Brief Psychiatric Rating Scale Total Score Research Articles

Safety and effectiveness of lurasidone in the treatment of Chinese schizophrenia patients: An interim analysis of post-marketing surveillance

BACKGROUND Schizophrenia is a psychiatric disorder characterized by chronic or recurrent symptoms. Lurasidone was licensed in China in 2019 for the treatment of adult schizophrenia in adults with a maximum dose of 80 mg/d. However, post-market surveillance (PMS) with an adequate sample size is required for further validation of the drug’s safety profile and effectiveness. AIM To conduct PMS in real-world clinical settings and evaluate the safety and effectiveness of lurasidone in the Chinese population. METHODS A prospective, multicenter, open-label, 12-wk surveillance was conducted in mainland China. All patients with schizophrenia from 10 sites who had begun medication with lurasidone between September 2019 and August 2022 were eligible for enrollment. Safety assessments included adverse events (AEs), adverse drug reactions (ADRs), extrapyramidal symptoms (EPS), akathisia, use of EPS drugs, weight gain, and laboratory values as metabolic parameters and the QTc interval. The effectiveness was assessed using the brief psychiatric rating scale (BPRS) from baseline to the end of treatment. RESULTS A total of 965 patients were enrolled in the full analysis set and 894 in the safety set in this interim analysis. The average daily dose was 61.7 ± 19.08 mg (mean ± SD) during the treatment. AEs and ADRs were experienced by 101 patients (11.3%) and 78 patients (8.7%), respectively, which were mostly mild. EPS occurred in 25 individuals with a 2.8% incidence, including akathisia in 20 individuals (2.2%). Moreover, 59 patients received drugs for treating EPS during the treatment, with an incidence of 6.6% which dropped to 5.4% at the end of the treatment. The average weight change was 0.20 ± 2.36 kg (P = 0.01687) with 0.8% of patients showing a weight gain of ≥ 7% at week 12 compared with that at the baseline. The mean values of metabolic parameters and the QTc interval at baseline and week 12 were within normal ranges. The mean changes in total BPRS scores were -8.9 ± 9.76 (n = 959), -13.5 ± 12.29 (n = 959), and -16.8 ± 13.97 (n = 959) after 2/4, 6/8, and 12 wk, respectively (P < 0.001 for each visit compared with the baseline) using the last-observation-carried-forward method. CONCLUSION The interim analysis of the PMS of adult patients with schizophrenia demonstrate the safety and effectiveness of lurasidone in the Chinese population. No new safety or efficacy concerns were identified.

Safety and effectiveness of oral medium to high dose blonanserin in patients with schizophrenia: subgroup analysis from a prospective, multicenter, post-marketing surveillance study in mainland China

BackgroundBlonanserin (BNS) had been undergoing post-market surveillance (PMS) since September 2018. Using the surveillance data, we did this analysis to assess the safety and effectiveness of different doses of BNS to explore a sufficient dose range of BNS in Chinese patients with schizophrenia (SZ).MethodsA 12-week, prospective, observational, single-arm, multicenter, open-label PMS was conducted. In this analysis, we divided the patients from PMS into low, medium to high, and high dose groups based on the dose of BNS they received, with medium to high dose group being the focus. The Brief Psychiatric Rating Scale (BPRS) scores at week 2 or 4, 6 or 8, and 12 were calculated to evaluate the effectiveness of BNS in improving psychiatric symptoms. The safety of BNS was reported as the incidence of adverse drug reactions.Results364 patients were included in the medium to high dose group, of which 321 completed the surveillance, with a dropout rate of 11.8%. The mean daily dose was 15.1 ± 1.92 mg. The BPRS total score was 50.1 ± 11.95 at baseline and decreased to 26.6 ± 7.43 at 12 weeks (P < 0.001). When compared with other groups, the median to high dose group achieved significantly more reduction in BPRS score at week 12 (P = 0.004 versus low dose and P = 0.033 versus higher dose). Extrapyramidal symptoms [EPS (46.4%)] were the most common adverse reactions in the medium to high group. The average weight gain during the surveillance was 0.5 ± 2.56 kg and prolactin elevation occurred in 2.2% patients. Most adverse reactions were mild.ConclusionsBNS at medium to high doses (mean 15.1 mg/d) significantly improved symptoms of SZ and was well-tolerated. Most ADRs were mild, and the likelihood of causing metabolic side effects and prolactin elevations was low. Medium to high dose of BNS is a more potent treatment choice for SZ.Trial registration number: ChiCTR2100048734. Date of registration: 2021/07/15 (retrospectively registered).

Mild Behavioral Impairment in Psychogeriatric Patients: Clinical Features and Psychopathology Severity.

The Mild Behavioral Impairment (MBI) concept was developed to determine whether late-onset persistent neuropsychiatric symptoms (NPSs) may be early manifestations of cognitive decline. Our study aims to investigate the prevalence and differentiating features of MBI with respect to major neurocognitive disorders (MNDs) and primary psychiatric disorders (PPDs). A total of 144 elderly patients who were referred to our psychogeriatric outpatient service were recruited. The severity of mental illness was evaluated by means of the Clinical Global Impression Severity scale, the severity of psychopathology was evaluated by means of the Brief Psychiatric Rating Scale (BPRS), and overall functioning was evaluated by means of the Global Assessment of Functioning scale. The sample included 73 (50.6%) patients with PPDs, 40 (27.8%) patients with MBI, and 31 (21.5%) patients with MNDs. Patients with MNDs reported the greatest severity of mental illness, the highest BPRS Total, Psychosis, Activation, and Negative Symptom scores, and the lowest functioning. Patients with MBI and PPDs had comparable levels of severity of mental illness and overall functioning, but MBI patients reported higher BPRS Total and Negative Symptom scores than PPD patients. Patients with MBI frequently reported specific clinical features, including a higher severity of apathy and motor retardation. These features merit further investigation since they may help the differential diagnosis between MBI and PPDs.

Potential role between inflammatory cytokines and Tie-2 receptor levels and clinical symptoms in patients with first-episode schizophrenia

BackgroundSchizophrenia (SCZ) is associated with chronic low-grade inflammation, which may be involved in the underlying pathological mechanism of the disease and may influence patient prognosis. We evaluated the differences in serum cytokine and Tie-2 receptor levels between patients with first-episode SCZ and healthy controls and explored the correlation thereof with clinical symptoms.MethodsSeventy-six participants were recruited for the present study, including 40 patients with first-episode SCZ and 36 healthy controls. Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) scores, demographic data, and blood samples were collected at baseline. A hypersensitive Meso Scale Discovery (MSD) electrochemiluminescence assay system was used to measure cytokine and Tie-2 receptor levels. Spearman’s correlation and stepwise linear regression were used to analyze the data.ResultsSerum interleukin-1β and -4 levels were significantly increased, and Tie-2 levels were significantly decreased, in first-episode SCZ patients as compared to healthy controls. IL-1β levels were positively correlated with total BPRS scores, resistance subscores, and PANSS positive subscores. Furthermore, IL-1β levels were negatively correlated with Tie-2 receptor expression levels. Stepwise linear regression analysis demonstrated that IL-1β levels correlated positively with PANSS positive subscores and BPRS total scores. PANSS negative subscores, general psychopathology subscores, and PANSS total scores had positive effects on the Tie-2 receptor. Receiver operating characteristic (ROC) curve analysis showed that IL-1β and Tie-2 were highly sensitive and specific for predicting first-episode SCZ symptoms and achieving an area under the ROC curve of 0.8361 and 0.6462, respectively.ConclusionOur results showed that patients with first-episode SCZ have low-grade inflammation. IL-1β and Tie-2 receptors may be important mediators between inflammation and vascular dysfunction in patients with SCZ and may underlie the increased cardiovascular disease in this population.Trial registrationThe clinical trial registration date was 06/11/2018, registration number was chiCTR1800019343.

Evaluation of the Relationships between Irisin Levels and Cognitive Functions in Individuals with Schizophrenia.

: Irisin is a myokine that is involved in neurogenesis, neuronal proliferation, and neuronal differentiation. Many research examine the relationship between irisin and schizophrenia. In this study, we aimed to evaluate the relationship between irisin levels and cognitive functions in individuals with schizophrenia. : Ninety-six individuals who were diagnosed with schizophrenia were included. The Brief Psychiatric Rating Scale (BPRS) was used to assess disease severity. To evaluate the cognitive functions of the patients, the trail-making test was evaluated with the A and B forms and the verbal memory processes scale. After a 12-hour night fast, samples of fasting blood were obtained from the participants. : There was no significant correlation between irisin, duration of disease, and BPRS total score. In the analysis performed, a positive correlation was found between the plasma irisin level and the error score of the trail-making test form B. Other than that, no correlation was found between irisin level and cognitive performance in schizophrenia patients. In addition, in subgroup analysis between genders, it was determined that the duration of the trail-making test B was longer in female schizophrenia patients. : In this study, there was a positive correlation between the trail-making test B-form error scores and the irisin levels. This relationship between impaired executive functions and irisin levels may suggest that the irisin level is increased as compensation for the impairment in executive functions. More research is needed to understand the role of irisin in cognitive impairment and schizophrenia.

Risk factors-related first episode postpartum psychosis among Egyptian women: the role of psychosocial and the biological factors

BackgroundThe risks associated with postpartum psychosis (PP) are poorly recognized in Egyptian women. We aimed to study the role of sociodemographic, psychosocial, obstetric, and biological factors in the occurrence of PP within 4 weeks after delivery in a sample of Egyptian women. We included 60 women with PP and 30 postpartum women without psychosis. All participants underwent a full medical assessment and psychiatric assessment using the Holmes and Rahe Stress Scale, the Brief Psychiatric Rating Scale (BPRS), and hormonal assessment (including estrogen levels and thyroid function tests) were performed for each woman.ResultsThe mean age of pregnancy of women with PP was significantly younger than that of controls (19.2 ± 2.04 years versus 24.37 ± 4.92 years). PP was significantly more common among primipara (73.3%), women who underwent cesarean sections (58.3%) and had thyroid dysfunction. The rates of low birth weight, and premature delivery were significantly higher among women with PP than among those without PP. The mean time-lapse from parturition to the onset of PP symptoms was 6.11 ± 1.62 days. Sleep disturbance, and irritability symptoms were the earliest symptoms of PP in our study. Plasma estrogen levels were significantly correlated with the total BPRS scores in patients with PP (P = 0.001).ConclusionsYoung age, primiparity, low birth weight, cesarean delivery, a rapid drop in the estrogen level and thyroid dysfunction all could contribute to the occurrence of PP.

BPRS domains, items and subgroups analyses, and CGI-I ratings in pooled data from non-interventional studies of aripiprazole once-monthly in schizophrenia (REACT study)

BackgroundPatients with schizophrenia may benefit from treatment with long-acting injectable (LAI) formulations of antipsychotics. Aripiprazole once-monthly (AOM) is an LAI that was tested in two non-interventional studies in Germany and Canada.MethodsHere, we report on analyses of pooled data from the two non-interventional studies. Patients were treated with AOM under real-life conditions. Data were analyzed for a timeframe of 6 months. We analyzed data on Brief Psychiatric Rating Scale (BPRS) domains and items, BPRS total scores in various patient subgroups (male vs. female patients, patients with disease duration ≤ 5 years and > 5 years, patients with different levels of disease severity at baseline), Clinical Global Impression – Improvement (CGI-I) ratings for the total population and subgroups, and comorbidities for the total population.ResultsData from 409 patients were included. 65.5% of the patients had comorbidities. Improvements were found in all BPRS domains and items. Furthermore, improvements were similar for male and female patients, patients with disease duration ≤ 5 years and > 5 years, and across different levels of disease severity at baseline. Numerically, more favorable results were found for younger patients, female patients, and those with shorter disease duration.ConclusionsAOM can be an effective treatment in the broad range of patients, across sexes, regardless of patient age and duration of disease, independently of disease severity, and across symptoms.Trial registrationNCT02131415 (May 6, 2014), vfa non-interventional studies registry 15960N.

Successful high dose antipsychotic treatment with cariprazine in patients on the schizophrenia spectrum: Real-world evidence from a Spanish hospital setting.

Real-world evidence fills in an important gap by providing data on the effectiveness and tolerability of new medications in everyday patients. In this data collection form a Spanish hospital, the effectiveness and tolerability of cariprazine were evaluated in 14 patients who were admitted to the hospital due to an acute episode of schizophrenia or schizoaffective disorder. The collected data included demographic characteristics, history of disorder and previous treatment, and details of cariprazine therapy such as dosing, side effects and measurements of effectiveness via scales. Difference between admission and discharge on the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression-Severity (CGI-S) scale scores were evaluated using the Wilcoxon Signed-Rank test. Significant improvement was detected in nearly all patients (one patient dropped out) as measured by the BPRS Total, Negative symptom, Positive symptom, and Hostility scores. At admission, patients were markedly-moderately ill and at discharge the severity was reduced to borderline ill and normal according to the CGI-S. The CGI-Improvement scale also indicated very much and much improvement at discharge. Importantly, patients left the hospital with high doses of cariprazine, i.e., 7.5 mg/day or even 9.0 mg/day, but this did not cause safety problems; cariprazine well-tolerated as only a few patients experienced side effects such as akathisia. The results provide novel evidence regarding the tolerability and effectiveness of cariprazine in high doses patients on the schizophrenia spectrum.

Effectiveness and safety of blonanserin in young and middle-aged female patients with schizophrenia: data from a post-marketing surveillance

BackgroundA post-marketing surveillance of blonanserin has been ongoing since September 2018. The aim of this study was to assess the effectiveness and safety of oral blonanserin in Chinese young and middle-aged female patients with schizophrenia in real clinical settings, using the data from the post-marketing surveillance.MethodsA 12-week, prospective, multi-center, open-label, post-marketing surveillance was conducted. Female patients aged 18–40 years were included in this analysis. The Brief Psychiatric Rating Scale (BPRS) was used to evaluate the effectiveness of blonanserin in improving psychiatric symptoms. The incidence of adverse drug reactions (ADRs) such as of extrapyramidal symptoms (EPS), prolactin elevation and the weight gain were used to evaluate the safety profile of blonanserin.ResultsA total of 392 patients were included both in the safety and full analysis sets, 311 patients completed the surveillance protocol. The BPRS total score was 48.8 ± 14.11 at the baseline, decreasing to 25.5 ± 7.56 at 12 weeks (P < 0.001, compared with baseline). EPS (20.2%) including akathisia, tremor, dystonia, and parkinsonism were found as the most frequent ADRs. The mean weight gain was 0.27 ± 2.5 kg at 12 weeks from the baseline. Four cases (1%) of prolactin elevation were observed during the period of surveillance.ConclusionBlonanserin significantly improved the symptoms of schizophrenia in female patients aged 18–40 years; the drug was well tolerated and had a low tendency to cause metabolic side effects, including prolactin elevation in these patients. Blonanserin might be a reasonable drug for the treatment of schizophrenia in young and middle-aged female patients.

Safety and Effectiveness of Blonanserin in Chinese Patients with Schizophrenia: An Interim Analysis of a 12-Week Open-Label Prospective Multi-Center Post-marketing Surveillance.

Schizophrenia is an unexplained, complex and serious mental illness. Blonanserin (BNS) is a new antipsychotic drug widely used in the treatment of schizophrenia. However, large-scale clinical studies have not been conducted in China. A multi-center, prospective, open-label, 12-week surveillance was carried out to evaluate the safety and effectiveness of BNS in patients with schizophrenia in China. Safety assessments included adverse drug reactions (ADRs), extrapyramidal symptoms (EPS), akathisia, concomitant medications for EPS by the end of treatment, and the changes in body weight from baseline by the end of treatment. The effectiveness was evaluated by the Brief Psychiatric Rating Scale (BPRS). From September 2018 to May 2020, of the 1,060 patients enrolled, 1,018 were included in the full analysis set (FAS) and safety set (SS), respectively. ADRs were developed in 205 patients among the included, the incidence being 20.1%. ADRs of EPS occurred in 169 patients, the incidence being 16.6%, ADRs of akathisia occurred in 90 patients, the incidence being 8.8%; concomitant therapeutic and prophylactic agents for EPS accounts for 19.2%; 4.0% of patients had a ≥7% increase in body weight from baseline at 12 weeks after initiating treatment. Using the last-observation-carried-forward (LOCF) method, the changes in total BPRS scores were -11.2 ± 10.17 (N = 1,018), -16.8 ± 12.69 (N = 1,018) and -20.6 ± 13.99 (N = 1,018) after 2/4, 6/8, or 12 weeks, respectively. 53.5% (545/1,018) patients showed response to blonanserin treatment in week 12. The post-marketing surveillance results of BNS demonstrates safety profile and effectiveness of the drug.

Vitamin D Deficiency and Risk Factors Related to Acute Psychiatric Relapses in Patients with Severe Mental Disorders: A Preliminary Study.

Previous studies have indicated that vitamin (Vit) D deficiency is frequent in psychiatric patients, regardless of diagnostic category. We aimed to assess whether acute psychiatric relapses in inpatients was associated with Vit D deficiency compared to stabilized outpatients. The cohort (152 total patients, 75 males and 77 females) had a mean age of 47.3 ± 14.4 years at admission and was grouped according to psychiatric diagnosis. Psychopathological symptom severity was assessed by the Brief Psychiatric Rating Scale (BPRS), a multidimensional symptom inventory. Total calcium serum levels were measured using standard laboratory methods, while plasma levels of 25-OH-Vit D and parathyroid hormone (PTH) were measured by automated chemiluminescence immunoassays. The psychiatric inpatient subgroup showed a significant difference in serum levels of 25-OH-Vit D and PTH (p < 0.001). Correlation analysis between serum levels of 25-OH-Vit D and BPRS total and subitem scores indicated a significantly negative relationship. In addition, linear regression analysis evidenced that the inpatient condition might predict low PTH and 25-OH-Vit D serum levels. Hospitalized psychiatric patients are at increased risk for Vit D deficiency regardless of their diagnostic categories. The mechanism underlying the association between acute psychiatric relapses and Vit D deficiency remains unclear. Therefore, screening for Vit D deficiency should pertain to the health assessment of patients with major psychiatric disorders.

Disrupted leptin-fatty acid biosynthesis is an early manifestation of metabolic abnormalities in schizophrenia.

BACKGROUNDInsulin resistance (IR) and impaired energy expenditure (IEE) are irreparable metabolic comorbidities in schizophrenia. Although mechanism(s) underlying IR and IEE remains unclear, leptin and fatty acid signaling, which has profound influence on insulin secretion/sensitivity, glucose metabolism and energy expenditure, could be disrupted. However, no association of plasma leptin with erythrocyte membrane fatty acids, body mass index (BMI), and psychotic symptoms in the same cohort of untreated patients with first-episode psychosis (FEP) or medicated patients with chronic schizophrenia (CSZ) is presented before. These studies are crucial for deciphering the role of leptin and fatty acids in the development of IR and IEE in schizophrenia.AIMTo determine the association between plasma leptin, erythrocyte membrane fatty acids, particularly, saturated fatty acids (SFAs), BMI and psychotic symptoms in patients with FEP and CSZ.METHODSIn this study, twenty-two drug naive patients with FEP, twenty-one CSZ patients treated with atypical antipsychotic drugs, and fourteen healthy control (CNT) subjects were analyzed. Plasma leptin was measured using sandwich mode enzyme-linked immunosorbent assay. Erythrocyte membrane SFAs were measured using ultrathin capillary gas chromatography. BMI was calculated by using the formula: weight (kg)/height (m2). Psychiatric symptoms were evaluated at baseline using brief psychiatric rating scale (BPRS), and positive and negative syndrome scale (PANSS). The total BPRS scores, positive and negative symptom scores (PANSS-PSS and PANSS-NSS, respectively) were recorded. Pearson correlation coefficient (r) analyses were performed to find the nature and strength of association between plasma leptin, PANSS scores, BMI and SFAs, particularly, palmitic acid (PA). RESULTSIn patients with FEP, plasma leptin not BMI was significantly lower (P = 0.034), whereas, erythrocyte membrane SFAs were significantly higher (P < 0.005) compared to the CNT subjects. Further, plasma leptin showed negative correlation with erythrocyte membrane SFAs-PA (r = −0.4972, P = 0.001), PANSS-PSS (r = −0.4034, P = 0.028), and PANSS-NSS (r = −0.3487, P = 0.048). However, erythrocyte membrane SFAs-PA showed positive correlation with PANSS-PSS (r = 0.5844, P = 0.0034) and PANSS-NSS (r = 0.5380, P = 0.008). In CSZ patients, plasma leptin, BMI, and erythrocyte membrane SFAs, all were significantly higher (P < 0.05) compared to the CNT subjects. Plasma leptin showed positive correlation with BMI (r = 0.312, P = 0.032) but not with PANSS scores or erythrocyte membrane SFAs-PA. However, erythrocyte membrane SFAs-PA showed positive correlation with PANSS-NSS only (r = 0.4729, P = 0.031). Similar changes in the plasma leptin and erythrocyte membrane SFAs have also been reported in individuals at ultra-high risk of developing psychosis; therefore, the above findings suggest that leptin-fatty acid biosynthesis could be disrupted before the onset of psychosis in schizophrenia.CONCLUSIONDisrupted leptin-fatty acid biosynthesis/signaling could be an early manifestation of metabolic comorbidities in schizophrenia. Large-scale studies are warranted to validate the above findings.

The Neutrophil-Lymphocyte Ratio Is Positively Correlated with Aggression in Schizophrenia.

To find biomarkers to assess the risk of aggression, we looked at the association between aggression and levels of body inflammation in patients with schizophrenia. The Modified Overt Aggression Scale (MOAS) score was used to divide the aggressive (n = 72) and nonaggressive (n = 141) groups. The Brief Psychiatric Rating Scale (BPRS) is a tool for determining the severity of a patient's condition. After measuring the number of inflammatory cells in the peripheral blood, the platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and monocyte-lymphocyte ratio (MLR) were estimated. We investigated the relationship between aggressive behavior, bodily inflammation, and BPRS. Before therapy, the aggressive group's BPRS score, white blood cell (WBC) count, neutrophil count, monocyte count, NLR, and MLR were considerably more significant than the nonaggressive group's. After therapy, statistically significant variations in total BPRS score and neutrophil count between the two groups. According to correlation analysis before and after treatment, aggressive behavior was positively connected with neutrophil count, NLR, and BPRS score. The presence of aggressive behavior in schizophrenic patients indicates the severity of the disorder to some degree. NLR can be used as an objective biomarker to quickly assess the risk of aggression in schizophrenic patients.

The effect on relapse rate and psychiatric symptomatology: Switching a combination of first- and second-generation antipsychotic polypharmacy to antipsychotic monotherapy in long-term inpatients with schizophrenia and related disorders. A pragmatic randomized open-label trial (SwAP trial)

BackgroundThere is little evidence to support the use of antipsychotic polypharmacy, and there are concerns about safety and side effects. Nonetheless, it is commonly used in the treatment of long-term inpatients with schizophrenia. This study investigated the effects of switching from a combination of first- and second-generation antipsychotics (FGA and SGA) to monotherapy (FGA or SGA) on relapse rates and psychiatric symptomatology. MethodsInstitutionalized patients with chronic psychotic disorders using a combination of SGA and FGA (n = 136) participated in a randomized open-label trial. The SWITCH group discontinued either FGA or SGA, the STAY group continued combination treatment. Relapse and psychotic symptoms were measured at baseline and during follow-up at 3, 6, and 9 months. Psychiatric symptomatology was measured using the Brief Psychiatric Rating Scale (BPRS). Relapse was defined as (i) an increase in BPRS score of at least 2 points on any item, or (ii) an increase of at least 4 points in total BPRS score and an adjustment of antipsychotics. ResultsA logistic regression model, corrected for sex, showed that the probability of relapse was significantly lower in the SWITCH group: 0.29 (95% CI 0.13–0.62). The protective effect of switching to monotherapy was attributable to patients continuing clozapine as monotherapy. For patients who did not experience a relapse nor dropped out, BPRS total scores decreased significantly more in the SWITCH group (p = 0.0001). ConclusionSwitching from a combination of FGA and SGA to monotherapy in long-term inpatients does not increase the relapse rate and may even reduce it.

Increased psychomotor retardation and tension as short-term neuropsychiatric adverse events of immune checkpoint inhibitors

Patients undergoing cancer treatment as well as cancer survivors commonly describe behavioral alterations. As a matter of fact, neuropsychiatric adverse events (NPAEs) have been extensively described with older immunotherapies, especially with interferon alfa. However, there are little data investigating the NPAEs of immune checkpoint inhibitors (ICIs). Therefore, the aim of this study is to evaluate the safety profile of ICI in terms of NPAEs. This is a prospective, interventional, self-controlled study. Participants receiving ICIs as unique therapy, between February and December 2019, were evaluated at the beginning of their treatment protocol, at 1 month and finally at 3 months. During the three evaluations, disease and patients' characteristics were assessed, as well as NPAEs using the Brief Psychiatric Rating Scale (BPRS) questionnaire, the psychological stress due to cancer's burden using the Herth hope index, and the performance status (PS) using the Eastern Cooperative Oncology Group (ECOG) score. Forty-four patients were enrolled, of whom 24 patients completed their three evaluation visits. No changes in BPRS total score were found throughout the study period. However, two subscores of the BPRS, "motor retardation" (P = 0.008) and "tension" or "nervousness" (P = 0.002), increased starting the 1st month of treatment. Moreover, age (r = 0.426, P = 0.038) and the baseline PS (P = 0.027) were the main risk factors of such manifestations. This study suggests that ICI could be responsible for motor retardation and increased tension starting the 1st month of treatment, with higher ECOG score and older age being the main risk factors.

The effect of ketamine on psychopathology and implications for understanding schizophrenia and its therapeutic use: a meta-analysis

AimsTo conduct a meta-analysis of the effect of ketamine on psychopathology in healthy volunteers and patients with schizophrenia, and the experimental factors affecting this.BackgroundKetamine is increasingly used to treat depression and other psychiatric disorders but can induce schizophrenia-like symptoms. Despite this, the consistency and magnitude of symptoms induced by ketamine, or what factors influence the effects of ketamine on these remain unknown.MethodMEDLINE, EMBASE and PsychINFO databases were searched for within-subject placebo controlled studies reporting symptoms using the Brief Psychiatric Rating Scale (BPRS) or Positive and Negative Syndrome Scale (PANSS) in response to an acute ketamine challenge in healthy participants or people with schizophrenia. Two independent investigators extracted study-level data for a random-effects meta-analysis. Total, positive and negative BPRS and PANSS scores were extracted. Sub-group analyses were conducted examining the effect of: blinding status, ketamine preparation, infusion method and time between ketamine and placebo condition. Standardized mean change scores were used as effect sizes for individual studies. Standardized mean changes between ketamine and placebo for total, positive and negative BPRS and PANSS were calculated.ResultOf 7819 citations retrieved, 36 studies involving healthy participants were included. The overall sample included 725 healthy volunteers exposed to both the ketamine and placebo condition. Ketamine induced a significant increase in transient psychopathology in healthy participants, for total (Standardized mean change (SMC) = 1.50 (95% CI = 1.23 to 1.77), p &lt; 0.0001), positive (SMC = 1.55 (95% CI = 1.29 to 1.81), p &lt; 0.0001) and negative (SMC = 1.16, (95% CI = 0.96 to 1.35), p &lt; 0.0001) symptom ratings, relative to the placebo condition. This effect was significantly greater for positive symptoms than negative symptoms (p = 0.004). Bolus followed by constant infusion increased ketamine's effect on positive symptoms relative to infusion alone (p = 0.006). Single-day study design increased ketamine's effect on total symptoms (p = 0.007), but age and gender did not moderate effects. There were insufficient studies for meta-analysis of studies in schizophrenia. Of these studies, two found a significant increase in symptoms with ketamine administration in total and positive symptoms. Only one study found an increase in negative symptom severity with ketamine.ConclusionThese findings show that acute ketamine administration induces schizophrenia-like symptomatology with large effect sizes but there is a greater increase in positive than negative symptoms, and when a bolus is used. These findings suggest bolus doses should be avoided in its therapeutic use to minimize the risk of inducing transient positive psychotic symptoms.

The difference of social cognitive and neurocognitive performance between patients with schizophrenia at different stages and influencing factors

ObjectsTo explore the specific features of cognitive function in patients with schizophrenia at different stages and its influencing factors. MethodsThe MATRICS Consensus Cognitive Battery (MCCB) and the Brief Psychiatric Rating Scale (BPRS) were administered to 208 patients with schizophrenia, including 158 clinically stable schizophrenia (CSS) and 50 first-episode patients with schizophrenia (FES), and 40 healthy controls (HC). Propensity score matching (PSM) was used to match the CSS and FES. Results(1) The MCCB and it,s sub-scale scores in patients with schizophrenia were lower than HC, but the score of emotion intelligence showed no significant difference between CSS and HC. (2) Before PSM, the cognitive scores of FES were significantly lower than CSS (except trail making A test, Hopkins verbal learning, category fluency). After PSM, patients with CSS still do better in performing trail making A test, emotional intelligence, continuous performances and MCCB total score. (3) BPRS total score, gender, group (FES vs CSS) and age were independent contributors to emotion intelligence, and BPRS total score had the biggest effect. (4) The effect of group (FES vs CSS) on MCCB total score and emotional intelligence was statistically significant. ConclusionsThere are significant cognitive deficits in patients with FES and CSS compared with HC. FES have greater cognitive impairments compared with CSS. Emotion intelligence of CSS may be even close to the level of HC. BPRS total score, gender, group (FES vs CSS) and age may be the independent contributors to social cognition. Group (FES vs CSS) may play an important effect on general cognition and social cognition.

Longitudinal investigation of the relationship between omega-3 polyunsaturated fatty acids and neuropsychological functioning in recent-onset psychosis: A randomized clinical trial

Alterations in polyunsaturated fatty acids (PUFAs), including omega-3 and omega-6, have been implicated in the pathophysiology of psychotic disorders, but little is known about their associations with neuropsychological functioning. The present study includes 46 recent-onset psychosis patients who participated in a larger (n = 50) double blind, placebo-controlled randomized clinical trial comparing 16 weeks of treatment with either risperidone + fish oil (FO) (EPA 740 mg and DHA 400 mg daily) or risperidone + placebo and completed neuropsychological assessments at the baseline timepoint. We investigated the relationship between baseline omega-3 (i.e., eicosapentaenoic acid, EPA; docosapentaenoic acid, DPA and docosahexaenoic acid, DHA) and omega-6 (i.e., arachidonic acid, AA) PUFA with baseline MATRICS Consensus Cognitive Battery (MCCB) and Brief Psychiatric Rating Scale (BPRS) scores. Twenty-five patients had neuropsychological data available at 16 weeks following participation in the clinical trial, which included 12 patients assigned to risperidone + FO and 13 patients assigned to risperidone + placebo. At baseline both higher DHA and EPA correlated significantly with better social cognition after controlling for functioning on other neuropsychological domains, total BPRS score, AA level and substance use. Also, at baseline higher AA correlated significantly with hostility/uncooperativeness after controlling for DHA + EPA + DPA, overall neuropsychological functioning and substance use. Patients treated with risperidone + FO demonstrated a significant longitudinal increase in social cognition that was significantly higher at 16 weeks compared to patients treated with risperidone + placebo. DHA also correlated significantly with social cognition at the 16-week timepoint. This study provides novel evidence for a differential role of omega-3 vs. omega-6 PUFA in neuropsychological deficits and symptoms in recent-onset psychosis and its treatment.

Characteristics of psychiatric manifestations among hospitalized COVID-19 patients and their correlation with disease severity - a cross sectional study.

COVID-19 severity, characteristics of psychiatric symptoms using a brief psychiatric rating scale, and sociodemographic variables were explored and evaluated. An exploratory study was conducted during the COVID-19 pandemic, from July 13th to July 26th 2020, in an isolation facility at the COVID-designated Sola hospital in Ahmedabad, India. A total of 201 inpatients diagnosed with COVID-19 by reverse transcription-polymerase chain reaction (RT-PCR) were included in this study. We assessed the presence and severity of psychiatric symptoms using the Brief Psychiatric Rating Scale (BPRS). Of the 201 COVID-19 patients, 63 (31.3%), 36 (18%), 16 (8%) and 14 (7%) experienced anxiety, tension, somatic concern and depressed mood respectively. The effect of the severity of COVID-19 on the mean of the total BPRS score was statistically signi- ficant (F = 17.2, p = 0.000). In the severe COVID-19 group, the mean of the total BPRS score (22.6 ± 4.8) was significantly higher than in the moderate (20.3 ± 4.0) and mild (19.1 ± 2.2) COVID-19 groups. High levels of serum ferritin, IL-6 and D-dimer were associated with the presence of neuropsychiatric symptoms like hallucinatory behavior and disorientation. The majority of COVID-19 patients experienced anxiety, tension and somatic concern. The presence of serious psy- chiatric symptoms like hallucinatory behavior and disorientation were predominantly seen in severe COVID-19 patients with signi- ficantly high serum inflammation and coagulation markers.

The relationship between plasma clozapine concentration and clinical outcome: a cross‐sectional study

There is no report that statistically evaluates the therapeutic reference (350-600ng/ml) and adverse drug reaction (ADR) range (>1000ng/ml) of clozapine (CLZ) recommended by the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) consensus guidelines in an isolated and large sampling study. We administered CLZ to 131 Japanese patients with treatment-resistant schizophrenia in a multicenter cross-sectional study. Plasma CLZ concentrations were assayed by high-performance liquid chromatography using trough sampling. The Brief Psychiatric Rating Scale (BPRS) and severe dose-dependent ADR (sedation, myoclonus, and seizures) were analyzed statistically after adjusting for possible confounders. The daily CLZ dosage showed a moderately positive relationship with the plasma concentration (r=0.49, p<0.001). Every 100ng/ml increase in plasma CLZ concentration improved the total BPRS score 1.95% (95% CI: 0.89-3.01, p<0.001) and the odds ratio (OR) 1.38 (95% CI: 1.14-1.66, p=0.001) for BPRS response. Compared with concentrations below 350ng/ml CLZ, 350-600ng/ml (11.12%; 95% CI: 2.52-19.72, p=0.012) and 600-1000ng/ml (11.05%; 95% CI: 2.40-19.71, p=0.013) showed significant improvement in the total BPRS score. Dosages above 1000ng/ml showed greater improvement (25.36%; 95% CI: 13.08-37.64, p<0.001) of the total BPRS score but more severe ADRs than dosages below 1000ng/ml (OR: 31.72; 95% CI: 1.04-968.81, p=0.048). The AGNP therapeutic reference range (350-600ng/ml) is useful, and a dose above 1000ng/ml is potentially more effective but carries the risk of severe ADRs in the central nervous system.