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Background: Identifying stable and consistent resting-state functional connectivity patterns across illness trajectories has the potential to be considered fundamental to the pathophysiology of schizophrenia. We aimed to identify consistent resting-state functional connectivity patterns across heterogeneous schizophrenia groups defined based on treatment response., Methods: In phase 1, we used a cross-sectional case-control design to characterize and compare stable independent component networks from resting-state functional magnetic resonance imaging scans of antipsychotic-naïve participants with first-episode schizophrenia (n = 54) and healthy participants (n = 43); we also examined associations with symptoms, cognition, and disability. In phase 2, we examined the stability (and replicability) of our phase 1 results in 4 groups (N = 105) representing a cross-sequential gradation of schizophrenia based on treatment response: risperidone responders, clozapine responders, clozapine nonresponders, and clozapine nonresponders following electroconvulsive therapy. Hypothesis-free whole-brain within- and between-network connectivity were examined., Results: Phase 1 identified posterior and anterior cerebellar hypoconnectivity and limbic hyperconnectivity in schizophrenia at a familywise error rate-corrected cluster significance threshold of p < .01. These network aberrations had unique associations with positive symptoms, cognition, and disability. During phase 2, we replicated the phase 1 results while comparing each of the 4 schizophrenia groups to the healthy participants. The participants in 2 longitudinal subdatasets did not demonstrate a significant change in these network aberrations following risperidone or electroconvulsive therapy. Posterior cerebellar hypoconnectivity (with thalamus and cingulate) emerged as the most consistent finding; it was replicated across different stages of treatment response (Cohen's d range -0.95 to -1.44), reproduced using different preprocessing techniques, and not confounded by educational attainment., Conclusions: Posterior cerebellar-thalamo-cingulate hypoconnectivity is a consistent and stable state-independent neural marker of schizophrenia., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Vertical rhythmic dyskinetic movements that are primarily drug-induced and affect solely the jaw, mouth, and lips without involving the tongue have been historically described as "rabbit" syndrome (RS). Evidence on the unique features and implications of this disorder remains limited. This literature review aims to evaluate the clinical-epidemiological profile, pathological mechanisms, and management of this movement disorder. Materials and Methods: Two reviewers identified and assessed relevant reports in six databases without language restriction published between 1972 and 2024. Results: A total of 85 articles containing 146 cases of RS were found. The mean frequency of RS among adults in psychiatric hospitals was 1.2% (range 0-4.4%). The mean age of affected patients was 49.2 (SD: 17.5), and 63.6% were females. Schizophrenia was the most frequent comorbidity found in 47.6%, followed by bipolar disorder (17.8%), major depressive disorder (10.3%), and obsessive-compulsive disorder (3.7%). Five cases were idiopathic. The most common medications associated with RS were haloperidol (17%), risperidone (14%), aripiprazole (7%), trifluoperazine (5%), and sulpiride (5%). The mean duration of pharmacotherapy before RS was 21.4 weeks (SD: 20.6). RS occurred in association with drug-induced parkinsonism (DIP) in 27.4% and with tardive dyskinesia (TD) in 8.2% of cases. Antipsychotic modification and/or anticholinergic drugs resulted in full or partial recovery in nearly all reported cases in which they were prescribed. Conclusions: RS occurs as a distinct drug-induced syndrome associated primarily but not exclusively with antipsychotics. Distinguishing RS from TD is important because the treatment options for the two disorders are quite different. By contrast, RS may be part of a spectrum of symptoms of DIP with similar course, treatment outcomes, and pathophysiology.

Good adherence to antipsychotic therapy helps prevent relapses in first-episode psychosis (FEP). We used data from the FEP-CAUSAL Collaboration, an international consortium of observational cohorts, to emulate a target trial comparing antipsychotics, with treatment discontinuation as the primary outcome. Other outcomes included all-cause hospitalization. We benchmarked our results to estimates from the European First Episode Schizophrenia Trial, a randomized trial conducted in the 2000s. We included 1097 patients with a psychotic disorder and less than 2 years since psychosis onset. Inverse-probability weighting was used to control for confounding. The estimated 12-month risks of discontinuation for aripiprazole, first-generation agents, olanzapine, paliperidone, quetiapine, and risperidone were 61.5% (95% CI, 52.5-70.6), 73.5% (95% CI, 60.5-84.9), 76.8% (95% CI, 67.2-85.3), 58.4% (95% CI, 40.4-77.4), 76.5% (95% CI, 62.1-88.5), and 74.4% (95% CI, 67.0-81.2), respectively. Compared with aripiprazole, the 12-month risk differences were -15.3% (95% CI, -30.0 to 0.0) for olanzapine, -12.8% (95% CI, -25.7 to -1.0) for risperidone, and 3.0% (95% CI, -21.5 to 30.8) for paliperidone. The 12-month risks of hospitalization were similar between agents. Our estimates support use of aripiprazole and paliperidone as first-line therapies for FEP. Benchmarking yielded similar results for discontinuation and absolute risks of hospitalization as in the original trial, suggesting that data from the FEP-CAUSAL Collaboration sufficed to remove confounding for these clinical questions. This article is part of a Special Collection on Mental Health., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: This study aimed to create and validate robust machine-learning-based prediction models for antipsychotic drug (risperidone) continuation in children and teenagers suffering from mania over one year and to discover potential variables for clinical treatment., Method: The study population was collected from the national claims database in China. A total of 4,532 patients aged 4-18 who began risperidone therapy for mania between September 2013 and October 2019 were identified. The data were randomly divided into two datasets: training (80%) and testing (20%). Five regularly used machine learning methods were employed, in addition to the SuperLearner (SL) algorithm, to develop prediction models for the continuation of atypical antipsychotic therapy. The area under the receiver operating characteristic curve (AUC) with a 95% confidence interval (CI) was utilized., Results: In terms of discrimination and robustness in predicting risperidone treatment continuation, the generalized linear model (GLM) performed the best (AUC: 0.823, 95% CI: 0.792-0.854, intercept near 0, slope close to 1.0). The SL model (AUC: 0.823, 95% CI: 0.791-0.853, intercept near 0, slope close to 1.0) also exhibited significant performance. Furthermore, the present findings emphasize the significance of several unique clinical and socioeconomic variables, such as the frequency of emergency room visits for nonmental health disorders., Conclusions: The GLM and SL models provided accurate predictions regarding risperidone treatment continuation in children and adolescents with episodes of mania and hypomania. Consequently, applying prediction models in atypical antipsychotic medicine may aid in evidence-based decision-making., (© 2024. The Author(s).)

Introduction: Long-acting injectable (LAI) antipsychotic medications can help improve treatment adherence in patients with schizophrenia and bipolar disorder. Despite this, they are underutilized. In 2003, intramuscular risperidone became the first available LAI atypical antipsychotic medication, and since then, a number of competing long-acting risperidone formulations have been brought to market, with additional options under active development. These include intramuscular, subcutaneous, long-acting oral, and implantable formulations., Areas Covered: This review summarizes currently available and emerging long-acting risperidone formulations, including efficacy and safety data, and practical considerations aimed to help prescribers distinguish one formulation from another., Expert Opinion: There is an expanding number of currently available LAI antipsychotic medications giving patients and providers an opportunity to personalize and individualize care. Rates of adherence to treatment in patients with schizophrenia and bipolar disorder are low, and individualizing care can help improve this. The risperidone LAI treatment landscape includes five options approved by the U.S. Food and Drug Administration, with others under clinical development. These options differ in regard to mode of administration, approved indications, available dose strengths, injection intervals, needle size, injection volume, storage, and other variables. Prescribers should be familiar with these differing options to help patients find the best fit for their individual needs.

Objectives: Risperidone is commonly prescribed off-label in children and adolescents to manage disruptive behavior. This study aimed to investigate continued benefits of risperidone after at least 1 year of treatment and effects of discontinuation on physical health. Methods: Thirty-five youths (aged 6-18 years, intelligence quotient [IQ] >70) who were treated with risperidone for at least 1 year in regular clinical practice receiving outpatient care were randomly assigned to double-blind continuation of risperidone during 16 weeks or continuation for 2 weeks, gradual dose lowering over 6 weeks, and placebo for 8 weeks. Primary outcome was the total Disruptive Behavior (D-total) score of the parent-reported Nisonger Child Behavior Rating Form-Typical IQ (NCBRF-TIQ). Secondary outcome measures were the clinician-rated Clinical Global Impressions-Improvement scale (CGI-I), the parent, child, and teacher-rated Strengths and Difficulties Questionnaire (SDQ), the parent-rated Retrospective Modified Overt Aggression Scale (R-MOAS), and several health parameters (Udvalg for Kliniske Undersøgelser Side Effect Rating Scale [UKU-SERS], dyskinesia, akathisia, parkinsonism, body mass index (BMI), waist circumference, and laboratory outcomes). Mixed models for repeated measures were conducted for continuous outcomes and a chi-square test for the CGI-I. Results: Discontinuation of risperidone, as compared with continuation, was not associated with significant changes in parent-reported disruptive behaviors. However, discontinuation was related to significant deterioration in parent-rated verbal aggression, teacher-rated behavioral functioning, clinician-rated general functioning, and significant improvements in weight, BMI, waist circumference, and glucose, insulin, and prolactin levels. Although 56% of participants in the discontinuation group experienced relapse, causing premature withdrawal from the study, 44% was able to successfully discontinue risperidone. Conclusion: Discontinuation of risperidone was associated with deterioration on some, but not all behavioral measures according to this explorative study. Discontinuation was associated with important health gains. Despite long-term benefits of risperidone, attempts to withdraw risperidone should be undertaken in individual children. This is a crucial step in preventing harm and fostering health.

Introduction: The aim of the study was to evaluate interaction effect of various augmentation strategies with clozapine in patients with Treatment-resistant schizophrenia., Methods: Data was extracted for change in positive and negative syndrome scale (PANSS) or brief psychiatric rating scale (BPRS) scores for monotherapy with various antipsychotic agents alone and their combination with clozapine. Individual patient data was generated using simulation of data (factorial trial framework) from published clinical trials for sample sizes from eight to 400 to evaluate interaction effect through linear modeling. Dose equivalents were calculated, and best fit models were determined for simulated data., Results: The polynomial model was found to be the best fit for the simulated data to determine interaction effect of combination. The clozapine augmentation with risperidone and ziprasidone was found to be antagonistic, whereas it was additive for haloperidol, aripiprazole, and quetiapine. A synergistic effect was observed for ECT combined with clozapine (Interaction effect: -7.62; p <0.001). A sample size of 250-300 may be sufficient to demonstrate a clinically significant interaction in future trials., Conclusion: Clozapine may be augmented with electroconvulsive therapy, leading to the enhancement of antipsychotic effect. Though some antipsychotics like aripiprazole demonstrate additive effects, they may also add to the adverse effects., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of competing Interest BD, BK, SK and BW received grant research support from The Netherlands Organization for Health Research and Development (ZonMW). RH received grant research support from ZonMW and Stichting de Merel. RG received grant research support from Erasmus Medical Center and Smarter Choices for Better Health. All other authors declare that they have no conflicts of interest.

Data on the role of CYP2D6 and CYP3A4/5 polymorphisms in relation to risperidone (RIS) pharmacokinetics (PK) in children are relatively limited and inconsistent. This is partially attributable to the limited coverage of CYP2D6 and CYP3A4/5 metabolizer phenotypes, particularly those of poor and ultrarapid metabolizers (PMs and UMs), which has led to calls for studies of populations with a non-European background that may carry variants that are less frequent in Europeans. Children ≤ 18 years old with at least 8 weeks of a RIS-based regimen were recruited from three autism centers in Riyadh, Saudi Arabia. The primary outcomes measured were plasma concentrations of RIS and 9-hydroxyrisperidone (9-OH-RIS) and their dose-adjusted (C/D) ratios as a function of phenotypes and activity score (AS). For accurate DNA genotyping, targeted pharmacogenomic testing with the Axiom PharmacoFocus Array was performed via examination of a broad collection of probesets targeting CYP2D6 and CYP3A4/5 variants. The frequency of genotypes/phenotypes and the impact of their allele translation and phenoconversion-predicted enzyme activity were examined. The final cohort included 83 individuals. The most common CYP2D6 phenotype in our population was normal metabolizers (NMs, 66.3%). Inconsistent with some previous studies, the three phenotypes of intermediate metabolizers (IMs), NMs, and UMs were significantly different in terms of RIS concentration, the RIS/9-OH-RIS ratio, the RIS C/D ratio and the 9-OH-RIS C/D ratio. According to AS analyses, there were statistically significant differences in the RIS concentration (P = 0.013), RIS/9-OH-RIS ratio (P < 0.001) and RIS C/D ratio (P = 0.030) when patients were categorized into AS ≤ 1 vs. AS > 1. None of the CYP3A4/5 star allele translated phenotypes revealed a significant influence on any of the RIS PK parameters. Notably, neither CYP2D6 nor CYP3A4/5 phenotyping demonstrated a significant impact on the total active moiety, suggesting that other gene variants could modulate RIS PK. The study confirmed the previously reported partial impact of the CYP2D6 gene on RIS PK. However, future studies using contemporary genotyping techniques targeting a wide range of variants in other candidate genes must be conducted to further examine their interactive effects on RIS PK and the clinical response., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Olanzapine and risperidone have emerged as the most widely used drugs as short-term prescription in the treatment of behavioral disturbances in dementia. The present systematic review and meta-analysis was hence performed to investigate the effectiveness and safety profile of olanzapine and risperidone in the treatment of behavioral and psychological symptoms of dementia (BPSD), aiming to provide updated suggestion for clinical physicians and caregivers., Design: Prospective controlled clinical studies were included, of which available data was extracted. Outcomes of BEHAVE-AD scores with the variation of grades, specific behaviors variables, as well as safety signals were pooled for the analysis by odds rates and weighted mean differences, respectively., Data Sources: Medline, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and WanFang., Eligibility Criteria: Prospective, controlled clinical studies, conducted to compare the effectiveness and safety profile of olanzapine and risperidone in the treatment of BPSD., Data Extraction and Synthesis: Interested data including baseline characteristics and necessary outcomes from the included studies were extracted independently by 2 investigators. BEHAVE-AD scale was adopted to assess the efficacy in the present study. All behaviors were evaluated at the time of the initiation of the treatment, as well as the completion of drugs courses. Adverse events were assessed with the criteria of Treatment Emergent Symptom Scale, or Coding Symbols for a Thesaurus of Adverse Reaction Terms dictionary. Weighted mean difference was used for the pooled analysis., Results: A total of 2427 participants were included in the present meta-analysis. Comparative OR on response rate, and remarkable response rate between olanzapine and risperidone was 0.65 (95% CI: 0.51-0.84; P = .0008), and 0.62 (95% CI: 0.50-0.78; P < .0001), respectively. There were statistical differences observed by olanzapine on the improvement of variables including delusions (WMD, -1.83, 95% CI, -3.20, -0.47), and nighttime behavior disturbances (WMD, -1.99, 95% CI, -3.60, -0.38) when compared to risperidone., Conclusion: Our results suggested that olanzapine might be statistically superior to risperidone on the reduction of BPSD of Alzheimer's disease, especially in the relief of delusions and nighttime behavior disturbances. In addition, olanzapine was shown statistically lower risks of agitation, sleep disturbance, and extrapyramidal signs., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Rationale: Changes in the density and diversity of gut microbiota in chronic use of methamphetamine have been mentioned as contributors to psychotic and anxiety symptoms, sleep problems, and loss of appetite., Objective: In this placebo-controlled clinical trial, we investigated the effect of the probiotic Lactobacillus Acidophilus in improving psychiatric symptoms among hospitalized patients with chronic methamphetamine use along with psychotic symptoms., Methods: 60 inpatients with a history of more than 3 years of methamphetamine use, were randomly assigned to one of two groups receiving either a probiotic capsule or placebo along with risperidone for 8 weeks based on a simple randomization method. In weeks 0, 4, and 8, patients were evaluated using the Brief Psychiatric Rating Scale (BPRS), Beck Anxiety Inventory (BAI), Pittsburgh Sleep Quality Index (PSQI), Simple Appetite Nutritional Questionnaire (SANQ), and Body Mass Index (BMI)., Results: Compared to the control group, patients receiving probiotics had better sleep quality, greater appetite, and higher body mass index (there were significant interaction effects of group and time at Week 8 in these variables (t = -3.32, B = -1.83, p = .001, d = 0.89), (t = 10.50, B = 2.65, p <.001, d = 1.25) and (t = 3.40, B = 0.76, p <.001, d = 0.30), respectively. In terms of the improvement of psychotic and anxiety symptoms, there was no statistically significant difference between the two groups., Conclusions: The use of probiotics was associated with improved sleep quality, increased appetite, and increased body mass index in patients with chronic methamphetamine use. Conducting more definitive clinical trials with larger sample sizes and longer-term follow-up of cases is recommended., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The present study was designed to evaluate the efficacy and safety of l-carnitine as an adjuvant agent to risperidone in the treatment of autism spectrum disorder (ASD)-associated behaviors. In this study, 68 children with confirmed ASD were randomly allocated to receive either l-carnitine (150 mg/day) or matched placebo in addition to risperidone. We utilized the Aberrant Behavior Checklist-Community Edition scale (ABC-C) and a checklist of potential adverse effects to assess changes in behavioral status and safety profile at weeks 0, 5 and 10 of the trial. The primary outcome was defined as a change in the irritability subscale score. Sixty patients with similar baseline characteristics completed the trial period. Although scores of ABC-C subscales significantly decreased in both groups over the trial period, the combination of l-carnitine and risperidone resulted in more reduction on the irritability and hyperactivity subscales compared to the combination of risperidone and placebo ( P  = 0.033 and P  < 0.001, respectively). However, changes in lethargy, stereotypic behavior and inappropriate speech subscales were similar between groups. In conclusion, l-carnitine adjuvant to risperidone could improve irritability and hyperactivity features in children with ASD. Results of this study should be considered preliminary and further clinical trials with larger sample sizes and longer follow-up periods are warranted., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Depressive and anxiety symptoms commonly manifested throughout the progression of schizophrenia. However, the prevalence of these symptoms, alongside their co-occurrence, remains uncertain, and clinical correlates remain elusive., Objectives: This study seeks to investigate the prevalence of such symptoms and their demographic and clinical associations among patients diagnosed with schizophrenia., Methods: The study included 19,623 patients diagnosed with schizophrenia based on the ICD-10 criteria. Participants were recruited from community-dwelling patients registered in the local health system in Hangzhou of China between August 1 and October 30, 2022., Results: The prevalence rates of depressive and anxiety symptoms, as well as their co-occurrence, were determined to be 19 % (95%CI = 18.5-19.6 %), 37.4 % (95%CI = 36.8-38.0 %), and 17.7 % (95%CI = 17.2-18.2 %), respectively. Patients prescribed quetiapine, olanzapine, and risperidone exhibited significantly lower prevalence rates of these symptoms (P < 0.01). Spearman's correlation analysis revealed a significant correlation between depressive symptoms and anxiety symptoms (r = 0.60, P = 0.006). Additionally, age, social relationships, and sleep status were significantly associated with depressive and anxiety symptoms, and their co-occurrence, in both univariate and multivariate analyses., Conclusion: Given the pervasive nature and detrimental consequences of these symptoms among individuals diagnosed with schizophrenia, comprehensive evaluation and implementation of efficacious interventions are highly recommended., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Pharmacogenetic markers are current targets for the personalized treatment of psychosis. Limited data exist on COMT and NRG1 polymorphisms in relation to risperidone treatment. This study focuses on the impact of COMT rs4680 and NRG1 (rs35753505, rs3924999) polymorphisms on risperidone treatment in schizophrenia spectrum disorders (SSDs). This study included 103 subjects with SSD treated with risperidone monotherapy. COMT rs4680, NRG1 rs35753505, and rs3924999 were analyzed by RT-PCR. Participants were evaluated via the Positive and Negative Syndrome Scale (PANSS) after six weeks. Socio-demographic and clinical characteristics were collected. COMT rs4680 genotypes significantly differed in PANSS N scores at admission: AG>AA genotypes ( p = 0.03). After six weeks of risperidone, PANSS G improvement was AA>GG ( p = 0.05). The PANSS total score was as follows: AA>AG ( p = 0.04), AA>GG ( p = 0.02). NRG1 rs35753504 genotypes significantly differed across educational levels, with CC>CT ( p = 0.02), and regarding the number of episodes, TT>CC, CT>CC ( p = 0.01). The PANSS total score after six weeks of treatment showed a better improvement for TT

Schizophrenia spectrum disorders (SSD) are a group of diseases characterized by one or more abnormal features in perception, thought processing and behavior. Patients suffering from SSD are at risk of developing life-threatening complications. Pharmacogenetic studies have shown promising results on personalized treatment of psychosis. In the current study, 103 patients diagnosed with SSD treated with risperidone as antipsychotic monotherapy were enrolled. Socio-demographics and clinical data were recorded, and laboratory tests and genotyping standard procedure for cytochrome P450 (CYP) 2D6*4 were performed. Patients were evaluated by the Positive and Negative Syndrome Scale (PANSS) on admission and at discharge. Based on the reduction in the PANSS total score, subjects were divided into non-responders, partial responders and full responders. Only 11 subjects had a full response to risperidone (10.67%), 53 subjects (51.45%) had a partial response, and 39 participants (37.86%) were non-responders. Patients at first episode psychosis showed significantly higher levels of blood glucose and prolactin levels, while chronic patients showed significantly higher LDL levels. Adverse drug reactions (ADR) such as tremor and stiffness significantly correlated with genetic phenotypes ( p = 0.0145). While CYP2D6 showed no impact on treatment response, ADR were significantly more frequent among poor and intermediate metabolizers.

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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims: Accumulating studies have assessed mortality risk associated with mood-stabilizers, the mainstay treatment for bipolar disorder (BD). However, existing data were mostly restricted to suicide risk, focused on lithium and valproate and rarely adequately adjusted for potential confounders. This study aimed to assess comparative mortality risk with all, natural and unnatural causes between lithium, valproate and three frequently prescribed second-generation antipsychotics (SGA), with adjustment for important confounders., Methods: This population-based cohort study identified 8137 patients with first-diagnosed BD, who had exposed to lithium ( n = 1028), valproate ( n = 3580), olanzapine ( n = 797), quetiapine ( n = 1975) or risperidone ( n = 757) between 2002 and 2018. Data were retrieved from territory-wide medical-record database of public healthcare services in Hong Kong. Propensity-score (PS)-weighting method was applied to optimize control for potential confounders including pre-existing chronic physical diseases, substance/alcohol use disorders and other psychotropic medications. PS-weighted Cox proportional-hazards regression was conducted to assess risk of all-, natural- and unnatural-cause mortality related to each mood-stabilizer, compared to lithium. Three sets of sensitivity analyses were conducted by restricting to patients with (i) length of cumulative exposure to specified mood-stabilizer ≥90 days and its medication possession ratio (MPR) ≥90%, (ii) MPR of specified mood-stabilizer ≥80% and MPR of other studied mood-stabilizers <20% and (iii) monotherapy., Results: Incidence rates of all-cause mortality per 1000 person-years were 5.9 (95% confidence interval [CI]: 4.5-7.6), 8.4 (7.4-9.5), 11.1 (8.3-14.9), 7.4 (6.0-9.2) and 12.0 (9.3-15.6) for lithium-, valproate-, olanzapine-, quetiapine- and risperidone-treated groups, respectively. BD patients treated with olanzapine (PS-weighted hazard ratio = 2.07 [95% CI: 1.33-3.22]) and risperidone (1.66 [1.08-2.55]) had significantly higher all-cause mortality rate than lithium-treated group. Olanzapine was associated with increased risk of natural-cause mortality (3.04 [1.54-6.00]) and risperidone was related to elevated risk of unnatural-cause mortality (3.33 [1.62-6.86]), relative to lithium. The association between olanzapine and increased natural-cause mortality rate was consistently affirmed in sensitivity analyses. Relationship between risperidone and elevated unnatural-cause mortality became non-significant in sensitivity analyses restricted to low MPR in other mood-stabilizers and monotherapy. Valproate- and lithium-treated groups did not show significant differences in all-, natural- or unnatural-cause mortality risk., Conclusion: Our data showed that olanzapine and risperidone were associated with higher mortality risk than lithium, and further supported the clinical guidelines recommending lithium as the first-line mood-stabilizer for BD. Future research is required to further clarify comparative mortality risk associated with individual SGA agents to facilitate risk-benefit evaluation of alternative mood-stabilizers to minimize avoidable premature mortality in BD.

We report the case of a man in his mid-80s with diabetes mellitus who presented to the emergency department with a 1-day history of right-sided choreiform movements and falls. Laboratory tests revealed blood glucose of 597 mg/dL. Non-contrast CT imaging of his head demonstrated a faint hyperdensity involving the left lentiform nucleus and brain MRI showed a hyperintensity in the left basal ganglia on T1-weighted images. These lesions are typical of diabetic striatopathy. Symptoms of hemichorea/hemiballismus did not resolve with glycaemic control and several pharmacological agents were tried with eventual improvement with risperidone. He was discharged to a rehabilitation facility and had mild persistent arm chorea at 6-month follow-up., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Prescriptions for atypical antipsychotics in children and adolescents are increasing globally. However, a precise understanding of the clinical variables and evidence that prescribers consider before using these agents is lacking. While empirical literature on the long-term safety and efficacy of these medications is available, the literature concerning their use in these younger age groups is relatively sparse. In this study, we examined the current prescribing patterns of medical professionals employed by a public health service in Australia., Methods: A survey examining their current practice when prescribing atypical antipsychotics to children and adolescents was completed by 103 physicians. Questions were asked about commonly prescribed atypical antipsychotics, indications, dose ranges, target symptoms, duration of treatment, and the evidence base(s) used when making treatment decisions., Results: Physicians prescribed atypical antipsychotics for a wide range of indications in this age group, with the most common agents being risperidone, quetiapine, and olanzapine. Adverse effects were reported as the main reason for treatment discontinuation. More than half of the respondents indicated that the most common source of guidance/evidence they referred to when initiating prescriptions were peers or expert opinion., Conclusions: Children and adolescents were prescribed a number of atypical antipsychotics for a variety of indications, with variable perceived confidence and a relatively heavy reliance on "own or peer experience" as opposed to good quality evidence. Challenges exist for both prescribers and policymakers, and further "head-to-head" studies are needed in this age group to ensure that a balance is maintained between therapeutic benefit and safety., Competing Interests: F.D.Z. was the recipient of an unrestricted award donated by the American Psychiatric Association, the American Psychiatric Institute for Research and Education (APIRE), and AstraZeneca (Young Minds in Psychiatry Award). He has also received research support from the German Federal Ministry for Economics and Technology, the European Commission, the Princess Margaret Hospital Foundation, the Telethon Perth Children’s Hospital Research Fund (TPCHRF), the Telethon Kids Institute in Perth, the German Society for Social Pediatrics and Adolescent Medicine, the Paul and Ursula Klein Foundation, the Dr August Scheidel Foundation, the Interdisciplinary Center for Clinical Research (IZKF) fund of the University Hospital of RWTH Aachen University, and a travel stipend donated by the Glaxo SmithKline Foundation. He is the recipient of an unrestricted educational grant, travel support, and speaker honoraria from Shire Pharmaceuticals, Germany. In addition, he has received support from the Raine Foundation for Medical Research (Raine Visiting Professorship) and editorial fees from Co-Action Publishing (Sweden). The remaining authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Despite the importance of a satisfying sexual life, most patients with schizophrenia spectrum disorders do not discuss sexual issue with their clinicians. The current study seeks to determine the prevalence and socio-clinical correlates of sexual dysfunction among patients with schizophrenia spectrum disorders receiving typical and atypical antipsychotic medications. The second objective is to determine the frequency and correlates of specific sexual dysfunction (desire, arousal, erection/lubrication and orgasm) by gender and drug type using the Arizona Sexual Experience Scale., Methodology: This cross-sectional study used standardized structured interviewer based survey to assess sexual dysfunction among patients with schizophrenia that are both sexually active and inactive at a tertiary hospital in Maiduguri from December 2020 to April 2021. Participants were also assayed for prolactin using ELISA Kit for a possible association with sexual dysfunction., Results: The overall prevalence of sexual dysfunction among patients with schizophrenia spectrum disorder receiving antipsychotics was 34% with patients on typical and atypical antipsychotics reporting rates of 36.8% and 24.6%, respectively. Among the typical and atypical antipsychotics, patients receiving haloperidol (40.3%) and risperidone (37.5%) reported a relatively higher frequency of sexual dysfunction compared to those receiving clozapine (18.2%). Independent correlates of sexual dysfunction were: female gender (OR = 1.89, 95% CI = 1.17-3.06; P = .010), being unmarried (OR = 1.51, 95% CI = 1.17-1.96; P = .001), pseudoparkinsonism (OR = 1.66, 95% CI = 1.02-2.69; P = .008), prolactin (OR = 2.15, 95% CI = 1.34-3.43; P = .001) and severity of illness (OR = 1.34, 95% CI = 1.03-1.75; P = .030)., Conclusion: Sexual dysfunction is prevalent among patients with schizophrenia spectrum disorder receiving either typical or atypical antipsychotics., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Risperidone is an atypical antipsychotic drug used to treat irritability and aggression in children and adolescents with autism spectrum disorder. In an earlier study, the sum trough concentration of risperidone and its metabolite (9-hydroxyrisperidone) was positively correlated with weight gain and effectiveness. The aim of this study was to determine the therapeutic window for risperidone sum trough concentrations that balances weight gain with treatment effectiveness in this population. In addition, the effect of therapeutic drug monitoring (TDM) on treatment optimization was simulated., Methods: In a retrospective cohort (n = 24 children), the target window for risperidone leading to the least increase in body mass index z-scores while retaining effectiveness as measured by the irritability subscale of the Aberrant Behavior Checklist was determined using receiver operating curve analysis. This target range was used to simulate the effect of TDM using a population PK model implemented in the software platform InsightRX. Dosing advice was based on plasma trough concentrations and the dose administered at 12 weeks to simulate whether more children would be on target at 24 weeks after the start of treatment., Results: A risperidone sum trough target range of 3.5-7.0 mcg/L would minimize increase in body mass index z-score and optimize effectiveness. Dosing advice using TDM and a population PK model would lead to a larger proportion of children achieving the target concentration range (62.5% versus 16.7%)., Conclusions: TDM may be a useful tool for optimizing risperidone treatment in children and adolescents with autism spectrum disorder., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.)

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., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The evidence of treatment options' efficacy on acute bipolar manic episodes is relatively less in youths than adults. We aimed to compare and rank the drug's efficacy, acceptability, tolerability, and safety for acute mania in children and adolescents., Method: We systematically reviewed the double-blinded, randomized controlled trials (RCTs) comparing drugs or placebo for acute manic episodes of bipolar disorder in children and adolescents using PRISMA guidelines. We searched PubMed/MEDLINE, EMBASE, Web of Science, EBSCO, Scopus, the Cochrane Central Register of Controlled Trials, and https://clinicaltrials.gov from inception until November 20, 2022. Response to treatment was the primary outcome, and random-effects network meta-analyses were conducted (PROSPERO 2022: CRD42022367455)., Results: Of 10,134 citations, we included 15 RCTs, including 2372 patients (47 % female), 15 psychotropic drugs, and the placebo. Risperidone 0.5-2.5 mg/day, aripiprazole 30 mg/day olanzapine, quetiapine 400 mg/day, quetiapine 600 mg/day, asenapine 5 mg/day, asenapine 10 mg, ziprasidone, and aripiprazole 10 mg were found to be effective (in comparison with placebo) in children and adolescents, respectively (τ 2  = 0.0072, I 2  = 10.2 %). The tolerability of aripiprazole 30 mg/day was lower than risperidone 0.5-2.5 mg/day and olanzapine. Oxcarbazepine had the highest discontinuation due to the adverse effects risk ratio., Limitations: Efficacy ranking of the treatments could be performed by evaluating relatively few RCT results, and only monotherapies were considered., Conclusions: Efficacy, acceptability, tolerability, and safety are changing with the doses of antipsychotics for children and adolescents with acute bipolar manic episodes. Drug selection and optimum dosage should be carefully adjusted in children and adolescents., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The rate of medication persistence was examined in patients with schizophrenia or schizoaffective disorder during switching from previously administered antipsychotics to brexpiprazole, a new dopamine D 2 receptor partial agonist. A multicenter, single-arm, open-label 24-week interventional study was conducted, consisting of two 12-week consecutive periods: an initial switch (by plateau cross-titration) with the subsequent period, followed by a second maintenance period. Prior antipsychotics were olanzapine or risperidone/paliperidone. The primary and secondary outcome measures were medication persistence rates after the first 12 weeks and changes from baseline in the Specific Levels of Functioning Scale (SLOF), Subjective Well-being under Neuroleptic drug treatment Short form (SWNS), and Positive and Negative Syndrome Scale (PANSS) scores, respectively. In total, 79 patients were administered brexpiprazole and the medication persistence rate at 12 weeks was 78.5%, which was significantly higher than the predefined threshold of 65%. Regarding the prior medication, the persistence rate at 12 weeks was 84.6% for olanzapine and 72.5% for risperidone/paliperidone. Significant improvements from baseline were observed in the SLOF, SWNS, and PANSS scores. There were no adverse events of concern. Thus, brexpiprazole appeared to be a suitable antipsychotic on switching from olanzapine, risperidone, or paliperidone., (© 2024 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Second-generation antipsychotics (SGAs) are widely used in treating schizophrenia and related disorders, also other mental disorders. However, the efficacy and safety of SGAs for treating other mental disorders is unclear. A systematic literature search for randomized, placebo-controlled trials of 11 SGAs for treating 18 mental disorders apart from schizophrenia were carried out from database inception to April 3, 2022. The primary outcome was the mean change in the total score for different mental disorders. The secondary outcome was the odds ratio (OR) of response, remission rates and risk ratio (RR) of adverse events (AEs). A total of 181 studies (N = 65,480) were included. All SGAs showed significant effects in treating other mental disorders compared with placebo, except autistic disorder and dementia. Aripiprazole is the most effective treatment for bipolar mania [effect size = -0.90, 95% CI: -1.59, -0.21] and Tourette's disorder [effect size = -0.80, 95% CI: -1.14, -0.45], olanzapine for bipolar depression [effect size = -0.86, 95% CI: -1.32, -0.39] and post-traumatic stress disorder [effect size = -0.98, 95% CI: -1.55, -0.41], lurasidone for depression [effect size = -0.66, 95% CI: -0.82, -0.50], quetiapine for anxiety [effect size = -1.20, 95% CI: -1.96, -0.43], sleep disorders [effect size = -1.2, 95% CI: -1.97, -0.58], and delirium [effect size = -0.36, 95% CI: -0.70, -0.03], and risperidone for obsessive-compulsive disorder [effect size = -2.37, 95% CI: -3.25, -1.49], respectively. For safety, AE items for each SGAs was different. Interestingly, we found that some AEs of OLZ, QTP, RIS and PALI have significant palliative effects on some symptoms. Significant differences in the efficacy and safety of different SGAs for treatment of other mental disorders should be considered for choosing the drug and for the balance between efficacy and tolerability for the specific patient., Competing Interests: Declaration of Competing Interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Non-adherence to medication significantly affects bipolar disorder outcomes. Long-Acting Injectable antipsychotics show promise by ensuring adherence and averting relapses., Areas Covered: This narrative review sought to evaluate the efficacy of second-generation injectable antipsychotics in bipolar disorder through searches in Embase, MEDLINE, and PsycInfo for randomized controlled trials and mirror-image studies.Risperidone and aripiprazole Long-Acting Injectables demonstrated effectiveness in preventing mood recurrences compared to placebos in adults with bipolar disorder. They showed superiority in preventing mania/hypomania relapses over placebos but did not appear to significantly outperform active oral controls. Notably, active controls seem to be more effective in preventing depression relapses than Long-Acting Injectables. Mirror-Image studies point toward the reduction of hospitalization rates following LAI initiation., Expert Opinion: The available evidence points thus toward the efficacy of LAIs, especially in managing manic episodes and reducing hospitalizations, The current evidence does not however immediately support prioritizing LAIs over oral medications in bipolar disorder treatment. More high-quality studies, especially comparing LAIs directly with active controls, are crucial to gain a comprehensive understanding of their efficacy. These findings highlight the need for further research to guide clinicians in optimizing treatment strategies for bipolar disorder.

Delusional infestation (DI) is the fixed false belief of pathogenic infestation of the skin or body despite no supporting medical evidence. It is a relatively rare condition with a reported prevalence of 1.48 per million people. Successful treatment can be challenging as patients are often reluctant to accept referral or involvement of psychiatric services. We report a retrospective cohort study of 49 consecutive patients with a diagnosis of DI, assessed in a regional psychodermatology service over a 6-year period. Low-dose antipsychotics (risperidone or olanzapine) were prescribed in 44 patients. We use our data to explore possible reasons why DI can be challenging to treat. Response to treatment and engagement with services is multifactorial. Our study emphasizes the importance of early assessment and supports the expansion of psychodermatology services in the UK., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Functional retentive overflow incontinence (retentive FI) is the most common cause of fecal soiling in children. Based on the clinical experiences, the treatment of retentive FI in patients with comorbid psychiatric disorders was accelerated when Risperidone was used as treatment for their psychiatric comorbidities; therefore, this study was conducted to evaluate the effect of risperidone in the treatment of retentive FI in children and adolescents., Methods: In this double-blind, randomized, placebo-controlled trial, 140 patients aged 4-16 years eligible for the study were randomized into two groups, receiving either 0.25-0.5 mg of Risperidone syrup (n = 70) or maltodextrin syrup (placebo group, n = 70) every 12 h daily for 12 weeks. Sociodemographic data, including age, sex, weight, height, BMI, BMI z-score, and socioeconomic status, was recorded, and the number of nocturnal FI, diurnal FI, and painful defecations was measured., Results: 136 participants (69 on Risperidone and 67 on placebo) were included in the study. Mean age of participants in the intervention and placebo groups were 7.2 ± 2.4 years and 8.0 ± 3.1 years, respectively. The mean number of nocturnal FI (P trend =0.39) and diurnal FI (P trend =0.48) in patients without psychiatric comorbidities, and the number of painful defecations for participants with and without psychiatric comorbidities (P = 0.49, P = 0.47, respectively) were not significantly different between the groups, but a significant effect was observed in diurnal FI after Risperidone treatment in patients with psychiatric comorbidities (P < 0.001)., Conclusion: Risperidone, when used along with other non-pharmacological interventions, may be helpful in treating FI in pediatric patients with psychiatric comorbidities., (© 2023. The Author(s).)

Peroxisome proliferator-activated receptor alpha (PPARα) and antipsychotic medications both influence polyunsaturated fatty acids (PUFA) homeostasis, and thus PPARα polymorphism may be linked to antipsychotic treatment response. Here we investigated whether the functional leucine 162 valine (L162V) polymorphism in PPARα influenced antipsychotic treatment in a group of psychosis patients (N = 186), as well as in a patient subgroup with risperidone, paliperidone, or combination treatment (N = 65). Antipsychotic-naïve first-episode patients and nonadherent chronic individuals were genotyped by polymerase chain reaction analysis. At baseline, and after 8 weeks of treatment with various antipsychotic medications, we assessed the patients' Positive and Negative Syndrome Scale (PANSS) scores; PANSS factors; and metabolic syndrome-related parameters, including fasting plasma lipid and glucose levels, and body mass index. In the total patient group, PPARα polymorphism did not affect PANSS psychopathology or metabolic parameters. However, in the subgroup of patients with risperidone, paliperidone, or combination treatment, PPARα polymorphism influenced changes in plasma LDL cholesterol. Specifically, compared to PPARα-L162L homozygous patients, PPARα-L162V heterozygous individuals exhibited significantly higher increases of LDL cholesterol levels after antipsychotic treatment. The PPARα polymorphism had a strong effect size, but a relatively weak contribution to LDL cholesterol level variations (∼12.8 %)., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Patients with schizophrenia constitute a particularly vulnerable group for oral diseases. Among the different factors involved, we aimed to examine the evidence of how drugs could contribute to the poorer oral health of this population., Material and Methods: An overview of the potential impact of medication on dental/oral health among people with schizophrenia was proposed focusing on selected literature., Results: Studies show a higher dental caries and degree of periodontal diseases in this population and point to drug-induced xerostomia as an important risk factor for oral health deterioration. The risk of dry mouth depends on not only antipsychotics, but also drugs with anticholinergic activity. We hypothesize that antipsychotic induced glycaemic alterations might contribute to reduced oral health, and that the antimicrobial activity of certain antipsychotics could have an impact on oral microbiota affecting oral condition. Pharmacovigilance data show that involuntary movements are caused by typical and some atypical antipsychotics. Dry mouth is most frequently reported for quetiapine and olanzapine, while clozapine is more frequently associated with sialorrhea., Conclusions: Literature clearly shows higher caries and periodontal disease in schizophrenic patients. However, overall, there is scarce literature about the potential influence of drugs in these disorders. Health professionals should be aware of this issue in order to implement adequate preventive measures in this vulnerable population.

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., (© 2023 John Wiley & Sons Ltd.)

Background: It has been hypothesized that smoking is associated with the severity of negative symptoms. Until now, no studies have investigated whether the impact of smoking on negative symptoms is dependent on antioxidants. This study was designed to evaluate the effect of smoking on therapeutic response and total antioxidants capacity (TAOC) in antipsychotic-naïve first-episode (ANFE) patients., Methods: The severity of the patient's symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). A total of 237 ANFE patients were recruited and treated with risperidone (oral tablets, 4-6 mg/day twice a day) for 12 weeks. PANSS was assessed at baseline and a 12-week follow-up. Plasma TAOC levels were also assayed at baseline and week 12., Results: Relative to nonsmokers with ANFE SZ, smokers had higher PANSS negative subscores. There was no significant difference in TAOC changes after 12 weeks of treatment with risperidone between smokers and non-smokers. However, we found greater improvement in negative symptoms in smokers compared to non-smokers. Further analysis in smokers with SZ demonstrated that improvements in negative symptoms were not associated with changes in TAOC., Conclusion: Our study suggested that smoking affected the severity of baseline negative symptoms and further contributed to their reduction after risperidone treatment. However, improvement in negative symptoms was not dependent on the changes in TAOC., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Up to 30% of patients with a diagnosis of treatment-resistant psychosis remain symptomatic despite an optimal trial with the gold standard treatment, clozapine. Emerging evidence suggests the clinical utility of long-acting injections (LAI) in such clinical scenarios. In this study, we aimed to describe clozapine augmentation with LAIs in an inner London hospital and explore the literature on the clinical effectiveness of this treatment modality., Methods: Patients prescribed clozapine, who were commenced on a LAI between 2007 and 2023 by the United Kingdom's largest mental health trust, were identified from electronic patient records. First, routine clinical data were used to describe the use, effectiveness, and safety of this augmentation strategy. Second, we conducted a literature search up to 1st June 2023 to identify published studies describing clinical outcomes after clozapine augmentation with a LAI. Clinical outcomes were collated and presented in a table, including hospitalisation rates and quantitative clinical assessments using validated scales., Results: Of the 1248 patients prescribed clozapine in SLaM, three patients (0.2%) received augmentation with the following LAIs: olanzapine embonate, paliperidone palmitate and pipotiazine palmitate. This treatment strategy was clinically effective and generally well tolerated in all three cases. Twelve published studies between 2010 and 2022 were included in the review. Eight distinct LAIs were reported (4 first and 4 second generation antipsychotics), with risperidone and paliperidone most widely studied. All the identified studies were observational including mirror-image studies, case series and case reports. Duration of follow up varied from 3 months to 3 years. There was evidence that the use of LAIs with clozapine can significantly reduce clinical symptoms, hospitalisation rates and bed days. No serious adverse effects were reported., Conclusion: This preliminary evidence suggests clinical utility of LAIs in alleviating residual symptoms and subsequently reducing hospitalisation rates in patients optimised on clozapine treatment. The current study warrants further investigations including a randomised controlled study to establish the clinical efficacy, tolerability, and place in therapy of this treatment modality., (© 2023 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Repetitive transcranial magnetic stimulation (rTMS) has been widely used in treating schizophrenia (SCH). However, the effects of the low frequency of rTMS combined with antipsychotics on the gut microbiome in chronic SCH have been poorly investigated. In the present study, psychiatric symptoms were assessed and the stool samples obtained from 33 adult patients with chronic SCH (at baselinephase), 27 after 2 weeks of treatment (rTMS combined with risperidone, SCH-2W), and 37 healthy controls (HC) were analyzed by 16S rRNA gene sequencing. We found that the reduction of phylum Proteobacteria, family Enterobacteriaceae and genera Escherichia-Shigella as well as the increase of genera norank&#95;f&#95;Lachnospiraceae might be related to the antipsychotic effect of rTMS combined with risperidone. These findings indicate that the brain-gut-microbiota axis might be involved in the therapeutic effect of rTMS combined with antipsychotic drugs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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 (CGIS) and Improvement (CGII) 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., Competing Interests: Declaration of competing interest ZBD, PS, and AB are employees of Gedeon Richter Plc. In the last three years SL has received honoraria as a consultant and/or advisor and/or for lectures and/or for educational material from Alkermes, Angelini, Eisai, Gedeon Richter, Janssen, Lundbeck, Medichem, Medscape, Merck Sharpp and Dome, Mitshubishi, Neurotorium, NovoNordisk, Otsuka, Recordati, Roche, Rovi, Sanofi Aventis, TEVA. In the past three years, SZL has declared no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

1,2-Diacetylbenze (C 10 H 10 O 2 , DAB) is a potential inducer or activator of toxic mechanisms. DAB exerts high absorption by the gastrointestinal tract and high blood-brain barrier penetration. However, only the effects of DAB on the central nervous system were reported, with a dearth of evidence of DAB's effects on the liver, which is more susceptible to toxic substances. Risperidone, an atypical antipsychotic drug, has been shown to protect against DAB-induced cognitive impairment in an animal model. Risperidone was found to have little or no effect on the liver after short-term administration. The question of whether risperidone can protect against DAB-induced liver dysfunction, particularly after short-term administration, is unknown. Thus, this study aimed to assess the hepatoprotective effects of risperidone on DAB-induced liver dysfunction in male C57BL/6 mice treated with DAB 5 mg/kg for 1 week and risperidone 0.125-0.25 mg/kg for 2 weeks. After exposure to DAB 5 mg/kg for 1 week, we found that DAB induced liver damage by increasing liver function biomarkers (GGT, ALT, and AST), reactive oxygen species, nitric oxide, and proinflammatory cytokines (IL-1α, IL-1β, IL-6, IL-12, and TNF- α), activating apoptosis (elevated Caspase-3 and Bax levels and reduced Bcl2 level), TLR4/JNK/NF-κB, Jak2/Stat5 pathways, and suppressing Jak2/Stat3 and IRS1/PI3K/AKT/MDM2 pathways. After a 2-week course of treatment, risperidone was able to lessen these effects; the higher dose (0.25 mg/kg) appeared to be more effective than the lower dose (0.125 mg/kg). To strengthen findings from in vivo analysis, in silico analysis also found three targets (Stat3, Caspase-3, AKT, IL-1β), two miRNAs (miR-26b-5p and miR-34a-5p), two transcription factors (NFKB1 and NFKB2), and numerous pathways ("AGE-RAGE signaling pathway in diabetic complications", "hepatitis B", "alcoholic liver disease", "apoptosis", and "liver cirrhosis") as the key molecular processes involved in the pathogenesis of DAB-induced liver damage and targeted by risperidone. The physicochemical characteristics and pharmacokinetics of DAB and risperidone also support the toxic effects of DAB and the beneficial properties of risperidone in the liver. In conclusion, these findings reflect the therapeutic effects of risperidone on DAB-induced liver dysfunction after 1 week and 2 weeks exposure to DAB and risperidone, respectively., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

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., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Little is known about antipsychotic prescription patterns among children and adolescents in Japan, particularly in outpatient settings. We investigated the prevalence and trends of antipsychotic prescription for outpatients aged ≤ 17 years receiving a first antipsychotic prescription from 2006 to 2012 based on a large-scale dispensation dataset. Measurements included age, sex, department of diagnosis and treatment, type of prescription (monotherapy or polytherapy), antipsychotic dosage, and concomitant psychotropic drugs. Of the 10,511 patients, 65.1% were aged 13-17 years, and 52.9% were males. Second-generation antipsychotic monotherapy prescriptions increased from 53.8% in 2006 to 78.3% in 2012. Risperidone was the most frequently prescribed antipsychotic, followed by aripiprazole and olanzapine. Approximately 25.0% of patients were prescribed an initial dose less than recommended. Second-generation antipsychotic monotherapy is currently the most frequent prescription pattern among outpatients aged ≤ 17 years receiving an initial antipsychotic prescription., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

Background and Objectives : To analyze the influence of parental presence and use of risperidone on social interaction and apathy among patients with Autism Spectrum Disorder (ASD). Materials and Methods : Cross-sectional study in a reference center for patients with ASD in a city in northeastern Brazil. The research was carried out using a sociodemographic questionnaire, the Dimensional Apathy Scale, and the Social Communication Questionnaire (SCQ) with the domains of social interaction, language, stereotypy, and communication. The referred questionnaire was answered by the parents or guardians of the children with ASD according to the DSM V criteria. Data were analyzed via independent t -test using the SPSS software version 20. Results : Interviews were conducted with 51 parents/guardians of autistic children with a mean age of 8.8 years (±2.95) and a predominance of males, 34 (66.7%). Of this total, 49 (96.1%) of the children attended school; 40 (78.4%) children were on medication, of which 38 (74.5%) were on risperidone. Those children on risperidone had a higher score on the SCQ scale ( p = 0.049) and on the domain of stereotyped behaviors ( p = 0.033), which indicated greater impairment. Another statistically relevant variable was the presence of married parents, whereby children who did not have the presence of married parents had a higher average of stereotyped behaviors compared to those who had married parents. Conclusions : The results showed differences in the means of social interactions for children on risperidone, especially regarding stereotyped behaviors. However, it is not possible to state whether this difference was due to the use of risperidone or whether they used risperidone precisely because of these behaviors. Also important was that children who had the presence of married parents showed fewer stereotyped behaviors. There was no difference in apathetic behavior between children.

Introduction: Long-acting injectable antipsychotics (LAIs) are an effective, but potentially underutilized treatment option in schizophrenia and other severe mental illnesses. Prescribing information typically focuses on how to initiate treatment from the corresponding oral formulations. However, in clinical practice other scenarios, such as switching from other oral antipsychotics or other LAIs, occur frequently, requiring guidance., Areas Covered: Pharmacodynamic properties of antipsychotics and their relation to rebound symptoms. Pharmacokinetic properties of LAIs and their implications for switching approaches. Specific approaches to switching to LAIs., Expert Opinion: The LAI landscape has evolved significantly in the last decade with more formulations available, longer dosing intervals, and extended indications. However, currently available LAIs have various shortcomings, e.g. short dosing intervals, need for oral supplementation, loading regimens, deep intramuscular injection and/or restricted indications. Recent improvements include a one-day initiation option for aripiprazole lauroxil, aripiprazole monohydrate once-monthly, risperidone in situ microparticles and subcutaneous risperidone. Future LAI developments should focus on longer dosing intervals, subcutaneous administration, expansion of LAIs beyond currently available antipsychotic agents and indications beyond schizophrenia and bipolar disorder. In the future, LAIs might become a first-line treatment after initial oral stabilization for chronic mental disorders with need for maintenance treatment and presence of significant non-adherence.

This mirror-image study aimed to evaluate the real-life effectiveness of long-acting injectable antipsychotics (LAI) in schizophrenia. Patients with schizophrenia initiating LAIs January 2015-December 2016 were enrolled from the French National Health Data System (SNDS). Standardized mean differences (SMD > 0.1 deemed clinically significant) were calculated for psychiatric healthcare resource utilization measures assessed one year before (during oral AP treatment) and one year after LAI initiation. LAI effectiveness was analyzed overall and by age group, gender and compliance to oral AP, defined as exposure to an AP for at least 80% of the year before LAI initiation. 12,373 patients were included. LAIs were more frequently initiated in men (58.1%), young (18-34 years, 42.0%) and non-compliant (63.7%) patients. LAI initiation was effective in reducing the number and duration of psychiatric hospitalizations and psychiatric emergency department (ED) admissions in non-compliant patients (SMD = -0.19, -0.26 and -0.12, respectively), but not in compliant patients. First-generation LAIs, paliperidone and aripiprazole LAIs reduced psychiatric hospitalizations (SMD = -0.20, -0.24, -0.21, respectively) and ED admissions (SMD = -0.15, -0.13, -0.15, respectively). No differences in effectiveness were found for age or gender. In compliant patients, only aripiprazole LAI reduced the number of psychiatric hospitalizations (SMD = -0.13). Risperidone and paliperidone LAIs increased hospitalization duration (SMD = 0.15 and 0.18, respectively). The prescription of LAIs (except risperidone) should be recommended in all non-compliant patients, even in women and patients aged 35 or older. The lower frequency of administration of LAIs than of oral APs may improve compliance and hence reduce the risk of relapse. Aripiprazole LAI may represent a treatment of choice for compliant patients that should be further investigated., (© 2023. The Author(s).)

Background: It remains a challenge to predict the long-term response to antipsychotics in patients with schizophrenia who do not respond at an early stage. This study aimed to investigate the optimal predictive cut-off value for early non-response that would better predict later non-response to antipsychotics in patients with schizophrenia., Methods: This multicenter, 8-week, open-label, randomized trial was conducted at 19 psychiatric centers throughout China. All enrolled participants were assigned to olanzapine, risperidone, amisulpride, or aripiprazole monotherapy for 8 weeks. The positive and negative syndrome scale (PANSS) was evaluated at baseline, week 2, week 4, and week 8. The main outcome was the prediction of nonresponse. Nonresponse is defined as a < 20% reduction in the total scores of PANSS from baseline to endpoint. Severity ratings of mild, moderate, and severe illness corresponded to baseline PANSS total scores of 58, 75, and 95, respectively., Results: At week 2, a reduction of < 5% in the PANSS total score showed the highest total accuracy in the severe and mild schizophrenia patients (total accuracy, 75.0% and 80.8%, respectively), and patients who were treated with the risperidone and amisulpride groups (total accuracy, 82.4%, and 78.2%, respectively). A 10% decrease exhibited the best overall accuracy in the moderate schizophrenia patients (total accuracy, 84.0%), olanzapine (total accuracy, 79.2%), and aripiprazole group (total accuracy, 77.4%). At week 4, the best predictive cut-off value was < 20%, regardless of the antipsychotic or severity of illness (total accuracy ranging from 89.8 to 92.1%)., Conclusions: Symptom reduction at week 2 has acceptable discrimination in predicting later non-response to antipsychotics in schizophrenia, and a more accurate predictive cut-off value should be determined according to the medication regimen and baseline illness severity. The response to treatment during the next 2 weeks after week 2 could be further assessed to determine whether there is a need to change antipsychotic medication during the first four weeks., Trial Registration: This study was registered on Clinicaltrials.gov (NCT03451734)., (© 2023. The Author(s).)

Objective: Despite advances in pharmacology, the treatment of schizophrenia (SZ) remains a challenge due to relapse after antipsychotic discontinuation and multiple adverse effects of antipsychotics. We hypothesized that a low dose of risperidone in combination with sertraline would reduce serious adverse effects without decreasing treatment response. This study aimed to examine the efficacy, safety, and tolerability of low-dose risperidone combined with sertraline to reduce risperidone dose and serious adverse effects in first-episode and medication-naive (FEMN) SZ patients., Methods: A total of 230 patients with FEMN SZ were randomly assigned to receive low-dose risperidone in combination with sertraline (RS group) or regular-dose risperidone (control group). The Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HAMD), and Personal and Social Performance Scale (PSP) were assessed at baseline and the end of the first, second, third, and sixth months. In addition, serum prolactin levels and extrapyramidal symptoms were measured at baseline and follow-up., Results: Repeated measures ANCOVA showed significant interaction effects of treatment by time on psychotic symptoms, as well as HAMD, PSP scores, prolactin levels, and extrapyramidal symptoms (all p < 0.05). Compared with the control group, the RS group had greater decreases in PANSS total score and its subscores and HAMD score (all p < 0.01) and a greater increase in PSP total score (p < 0.01). Notably, side effects were lower in the RS group relative to the control group. Improvements in HAMD and PANSS total scores, changes in prolactin levels and gender predicted improvements in PSP from baseline to month 6., Conclusions: Our study suggests that low-dose risperidone in combination with sertraline was more effective for psychotic symptoms and psychosocial functioning, with significantly fewer adverse effects in patients with FEMN SZ., Trial Registration Number: ClinicalTrials.gov, NCT04076371., (© 2023. The Author(s).)