Positive And Negative Syndrome Scale Subscales Research Articles

Randomized, placebo-controlled, double-blind study assessing the efficacy and safety of paliperidone palmitate in Asian patients with schizophrenia

BackgroundThis 13-week, double-blind study was conducted to confirm the efficacy and safety of paliperidone palmitate (PP), at dosing regimens approved in other countries, in Asian patients with schizophrenia.MethodsAsian patients (aged ≥20 years) diagnosed with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision criteria), and having a Positive and Negative Syndrome Scale (PANSS) total score of 60 to 120 were enrolled and randomized (1:1) to a PP or placebo group. Patients received PP intramuscularly at recommended doses: initiation dose 150 mg equivalent (eq) PP on day 1 and 100 mg eq PP on day 8 (deltoid); and a monthly maintenance dose of 75 mg eq PP on days 36 and 64 (deltoid or gluteal). The change from baseline to week 13 in PANSS total scores (primary endpoint), Clinical Global Impression-Severity (CGI-S) scores, and PANSS Marder factor scores and subscales, and responder rate at week 13 were evaluated. Safety was also assessed.ResultsThe PANSS total score (P<0.0001, least-squares mean change from baseline to week 13: PP, −3.5; placebo, +6.2), CGI-S score (P<0.0001), and PANSS Marder factor scores (P≤0.0025) were significantly improved at week 13 in the PP group versus placebo. More treatment responders (≥30% decrease in PANSS total score) were in the PP group (22.8%) versus placebo (8.5%). Insomnia (PP 17.0% versus placebo 15.2%), injection site pain (13.2% versus 6.7%), nasopharyngitis (12.6% versus 6.1%), psychiatric symptoms (11.3% versus 26.2%), and extrapyramidal symptoms (10.1% versus 4.9%) were the most frequently occurring treatment-emergent adverse events.ConclusionPP is efficacious for Asian patients with schizophrenia at the dosing regimen approved in other countries, with a similar safety and tolerability profile.

Add-on Treatment of Benzoate for Schizophrenia

In addition to dopaminergic hyperactivity, hypofunction of the N-methyl-d-aspartate receptor (NMDAR) has an important role in the pathophysiology of schizophrenia. Enhancing NMDAR-mediated neurotransmission is considered a novel treatment approach. To date, several trials on adjuvant NMDA-enhancing agents have revealed beneficial, but limited, efficacy for positive and negative symptoms and cognition. Another method to enhance NMDA function is to raise the levels of d-amino acids by blocking their metabolism. Sodium benzoate is a d-amino acid oxidase inhibitor. To examine the clinical and cognitive efficacy and safety of add-on treatment of sodium benzoate for schizophrenia. A randomized, double-blind, placebo-controlled trial in 2 major medical centers in Taiwan composed of 52 patients with chronic schizophrenia who had been stabilized with antipsychotic medications for 3 months or longer. Six weeks of add-on treatment of 1 g/d of sodium benzoate or placebo. The primary outcome measure was the Positive and Negative Syndrome Scale (PANSS) total score. Clinical efficacy and adverse effects were assessed biweekly. Cognitive functions were measured before and after the add-on treatment. Benzoate produced a 21% improvement in PANSS total score and large effect sizes (range, 1.16-1.69) in the PANSS total and subscales, Scales for the Assessment of Negative Symptoms-20 items, Global Assessment of Function, Quality of Life Scale and Clinical Global Impression and improvement in the neurocognition subtests as recommended by the National Institute of Mental Health's Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative, including the domains of processing speed and visual learning. Benzoate was well tolerated without significant adverse effects. Benzoate adjunctive therapy significantly improved a variety of symptom domains and neurocognition in patients with chronic schizophrenia. The preliminary results show promise for d-amino acid oxidase inhibition as a novel approach for new drug development for schizophrenia.

Effect of Aripiprazole on Cognitive Function and Hyperprolactinemia in Patients with Schizophrenia Treated with Risperidone

ObjectiveThis study aimed to assess the efficacy of aripiprazole for the management of cognitive impairments and hyperprolactinemia in patients with schizophrenia on a stable dose of risperidone.MethodsThirty-five subjects stabilized on risperidone (3-6 mg/day) for a minimum of 3 months were enrolled in a double-blind, placebo-controlled phase for 12 weeks and an open-label phase for another 12 weeks. Subjects were randomly assigned to receive 10 mg/day aripiprazole (n=17) or placebo (n=18). Over the following 12 weeks, the the aripiprazole group received a flexible dose of aripiprazole while tapering risperidone. At baseline, week 12, and week 24, subjects were evaluated using the Positive and Negative Syndrome Scale (PANSS), Extrapyramidal Syndrome Rating Scale (ESRS), and standardized neuropsychological assessments. Serum prolactin levels were checked at baseline, week 1, week 2, and week 24.ResultsThe mean change in total PANSS and cognitive function test scores between baseline and endpoint were similar in the aripiprazole and placebo groups. Scores on the ESRS and negative subscale of PANSS differed significantly between groups in both phases of the study (p<0.05), indicating a positive effect of aripiprazole. Compared with placebo, aripiprazole significantly reduced mean baseline serum prolactin levels within 1 week (p=0.015).ConclusionAdjunctive treatment with and switching to aripiprazole were not associated with improved cognitive function in patients with schizophrenia receiving risperidone; however, aripiprazole treatment decreased negative symptoms and risperidone-induced motor side effects and lowered serum prolactin levels.

Comparison of the effects of Sertindole and Olanzapine on Cognition (SEROLA): a double-blind randomized 12-week study of patients diagnosed with schizophrenia

To assess the cognitive effects of sertindole and olanzapine in patients diagnosed with schizophrenia. Cognition was the primary outcome of the study. This was a 12-week double-blinded randomized clinical controlled trial. Participants were randomized to either 16-24 mg of sertindole or 10-20 mg of olanzapine. The study had a low recruitment rate (N = 9) and was terminated before the expected number of patients was reached. No significant differences between groups were found at study end on any of the 32 cognitive subtests. A simple sign test did not show any of the comparator drugs trending towards being superior on the majority of tests. Mean change on Positive and Negative Syndrome Scale (PANSS) total and PANSS subscales from baseline to end of study were not significantly different between treatment groups. Similar results on cognition and PANSS was seen on completers and last observation carried forward analysis. In this study we did not find any significant differences between sertindole or olanzapine on PANSS subscales or neurocognitive tests in a population consisting of patients diagnosed with schizophrenia.

Adjunctive Lisdexamfetamine Dimesylate Therapy in Adult Outpatients With Predominant Negative Symptoms of Schizophrenia: Open-Label and Randomized-Withdrawal Phases

Negative symptoms of schizophrenia (NSS), related to hypodopaminergic activity in the mesocortical pathway and prefrontal cortex, are predictive of poor outcomes and have no effective treatment. Use of dopamine-enhancing drugs (eg, psychostimulants) has been limited by potential adverse effects. This multicenter study examined lisdexamfetamine dimesylate (LDX), a d-amphetamine prodrug, as adjunctive therapy to antipsychotics in adults with clinically stable schizophrenia and predominant NSS. Outpatients with stable schizophrenia, predominant NSS, limited positive symptoms, and maintained on stable atypical antipsychotic therapy underwent a 3-week screening, 10-week open-label adjunctive LDX (20-70 mg/day), and 4-week, double-blind, randomized, placebo-controlled withdrawal. Efficacy measures included a modified Scale for the Assessment of Negative Symptoms (SANS-18) and Positive and Negative Syndrome Scale (PANSS) total and subscale scores. Ninety-two participants received open-label LDX; 69 received double-blind therapy with placebo (n=35) or LDX (n=34). At week 10 (last observation carried forward; last open-label visit), mean (95% confidence interval) change in SANS-18 scores was -12.9 (-15.0, -10.8; P<0.0001). At week 10, 52.9% of participants demonstrated a minimum of 20% reduction from baseline in SANS-18 score. Open-label LDX was also associated with significant improvement in PANSS total and subscale scores. During the double-blind/randomized-withdrawal phase, no significant differences (change from randomization baseline) were found between placebo and LDX in SANS-18 or PANSS subscale scores. In adults with clinically stable schizophrenia, open-label LDX appeared to be associated with significant improvements in negative symptoms without positive symptom worsening. Abrupt LDX discontinuation was not associated with positive or negative symptom worsening. Confirmation with larger controlled trials is warranted.

Detachment, Compartmentalization, and Schizophrenia: Linking Dissociation and Psychosis by Subtype

To explain the phenomenological overlap between dissociation and schizophrenia, a dissociative subtype of schizophrenia has been proposed as a possibility. Dissociation is often believed to be organized on a continuum, although 2 qualitatively different phenomena can be distinguished in theory, research, and clinical practice: (a) states of separation from self or environment (detachment dissociation) and (b) inaccessibility of normally accessible mental contents (compartmentalization dissociation). This study used the Positive and Negative Syndrome Scale (PANSS) and the Association for Methodology and Documentation in Psychiatry module for the interview assessment of dissociation to investigate the relationships between PANSS subscales, detachment dissociation, and compartmentalization dissociation in a sample of 72 patients with schizophrenia. A confirmatory factor analysis sustained the bipartite model, yielding factors that grouped dissociative items around amnesia and depersonalization/derealization. The latter factor also contained identity disturbances and was therefore not entirely consistent with the theoretical formulations of detachment dissociation. It is important to note that the structure of those factors may be influenced by the symptoms of schizophrenia to which they were specifically linked: The factor containing depersonalization/derealization was connected to the positive symptoms subscale of the PANSS, whereas the factor containing amnesia was associated with the negative subscale. Hence, a dichotomy of dissociation is confirmed inasmuch as its subtypes are as distinguishable as PANSS subscales. This has implications on theoretical and clinical levels.

Clinical symptoms and cognitive impairment associated with male schizophrenia relate to plasma manganese superoxide dismutase activity: A case-control study

Several lines of evidence suggest that excessive reactive oxygen species-induced oxidative damage may underlie cognitive impairment in psychiatric disorders. A growing body of evidence show that oxidative damage may relate to the range of cognitive deficits associated with schizophrenia. In this study we examine one of the primary antioxidant defense enzymes manganese superoxide dismutase (MnSOD), and whether it relates to cognitive deficits in schizophrenia. We recruited 185 chronic male schizophrenia patients and 132 male controls and compared results from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and plasma MnSOD activity between groups. Symptom severity in patients with schizophrenia was assessed with the Positive and Negative Syndrome Scale (PANSS). Our results showed that MnSOD activities were significantly lower in patients than controls (p<0.05). Cognitive scores on the RBANS and nearly all of its five subscales (all p<0.001) except for the Visuospatial/Constructional index were significantly lower in schizophrenia patients than normal controls. MnSOD was negatively correlated with the general psychopathology subscale of PANSS, PANSS total score, positive symptoms and RBANS total score in patients with schizophrenia. Our findings add to growing evidence that oxidative stress may be involved in the psychopathology of male schizophrenia, and its associated cognitive impairment.

Pharmacokinetic–pharmacodynamic modelling of antipsychotic drugs in patients with schizophrenia: Part II: The use of subscales of the PANSS score

Background and objectivesThe superiority of atypical antipsychotics (also known as second-generation antipsychotics (SGAs)) over typical antipsychotics (first generation antipsychotics (FGAs)) for negative symptom control in schizophrenic patients is widely debated. The objective of this study was to characterize the time course of the scores of the 3 subscales (positive, negative, general) of the Positive and Negative Syndrome Scale (PANSS) after treatment of patients with antipsychotics, and to compare the control of negative symptom by SGAs versus a FGA (haloperidol) using pharmacokinetic and pharmacodynamic (PKPD) modelling. In addition, to obtain insight in the relationship between the clinical efficacy and the in vitro and in vivo receptor pharmacology profiles, the D2 and 5-HT2A receptor occupancy levels of antipsychotics were related to the effective concentrations. MethodsThe PKPD model structure developed earlier (part I) was used to quantify the drug effect using the 3 PANSS subscales. The maximum drug effect sizes (Emax) of oral SGAs (risperidone, olanzapine, ziprasidone, and paliperidone) across PANSS subscales were compared with that of haloperidol, while accounting for the placebo effect. Using the estimates of PKPD model parameters, the effective concentrations (Ceff) needed to achieve 30% reduction in the PANSS subscales were computed. Calculated effective concentrations were then correlated with receptor pharmacology profiles. ResultsPositive symptoms of schizophrenia responded well to all antipsychotics. Olanzapine showed a better effect towards negative symptoms than the other SGAs and haloperidol. Dropout modelling results showed that the probability of a patient dropping out from a trial was associated with all subscales, but was more strongly correlated with the positive subscale than with the negative or the general subscales. Our results suggest that different levels of D2 or 5-HT2A receptor occupancy are required to achieve improvement in PANSS subscales. ConclusionsThis PKPD modelling approach can be helpful to differentiate the effect of antipsychotics across the different symptom domains of schizophrenia. Our analysis revealed that olanzapine seems to be superior in treating the negative symptoms compared to other non-clozapine SGAs. The relationship between receptor pharmacology profiles of the antipsychotics and their clinical efficacy is not yet fully understood.

757 – Individual items scores vs. total scores of the schizophrenia syndrome on purpose of the relationships with the total antioxidant capacity

Relationships between total antioxidant capacity (TAC) and psychopathology in schizophrenia is controversial. Different methodological approaches may be a bias factor. The aim of this research is to analyze the relationship between psychopathology as individual items and psychopathology as syndromes with the serum TAC concentration in schizophrenic patients. 20 DSM-IV paranoid schizophrenic outpatients were recruited from the psychiatric outpatient's clinic of the University Hospital of the Canary Islands. The severity of schizophrenia symptoms was measured with the Positive and Negative Syndrome Scale (PANSS). Blood samples were collected at 12:00 and 00:00 hours. Relationships between quantitative variables were assessed with the Pearson's correlation coefficient. There was a significant correlation between the PANSS positive subscale and the nocturnal TAC levels (r=0.527, p< 0.02). The PANSS negative subscale was not correlated with TAC concentrations. Item by item scores of the positive and negative PANSS correlations with nocturnal and diurnal TAC levels revealed that only item 6 (suspicion) of the positive PANSS subscale was significantly correlated with the nocturnal TAC concentrations (r=0,491, p< 0.03). Only item 3 (poor contact) of the negative PANSS subscale was also significantly correlated with the nocturnal TAC concentrations (r=0,516, p< 0.02). We strongly recommend analyzing not only global scores of psychopathology but individual items scores when researching on biological markers in schizophrenia. This study was partly supported by a grant (PI: 08/115) of the Fundacion Canaria de Investigacion y Salud (FUNCIS). None of the authors have conflict of interest to disclose.

Poster #211 THE BEHAVIORAL PROFILE OF TP-10 IN RODENTS AND NON-HUMAN PRIMATES SUPPORTS PDE10A INHIBITION AS A NOVEL TREATMENT APPROACH FOR SCHIZOPHRENIA

The superiority of atypical antipsychotics (also known as second-generation antipsychotics (SGAs)) over typical antipsychotics (first generation antipsychotics (FGAs)) for negative symptom control in schizophrenic patients is widely debated. The objective of this study was to characterize the time course of the scores of the 3 subscales (positive, negative, general) of the Positive and Negative Syndrome Scale (PANSS) after treatment of patients with antipsychotics, and to compare the control of negative symptom by SGAs versus a FGA (haloperidol) using pharmacokinetic and pharmacodynamic (PKPD) modelling. In addition, to obtain insight in the relationship between the clinical efficacy and the in vitro and in vivo receptor pharmacology profiles, the D2 and 5-HT2A receptor occupancy levels of antipsychotics were related to the effective concentrations.The PKPD model structure developed earlier (part I) was used to quantify the drug effect using the 3 PANSS subscales. The maximum drug effect sizes (Emax) of oral SGAs (risperidone, olanzapine, ziprasidone, and paliperidone) across PANSS subscales were compared with that of haloperidol, while accounting for the placebo effect. Using the estimates of PKPD model parameters, the effective concentrations (Ceff) needed to achieve 30% reduction in the PANSS subscales were computed. Calculated effective concentrations were then correlated with receptor pharmacology profiles.Positive symptoms of schizophrenia responded well to all antipsychotics. Olanzapine showed a better effect towards negative symptoms than the other SGAs and haloperidol. Dropout modelling results showed that the probability of a patient dropping out from a trial was associated with all subscales, but was more strongly correlated with the positive subscale than with the negative or the general subscales. Our results suggest that different levels of D2 or 5-HT2A receptor occupancy are required to achieve improvement in PANSS subscales.This PKPD modelling approach can be helpful to differentiate the effect of antipsychotics across the different symptom domains of schizophrenia. Our analysis revealed that olanzapine seems to be superior in treating the negative symptoms compared to other non-clozapine SGAs. The relationship between receptor pharmacology profiles of the antipsychotics and their clinical efficacy is not yet fully understood.

One-year functional outcomes of naturalistically treated patients with schizophrenia

Against the background of the growing evidence that the patient's functioning significantly influences the course and outcome of schizophrenia, the aims of this analysis were to examine what proportion of patients achieve functional outcome criteria after 1 year, and to identify clinical and sociodemographic predictive factors for functional remission. Patients with the diagnosis of schizophrenia who were treated as inpatients at the beginning of the study were examined within a naturalistic follow-up trial. The present study reports on the time frame from admission to discharge of an inpatient treatment period and the 1-year follow-up assessment. The Global Assessment of Functioning (GAF) Scale and Social and Occupational Functioning Assessment Scale (SOFAS) were evaluated with respect to functional outcome, whereas Positive and Negative Syndrome Scale (PANSS) scores were rated as psychopathological outcome measures. Functional remission thresholds were defined according to a GAF score of ≥61 points and a SOFAS score ≥61 points. Symptomatic remission criteria were applied according to the remission criteria of the Schizophrenia Working Group. The Strauss–Carpenter Prognostic Scale (SCPS), the Phillips Premorbid Adjustment Scale, medical history, sociodemographic and psychopathologic parameters were evaluated in order to find valuable predictors for functional remission. One year after discharge from inpatient treatment, 211 out of 474 patients were available for analysis according to both rating scales used to assess functional remission (GAF and SOFAS). Forty-seven percent of patients fulfilled criteria for functional remission (GAF and SOFAS) at discharge and 51% of patients at the 1-year follow-up visit. With regard to symptomatic remission criteria, the corresponding remitter rates were 61% of patients at discharge and 54% at the 1-year follow-up visit. Forty-two percent of patients fulfilled both remission criteria at discharge and 37% at the 1-year follow-up visit. A significant association was found between functional and symptomatic remission at discharge and at the 1-year follow-up visit. The strongest predictors for functional remission at the 1-year follow-up visit were: a higher SCPS total score at admission, a lower number of previous hospitalizations, a status of employment, lower scores in all PANSS subscales at discharge, a better premorbid social adjustment, the occurrence of a first psychotic episode, a younger age, a lower PANSS negative subscore at admission, a status of being an early responder, a shorter duration of inpatient treatment, a later age of onset, and female gender.

P-1301 - Cross-cultural differences in the positive and negative syndrome scale (PANSS) among european and japanese raters

Introduction In clinical trials, good inter-rater reliability reduces error and influences statistical power. PANSS rater differences across cultures are rarely investigated. Objectives To conduct a cross-cultural analysis for European and Japanese PANSS raters, theorized to have unique frames of reference for schizophrenia assessments. Aims To examine reliability with Gold Standard scores (GS); to compare PANSS subscales. Methods There were 170 raters from Europe (73) and Japan (97). Analysis: scale-level for internal consistency (Cronbach α) and inter-rater reliability (ICC); item-level using Rasch and Differential Item Functioning (DIF). Results Internal consistency for PANSS Positive, Negative, and General Psychopathology subscales exceeded α = .99 for both groups. ICCs were higher for Europeans for all subscales. The average Inter-Item Correlation (IIC) with GS was highest for the Positive subscale (Europe, r = .901; Japan, r = .883). Average IIC with GS was lowest for both groups for the Negative subscale (Europe, r = .453; Japan, r = .323). For Negative items, accuracy with GS for Europeans was 46.58% to 89.04%, and 18.56% to 73.20% for Japanese. For PANSS Total, the average IIC was r = .721 (Europe) and r = .659 (Japan). European raters endorsed higher scores on P1.Delusions, P7.Hostility, N1.Blunted Affect, N5. Abstract Thinking. Japanese raters endorsed higher scores on N7.Stereotyped Thinking. Conclusions There were significant differences in several PANSS items, possibly due to disparities between original and translated scale versions, cultural differences in interpreting items, or PANSS scoring parameters. Identifying culturally problematic items can help to tailor PANSS training to diverse geographic regions.

Use of NON-PARAMETRIC Item Response Theory to develop a shortened version of the Positive and Negative Syndrome Scale (PANSS)

BackgroundNonparametric item response theory (IRT) was used to examine (a) the performance of the 30 Positive and Negative Syndrome Scale (PANSS) items and their options ((levels of severity), (b) the effectiveness of various subscales to discriminate among differences in symptom severity, and (c) the development of an abbreviated PANSS (Mini-PANSS) based on IRT and a method to link scores to the original PANSS.MethodsBaseline PANSS scores from 7,187 patients with Schizophrenia or Schizoaffective disorder who were enrolled between 1995 and 2005 in psychopharmacology trials were obtained. Option characteristic curves (OCCs) and Item Characteristic Curves (ICCs) were constructed to examine the probability of rating each of seven options within each of 30 PANSS items as a function of subscale severity, and summed-score linking was applied to items selected for the Mini-PANSS.ResultsThe majority of items forming the Positive and Negative subscales (i.e. 19 items) performed very well and discriminate better along symptom severity compared to the General Psychopathology subscale. Six of the seven Positive Symptom items, six of the seven Negative Symptom items, and seven out of the 16 General Psychopathology items were retained for inclusion in the Mini-PANSS. Summed score linking and linear interpolation was able to produce a translation table for comparing total subscale scores of the Mini-PANSS to total subscale scores on the original PANSS. Results show scores on the subscales of the Mini-PANSS can be linked to scores on the original PANSS subscales, with very little bias.ConclusionsThe study demonstrated the utility of non-parametric IRT in examining the item properties of the PANSS and to allow selection of items for an abbreviated PANSS scale. The comparisons between the 30-item PANSS and the Mini-PANSS revealed that the shorter version is comparable to the 30-item PANSS, but when applying IRT, the Mini-PANSS is also a good indicator of illness severity.

P.3.c.059 Incidence, onset, and duration of treatment-emergent somnolence with asenapine in adult patients with schizophrenia or bipolar disorder

Background: The atypical antipsychotic olanzapine has been approved for the treatment of schizophrenia in Europe since 1996 but has been used primarily as a second-line treatment to the less expensive typical agents. However, similar to other atypical antipsychotic drugs, olanzapine has a lower risk of inducing extrapyramidal symptoms, tardive dyskinesia, neuroleptic malignant syndrome, and sexual dysfunction compared with the typical antipsychotic drugs.Objective: The aim of this study was to determine whether patients with schizophrenia who have a poor response to their present antipsychotic therapy would show improvement when switched to olanzapine.Methods: This 13-week, multicenter, open-label, nonrandomized trial was conducted at 5 centers in Lithuania. Patients were started on oral olanzapine 10-mg tablets once daily, which could be adjusted by 5 mg/d in the dosing range of 5 to 20 mg/d. The primary efficacy measure was the total score on the Brief Psychiatric Rating Scale (BPRS), which was extracted from the Positive and Negative Syndrome Scale (PANSS). Efficacy response rate was defined a priori as the percentage of patients achieving ≥40% improvement in the BPRS total score. Secondary assessments included the PANSS total and BPRS and PANSS subscales and scores on the Clinical Global Impression-Severity of Illness (CGI-S), the CGI-Global Improvement (CGI-I), and the Patient Global Impression-Improvement (PGI-I) tests. Tolerability was primarily measured by assessing the incidence of treatment-emergent adverse events (AEs) according to the Udvalg fuer Kliniske Undersogelser (UKU) Side Effect Rating Scale and laboratory analyses.Results: Twenty-four patients (13 men [54.2%]; mean [SD] age, 32.4 [8.1] years) entered the study. Twenty-three (95.8%) of the 24 patients completed the study. The mean (SD) daily dosage of olanzapine was 11.40 (2.18) mg/d. The total mean (SD) BPRS score improved significantly from 37.8 (7.9) to 19.5 (13.7) (P < 0.001). The response rate was 58.3% (14/24 patients). The mean positive and negative BPRS scores and the mean total and subscale PANSS scores all improved significantly from baseline (P < 0.001). The mean (SD) CGI-S score improved significantly from 4.8 (0.8) at baseline to 3.5 (1.1) at end point (P < 0.001). Twenty-two patients (91.7%) showed improvement on the CGM scale. Similar improvement was found on the PGM scale. Treatment-emergent AEs occurred in 7 patients (29.2%). Improvement was found on 31 of the 48 UKU scale items; no change was shown on 15 items; and slight worsening was shown on 2 items. No clinical abnormalities were detected during the study.Conclusion: In this study of Lithuanian patients with schizophrenia, significant improvement was shown in all efficacy measures. In addition, olanzapine was well tolerated in these patients.

Adjunctive treatment of bimodal repetitive transcranial magnetic stimulation (rTMS) in pharmacologically non-responsive patients with schizophrenia: A preliminary study

We evaluated the efficacy of bimodal repetitive transcranial magnetic stimulation (rTMS) in treating pharmacologically non-responsive patients with schizophrenia. Ten patients with DSM-IV schizophrenia, unresponsive to pharmacological treatment, underwent treatment with 15 rTMS sessions, as an adjunctive therapy, for three weeks. Each session comprised 40 trains, beginning every 30s: 20 trains of 10 Hz rTMS to the left dorsolateral prefrontal cortex (DLPFC) with a 3-s duration and 20 trains of 1 Hz rTMS to the left temporoparietal cortex (TPC) with a 30-s duration. We assessed patients via the Positive and Negative Syndrome Scale (PANSS) and Korean Version of the Calgary Depression Scale for Schizophrenia (K-CDSS), at five time points: baseline, Days 8, 15, and 22, and 1 week after final treatment (Day 29). Patients who agreed to take neurocognitive tests underwent neurocognitive function evaluations at baseline and 1 week after final treatment. At Day 29, all PANSS subscale scores in had decreased significantly compared to baseline (Z=-2.214, p=0.027, positive; Z=-2.132, p=0.033, negative; Z=-2.023, p=0.043, general pathology; Z=-2.371, p=0.018, total). Effect over time was significant for the PANSS positive and negative subscale scores and total score (χ(2)=13.35, p=0.010; χ(2)=10.27, p=0.036; and χ(2)=16.50, p=0.002, respectively) but not for the general pathology subscale. Among the neurocognitive tests, the fourth and fifth trials and total K-AVLT scores showed significant increases (Z=-2.041, p=0.041; Z=-2.251, p=0.024; and Z=-2.201, p=0.028, respectively), suggesting improvement in short-term auditory verbal memory. Bimodal rTMS stimulation of left DLPFC and left TPC induced clinical improvement in pharmacologically non-responsive schizophrenia patients and may have improved their short-term verbal memories.

Cross‐ethnic differences in severity of symptomatology of individuals with first‐episode schizophrenia spectrum disorder

The aims of this study were to describe the relationship between ethnicity and severity of baseline symptomatology in a sample of Asian individuals with first-episode schizophrenia spectrum disorder, and to determine if ethnicity predicts severity of symptomatology independent of gender, duration of untreated illness, premorbid functioning, and age of illness onset. This descriptive study included all Chinese, Malay and Indian individuals consecutively admitted into an early intervention programme for treatment of first-episode schizophrenia spectrum disorder. Comparisons of mean scores among the three ethnic groups were performed using analysis of variance, while chi-squared tests were used to compare proportions. Subsequent pair-wise comparisons were performed with Bonferroni corrected statistic to examine specific ethnic group differences. Multivariate regression analyses were conducted to identify factors significantly associated with the severity of different clinical dimensions of schizophrenia measured using the Positive and Negative Syndrome Scale (PANSS). The analyses involved 503 individuals. The mean PANSS scores were significantly different between the ethnic groups across the PANSS subscales. A post-hoc analysis showed that Malays scored significantly higher than Chinese did across the PANSS subscales. Malays also scored significantly higher than Indians did on the negative scale and the general psychopathology scale. Being Malay compared with Chinese consistently predicted more severe positive, negative and general psychopathology symptoms. The results indicated that the severity of baseline symptomatology of individuals with first-episode schizophrenia spectrum disorders differed by ethnicity. Premorbid functioning appears to act as a potential mediator of the effects of ethnicity on the severity of psychotic symptoms.

P03-358 - Study on the executive function and learning ability in first-episode schizophrenia patients

IntroductionCognitive dysfunction was thought to be one of the core features of schizophrenia. And the executive function of the patients was paid more attention by more and more researchers and clinicians.ObjectivesTo investigate the executive function and the learning ability of the patients with first-episode schizophrenia, and their relationships with psychiatric symptoms.MethodsFifty cases of first-episode schizophrenia patients and fifty age- and gender-matched healthy controls were tested by a computerized version of Tower of London (TOL) test. The scores of the Positive and Negative Syndrome Scale(PANSS) in the group of schizophrenia patients were over 60.ResultsThe numbers of the correct answer [x1 :(14.62 ± 4.12), x2: (14.80 ± 4.70)] during the first session and the second session of the TOL test of the patients group were significantly lower than that of the control group [x1: (17.48 ± 3.79), x2:(18.68 ± 3.19)], and the reaction times [t1: (9.27 ± 4.37) seconds, t2: (9.51 ± 5.58) seconds] of the two sessions of TOL were longer than the control group [t1: (7.28 ± 2.04) seconds, t2: (6.67 ± 1.51) seconds], P &lt; 0.01. For the control group, x2 was significantly greater than x1, and t2 shorter than t1 (P &lt; 0.01), while for the patients group, there was no difference between the performances of the first session and the second session. The scores of TOL in the schizophrenia patients were correlated with the negative symptom score of PANSS (P &lt; 0.05) and were not correlated with the scores of other subscales of PANSS (P &gt; 0.05).ConclusionsThe executive function and the learning ability of schizophrenia are impaired and the cognitive dysfunction is correlated with negative symptoms.

Risperidone in the treatment of Schizophrenia

Risperidone is a second generation antipsychotic agent, with potent serotonin 5-HT2A and dopamine D2 receptor blocking effects. Specifically, risperidone possesses a unique balance of serotonin and dopamine antagonism, namely that its affinity for 5-HT2A receptors is significantly greater than its affinity for D2 receptors. Risperidone is well-established medication, with the proven effects on positive and negative symptoms of schizophrenia. The aim of research was to establish the effectiveness and safety of risperidone in patients with schizophrenia. The sample consisted of 60 subjects, age ranged was between 18-60 years, both genders, who met the criteria for the diagnosis various types of schizophrenia, according to ICD-10 (International Statistical Classification of Diseases). They were enrolled in the study as outpatient and inpatient setting. All subjects signed informed consent before entering into this study which had been conducted at the Psychiatric Clinic, University Clinical Center Sarajevo. Study was designed for 8-week, open-label, flexible-dose observational study. The subjects had to have a total score > -40 on Positive and Negative scale -two parts of the Positive and Negative Syndrome Scale (PANSS), and to be able to discontinue current antipsychotic medications. The primary efficacy parameter was the percent of score difference between baseline and week 8 of therapy on two above-mentioned PANSS subscales. The difference was considered as significant improvement if decrease from the baseline was 20% or more. The secondary efficacy parameter was subjective clinical evaluation of efficacy with five possible answers: very good, good, moderate, not satisfactory, not possible to evaluate. It was measured at the end of observational period by the investigator. All 60 enrolled patients completed the study. After the 8 weeks of treatment, 54/60 patients (90%) had clinically significant improvement of 20% or more decreased total PANSS score (Positive and Negative subscale). In 6/60 patients (10%) clinical improvement was also reported with less of 20% decreased total PANSS score. The side effects were registered in 8/60 patients (13.32%). The mild extrapyramidal symptoms registered in 1/60 (11.66%) patients, whom dose of risperidone was reduced. Increase of prolactine in 7/60 (11.66%), patients, whose dose of risperidone also were reduced. Average weight gain was 0.84 kg. In this study Risperidone has shown very good effectiveness and safety.

P.3.c.034 A 6-month naturalistic study of outcome in schizophrenic out-patients, treated with olanzapine

The study objectives were to evaluate the efficacy, safety, tolerability, and pharmacokinetics of RP5063 versus placebo. The study was conducted in adults with acute exacerbation of schizophrenia or schizoaffective disorder. This 28-day, multicenter, placebo-controlled, double-blind study randomized 234 subjects to RP5063 15, 30, or 50 mg; aripiprazole; or placebo (3:3:3:1:2) once daily. The aripiprazole arm was included solely to show assay sensitivity and was not powered to show efficacy. The primary endpoint was change from baseline to Day 28/EOT (End-of-Treatment) in Positive and Negative Syndrome Scale (PANSS) total score; secondary endpoints included PANSS subscales, improvement ≥ 1 point on the Clinical Global Impressions-Severity (CGI-S), depression and cognition scales.The primary analysis of PANSS Total showed improvement by a mean (SE) of − 20.23 (2.65),− 15.42 (2.04), and − 19.21 (2.39) in the RP5063 15, 30, and 50 mg arms, versus − 11.41 (3.45) in the placebo arm. The difference between treatment and placebo reached statistical significance for the 15 mg (p = 0.021) and 50 mg (p = 0.016) arms.Improvement with RP5063 was also seen for multiple secondary efficacy outcomes. Discontinuation for any reason was much lower for RP5063 (14%, 25%, 12%) versus placebo (26%) and aripiprazole (35%). The most common treatment-emergent adverse events (TEAE) in the RP5063 groups were insomnia and agitation. There were no significant changes in body weight, electrocardiogram, or incidence of orthostatic hypotension; there was a decrease in blood glucose, lipid profiles, and prolactin levels.In conclusion, the novel dopamine serotonin stabilizer, RP5063 is an efficacious and well-tolerated treatment for acute exacerbation of schizophrenia or schizoaffective disorder.

P.3.c.026 Risperidone depot versus zuclopenthixol depot for schizophrenia and schizophrenialike psychoses: real world outcomes

The study objectives were to evaluate the efficacy, safety, tolerability, and pharmacokinetics of RP5063 versus placebo. The study was conducted in adults with acute exacerbation of schizophrenia or schizoaffective disorder. This 28-day, multicenter, placebo-controlled, double-blind study randomized 234 subjects to RP5063 15, 30, or 50 mg; aripiprazole; or placebo (3:3:3:1:2) once daily. The aripiprazole arm was included solely to show assay sensitivity and was not powered to show efficacy. The primary endpoint was change from baseline to Day 28/EOT (End-of-Treatment) in Positive and Negative Syndrome Scale (PANSS) total score; secondary endpoints included PANSS subscales, improvement ≥ 1 point on the Clinical Global Impressions-Severity (CGI-S), depression and cognition scales.The primary analysis of PANSS Total showed improvement by a mean (SE) of − 20.23 (2.65),− 15.42 (2.04), and − 19.21 (2.39) in the RP5063 15, 30, and 50 mg arms, versus − 11.41 (3.45) in the placebo arm. The difference between treatment and placebo reached statistical significance for the 15 mg (p = 0.021) and 50 mg (p = 0.016) arms.Improvement with RP5063 was also seen for multiple secondary efficacy outcomes. Discontinuation for any reason was much lower for RP5063 (14%, 25%, 12%) versus placebo (26%) and aripiprazole (35%). The most common treatment-emergent adverse events (TEAE) in the RP5063 groups were insomnia and agitation. There were no significant changes in body weight, electrocardiogram, or incidence of orthostatic hypotension; there was a decrease in blood glucose, lipid profiles, and prolactin levels.In conclusion, the novel dopamine serotonin stabilizer, RP5063 is an efficacious and well-tolerated treatment for acute exacerbation of schizophrenia or schizoaffective disorder.