Predictive Validity of the 5-Factor PANSS Model in Acute Schizophrenia: Early Response to Aripiprazole and Brexpiprazole.

BackgroundThere is a substantial body of evidence linking unconjugated bilirubin to schizophrenia. Most of the earlier research has found a statistically significant relationship between the two factors.Aim of the workTo study the level of unconjugated bilirubin in individuals with acute schizophrenia and to investigate its correlation with neuropsychological, psychopathological, and psychosocial aspects of the disorder.Patients and methodsEighty schizophrenia patients were included in the sample, they had multiple previous episodes and were in acute episodes at the time of recruitment. Forty healthy individuals were recruited for the control group. The DSM-IV was used to diagnose the subjects, and the Trail Making Test (TMT), Positive and Negative Syndrome Scale (PANSS), General Assessment of Function (GAF), and Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) were used to evaluate the subjects’ social functioning, symptom severity, and cognitive functioning. A blood sample was drawn to measure serum bilirubin level. We analyzed the relationship and correlation of unconjugated bilirubin with the previous scale scores.ResultsCompared to healthy control individuals, who volunteered to participate, schizophrenia patients reported significantly higher levels of both total and indirect bilirubin. One subject (with schizophrenia) had an abnormally elevated total bilirubin level (> 1.2 mg/dL). Neither the direct nor the indirect bilirubin levels (> 0.3 mg/dl or > 1.2 mg/dL) were clinically abnormal in any of the patients. PANSS total score, PANSS N score, and PANSS G score were found to have a statistically significant positive connection with levels of total, direct, and indirect bilirubin. Age, gender, smoking, BMI, Total PANSS, PANSS P, PANSS N, PANSS G, GAF, TMT-A, TMT-B, antipsychotic medication, psychotic disorder duration, and duration of untreated psychosis were not predictive of total or indirect bilirubin levels, according to linear regression analysis. However, Total PANSS, PANSS N, and PANSS G were significantly predictive for direct bilirubin levels.ConclusionA statistically significant difference in total and unconjugated bilirubin mean serum levels between schizophrenia patients and healthy individuals was found. More studies are recommended to revise the contradictory results in literature on the unconjugated bilirubin and Schizophrenia.

Pharmacogenetics of treatment in first-episode schizophrenia: D3 and 5-HT2C receptor polymorphisms separately associate with positive and negative symptom response

Aripiprazole in the treatment of acute episode of schizophrenia: a real-world study in China.

Introduction The findings of studies examining the association of cognition with symptoms or functioning in schizophrenia are contradictory. Aim To investigate the clinical and functional correlates of general intelligence in schizophrenia. Method Forty-nine stabilized individuals with schizophrenia were recruited in a cross-sectional study. Intelligence was assessed using the Wechsler Adult Intelligence Scale III (WAIS). Clinical symptoms were measured with the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Scale (CGI). Functioning was assessed with the Global Assessment of Functioning Scale (GAF) and the Strauss-Carpenter Scale (SCS). Separate linear regression analyses were conducted using WAIS full scale as the dependent variable and the following predictors: PANSS total or PANSS positive or PANSS negative scores or CGI or GAF or SCS scores. Significant predictors were entered in one final overall model. Age and gender were entered as covariates in all analyses. Results ANOVA models for PANSS total, positive and negative psychopathology scores and SCS scores were not significant. However, negative symptoms were inversely associated with intelligence (B=−0.61, 95% CI=−1.012, −0.209, t =−3.06, df=45, P =0.004). CGI scores inversely correlated with WAIS total scores (B=−6.078, 95% CI=−9.029, −3.128, t =−4.151, df=44, P t =2.679, df=45, P =0.01). In the final (overall) model, only CGI remained significant. One unit increase in CGI (e.g. mildly versus moderately ill) was associated with 5.2 units decrease in full IQ scores (B=−5.168, 95% CI=−9.257, −1.078, t =−2.550, df=0.002, P =0.015). Conclusions Clinical global impression of stabilized individuals with schizophrenia predicts their level of general intelligence.

Facilitating the development of safe and effective medications for schizophrenia is a public health imperative. To evaluate the association of shortening randomized clinical trial (RCT) duration with the modification of the Positive and Negative Syndrome Scale (PANSS) for the design of RCTs of medications for schizophrenia and to offer perspective on an alternative regulatory pathway to the historically accepted trial duration and response assessment. A database was created consisting of clinical trial data from 32 placebo-controlled RCTs of 8 atypical antipsychotic drugs approved by the US Food and Drug Administration (FDA) between January 1, 2001, and December 31, 2015. The database included information on total and individual PANSS item ratings, demographic characteristics, disposition, and adverse events (AEs). All clinical trials submitted to 8 new drug applications of atypical antipsychotic drugs were selected. Quality control checks were performed to ensure that the collected data were consistent with the reported results of each trial. Data were collected from March 15, 2015, to September 30, 2015. Data analysis was conducted from October 1, 2015, to June 20, 2016. The following analyses were performed: (1) longitudinal assessment of mean change from baseline in total PANSS score, (2) correlation analyses between change from baseline in total PANSS score at week 6 and earlier time points, (3) concordance analyses of outcomes across trials between week 6 and earlier time points using total PANSS and modified PANSS, and (4) analyses of time course of treatment-emergent AEs. The final database contained data from 14 219 participants enrolled in 32 drug trials; 9805 of 14 219 participants (69.0%) were male and were either white (7183 [50.5%]) or black (4346 [30.6%]) individuals. The mean (SD) age during treatment was 38.9 (10.9) years, and the mean (SD) age at schizophrenia diagnosis was 25 (8.5) years. Statistically significant separation between treatment response and placebo response was observed after 1 week of treatment. The overall concordance rate across treatment groups steadily increased from week 1 to week 4 (68.0% for week 1, 74.0% for week 2, 83.0% for week 3, and 93.0% for week 4). Trends in AE occurrence were evident by week 1 and percentage of AEs were similar across weeks 3, 4, and 6. The overall concordance rate between change from baseline in the modified PANSS score and change from baseline in the total PANSS score was 93.0% (80 of 86 treatment groups) at week 4 and 97.7% (84 of 86 treatment groups) at week 6. Shortening the trial duration to 4 weeks increased the required sample size to 502 participants. Using the modified PANSS as the end point, the sample size for a 4-week trial was 402 participants and 296 participants for a 6-week trial. Findings from this analysis suggest that there is the potential to streamline the design of schizophrenia drug clinical trials. Trial sponsors may consider incorporating these strategies and are encouraged to consult with the FDA early in the drug development process.

Objective The study was designed to evaluate the efficacy and safety of flexible doses of paliperidone extended-release tablets (paliperidone ER) (3 -12) mg/d comparing with olanzapine (5 -15)mg/d in acute hospitalized patients with schizophrenia. Methods All 288 hospitalized patients with DSM-Ⅳ schizophrenia were randomized into paliperidone ER ( n = 143 ) or olanzapine ( n=145 ) treatment in a 6-week, multicenter, double-blind, parallel-group study. The primary efficacy measure was the total score changes of the Positive and Negative Syndrome Scale (PANSS). Clinical Global Impression (CGI),response rate and Visual Analogue Scale (VAS) were adopted as secondary efficacy measures. Results Both paliperidone ER and olanzapine groups demonstrated a significant improvement in total PANSS score (P<0.001). The PANSS total score in paliperidone ER group was reduced (32.3 ± 17.1) at end point,and olanzapine group (34.1 ± 17.4). There was no statistically significant difference between the two groups (P =0.369) after 6-week treatment. There were no statistical differences between two groups in CGI,response rate and VAS sleep quality assessments by the end of the treatment. The common adverse events were extrapyramidal symptoms, insomnia, constipation and prolactin increasing in paliperidone ER group,and somnolenee, EPS, abnormal liver function and abnormal lipid metabolism in olanzapine group.Conclusion Paliperidone ER and olanzapine are similarly effective in significantly improving the symptoms of inpatient with acute schizophrenia. Paliperidone ER demonstrates a favorable safety profile with fewer somnolence, abnormal liver function and abnormal lipid metabolism comparing with olanzapine. Key words: Schizophrenia; Treatment outcom; Paliperidone extended-release tablets; Olanzapine; Safety

Asian populations may differ from other races in response to antipsychotics. Studies of aripiprazole in Asian populations are scarce. This study aimed to investigate the efficacy, safety, and tolerability of aripiprazole in Chinese patients with acute schizophrenia or schizoaffective disorder. This 4-week, double-blind, randomized, parallel study was conducted in 5 medical centers in Taiwan between March 2004 and January 2005. A total of 83 patients with a primary DSM-IV diagnosis of schizophrenia or schizoaffective disorder were randomly assigned (with a randomization ratio of 3:2) to 15 mg/day of aripiprazole (N = 49) or 6 mg/day of risperidone (N = 34). Efficacy measures included the Positive and Negative Syndrome Scale (PANSS) total, positive, and negative scores and Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement scale scores. Extrapyramidal symptoms (EPS), weight gain, serum prolactin level, QTc interval, and self-reported adverse events were assessed as measures of safety and tolerability. Both the aripiprazole and risperidone groups showed statistical improvement from baseline in PANSS total, PANSS positive, PANSS negative, and CGI-S scores at study endpoint (all p < .001). Significant improvement was noted in the first week of treatment for both treatment groups. There were no significant differences in efficacy measures between treatment groups. Aripiprazole showed significantly less EPS liability as assessed by the Simpson-Angus Scale (p < .005) and less serum prolactin level elevation (p < .001) than risperidone. Both groups showed mild weight gain. No patients showed clinically significant QTc interval prolongation in this study. Compared with risperidone 6 mg/day, aripiprazole 15 mg/day has comparable efficacy and favorable safety and tolerability profiles in the short-term treatment of Chinese patients with acute schizophrenia. In this group of Chinese patients, the overall response to aripiprazole did not differ from that of white patients. ClinicalTrials.gov identifier NCT00283179.

This 6-week trial assessed the efficacy, tolerability, and safety of the investigational psychopharmacologic agent asenapine versus placebo and risperidone in patients with acute schizophrenia (DSM-IV criteria). In a study conducted from August 2001 to May 2002, patients were randomly assigned to receive sublingual asenapine 5 mg b.i.d., placebo b.i.d., or oral risperidone 3 mg b.i.d. The primary outcome measure was improvement from baseline in Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcomes included changes in Clinical Global Impressions-Severity of Illness (CGI-S) score and scores on PANSS positive, negative, and general psychopathology subscales. The intent-to-treat population comprised 174 patients who received >or= 1 dose of study drug and >or= 1 postbaseline assessment. At study end or last observation, mean improvements on PANSS total, negative subscale, and general psychopathology subscale scores were all significantly greater with asenapine than with placebo (p < .005, p = .01, and p < .005, respectively). Compared with placebo, improvements on CGI-S and PANSS positive subscale scores were significantly greater with both asenapine (p < .01 and p = .01) and risperidone (p < .005 and p < .05). Overall incidence rates of adverse events were comparable for asenapine and placebo, whereas risperidone was associated with substantial weight gain and prolactin elevation. Asenapine was effective and well tolerated in patients with acute schizophrenia and may provide a new option for control of negative symptoms.

Aripiprazole lauroxil (AL) is a long-acting injectable atypical antipsychotic that was evaluated for the treatment of schizophrenia in a randomized, placebo-controlled, Phase 3 study. Here, we present exploratory analyses of supportive efficacy endpoints. Patients experiencing an acute exacerbation of schizophrenia received AL 441 mg intramuscularly (IM), AL 882 mg IM, or matching placebo IM monthly. Supportive endpoints included changes from baseline at subsequent time points in Clinical Global Impression-Severity (CGI-S) scale score; Positive and Negative Syndrome Scale (PANSS) Total score; PANSS Positive, Negative, and General Psychopathology subscale scores; PANSS Marder factors (post hoc); and PANSS responder rate. Overall response rate, based on PANSS Total score and Clinical Global Impression-Improvement (CGI-I) scale score, was also analyzed. Of 622 patients who were randomized, 596 had ≥1 post-baseline PANSS score. Patients were markedly ill at baseline (mean PANSS Total scores 92-94). Compared with placebo, CGI-S scores; PANSS Positive, Negative, and General Psychopathology subscale scores; and PANSS Marder factors were all significantly (p<0.001) improved by Day 85 with both AL doses, with significantly lower scores starting from Day 8 in most instances. Treatment response rates were significantly (p<0.001) greater with both doses of AL vs placebo. AL demonstrated robust efficacy on CGI-S score, PANSS subscale scores, PANSS Marder factors, and response rates. Study limitations included use of a fixed dose for initial oral aripiprazole and fixed monthly AL doses without the option to individualize the oral initiation dosing or injection frequency for efficacy, tolerability, or safety.

Aripiprazole is an investigational agent for treating schizophrenia that has a novel pharmacologic profile. The present study investigated the efficacy, safety, and tolerability of aripiprazole and haloperidol compared with placebo. A 4-week, double-blind, randomized study, conducted at 36 U.S. centers between July 1997 and June 1998, compared aripiprazole (15 mg/day, 30 mg/day) to placebo, with haloperidol (10 mg/day) as an active control. Fixed doses of each agent were administered from day 1 throughout the study. A total of 414 patients with a primary DSM-IV diagnosis of schizophrenia or schizoaffective disorder were randomized. Efficacy measures included the Positive and Negative Syndrome Scale (PANSS) total, PANSS positive, PANSS negative, PANSS-derived Brief Psychiatric Rating Scale (BPRS) core, Clinical Global Impressions (CGI)-Severity of Illness, and mean CGI-Improvement scores. Safety and tolerability evaluations included extrapyramidal symptoms (EPS), weight gain, serum prolactin level, and QTc interval. Both doses of aripiprazole and haloperidol, 10 mg, produced statistically significant (p < or = .05) improvements from baseline in PANSS total, PANSS positive, PANSS-derived BPRS core, and CGI-Severity scores and significantly lower CGI-Improvement scores at endpoint, compared with placebo. Aripiprazole, 15 mg, and haloperidol, 10 mg, significantly improved PANSS negative score compared with placebo. Both aripiprazole doses and haloperidol separated from placebo for PANSS total scores at week 2. Unlike haloperidol, aripiprazole was not associated with significant EPS or prolactin elevation at endpoint compared with placebo. There were no statistically significant differences in mean changes in body weight across the treatment groups versus placebo, and no patients receiving aripiprazole experienced clinically significant increases in QTc interval. Aripiprazole, effective against positive and negative symptoms, is a safe and well-tolerated potential treatment for schizophrenia and schizoaffective disorder.

The awareness of social inference task (TASIT) updated: Signal detection theory (SDT) in emotion recognition and its link to psychotic symptoms

Sensitivity of individual items of the Positive and Negative Syndrome Scale (PANSS) and items subgroups to differentiate between placebo and drug treatment in schizophrenia

Brexpiprazole (BPZ) is a novel antipsychotic drug in the category of serotonin-dopamine activity modulators (SDAMs). It is expected to be effective in the treatment of schizophrenia because of its low side effects and its ability to reduce psychosis. However, clinical data in Japan are still insufficient. We prescribed BPZ to 41 schizophrenic patients; 9 of the 41 dropped out and 32 were retrospectively reviewed for psychiatric symptoms using the positive and negative syndrome scale (PANSS). The results showed that there was significant improvement in the total score, the positive scale, the negative scale and the general psychopathology scale, all after 4 weeks. The improvement started after 1 week for the total score, the positive scale and the general psychopathology scale, and after 2 weeks for the negative scale. The results suggest that BPZ is effective not only for positive symptoms in the acute phase, but also for negative symptoms after the subacute phase. Further studies are needed to investigate the efficacy of BPZ by patient's characteristics as well as by sub-items of the PANSS.

White matter volume not associated with hallucinations in clinical high risk and first-episode psychosis: A voxel-based morphometry study.

BackgroundIt is common knowledge that antipsychotic treatment improves the symptomatology in schizophrenia, especially for the psychotic and general symptoms. It is also a fact that patients with schizophrenia often report a reduced quality of life compared to healthy controls. In this study we aim at examining the relation between self-reported quality of life (QLS), psychopathological symptoms and level of function before and after antipsychotic treatment. We hypothesize that there will be a correlation between QLS and severity of symptoms before treatment. Further we expect an improvement in QLS after treatment and that this improvement will correlate with improvement in symptomatology.MethodsAs a part of a large multimodal study on antipsychotic naïve patients with schizophrenia, 69 patients were recruited. Their psychopathology was measured with the Positive and Negative Syndrome Scale (PANSS), level of function was estimated using Global Assessment of Function (GAF), and QLS was reported by answering a questionnaire. Patients were treated with individual doses of Amisulpride for six weeks, after which they were reexamined.The questionnaire regarding QLS counts 21 questions, divided into four domains: Self and present life (i.e. “how satisfied are you with your present life”), social relations (“how satisfied are you with your current social life”), Living situation (“how much do you like the place you live”) and Work situation (“How satisfied are you with the work you do”). Higher scores indicate higher satisfaction within the domain. Since the follow up period was only 6 weeks, we focused on self and present life (SPL) and social relations (SR), as we did not expect the living and work situation to change significantly within this period.ResultsBaseline data were available on 48 patients, mean age 25 years (6.1), 31 males (65%).Their PANSS total score was 84 (16.0), GAF was 41(9.4), SPL-score was 13 (5.3) SR-score 10(5.3). For SPL as well as SR, there was a negative correlation with PANSS-total, PANSS-negative and PANSS- general (p-values<0.007). Follow-up data were available on 33 patients, mean age 25 years (6.6), 19 males (58%). They received 273 (163.3) mg Amisuplride. PANSS total was 68 (14.4) and GAF was 53 (15.7), SPL-score was 14 (3.9) SR-score 11(4.6). Paired T-test showed a significant improvement in PANSS total, PANSS positive, PANSS general and GAF (all p-values<0.001). There was also an improvement in SR (p=0.003), but no significant improvement in SPL and PANSS negative score (p=0.12 and p=0.5).There were no correlations between neither of the QLS scores and any psychopathology scores at follow up. Likewise, there was no correlation between change in QLS scores and change in psychopathology. However, there was a negative correlation with change in SPL and medication dose (p=0.009)DiscussionIn this study, we found that antipsychotic naïve patients with most severe symptoms had the lowest self-reported QLS. This relation was only observed for negative and general symptoms, but not for positive symptoms or GAF score. As expected there was a treatment induced improvement in positive and general symptoms as well as GAF score. Likewise, patients improved on QLS, but only on SR and not in the overall measure of SPL. This may partly be because antipsychotic medication primarily improves positive symptoms, which were not correlated with QLS. Additionally, there was even a negative correlation with medication dose, indicating that patients with higher doses had the least improvement I SPL score. The results indicate that there is not a simple relationship between antipsycotic induced improvement in psychopathology and selfreported QLS. High doses of medication may even reduce QLS.