Total Brief Psychiatric Rating Scale Research Articles

Prescriptive factors for intensive home treatment in acute psychiatry: a secondary analysis of a randomised controlled trial

BackgroundIntensive home treatment (IHT) aims to prevent psychiatric hospitalisation. Although this intervention is well tested, it is still unknown for whom this intervention works best. Therefore, this study aims to explore prescriptive factors that moderate the effect of IHT compared to care as usual (CAU) on symptom severity.MethodsUsing data from a randomised controlled trial, 198 participants that experience an exacerbation of acute psychiatric symptoms were included in this secondary analysis. In order to maximise clinical relevance, generally available environmental and clinical baseline factors were included as tentative moderators: age, gender, employment status, domestic situation, psychiatric disorders, psychological symptoms, psychosocial functioning, alcohol and other substance use. The outcome variable symptom severity was measured using the Brief Psychiatric Rating Scale (BPRS) and collected at 26 and 52 weeks post-randomisation. Multiple regression analysis was used to examine which participants’ characteristics moderate the effect of IHT on the total BPRS score.ResultsOur results suggest that being employed (B = 0.28, SE = 0.13, 95% CI = 0.03–0.53, p = 0.03) at baseline seems to have a moderation effect, which result in lower symptom severity scores at 26 weeks follow-up for patients who received IHT. This effect was not found at 52 weeks.ConclusionsOn the basis of the number of factors tested, there is no evidence for robust outcome moderators of the effect of IHT versus CAU. Our conclusion is therefore that IHT can be offered to a diverse target population with comparable clinical results.Trial registrationThis trial is registered (date of registration: 2016-11-23) at the international clinical trials registry platform (NTR6151).

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.

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.

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.

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.

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.

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.

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.

The effects of intensive home treatment on self-efficacy in patients recovering from a psychiatric crisis

BackgroundThis study evaluated whether providing intensive home treatment (IHT) to patients experiencing a psychiatric crisis has more effect on self-efficacy when compared to care as usual (CAU). Self-efficacy is a psychological concept closely related to one of the aims of IHT. Additionally, differential effects on self-efficacy among patients with different mental disorders and associations between self-efficacy and symptomatic recovery or quality of life were examined.MethodsData stem from a Zelen double consent randomised controlled trial (RCT), which assesses the effects of IHT compared to CAU on patients who experienced a psychiatric crisis. Data were collected at baseline, 6 and 26 weeks follow-up. Self-efficacy was measured using the Mental Health Confidence Scale. The 5-dimensional EuroQol instrument and the Brief Psychiatric Rating Scale (BPRS) were used to measure quality of life and symptomatic recovery, respectively. We used linear mixed modelling to estimate the associations with self-efficacy.ResultsData of 142 participants were used. Overall, no difference between IHT and CAU was found with respect to self-efficacy (B = − 0.08, SE = 0.15, p = 0.57), and self-efficacy did not change over the period of 26 weeks (B = − 0.01, SE = 0.12, t (103.95) = − 0.06, p = 0.95). However, differential effects on self-efficacy over time were found for patients with different mental disorders (F(8, 219.33) = 3.75, p < 0.001). Additionally, self-efficacy was strongly associated with symptomatic recovery (total BPRS B = − 0.10, SE = 0.02, p < 0.00) and quality of life (B = 0.14, SE = 0.01, p < 0.001).ConclusionsAlthough self-efficacy was associated with symptomatic recovery and quality of life, IHT does not have a supplementary effect on self-efficacy when compared to CAU. This result raises the question whether, and how, crisis care could be adapted to enhance self-efficacy, keeping in mind the development of self-efficacy in depressive, bipolar, personality, and schizophrenia spectrum and other psychotic disorders. The findings should be considered with some caution. This study lacked sufficient power to test small changes in self-efficacy and some mental disorders had a small sample size.Trial registration This trial is registered at Trialregister.nl, number NL6020.

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.

Using data from schizophrenia outcome study to estimate the time to treatment outcome and the early-response cut-off score that predicts outcome at week 16

Background Being able to make an estimation of the time to clinical outcome, and making predictions early during treatment about the possibility of later response/non-response to treatment, is an important asset that can help to guide treatment strategies and counsel patients and caregivers about treatment expectations. Objectives The study aimed to determine the time course to treatment outcome and the psychopathological cut-off score at week 4 that predicts outcome at week 16. Methods This was a naturalistic follow-up study of 160 incident cases of schizophrenia over 16 weeks. Four intervals of follow-up clinical assessments were done. Standard criteria for response and remission were applied. Results The mean (median) times, in weeks, to response and remission using Brief Psychiatric Rating Scale (BPRS) data were 8.1(8.0); 8.4(8.0); and 10.9 (12.0), respectively. The Areas Under the Curves were high, for response (0.909; 95% C.I., 0.85-0.97) and remission (0.86; 95% C.I., 0.81 -0.94) at week 16. A cut-off score of 20.7% reduction in the total BPRS score at week 4, predicted response status (79.5% sensitivity, 84.2% specificity) and remission status (77.6% sensitivity, 73.3% specificity) at week 16. In addition, a cut-off of 10.21% reduction in the total Scale for Assessment of Negative Symptoms (SANS) score at week 4, predicted response (70.8% sensitivity, 95.5% specificity) at week 16. Discussion The results are in line with the general clinical impression that, by 2 months, most acutely ill inpatients are fit for discharge; and introduced for further investigation 10.21% reduction in SANS Score as a marker of treatment resistance in schizophrenia.

Association of Ketamine With Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia

Ketamine hydrochloride is increasingly used to treat depression and other psychiatric disorders but can induce schizophrenia-like or psychotomimetic symptoms. Despite this risk, the consistency and magnitude of symptoms induced by ketamine or what factors are associated with these symptoms remain unknown. To conduct a meta-analysis of the psychopathological outcomes associated with ketamine in healthy volunteers and patients with schizophrenia and the experimental factors associated with these outcomes. MEDLINE, Embase, and PsychINFO databases were searched for within-participant, placebo-controlled studies reporting symptoms using the Brief Psychiatric Rating Scale (BPRS) or the Positive and Negative Syndrome Scale (PANSS) in response to an acute ketamine challenge in healthy participants or patients with schizophrenia. Of 8464 citations retrieved, 36 studies involving healthy participants were included. Inclusion criteria were studies (1) including healthy participants; (2) reporting symptoms occurring in response to acute administration of subanesthetic doses of ketamine (racemic ketamine, s-ketamine, r-ketamine) intravenously; (3) containing a placebo condition with a within-subject, crossover design; (4) measuring total positive or negative symptoms using BPRS or PANSS; and (5) providing data allowing the estimation of the mean difference and deviation between the ketamine and placebo condition. Two independent investigators extracted study-level data for a random-effects meta-analysis. Total, positive, and negative BPRS and PANSS scores were extracted. Subgroup analyses were conducted examining the effects of blinding status, ketamine preparation, infusion method, and time between ketamine and placebo conditions. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Standardized mean differences (SMDs) were used as effect sizes for individual studies. Standardized mean differences between ketamine and placebo conditions were calculated for total, positive, and negative BPRS and PANSS scores. The overall sample included 725 healthy volunteers (mean [SD] age, 28.3 [3.6] years; 533 [73.6%] male) exposed to the ketamine and placebo conditions. Racemic ketamine or S-ketamine was associated with a statistically significant increase in transient psychopathology in healthy participants for total (SMD = 1.50 [95% CI, 1.23-1.77]; P < .001), positive (SMD = 1.55 [95% CI, 1.29-1.81]; P < .001), and negative (SMD = 1.16 [95% CI, 0.96-1.35]; P < .001) symptom ratings relative to the placebo condition. The effect size for this association was significantly greater for positive than negative symptoms of psychosis (estimate, 0.36 [95% CI, 0.12-0.61]; P = .004). There was significant inconsistency in outcomes between studies (I2 range, 77%-83%). Bolus followed by constant infusion increased ketamine's association with positive symptoms relative to infusion alone (effect size, 1.63 [95% CI, 1.36-1.90] vs 0.84 [95% CI, 0.35-1.33]; P = .006). Single-day study design increased ketamine's ability to generate total symptoms (effect size, 2.29 [95% CI, 1.69-2.89] vs 1.39 [95% CI, 1.12-1.66]; P = .007), but age and sex did not moderate outcomes. Insufficient studies were available for meta-analysis of studies in schizophrenia. Of these studies, 2 found a statistically significant increase in symptoms with ketamine administration in total and positive symptoms. Only 1 study found an increase in negative symptom severity with ketamine. This study found that acute ketamine administration was associated with schizophrenia-like or psychotomimetic symptoms with large effect sizes, but there was a greater increase in positive than negative symptoms and when a bolus was used. These findings suggest that bolus doses should be avoided in the therapeutic use of ketamine to minimize the risk of inducing transient positive (psychotic) symptoms.

Evaluation of Childhood Sluggish Cognitive Tempo (SCT) Among the Patients With Substance Use Disorder, Substance Induced Psychosis and Childhood ADHD

Objective: Substance use disorders (SUDs) include a pathological pattern of behaviors related with the effects of the drug used and are associated with substance-induced psychosis (SIP). Individuals with lower levels of self-control are particularly predisposed to develop SUDs and SIP. The purpose of this study was to evaluate whether childhood sluggish cognitive tempo (SCT), which is a problem distinct from but related with ADHD, is associated with SUDs and SIP. Method: Fifty-seven SUD patients who had childhood ADHD symptoms and at least one SIP attack were enrolled the study. Patients were evaluated by Brief Psychiatric Rating Scale (BPRS), Wender-Utah Rating Scale (WURS), and SCT Scale. Results: The rate of childhood SCT comorbidity was 63.8%. The total BPRS and conceptual disorganization, motor retardation, unusual thought content, blunted affect, excitement, and disorientation scores were higher in the childhood SCT group. SCT and WURS scores were positively correlated with BPRS scores but WURS scores were correlated with more psychotic symptoms and the correlations were stronger in WURS than SCT except “conceptual disorganization,” “motor retardation.” and “blunted affect.” Using linear regression analysis, we found that both childhood SCT and WURS scores significantly predicted the BPRS total, motor retardation, unusual thought content, blunted affect and excitement scores. Finally, the results of multivariate stepwise regression analyses indicated that tension and guilt significantly predicted WURS while blunted affect and conceptual disorganization predicted SCT scores. Conclusion: Approximately, 7 in 10 patients in this group seem to have had childhood SCT. SCT patients showed more proneness to psychotic symptoms when compared with others. In addition, there was a relationship between blunted affect, conceptual disorganization, and SCT.

Valproate preparations for agitation in dementia.

Agitation has been reported in up to 90% of people with dementia. Agitation in people with dementia worsens carer burden, increases the risk of injury, and adds to the need for institutionalisation. Valproate preparations have been used in an attempt to control agitation in dementia, but their safety and efficacy have been questioned. To determine the efficacy and adverse effects of valproate preparations used to treat agitation in people with dementia, including the impact on carers. We searched ALOIS - the Cochrane Dementia and Cognitive Improvement Group's Specialized Register on 7 December 2017 using the terms: valproic OR valproate OR divalproex. ALOIS contains records from all major health care databases (the Cochrane Library, MEDLINE, Embase, PsycINFO, CINAHL, LILACS) as well as from many trials databases and grey literature sources. Randomised, placebo-controlled trials that assessed valproate preparations for agitation in people with dementia. Two review authors independently screened the retrieved studies against the inclusion criteria and extracted data and assessed methodological quality of the included studies. If necessary, we contacted trial authors to ask for additional data, including relevant subscales, or for other missing information. We pooled data in meta-analyses where possible. This is an update of a Cochrane Review last published in 2009. We found no new studies for inclusion. The review included five studies with 430 participants. Studies varied in the preparations of valproate, mean doses (480 mg/day to 1000 mg/day), duration of treatment (three weeks to six weeks), and outcome measures used. The studies were generally well conducted although some methodological information was missing and one study was at high risk of attrition bias.The quality of evidence related to our primary efficacy outcome of agitation varied from moderate to very low. We found moderate-quality evidence from two studies that measured behaviour with the total Brief Psychiatric Rating Scale (BPRS) score (range 0 to 108) and with the BPRS agitation factor (range 0 to 18). They found that there was probably little or no effect of valproate treatment over six weeks (total BPRS: mean difference (MD) 0.23, 95% confidence interval (CI) -2.14 to 2.59; 202 participants, 2 studies; BPRS agitation factor: MD -0.67, 95% CI -1.49 to 0.15; 202 participants, 2 studies). Very low-quality evidence from three studies which measured agitation with the Cohen-Mansfield Agitation Index (CMAI) were consistent with a lack of effect of valproate treatment on agitation. There was variable quality evidence on other behaviour outcomes reported in single studies of no difference between groups or a benefit for the placebo group.Three studies, which measured cognitive function using the Mini-Mental State Examination (MMSE), found little or no effect of valproate over six weeks, but we were uncertain about this result because the quality of the evidence was very low. Two studies that assessed functional ability using the Physical Self-Maintenance Scale (PSMS) (range 6 to 30) found that there was probably slightly worse function in the valproate-treated group, which was of uncertain clinical importance (MD 1.19, 95% CI 0.40 to 1.98; 203 participants, 2 studies; moderate-quality evidence).Analysis of adverse effects and serious adverse events (SAE) indicated a higher incidence in valproate-treated participants. A meta-analysis of three studies showed that there may have been a higher rate of adverse effects among valproate-treated participants than among controls (odds ratio (OR) 2.02, 95% CI 1.30 to 3.14; 381 participants, 3 studies, low-quality evidence). Pooled analysis of the number of SAE for the two studies that reported such data indicated that participants treated with valproate preparations were more likely to experience SAEs (OR 4.77, 95% CI 1.00 to 22.74; 228 participants, 2 studies), but the very low quality of the data made it difficult to draw any firm conclusions regarding SAEs. Individual adverse events that were more frequent in the valproate-treated group included sedation, gastrointestinal symptoms (nausea, vomiting, and diarrhoea), and urinary tract infections. This updated review corroborates earlier findings that valproate preparations are probably ineffective in treating agitation in people with dementia, but are associated with a higher rate of adverse effects, and possibly of SAEs. On the basis of this evidence, valproate therapy cannot be recommended for management of agitation in dementia. Further research may not be justified, particularly in light of the increased risk of adverse effects in this often frail group of people. Research would be better focused on effective non-pharmacological interventions for this patient group, or, for those situations where medication may be needed, further investigation of how to use other medications as effectively and safely as possible.

A potential role for adjunctive omega-3 polyunsaturated fatty acids for depression and anxiety symptoms in recent onset psychosis: Results from a 16 week randomized placebo-controlled trial for participants concurrently treated with risperidone

Omega-3 treatment studies for multi-episode schizophrenia or clinical high risk for conversion to psychosis states have had variable, and often negative, results. To examine adjunctive omega-3 treatment for recent onset psychosis, participants aged 15–40 years with recent onset schizophrenia-spectrum (n = 46) or bipolar (n = 4) disorders and current psychotic symptoms were treated for 16 weeks with risperidone and randomly-assigned omega-3 (EPA 740 mg and DHA 400 mg daily) or matching placebo. The primary outcome measure was the Brief Psychiatric Rating Scale (BPRS) total score. Mean lifetime antipsychotic exposure was 18.1 days. Length of time in treatment, risperidone dose and number of omega-3/placebo capsules taken did not differ between conditions. Longitudinal analysis of the total BPRS score revealed a trend level (p = 0.0826) treatment effect favoring omega-3 treatment. Lorazepam was an allowed concomitant medication. Among the subgroup (N = 23) who did not receive lorazepam, the treatment effect on BPRS total scores favoring omega-3 was significant (p = 0.0406) and factor scores analyses revealed a substantial decrease in depression-anxiety with omega-3 but no change with placebo (treatment-by-time interaction, p = 0.0184). Motor side effects did not differ between conditions. Analysis of Systematic Assessment for Treatment Emergent Events assessments revealed fewer adverse events overall with omega-3 compared with placebo with the largest differences between conditions (all favoring omega-3) on confusion, anxiety, depression, irritability, and tiredness/fatigue. These results suggest that omega-3 adjuvant treatment is a potential option for depression and anxiety symptoms of people with recent onset psychosis. Further research is needed to confirm this potential.Clinical trial registration: NCT01786239

F115. INSIGHT AND MANIC SYMPTOMS IN PATIENTS WITH CHRONIC SCHIZOPHRENIA IN THE KOREAN COMMUNITY

BackgroundMany studies have highlighted the similarity of the symptoms between bipolar disorders and schizophrenia. Moreover, there are no pathognomonic symptoms that can differentiate these two disorders, and 9% of schizophrenia patients have experienced a manic syndrome in their lifetime. Insight about their symptoms and illness is very important factor for the differential diagnosis and the management in schizophrenia. To examine the relationship among the insight, the psychotic and manic symptoms, and clinical variables in patients with chronic schizophrenia.MethodsSeventy-four participants (male 44, female 30) with chronic schizophrenia in community mental health facilities have been evaluated with the Scale to assess Unawareness of Mental Disorder (SUMD), the Mood Disorder Questionnaire (MDQ), and the Brief Psychiatric Rating Scale (BPRS).ResultsThe mean number of previous admission was 3.85. Their drug adherence was favorable (6.73 day/week). Mean CGI-S score was 3.8. Thirty-five percent of subject were MDQ positive (cutoff point = 7 or more). Among SUMD, “awareness of effect of medication” showed significant negative correlation (r = -0.33) with total MDQ score not with total BPRS score. The negative correlation was more obvious in participants with negative MDQ (total MDQ score 6 or less, r = -0.31). Several MDQ items (irritability, r = -0.25; decreased sleep, r = -0.27; thought racing, r = -0.28; and easy distractibility, r = -0.40) negatively correlated with “awareness of effect of medication”. In contrast, only one item (guilt feeling, r = -0.27) of BPRS revealed this correlation. Individual items in MDQ and BPRS rarely correlated with each other. Total MDQ score was not correlated with duration of illness and medication adherence.DiscussionManic symptoms were frequently detected even in schizophrenia as reported in previous studies. This made it difficult to differentially diagnose the disorder using only the total MDQ score. There was possible relationship between these manic symptoms and their insight. Identifying manic symptoms in schizophrenia would be considerable in clinical setting.

Effect of Olanzapine on Clinical and Polysomnography Profiles in Patients with Schizophrenia.

Acute and short-term administration of olanzapine has a favorable effect on sleep in schizophrenia patients. This study aimed to clarify the effect of olanzapine on polysomnographic profiles of schizophrenia patients during the acute phase of illness after controlling for previous drug exposure. Twenty-five drug-naïve or drug-free schizophrenia patients were assessed at baseline and after six weeks of olanzapine treatment on Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale (PANSS), and Udvalg for Kliniske Undersogelser (UKU) side-effect rating scale and a whole-night polysomnography; fifteen patients completed the study. There was a significant reduction in all psychopathological variables with maximum reduction in PANSS total, BPRS total, and PANSS positive scores. A significant increase in total sleep time (TST), sleep efficiency (SE), nonrapid eye movement (NREM) stage 1 duration, stage 3 duration, stage 4 duration, and stage 4 percentage of TST, number of rapid eye movement (REM) periods, REM duration, and REM percentage of TST was observed. REM latency at baseline inversely predicted the reduction in BPRS total and PANSS total and positive scores. In summary, short-term treatment with olanzapine produced significant improvement in clinical and polysomnography profiles of patients with schizophrenia with shorter REM latency predicting a good clinical response.