the population who were given the drug. Aminitriptyline and anticholinergic drug Trihexphenidyl also showed satisfactory results in terms of efficacy. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the factors affecting the concentrations of the active moiety of risperidone (RIS) and its active metabolite 9-hydroxyrisperidone (9-OH-RIS) in psychiatric outpatients taking immediate-release formulations. Methods: This is a retrospective study on the therapeutic drug monitoring (TDM) data regarding RIS and 9-OH-RIS in adult psychiatric outpatients. TDM data with simultaneous RIS and 9-OH-RIS monitoring from March 2018 to February 2020 and relevant medical records (including dosage, dosage form, sex, age, diagnosis, combined medication, and comorbid disease) from 399 adult psychiatric outpatients (223 males and 176 females) were included in this study. Results: The daily dose of RIS was 5.56 ± 2.05 mg, the concentration of total active moiety was 42.35 ± 25.46 ng/mL, and the dose-adjusted plasma concentration (C/D) of active moiety was 7.83 ± 3.87 (ng/ml)/(mg/day). Dose, sex, and age were identified as important factors influencing concentrations of RIS and 9-OH-RIS in adult psychiatric outpatients. Conclusions: Individualized medication adjustments should be made according to the specific conditions of psychiatric outpatients. The findings strongly support the use of TDM to guide dosing decisions in psychiatric outpatients taking RIS. [ABSTRACT FROM AUTHOR]

• The permeation of risperidone was significantly increased by using the microemulsion formulation. • Use of selected permeation enhancers in the microemulsion formulation showed synergistic effect on transdermal delivery of risperidone across the skin. • The microemulsion formulation using penetration enhancers is capable of increasing permeation of risperidone by 14-fold higher than the control formulation. The aim of this study was to develop and characterize microemulsion formulations using penetration enhancers as potential transdermal delivery systems for risperidone. Initially, a simple formulation of risperidone in Propylene Glycol (PG) was prepared as a control formulation, together with formulations incorporating various penetration enhancers, alone and/or in combination, and also microemulsion formulations with various chemical penetration enhancers, were prepared and all were evaluated for risperidone transdermal delivery. An ex-vivo permeation study was carried out using human cadaver skin and vertical glass Franz diffusion cells to compare all the microemulsion formulations. The microemulsion prepared from oleic acid as the oil (15%), Tween 80 (15%) as the surfactant and isopropyl alcohol (20%) as the co-surfactant, and water (50%) showed higher permeation with a flux value of 32.50±3.60 ug/hr/sq.cm, a globule size of 2.96±0.01 nm, a polydispersity index of 0.33±0.02 and pH of 4.95. This novel in vitro research disclosed that an optimized microemulsion formulated using penetration enhancers was able to increase permeation of risperidone by 14-fold compared to the control formulation. The data suggested that microemulsions may be useful in the delivery of risperidone via the transdermal route. [ABSTRACT FROM AUTHOR]

D-Amino acid oxidase (DAO), a D-amino acid metabolizing enzyme, is reportedly associated with the psychiatric disease schizophrenia, suggesting a role for DAO inhibitors in its treatment. We have previously reported that DAO catalyzes the conversion of nonfluorescent 6-methylthio-D-kynurenine (MeS-D-KYN) to fluorescent 5-methylthiokynurenic acid (MeS-KYNA) in vitro. The present study aimed to determine the potential of MeS-D-KYN in evaluating DAO activity in vivo using renal microdialysis technique in rats. Male Sprague-Dawley rats were subjected to linear microdialysis probe implantation in the left kidney. Continuous perfusion of MeS-D-KYN was maintained, and DAO activity in the kidney cortex was evaluated by measuring the MeS-KYNA content in the microdialysate. The microdialysate was collected every 30 min and analyzed by high-performance liquid chromatography with fluorescence detection, monitored at 450 nm with an excitation wavelength of 364 nm. A significant production of MeS-KYNA was observed during, but not before, infusion of MeS-D-KYN, indicating that this compound is not endogenous. MeS-KYNA production was suppressed by the co-infusion of DAO inhibitor, 5-chlorobenzo[d]isoxazol-3-ol (CBIO), suggesting that MeS-D-KYN was converted to MeS-KYNA by renal DAO. Moreover, oral administration of CBIO effectively suppressed DAO activity in a dose-dependent manner. DAO converted MeS-D-KYN to MeS-KYNA in vivo, suggesting the potential of this compound in evaluating DAO activity. The use of the renal microdialysis technique developed in this study facilitates the monitoring of DAO activity in live experimental animals. [ABSTRACT FROM AUTHOR]

Rationale: Inadequate responses to current schizophrenia treatments have accelerated research into novel therapeutic approaches. Objectives: This study investigated the efficacy and tolerability of adjunctive L-theanine, an ingredient with neuroimmunomodulatory and neuroprotective properties, for chronic schizophrenia. Methods: Eighty chronic schizophrenia inpatients were equally assigned to receive risperidone (6 mg/day) plus either L-theanine (400 mg/day) or matched placebo in this 8-week, randomized, parallel-group, double-blind, placebo-controlled trial. The participants were assessed using the Positive and Negative Syndrome Scale (PANSS) by recording the results of subscales at baseline and weeks 4 and 8 to measure treatment efficacy. Additionally, the participants were assessed for the Hamilton Depression Rating Scale (HDRS) and adverse events, including the Extrapyramidal Symptom Rating Scale (ESRS). Results: Sixty patients, 30 in each group, were included in the analyses. All baseline demographic and clinical characteristics were comparable between the groups (p-values > 0.05). The reduction rates from baseline to endpoint in negative, general psychopathology, and total scores of PANSS were greater in the L-theanine group (p-values = 0.03, 0.01, and 0.04, respectively). Regarding general psychopathology scores, the reduction in the L-theanine group was also greater until week 4 (p-value < 0.01). The time × treatment interaction effect was significant on negative (p-value = 0.03), general psychopathology (p-value < 0.01), and total (p-value = 0.04) scores of PANSS, indicating additional improvements in the L-theanine group. The HDRS and side effects were comparable between the groups (p-values > 0.05). Conclusions: L-Theanine adjunct to risperidone safely and tolerably outperformed adjunctive placebo for schizophrenia, and promising evidence indicated its effects on primary negative symptoms, which need to be scrutinized in further studies. Trial registration: The study protocol was registered and published prospectively in the Iranian Registry of Clinical Trials (http://www.irct.ir; registration number: IRCT20090117001556N133) on 2020–12-12. [ABSTRACT FROM AUTHOR]

Schizophrenia (SZ) is among the twenty most disabling diseases worldwide. Subjective quality of life, well-being, and satisfaction are core elements to achieving personal recovery from the disorder. Long-acting injectable second-generation antipsychotics (SGA-LAIs) represent a valid therapeutic option for the treatment of SZ as they guarantee good efficacy and adherence to treatment. The aim of this rapid review is to summarize the evidence on the efficacy of SGA-LAIs in improving subjective quality of life, well-being, and satisfaction. The PubMed database was searched for original studies using SGA, LAI, risperidone, paliperidone, aripiprazole, olanzapine, SZ, and psychosis as keywords. Twenty-one studies were included: 13 clinical trials, 7 observational studies, and 1 post hoc analysis. It has been shown that SGA-LAIs bring an improvement to specific domains of subjective and self-rated quality of life, well-being, or satisfaction in prospective observational studies without a control arm and in randomized controlled trials versus placebo. The superiority of SGA-LAIs as compared with oral equivalents and haloperidol-LAI has been reported by some randomized controlled and observational studies. Although promising, the evidence is still limited because of the lack of studies and several methodological issues concerning the choice of the sample, the evaluation of the outcome variables, and the study design. New methodologically sound studies are needed. [ABSTRACT FROM AUTHOR]

Schizophrenic patients often face challenges with adherence to oral regimens. The study aimed to highlight the potentiality of intranasal ethanol/glycerin-containing lipid-nanovesicles (glycethosomes) incorporated into in situ gels for sustaining anti-psychotic risperidone (RS) release. The Box–Behnken Design (BBD) was followed for in vitro characterization. Glycethosomal-based in situ gels were examined by physical, ex vivo, and in vivo investigations. The ethanol impact on minimizing the vesicle size (VS) and enhancing the zeta potential (ZP) and entrapment efficiency (EE%) of nanovesicles was observed. Glycerin displayed positive action on increasing VS and ZP of nanovesicles, but reduced their EE%. After incorporation into various mucoadhesive agent-enriched poloxamer 407 (P407) in situ gels, the optimized gel containing 20% P407 and 1% hydroxypropyl methyl cellulose-K4M (HPMC-K4M) at a 4:1 gel/glycethosomes ratio showed low viscosity and high spreadability with acceptable pH, gel strength, and mucoadhesive strength ranges. The ethanol/glycerin mixture demonstrated a desirable ex vivo skin permeability of RS through the nasal mucosa. By pharmacokinetic analysis, the optimized gel showed eight-fold and three-fold greater increases in RS bioavailability than the control gel and marketed tablet, respectively. Following biochemical assessments of schizophrenia-induced rats, the optimized gel boosted the neuroprotective, anti-oxidant, and anti-inflammatory action of RS in comparison to other tested preparations. Collectively, the intranasal RS-loaded glycethosomal gel offered a potential substitute to oral therapy for schizophrenic patients. [ABSTRACT FROM AUTHOR]

Purpose: Biodegradable poly(lactide-co-glycolide) (PLGA) microparticles loaded with either risperidone or naltrexone were prepared from an emulsification homogenization process. The objective of this study was to determine the impact the post-treatment temperature has on the properties and subsequent performance of the microparticles. Methods: The post-treatment temperature of an ethanolic solution was characterized from 10 ~ 35ºC for the naltrexone and risperidone micropartilces. Results: The wash temperature resulted in a typical triphasic in vitro release pattern at low wash temperatures or a biphasic pattern consisting of an elevated release rate at higher post-treatment temperatures. The post-treatment temperature largely influences the particle morphology, residual solvent levels, glass transition temperature, and drug loading and is molecule dependent, whereby these characteristics subsequently influence the drug release rate. Conclusion: The study highlights the importance of both the post-treatment process and control during manufacturing to obtain a formulation within the desired product profile. [ABSTRACT FROM AUTHOR]

The article presents a case study of an elderly woman with schizophrenia treated with risperidone and olanzapine. It is reported that despite previous successful treatment with risperidone, her condition worsened, leading to a massive bilateral pulmonary embolism (PE) with cardiac arrest. It further highlights the need for tailored venous thromboembolism (VTE) prevention strategies for elderly psychiatric inpatients due to multiple risk factors.

Examining the heterogeneity of negative symptoms of schizophrenia contributes to the identification of available treatment targets. Generally, prior evidence classified three to four symptom treatment response trajectory groups over the course of positive symptoms, yet, no evidence exists regarding the heterogeneity of medium-term response to predominant negative symptoms. The current post-hoc analysis aims to identify the heterogeneity in negative symptom treatment response trajectories among patients with predominant negative symptoms who received either cariprazine or risperidone for 26 weeks. Treatment response was analyzed based on the: the Positive and Negative Syndrome Scale Factor Score for Negative Symptoms (PANSS-FSNS), and the Clinical Global Impression Severity (CGI S) and Improvement (CGI I) scales. To identify subgroups of patients with a similar course of treatment response, group-based trajectory modelling was utilized. Results demonstrated that in comparison with competing models, a single trajectory best described the treatment response of patients with predominant negative symptoms. The results indicate that patients with predominant negative symptoms with over ten years of schizophrenia respond rapidly to adequate treatment and follow a course of steady improvement. [ABSTRACT FROM AUTHOR]

Anxiety and ejaculation share similar sympathetic neuronal pathways and hence they may coincide. In this case report, we describe a 30-year-old male with ongoing perceptual disturbances and spontaneous ejaculations that occur without sexual arousal. The patient ultimately benefited from pharmacological therapy with risperidone. [ABSTRACT FROM AUTHOR]

Background: We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of blonanserin and risperidone for the treatment of schizophrenia and to provide reliable pharmacotherapeutic evidence for in the clinical treatment of schizophrenia. Methods: We systematically searched the PubMed, Cochrane Library, Embase, Chinese Biomedical Literature Database (CBM), and China National Knowledge Infrastructure (CNKI) databases for head-to-head randomized controlled trials that compared blonanserin with risperidone for the treatment of schizophrenia. We extracted the following data: author, year, country, diagnostic criteria, sample size, course of treatment, dosage and outcomes. Our main endpoint was the changes in the Positive and Negative Syndrome Scale (PANSS) total scores. Meta-analysis of the included data was conducted by RevMan 5.3 software. We used the GRADE criteria to evaluate the certainty of the evidence. Results: A total of 411 studies were initially; 8 trials were eligible and were included in our analysis (N = 1386 participants). Regarding efficacy, there was no difference in changes in the PANSS total scores between the two groups (P > 0.05). In terms of safety, compared to risperidone, the incidence of serum prolactin increases and weight gain in the blonanserin group was lower (P<0.05), but the incidence of extrapyramidal symptoms (EPS) was higher (P<0.05). Conclusion: The efficacy of blonanserin is similar to that of risperidone, but it is unclear whether blonanserin is more effective than risperidone at improving cognitive and social function. More high-quality studies are needed to verify the efficacy and safety of blonanserin in the future. [ABSTRACT FROM AUTHOR]

Background: Early onset anorexia nervosa (EOAN) is a subclassification of AN, defined by an onset before 14 years, and characterized by specific demographic, neuropsychological, and clinical features. The present study aims to provide naturalistic data on a wide sample with EOAN, focusing on psychopathological and nutritional changes occurring in the context of a multidisciplinary hospital intervention, as well as the rate of rehospitalizations during a 1‐year follow‐up. Method: Observational, naturalistic study adopting standardized criteria for EOAN (onset before 14 years). EOAN were compared to adolescent‐onset AN (AOAN) patients (onset after 14 years) by demographic, clinical, psycho and treatment variables. Psychopathology was assessed at admission (T0) and discharge (T1) with self‐administered psychiatric scales for children and adolescents (SAFA) subtests for Eating Disorders, Anxiety, Depression, Somatic symptoms, and Obsessions. Then, potential differences of T0–T1 changes in psychopathological and nutritional variables were assessed. Finally, rates of re‐hospitalizations at 1‐year post‐discharge follow‐up were assessed with Kaplan–Meier analyses. Results: Two‐hundred thirty‐eight AN individuals (EOAN = 85) were enrolled. When compared to AOAN, EOAN participants were more frequently males (X2 = 5.360, p =.021), more frequently received nasogastric‐tube feeding (X2 = 10.313, p =.001), and risperidone (X2 = 19.463, p <.001), obtained a greater T0‐T1 improvement in body‐mass index percentage (F[1.229] = 15.104, p <.001, η2 = 0.030), with higher 1‐year freedom from re‐hospitalization (hazard ratio, 0.47; Log‐rank: X2 = 4.758, p =.029). Conclusion: In this study, describing the broadest EOAN sample available in literature so far, EOAN patients received specific interventions and obtained better outcomes at discharge and follow‐up when compared to AOAN. Longitudinal, matched studies are required. [ABSTRACT FROM AUTHOR]

Several lines of evidence suggest that scarcity of the gaseous molecule nitric oxide (NO) is associated with the pathogenesis of schizophrenia. Therefore, compounds, such as NO donors, that can normalize NO levels might be of utility for the treatment of this pathology. It has been previously shown that the NO donor molsidomine attenuated schizophrenia-like behavioral deficits caused by glutamate hypofunction in rats. The aim of the current study was to investigate the efficacy of molsidomine and that of the joint administration of this NO donor with sub-effective doses of the non-typical antipsychotics clozapine and risperidone to counteract memory deficits associated with dysregulation of the brain dopaminergic system in rats. Molsidomine (2 and 4 mg/kg) attenuated spatial recognition and emotional memory deficits induced by the mixed dopamine (DA) D1/D2 receptor agonist apomorphine (0.5 mg/kg). Further, the joint administration of sub-effective doses of molsidomine (1 mg/kg) with those of clozapine (0.1 mg/kg) or risperidone (0.03 mg/kg) counteracted non-spatial recognition memory impairments caused by apomorphine. The present findings propose that molsidomine is sensitive to DA dysregulation since it attenuates memory deficits induced by apomorphine. Further, the current findings reinforce the potential of molsidomine as a complementary molecule for the treatment of schizophrenia. [ABSTRACT FROM AUTHOR]

Objectives: Risperidone, a dopamine and serotonin antagonist or a second-generation (atypical) antipsychotic drug, is commonly prescribed for various psychiatric disorders, including schizophrenia, bipolar disorder, and autism spectrum disorders. While effective, risperidone often leads to hyperprolactinemia, impacting about 40%–80% of patients. In this study, we intended to examine the prevalence of hyperprolactinemia in Taiwanese patients with schizophrenia who received risperidone medication and to analyze potential links between prolactin blood levels and clinical variables. Methods: Patients with schizophrenia receiving risperidone monotherapy were included in this cross-sectional study. Blood levels of prolactin and metabolic parameters were measured. Results: A total of 176 participants diagnosed with schizophrenia, including 87 women and 89 men, were enrolled in our study. The prevalence of hyperprolactinemia and metabolic syndrome was 75.6% and 31.8%, respectively. Patients with hyperprolactinemia showed significantly higher insulin blood levels (p < 0.05) and significantly higher homeostasis model assessment for insulin resistance (HOMA-IR) indexes (p < 0.05) than those without hyperprolactinemia. The results of multivariate linear regression analysis showed that female sex (p = 0.001), HOMA-IR index (p < 0.01), and risperidone daily dosage (p < 0.05) were significantly associated with prolactin blood level. Conclusion: This study adds to the existing knowledge concerning risperidone-induced hyperprolactinemia in Taiwanese patients with schizophrenia. Hyperprolactinemia and metabolic syndrome are prevalent in patients with schizophrenia treated with risperidone. Clinicians are advised to be aware of these problems and monitor them regularly with their patients who receive treatment with risperidone. [ABSTRACT FROM AUTHOR]

Background: Neuropathic pain results from lesions or diseases affecting the somatosensory system. The management of a patient with chronic neuropathic pain remains a challenge several studies report the analgesic effect of serotonin receptor antagonists in different models of experimental pain. The present study was designed to study the effect of systemic administration of risperidone, on behavioral scores of neuropathic pains in chronic constriction (CCI) model in rats. Methods: Inducing neuropathic pain with the CCI model which causes heat hyperalgesia, heat, and mechanical allodynia was performed on rats, and then, in two phases, risperidone effect was determined. In the acute phase, risperidone 1, 2, 4 mg was administered for three groups half an hour before behavioral tests on the 7th, 14th, and 21st day after surgery, and in the chronic phase, risperidone 1, 2, and 4 mg was administered for three different groups from the 1st to 14th days after surgery than on 14th-day behavioral scores were performed. For gene expression analysis, samples are taken from spinal cord tissues in lumbar segments. Results: This study shows chronic administration of risperidone as an antipsychotic drug was effective on heat hyperalgesia and allodynia. However, only the max dosage (4 mg) of risperidone showed meaningful improvement in increasing mechanical allodynia. However, acute administering of risperidone did not show any meaningful changes in behavioral tests on neuropathic pain induced by chronic constriction injury of the sciatic nerve in rats. In addition, gene expression results showed an increase in IL-4 and IL-10 gene expression in the risperidone group compared to the sham group. Conclusion: This study suggests the helpful preventive effects of risperidone in developing and increasing neuropathic pain, but it does not have any instant effect. [ABSTRACT FROM AUTHOR]

Introduction: Co-occurring cannabis use and psychosis is an increasing problem. No single behavioral or pharmacologic treatment has emerged as clearly superior. To address the gap, this nonrandomized, quality improvement project compares outcomes for adolescents with co-occurring cannabis use disorder and psychosis prescribed risperidone or aripiprazole. Materials and Methods: This project is a retrospective chart review of 110 adolescents (ages 13–21 years) hospitalized for psychosis and co-occurring cannabis use disorder. The primary outcomes are length of stay and length of stay index. Results: Adolescents prescribed risperidone compared with aripiprazole had a significantly greater length of stay (9.7 days vs. 5.8 days, p = 0.002) and length of stay index (1.4 vs. 0.79, p = 0.004). Conclusions: Adolescents hospitalized for co-occurring psychosis and cannabis use disorder had a significantly longer length of stay and length of stay index. These data are consistent with a more rapid reduction in acute psychotic symptoms for aripiprazole compared with risperidone in the context of co-occurring cannabis use disorder. [ABSTRACT FROM AUTHOR]

Objective To provide evidence for clinical safety of risperidone based on the FAERS database. Methods Adverse event reports for lurasidone as a suspected drug were collected from the FAERS database for 15 quarters from January 1,2020,to March 31,2023. After standardizing the adverse drug reaction terms, the proportional reporting ratio (PRR) and the reporting odds ratio (ROR) methods were used for signal detection of adverse reactions. Results A total of 11 168 case reports of adverse reactions to lurasidone were extracted from the FAERS database, most of which were male patients (7 525,67. 38%). The age group with the highest distribution was 18-＜45 years old (2 302,20. 61%). The majority of adverse events occurred within 0-30 days of drug administration, with 1453 cases accounting for 13. 01% of the total. In the detection of adverse reactions using the ROR and PRR methods, a total of 526 signals were detected, with the highest number of signals being related to the nervous system (112). Conclusion The use of lurasidone is associated with the occurrence of severe adverse reactions, especially prolonged hospitalization. Metabolic disorders caused by lurasidone, such as obesity and hyperprolactinemia, have a high signal, and caution should be exercised for the occurrence of these adverse reactions during clinical use. [ABSTRACT FROM AUTHOR]