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Background Patient-centered outcomes research (PCOR) emphasizes the patient perspective and input to inform the research process with the aim to improve the quality of care. Given PCOR's emphasis on the patient perspective, methods to incorporate patient-reported outcomes (PROs) are important. Electronic PROs (ePROs) have been implemented successfully in many populations; however, many of these measurements do not incorporate patient perspective in the development of ePROs. For epilepsy and seizure disorders, user perspectives are key to developing measurements that capture real-time data, as seizures are not timed events; therefore, patients can wait days or even weeks and then try to recall their experience which can lead to variations in recall. ePRO can provide the necessary assurance that data were entered by the patient at the time the episode occurs. The aim of the present study was to assess patient perceptions of completing ePROs, expectations of ePRO devices for PCOR and on-site clinical visit in order to guide the development of successful ePRO deployment in seizure-related disorders. Methods This study used a naturalistic cohort design. A sample of 713 persons completed an online survey which consisted of 11 situational questions. Of the 713 individuals, results from 640 participants were included. Results were compared using a Wilcoxon signed-rank test. Results Most participants (71.9%) were able to accurately identify a seizure and 86.3% of participants felt it would be beneficial to have a short training on seizure symptoms prior to completing a daily seizure diary, and seizures should be reasonably reported within 10 mins (n = 426, 66.6%). Participants endorsed that repetitive movements and loss of consciousness as the most predominant symptoms they would look for in an ePRO. A majority of participants, 67.0% indicated that they regularly use accessibility features on using smartphones and tablets, and 38.6% indicated they would like to see more than one item per screen but only if they are related and to see all text in a larger size with scrolling features using fingers (n = 246; 38.4%). Conclusion This study has demonstrated the importance of developing ePROs that satisfy the needs of the participants and caregivers without compromising the scientific and clinical aspects of the disease construct. Developing tools using participant needs, observations, characteristics and input is essential to putting the participant perspective in patient-centered outcomes research.

Individuals from academia, the pharmaceutical industry, and regulators reevaluated earlier recommendations for the design of clinical trials for negative symptoms based on data from recent large trials. A session in February, 2018 at the International Society of CNS Clinical Trails and Methodology (ISCTM) annual meeting reviewed results from selected trials that reported findings between 2013 and 2018. The group reached a consensus on prior recommendations that should be reconsidered in future trials which included: (1) How can placebo effects be minimized? (2) Should global measures of negative symptoms be included? (3) Should a new drug targeting negative symptoms be tested in a monotherapy design or in an add-on design? (4) Can new information from negative symptom trials inform the selection of clinical outcome assessments (COA’s) for future trials? For each of these issues new data was evaluated, discussed by the group, and in some cases the earlier recommendations were revised.

The MATRICS Consensus Cognitive Battery (MCCB) was developed to assess cognitive treatment effects in schizophrenia clinical trials, and is considered the FDA gold standard outcome measure for that purpose. The aim of the present study was to establish pre-treatment psychometric characteristics of the MCCB in a large pooled sample. The dataset included 2616 stable schizophrenia patients enrolled in 15 different clinical trials between 2007 and 2016 within the United States (94%) and Canada (6%). The MCCB was administered twice prior to the initiation of treatment in 1908 patients. Test-retest reliability and practice effects of the cognitive composite score, the neurocognitive composite score, which excludes the domain Social Cognition, and the subtests/domains were examined using Intra-Class Correlations (ICC) and Cohen's d. Simulated regression models explored which domains explained the greatest portion of variance in composite scores. Test-retest reliability was high (ICC=0.88) for both composite scores. Practice effects were small for the cognitive (d=0.15) and neurocognitive (d=0.17) composites. Simulated bootstrap regression analyses revealed that 3 of the 7 domains explained 86% of the variance for both composite scores. The domains that entered most frequently in the top 3 positions of the regression models were Speed of Processing, Working Memory, and Visual Learning. Findings provide definitive psychometric characteristics and a benchmark comparison for clinical trials using the MCCB. The test-retest reliability of the MCCB composite scores is considered excellent and the learning effects are small, fulfilling two of the key criteria for outcome measures in cognition clinical trials.

Background Many individuals with chronic or treatment resistant schizophrenia experience multiple relapses or treatment failures during the course of the illness. Some of these relapses are due to poor treatment compliance that is inherent to schizophrenia. Poor insight may be a leading cause for partial- or non-adherence to treatment as a high proportion of individuals with schizophrenia are partially or completely unaware of their mental disorder. The first two years after stabilization are thought to be key for long-term functional and clinical prognosis. In the present study, we first estimated the rate of treatment failure or relapse following clinical stability at one and two years, investigate the time to occurrence of relapse among individuals with chronic schizophrenia and the association between baseline clinical features recorded during the inpatient hospitalization and relapse at one- and two-year time points. We hypothesized that lack of insight, as measured by the PANSS item G12, would be a greater predictor of relapse than other characteristics previously suggested as possible predictors, including other symptoms from the PANSS, age, duration of illness, age at onset of illness, substance use, number of prior hospitalizations, and length of stay of the pre-discharge hospitalization. Methods A total of 138 participants diagnosed with schizophrenia or schizo-affective disorder were assessed with a comprehensive assessment at one year and two-year following discharge from a long-term psychiatric facility. Regression models were used to determine factors predicting time to relapse and other elements of functioning. Baseline factors examined included PANSS, MCCB, PSP, demographics and treatment variables. Results Relapse rates were 56.52% (n=78 of 138) by Year 1, and 69.56% (n=96 of 138) by end of Year 2. The estimated relapse-free period for all individuals at the end of the study was 8.78 months. The backward elimination (–2 log likelihood=189.59, χ2=9.01, df=2, p=.021) showed that the best predictive variables for relapse were lack of insight/judgment as assessed by PANSS item G12 at baseline (B=.20, SE=.09, df=1, p=.011, Exp[B]=1.36), lifetime years of substance use (B=.16, SE=.11, df=1, p=.029, Exp[B]=1.33), PANSS Factor baseline score on Disorganization (B=.15, SE=.12, df=1, p=.031, Exp[B]=1.56), and number of previous hospitalizations (B=.13, SE=.11, df=1, p=.048, Exp[B]=1.23). No other baseline variables were found to be significant. Discussion Poor insight is a fundamental symptom of schizophrenia that, while not entirely and uniformly expressed in all individuals, is among the most common symptoms across subjects. Our study shows that the numerous negative consequences of lack of insight should lead clinicians and researchers to make insight a high priority for allocation of clinical resources. Effective approaches to managing these predictive characteristics will allow affected individuals and their families and care providers to take part in collaborative treatment and relapse risk-management paradigms.

Background The Virtual Reality Functional Capacity Assessment Tool (VRFCAT) is an “applied” game-based assessment that uses a multi-level functional task to assess instrumental activities of daily living (iADL). This study examines the feasibility, convergent validity, and predictive ability of the VRFCAT in a sample of inpatients with chronic schizophrenia. Methods Inpatients with a DSM-5 diagnosis of schizophrenia or schizoaffective disorder, completed the VRFCAT prior to discharge. The UPSA-B, SLOF, and PSP were administered, both at baseline and after four-weeks in the community. VRFCAT performance scores were compared to published data from the VRFCAT validation study. Results All 62 participants completed the VRFCAT. Compared to the performance of stable outpatients, participants performed 1.50 SDs below the VRFCAT mean adjusted total time (ATT) (Validation study: Mean T Score = 32.5, SD = 16.59) with more errors. The VRFCAT ATT T-score was significantly correlated with baseline UPSA-B total score (p = 0.005) and PSP Global score (p = 0.010). 34 participants completed the follow-up period (55%), and 28 were lost to follow-up. There were no statistically significant differences in VRFCAT scores between these two groups (all p > 0.29). The VRFCAT composite score at baseline was significantly associated with the UPSA-B total score (p = 0.010) and the PSP total score (p = 0.008) at four-weeks, as was the PSP Socially Useful Activities subscale score (p = 0.006). Conclusion The VRFCAT is a valid measure of iADLs in inpatients with chronic schizophrenia. The VRFCAT predicted instrumental functioning four-weeks post-discharge. Future studies should examine other moderators of measures of functional capacity pre-discharge, predicting function later in the community.

This study demonstrates the quantitative characteristics of the first patient-reported outcome (PRO) tool developed for patients with nontransfusion-dependent β-thalassemia (NTDT), the NTDT-PRO© . A multicenter validation study was performed over 24 weeks, involving 48 patients from Italy, Lebanon, Greece, and Thailand. Most patients were female (68.8%), with a median age of 34.5 years (range, 18-52); 66.7% were diagnosed with β-thalassemia intermedia, and median time since diagnosis was 22 years (range, 0-43). The NTDT-PRO comprises 6 items across 2 domains (Tiredness/Weakness and Shortness of Breath [SoB]), and was valid and reliable, with good consistency. At baseline, most patients reported symptoms as present via the NTDT-PRO, and were highly compliant, ≥90% completing the NTDT-PRO tool. In a pairwise correlation analysis, all items were positively correlated. Correlations between NTDT-PRO and existing tools-36-Item Short Form Health Survey version 2 (SF-36v2) and Functional Assessment of Cancer Therapy-Anemia (FACT-An)-were assessed at weeks 1, 3, and 12; robust correlations were seen between SoB and SF-36v2-Vitality (rs = -0.53), and between SoB and Fact-An-Fatigue Experience (rs = -0.66) at week 1. Internal consistency was high for both Tiredness/Weakness (Cronbach alpha, 0.91) and SoB (Spearman-Brown coefficient, 0.78); intraclass correlation coefficients were high (Tiredness/Weakness, 0.88 and 0.97; SoB, 0.92 and 0.98), demonstrating stability. Further studies are required to fully support the validity of this tool, this study demonstrated the usefulness of the NTDT-PRO in the clinical setting and for longitudinal clinical research, particularly in trials where patient health-related quality of life is expected to change.

Background Transcranial direct-current stimulation (tDCS), a non-invasive neurostimulation treatment, has been reported in a number of sham-controlled studies to show significant improvements in treatment-resistant auditory hallucinations in schizophrenia patients, primarily in ambulatory and higher-functioning patients, but little is known of the effects of tDCS on hospitalized, low-functioning inpatients. Objective/Hypothesis The purpose of this study was to examine the efficacy and safety of tDCS for auditory hallucinations in hospitalized ultra-treatment-resistant schizophrenia (TRS) and to evaluate the effects of tDCS on cognitive functions. We hypothesized that treatment non-response reported in previous tDCS studies may have been due to the insufficient duration of direct-current stimulation. Methods Inpatient participants with DSM-V schizophrenia, long-standing treatment-resistance, and auditory verbal hallucinations (AVH) participated in this 4-week sham-controlled, randomized trial. Assessments included the Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB) at baseline and endpoint (at the end of Week 4), and the Auditory Hallucinations Rating Scale (AHRS) administered at baseline, endpoint, and weekly throughout the study. Participants were randomized to receive active vs. sham tDCS treatments twice daily for 4 weeks. Results Twenty-eight participants were enrolled (tDCS, n = 15; control, n = 13) and 21 participants completed all 4 weeks of the trial. Results showed a significant reduction for the auditory hallucination total score (p ≤ 0.05). We found a 21.9% decrease in AHRS Total Score for the tDCS group and a 12.6% decrease in AHRS Total Score for the control group. Significant reductions in frequency, number of voices over time, length of auditory hallucinations, and overall psychopathology were also observed for the tDCS group. When assessing cognitive functioning, only Working Memory showed improvement for the tDCS group. Conclusion Although there was only a small improvement noted in auditory hallucination scores for the tDCS group, this improvement was meaningful when compared to no standard treatment of the control group. While this makes the interpretation of clinical significance debatable, it does confirm that tDCS combined with pharmacological intervention can provide clinical gains over pharmacological intervention alone. Therefore, tDCS treatment appears to be effective not only for ambulatory, higher-functioning patients, but also for patients with ultra-treatment-resistant schizophrenia.

Objective Current dopamine-blocking antipsychotic drugs have little impact on the cognitive deficits associated with schizophrenia. We evaluated whether MIN-101, a molecule that combines sigma-2 antagonism and 5-HT2A antagonism, might improve cognitive deficits in individuals with moderate to severe negative symptoms in schizophrenia. Methods Individuals (N = 244) aged 18 to 60 years with stable symptoms of DSM-5-defined schizophrenia and moderate to severe negative symptoms were randomized to placebo (n = 83), MIN-101 32 mg (n = 78), or MIN-101 64 mg (n = 83) in a 12-week, phase 2b, prospective, double-blind, placebo-controlled, parallel-group trial between May 2015 and December 2015. In a post hoc analysis, mean z and T score changes from baseline at 12 weeks of treatment in the cognitive composite score and individual tests on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery were compared between MIN-101 and placebo. Results A total of 79 patients (95.2%) from the placebo group, 76 (97.4%) from the MIN-101 32 mg group, and 79 (95.2%) from the MIN-101 64 mg group completed the BACS at baseline. The BACS token motor (P = .04), verbal fluency (P = .01), and composite z scores (P = .05) showed significant improvements in the MIN-101 32 mg group compared to the placebo group. At week 4, the clinical improvements from baseline in the Positive and Negative Syndrome Scale (PANSS) negative factor showed a significant correlation with improvements from baseline on the BACS composite in the 64 mg group (r = -0.292, P = .020). At week 12, improvement in the PANSS negative factor showed significant correlations with improvements in the BACS composite (r = -0.408, P = .002), Trail Making Test (r = -0.394, P = .003), and verbal memory (r = -0.322, P = .017) for the 64 mg group. Conclusions Results suggest a possible benefit of MIN-101 on cognitive performance in individuals with schizophrenia with stable positive symptoms and concurrent clinically significant negative symptoms. Trial registration EU Clinical Trials Register identifier: 2014-004878-42​.

Background: The Brief Assessment of Cognition in Schizophrenia (BACS) is a pen-and-paper cognitive assessment tool that has been used in hundreds of research studies and clinical trials, and has normative data available for generating age- and gender-corrected standardized scores. A tablet-based version of the BACS called the BAC App has been developed to allow standardized presentation of task instructions and stimuli, audio-recording of subject responses, and automatized scoring and data management. Development of the BAC App was aimed at reducing rater burden and variability. Our validation study compared performance on the traditional BACS and the BAC App in patients with schizophrenia and healthy controls. Test equivalency was assessed, and the applicability of paper-based normative data was evaluated. An ongoing follow-up study examines BAC App performance in large-scale census-matched normative sample.

Background: Assessment of functional capacity is vital in establishing an understanding of real world functioning in patients with cognitive impairment in schizophrenia. Most available tests of functional capacity are paper and pencil tests, or are not fully computerized. The Virtual Reality Functional Capacity Assessment Tool (VRFCAT), developed by NeuroCog Trials, is a novel VR program, which provides a sequence of typical and real life community tasks. It offers ecological validity and complements the clinical assessment of functional capacity The aim of the present study was (1) to examine the feasibility of the VRFCAT in a population of very low functioning patients with Treatment resistance schizophrenia (TRS), (2) to relate the performance of the study patients to standardized VRFCAT performance data of higher functioning patients (Keefe et al,. 2016) and (3) to validate the performance level with other concurrent function measures.

International Society for CNS Clinical Trials and Methodology convened an expert working-group that assembled consistency/inconsistency flags for the Positive and Negative Syndrome Scale (PANSS). Twenty-four flags were identified and divided based on extent to which they represent error (Possibly, Probably, Very probably or definitely). The flags were applied to assessments derived from the NEWMEDS data repository and the CATIE clinical trial data. Almost 40% of ratings had at least one inconsistency flag raised and 10% had two. Application of flags to clinical rating can improve reliability and validity of trials.

Background The Positive and Negative Syndrome Scale (PANSS) assesses multiple domains of schizophrenia. Evaluation of each of these domains was conducted to assess differences in the characteristics of psychopathology and their relative predominance in sub-populations. Method Subjects (N = 1,832) with DSM-IV schizophrenia were represented in three sub-populations: First Episodes, n = 305, Chronic Inpatients, n = 694, and Ambulatory Outpatients, n = 833. Nonparametric Item Response Analysis (IRT) was performed with Option Characteristic Curves (OCC), Item Characteristic Curves (ICC), slopes and item biserial correlation. Items were characterized as Very Good, Good, or Weak based on specified operational criteria for item selection. Results First episode patients were represented by negative, disorganized hostility and anxiety. Some negative domain items (Poor Rapport, Passive/Apathetic Social Withdrawal) and most positive domain items were scored as Weak. For chronic inpatients, all items of the anxiety domain and some items of the positive domain (Suspiciousness/Persecution, Stereotyped Thinking, Somatic Concerns) were Weak; for all other domains, items were Very Good or Good. For ambulatory outpatients, most items in the anxiety and hostility domain were scored as Weak. The majority of PANSS items were either Very Good or Good at assessing the overall illness severity: chronic inpatients (73.33%, 22 items), first episodes (60.00%, 18 items), and only 46.67% (14 items) in the ambulatory group. Conclusion Findings confirm differences in symptom presentation and predominance of particular domains in subpopulations of schizophrenia. Identifying symptom domains characteristic of subpopulations may be more useful in assessing efficacy endpoints than total or subscale scores.

Background Transcranial direct-current stimulation (tDCS), a noninvasive neurostimulation treatment, has been reported to show improvements in treatment-resistant auditory hallucinations in patients with schizophrenia. tDCS administered over a limited number of sessions effectively produced lasting attenuation of auditory hallucinations in otherwise stable outpatients. It has also been shown that tDCS may be a useful intervention for ameliorating cognitive deficits in patients with chronic schizophrenia. The purpose of this study was to test tDCS for auditory hallucinations in ultra-treatment resistant schizophrenia to assess if this form of neurostimulation can alleviate treatment-refractory auditory hallucination symptoms up to 4 weeks after the final treatment. In addition, we also wanted to examine the effects of tDCS on cognitive functions. Methods 28 inpatients with DSM-V schizophrenia and long-standing treatment resistance and persistent auditory verbal hallucinations were recruited. Each individual participated in behavioral assessments at baseline, endpoint and follow-up [PANSS and Auditory Hallucinations Rating Scale (AHRS) and MCCB cognitive battery] and were randomized to receive active vs. sham tDCS treatments. For active treatment, patients had the inhibitory (cathodal) tDCS electrode placed over left auditory cortex relative to an excitatory (anodal) electrode placed over frontal cortex on the right side. tDCS treatments took place for 20 min twice daily for 5 consecutive days. Assessment batteries were repeated following the 4 weeks of treatment. The Chattanooga, dual channel CHA-1335 stimulator with two 7 × 5 cm (35 cm2) sponge electrodes soaked in a saline solution (0.9% NaCl) was used for the delivery of 2 mA current. Results A total of 28 subjects were enrolled (tDCS, n = 13; Control, n = 15). 20 subjects completed the trial. 3 subjects dropped out of the active tDCS treatment group, while 4 subjects did not complete the control treatment due to early discharge from the hospital. Most subjects were male (tDCS n = 10, 76.9%; Control n = 6, 40.0%). Length of present psychiatric admission ranged from 1–25 months, with a mode of 2 months (n = 12) and average of 2.9 months. Participating inpatients were on clozapine, haloperidol, paliperidone depot, fluphenazine decanoate, paliperidone, olanzapine, and risperidone as primary medications. Repeated Measures ANOVA showed a significant difference for the auditory hallucination total score, frequency and number of voices over time (p < 0.05) with greater reduction in scores observed for the tDCS group. Improvements were maintained after 4 weeks. There was no significant change over time observed for the PANSS positive symptoms or total score, or for the PANSS Hallucinatory Behavior item score. When assessing cognitive functioning, only Working Memory change was significant (p = 0.048) between the tDCS and the Control group with the tDCS group showing significant improvement in T-Score as compared to the Control group. Discussion Subjects who received tDCS treatment showed a significant reduction in the frequency, number of voices, and total scores of their auditory hallucination. Additionally, subjects in the tDCS group showed significant improvement in the Working Memory. Our results indicate that patients who have been ultra-resistant to antipsychotic treatments and who received tDCS treatment presented with robust diminution of their auditory hallucinations. We conclude that tDCS seems to be effective not only for ambulatory, higher functioning patients, but also for much lower functioning patients with medication-refractory auditory verbal hallucinations.

Background: The Positive and Negative Syndrome Scale (PANSS) is a widely used assessment for patients with schizophrenia across clinical and research settings. This scale allows the classification of the psychotic symptoms to better understand the psychopathology in patients with schizophrenia. There are no available data on the different components of psychopathology in Arab patients with schizophrenia. Objectives: This study examined the factor structure of the validated Arabic version of the PANSS in a sample of Arab patients with schizophrenia. Methods: The Arabic version of the PANSS was administered to 101 patients with schizophrenia, and principal component analysis (PCA) was carried out after the cross-cultural adaptation and validation of this version. Results: This sample had more males (66.3%) than females (33.7%) with a mean age of 35.03 years (SD = 9.99). PCA showed that 28 items loaded on 5 components: cognitive, negative, excited, depressed and positive. These factors explained 63.19% of variance. The 2 remaining items, grandiosity and somatic concerns, did not load well on any of these components. Conclusion: Our results support the common 5-dimension PANSS model shown in other cultures with different languages. Nevertheless, there were minor differences, which could reflect cultural or semantic differences.

Background Patients with schizophrenia commonly show both depressive and negative symptoms that can differentially affect the prognosis and course of treatment. The Calgary Depression Scale for Schizophrenia (CDSS) was designed to distinguish between depression and negative symptoms in patients with schizophrenia. The purpose of this study is to validate an Arabic version of the CDSS among patients with schizophrenia. Methods The diagnosis of schizophrenia was confirmed using the Arabic Mini International Neuropsychiatric Interview 6 (MINI 6). A standardized translation back-translation process was adopted. One rater administered the Arabic CDSS to subjects with schizophrenia as well as to a control group who should not have any psychiatric disorder except for depression. Another rater, blinded to the results administered the already validated Arabic version of Beck Depression Inventory-II (BDI-II). Results We recruited 102 patients and 102 controls subjects. The CDSS showed good internal consistency in the active group (Cronbach’s alpha = 0.82). The Intraclass Coefficient correlations (ICC) for the inter-rater reliability (n = 21) was 0.90, p

Background: The Positive and Negative Syndrome Scale (PANSS) is widely used for patients with schizophrenia. This scale is reliable and valid. The PANSS was translated and validated in several languages. Objective: The aim of this study was to translate and validate the PANSS in the Arab population. Subjects and Methods: The PANSS was translated into formal Arabic language using the back-translation method. 101 Arab patients with schizophrenia and 98 Arabs with no diagnosis of any mental disorder were recruited. The Arabic version of the Mini International Neuropsychiatric Interview (MINI-6) was used as a diagnostic tool to confirm the diagnosis of schizophrenia or rule out any diagnosis for the healthy control group. Reliability of the scale was assessed by calculating internal consistency, interrater reliability and test-retest reliability. Construct validity was assessed using the Arabic version of the MINI-6. PANSS total scores were correlated with the Clinical Global Impression-Severity scale. Results: Our findings showed that the internal consistency was good (0.92). Scores on the PANSS of the patients were much higher than those of the healthy controls. The PANSS showed good interrater reliability and test-retest reliability (0.92 and 0.75, respectively). In comparison with the MINI-6, the PANSS showed good sensitivity and specificity, which implies good construct validity of this version. Conclusion: In conclusion, the Arabic version of the PANSS is a reliable and valid instrument for the assessment of patients with schizophrenia in the Arab population.

Despite numerous studies of diabetes mellitus type II (DM-II) in schizophrenia and schizoaffective disorder, there have been no studies on the glycemic effects of switching patients with long-standing symptomatic DM-II from their current antipsychotic regimen to ziprasidone.An open-label, prospective inpatient study was conducted with 26 suboptimally responding inpatients with DSM-IV diagnoses of schizophrenia or schizoaffective disorder and comorbid DM-II who were switched to ziprasidone monotherapy and followed for 8 weeks. Outcome measures were fasting glucose, triglycerides, cholesterol, insulin levels, capillary blood glucose levels and weight. After a 3-week cross-titration period, patients were treated with ziprasidone up to a dose of 320 mg daily.Of the 26 study participants, 16 completed the entire study period of 63 days and 10 (38.46%) discontinued participation, primarily due to psychotic relapse. There was a statistically significant reduction in fasting glucose (F=4.43, p=0.05; 14.68 mg/dL mean reduction), capillary blood glucose levels (F=8.90, p=0.01; 25.36 mg/dL mean reduction), weight (F=4.46, p=0.05; 4.68 lb mean weight loss) and Body Mass Index (F=4.40, p=0.05; 3.62 kg/m(2) mean reduction). There was also a reduction in the use of antidiabetic medications after the switch to ziprasidone. Nine (34.62%) patients met criteria for metabolic syndrome (MetS) at baseline, as compared to 4 (15.38%) at endpoint. No change was observed in positive symptoms (F=0.62, p=0.44), negative symptoms (F=1.47, p=0.24) and in total PANSS score (F=0.12, p=0.74).This study suggests significant improvement in metabolic side effects and MetS in the subset of the patients who were able to tolerate switching from a polypharmacy regimen to ziprasidone. There was a large discontinuation rate, which limited the sustained beneficial effects of ziprasidone. The decision to switch to ziprasidone in patients with prior suboptimal response has to balance the potential metabolic benefits and the potential relapse risks of the individual patient first and foremost.

Quetiapine is often prescribed at doses higher than those approved by regulatory authorities, with limited evidence from controlled trials. The objective of this study was to assess the safety, tolerability, and efficacy of high-dose quetiapine (1200 mg/d) compared with a standard dose of 600 mg/d among patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, schizophrenia or schizoaffective disorder hospitalized at 2 state-operated psychiatric facilities. In order to be eligible for randomization, subjects were required to prospectively fail to demonstrate an initial therapeutic response during a 4-week run-in phase with quetiapine at 600 mg/d (immediate release and dosed twice a day). Lack of an adequate initial response was defined a 15% or lower decrease in the Positive and Negative Syndrome Scale total score. Patients were then randomized to either continue quetiapine at 600 mg/d for an additional 8 weeks or to receive 1200 mg/d quetiapine instead. No significant differences were observed between the high dose (n = 29) and standard dose (n = 31) groups in change from baseline to endpoint on extrapyramidal symptoms, electrocardiographic changes, or most laboratory measures between groups. There was a significant difference between groups for triglycerides (P = 0.035), and post hoc tests revealed a decrease in triglycerides from baseline (mean [SD], 162.7 [59.3] mg/dL) to endpoint (mean [SD], 134.8 [ 62.7] mg/dL) for the 600 mg/d group (P = 0.019). The mean change in the Positive and Negative Syndrome Scale total score did not differ between groups. In conclusion, quetiapine at 1200 mg/d, although reasonably tolerated, did not confer any advantages over quetiapine at 600 mg/d among patients who had failed to demonstrate an adequate response to a prospective 4-week trial of 600 mg/d.

To assess the impact of adjunctive aripiprazole versus adjunctive placebo treatment on suicidality in patients with major depressive disorder.Data were pooled from 2 identical aripiprazole augmentation studies. Patients with DSM-IV-TR-diagnosed major depressive disorder with an inadequate response to 8 weeks of prospective antidepressant treatment were randomly assigned to adjunctive placebo or adjunctive aripiprazole (2-20 mg/d) treatment for 6 weeks. Adverse events related to suicidality were identified in the adverse event database using the Medical Dictionary for Regulatory Activities-preferred term. Treatment-emergent suicidal ideation was defined using item 10 (suicidality) of the Montgomery-Åsberg Depression Rating Scale (MADRS) and item 18 (suicidality) of the Inventory of Depressive Symptomatology (IDS).In total, 737 patients were included in the safety database (aripiprazole n = 371; placebo n = 366). No suicides were reported. There were no treatment-emergent, suicide-related adverse events in the aripiprazole group; 2 patients in the placebo group had ≥ 1 adverse event related to suicide (both suicidal ideation). More placebo than aripiprazole patients25 years old experienced a 2-point (P.01) or 1-point (P.05) worsening of MADRS item 10 scores. For this age group, 2-point improvement in MADRS item 10 scores and 1-point improvement of IDS item 18 scores were significantly more common in aripiprazole patients than placebo patients (both P.05).This post hoc analysis demonstrated that adjunctive aripiprazole treatment in patients with depression with a history of an inadequate response to antidepressant medication is associated with a decreased rate of suicidality in a group of subjects not at significant risk. Prospective trials directly assessing suicidality are needed to further understand the benefits of an adjunctive antipsychotic in an at-risk population.clinicaltrials.gov Identifiers: NCT00095823 and NCT00095758.

A program evaluation examined a long-term cognitive skills inpatient program (STAIR) in reducing rehospitalization and rearrest rates in mental illness. Psychiatric and criminal histories were obtained. Psychological tests were administered. After discharge, monthly follow-up was obtained. One hundred forty-five patients completed the STAIR program and were followed for a range of six to 60 months after discharge. Thirty-one (21.4%) remained stable, 67 (46.2%) were rehospitalized, and 47 (32.4%) were rearrested and/or rehospitalized. Group membership was predicted by STAIR admission age and outpatient medication compliance. Significantly, fewer arrests, hospitalizations, and days institutionalized occurred post-STAIR. Medication compliance is the single most enduring factor associated with clinical stability and prevention of criminal behavior. Other factors’ impact may vary depending on the length of stay in the community. Long-term inpatient programs (e.g., STAIR) may be helpful to some of these patients.

Background: After noting a significant reduction in aggression and agitation in treatment-refractory patients with molindone augmentation in severely aggressive inpatients, the authors conducted a retrospective medical records review to assess the possible anti-aggressive role of molindone treatment in a larger cohort of treatment-refractory inpatients. Method: Twenty-four weeks of data from thirty inpatients who were consecutively augmented with molindone, including progress notes, orders for seclusion, chemical restraint, and scores on the Agitation-Calmness Evaluation Scale (ACES) were systematically collected. The number of seclusions, number of as-needed medications (PRNs) and ACES scores were used to tabulate the frequency of aggression and agitation episodes during the 8-week period before, 8 weeks after, and 9 through 16 weeks after the initiation of molindone augmentation treatment. Results: Over the observation period of twenty-four weeks, the number of episodes of PRN medication administration ...

OBJECTIVE Primary negative symptoms are intrinsic to the pathology of schizophrenia and are associated with significant deficits in motivation, verbal and nonverbal communication, affect, and cognitive and social functioning. Overall, atypical antipsychotic medications have been found to be more efficacious than conventional antipsychotics in the treatment of negative symptoms, based on studies with acute patients. Results have been confounded by concomitant improvements in positive, depressive, and extrapyramidal symptoms. This 12-week, double-blind, controlled study aimed to examine the effects of the atypical antipsychotic olanzapine versus haloperidol on persistent, primary negative symptoms and neurocognitive functions in stable schizophrenic patients with the deficit syndrome and low levels of concomitant positive, depressive, and extrapyramidal symptoms. METHOD Thirty-five patients with DSM-IV-TR schizophrenia and predominant negative symptoms were randomly assigned in a 12-week double-blind study to either olanzapine (15-20 mg/day) or haloperidol (15-20 mg/day). Patients taking haloperidol received additional blinded benztropine. Inclusion criteria were Positive and Negative Syndrome Scale (PANSS) negative score of >or=20, PANSS positive score < 20, and fulfilling the criteria for the Schedule for the Deficit Syndrome. The PANSS, Clinical Global Impressions, Hamilton Rating Scale for Depression (HAM-D), Simpson-Angus Scale, and Abnormal Involuntary Movement Scale were assessed at regular subsequent intervals. A neuropsychological battery examining declarative verbal learning memory, attention and processing speed, executive functioning, and simple motor functioning domains of cognition was assessed at baseline and endpoint. The study ran from September 1998 through May 2005. RESULTS CLINICAL RESULTS There was a statistically significant difference for PANSS negative symptoms (F = 5.44, df = 1,15; p

A functional polymorphism of the catechol-O-methyltransferase (COMT) gene (Val158Met) partially appears to influence cognitive performance in schizophrenia subjects and healthy controls by modulating prefrontal dopaminergic activity. This study evaluated the association of the COMT Val108/158 Met genotype with response to computerized neurocognitive remediation (CRT).145 subjects with DSM-IV-TR schizophrenia or schizoaffective disorder were genotyped via saliva sampling. Subjects were evaluated on neurocognitive assessments (MATRICS) and clinical symptoms (PANSS) at baseline and endpoint after 12weeks of CRT. "Improvement" was defined as ≥67% of cognitive domains (≥4) showing performance increases. If ≤67% (≤2) of domains improved, the change was defined as "minimal improvement." A general linear model was conducted for change of each cognitive domain.Of 145 subjects, data from 138 subjects were usable. Distribution of COMT genotype: Met/Met: 28 (20.29%), Val/Met: 61 (44.20%), and Val/Val: 49 (35.51%). No significant differences were seen among genotype groups at baseline or across genotype group for "Improvement" vs. "Minimal Improvement." GLM analysis showed significant differences in Verbal Learning (p=0.003), Visual Learning (p=0.014) and Attention/Vigilance (p=0.011) favoring Met/Met and Val/Met groups.The low activity Met allele (Met/Met; Val/Met) was associated with significantly greater improvements in the MATRICS domains of Verbal Learning, Visual Learning and Attention/Vigilance after CRT.

Background: Significant increase in life expectancy has been observed in patients with β-thalassemia in recent years. The improved survival, however, is accompanied by significant ongoing healthcare needs related to the chronic condition; therefore, quality of life (QoL) has emerged as a fundamental focus of comprehensive patient care. We compared QoL outcomes between transfusion-dependent (TD) and non-transfusion-dependent (NTD) patients with β-thalassemia in the routine clinical care setting. Method: Adult patients with β-thalassemia were prospectively enrolled in an observational study in Italy, Greece, Lebanon, and Thailand. All patients completed Short Form 36 Health Survey version 2 (SF-36v2) and Functional Assessment of Cancer Therapy (FACT)-Anemia (An) questionnaires at baseline, and then once every 3 weeks using a hand-held electronic device. This analysis evaluated QoL between TD and NTD patients at study entry. Transfusion dependent was defined as receiving ≥ 6 red blood cell (RBC) units in the 24 weeks prior to study entry and no transfusion-free period for ≥ 35 days during that period. Results: A total of 102 patients with β-thalassemia were enrolled, of which 52 were TD and 50 NTD. The mean age of patients was 31.2 years and 70 (68.6%) were females. On average, patients with TD β-thalassemia were 3.6 years younger (P= 0.06) and had moderately higher hemoglobin values at baseline (8.8 vs 8.2 g/dL; P= 0.02). At study entry, all (100%) patients with TD β-thalassemia had received RBC transfusions within the 24 weeks prior to study entry, as per inclusion criteria, versus 5 (10%) patients with NTD β-thalassemia who had received RBC transfusions during the same time period. Patients with NTD β-thalassemia reported lower QoL on all domains and summary scores as captured by the SF-36v2 questionnaire, except for Role-Physical. On average, patients with NTD β-thalassemia experienced statistically significant lower QoL versus their TD counterparts on the domains of General Health (39.5 vs 44.0; P= 0.01), Vitality (49.3 vs 53.7; P= 0.01), and Mental Health (46.8 vs 50.8; P= 0.01), and in the Mental Component Summary Score (46.5 vs 50.8; P= 0.01). Similarly, patients with NTD β-thalassemia reported worse QoL scores from the FACT-An questionnaire on all domains and statistically significant differences were observed for Emotional Well-Being (18.5 vs 20.0; P= 0.02), Functional Well-Being (20.0 vs 23.2; P < 0.01), and FACT-General (82.9 vs 89.4; P= 0.01). Conclusions: In the routine clinical care setting, there are critical unmet medical needs for patients with NTD β-thalassemia as they experience worse QoL on many domains compared with patients with TD β-thalassemia. There is a need for new interventions to treat patients with NTD β-thalassemia and reduce their burden of disease. Disclosures Cappellini: Vifor: Honoraria; Novartis: Speakers Bureau; Celgene: Honoraria; Sanofi-Genzyme: Honoraria, Research Funding, Speakers Bureau. Kattamis: National and Kapodistrian University of Athens: Employment; Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy. Viprakasit: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Siriraj Hospital: Employment; Shire: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding. Sutcharitchan: Celgene: Research Funding; Chulalongkorn University: Consultancy, Employment. Mahmoud: Celgene: Employment. Pariseau: Celgene: Employment. Laadem: Celgene: Employment, Equity Ownership. Khan: Nathan S. Kline Institute for Psychiatric Research; Manhattan Psychiatric Center: Employment. Hu: Celgene: Employment, Equity Ownership. Taher: Novartis Pharmaceuticals: Honoraria, Research Funding; Celgene: Research Funding.

Background: Significant cognitive impairment is already seen in first-episode psychosis (FEP) and degree of impairment is a moderator of long-term outcomes. Does specialized FEP treatment improve cognitive functioning? The NIMH sponsored RAISE-ETP study allows comparison of NAVIGATE, a coordinated specialty care intervention designed for FEP, to Community Care (CC) in a randomized clinical trial. (RCT)

BACKGROUND Considering the increasing attention to the study of failed clinical trials, the goal of this study was to identify the sources of unreliability in a failed clinical trial by assessing scores on the Positive and Negative Syndrome Scale (PANSS). METHODS This study is a substudy from a failed phase 2 double-blind, placebo-controlled trial of schizophrenia. Using the generalizability theory, this substudy assesses reliability on 3 conditions: raters, time points (PANSS evaluations, 1 week apart), subjects for 3 groups (placebo responders, placebo nonresponders, and treatment group). RESULTS The placebo response rate was 40.07% (32/71). For all PANSS positive symptom items, the most variability was for raters (range, 33%-72%) for the placebo responders, 31% to 68% for the placebo nonresponders, and 29% to 60% for the treatment group. The variability of the interaction of rater and time point was the second source of unreliability, with an average of 12.28% compared to 12.00% for the placebo nonresponders and 10.00% for the treatment group. All items of the negative symptom subscale showed the most percent variability for raters, for all groups. For general psychopathology items (except preoccupation), raters accounted for the most variability in the scores for placebo responders with an average of 51.00% across items. A similar pattern was observed for the placebo nonresponders and for the treatment group; for the treatment group, the interaction between rater and time point accounted for the most variability for somatic concern and anxiety. CONCLUSIONS Results confirm the efficacy of applying the generalizability theory to the estimation of reliability to identify a source of unreliability and provide evidence for the relationship between low reliability and failed trials. Findings can be used to guide data monitoring, rater training, and identification of PANSS items, which may require supplementary training.

Background: Considering the scarcity of longitudinal assessments of reliability, there is need for a more precise understanding of cognitive decline in Alzheimer’s Disease (AD). The primary goal was to assess longitudinal changes in inter-rater reliability, test retest reliability and internal consistency of scores of the ADAS-Cog. Methods: 2,618 AD subjects were enrolled in seven randomized, double-blind, placebo-controlled, multicenter-trials from 1986 to 2009. Reliability, internal-consistency and cross-sectional analysis of ADAS-Cog and MMSE across seven visits were examined. Results: Intra-class correlation (ICC) for ADAS-Cog was moderate to high supporting their reliability. Absolute Agreement ICCs 0.392 (Visit-7) to 0.806 (Visit-2) showed a progressive decrease in correlations across time. Item analysis revealed a decrease in item correlations, with the lowest correlations for Visit 7 for Commands (ICC=0.148), Comprehension (ICC=0.092), Spoken Language (ICC=0.044). Discussion: Suitable assessment of AD treatments is maintained through accurate measurement of clinically significant outcomes. Targeted rater education ADAS-Cog items over-time can improve ability to administer and score the scale.

Background Nonparametric 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. Methods Baseline 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. Results The 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. Conclusions The 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.

Background Galantamine, a reversible cholinesterase inhibitor with effects on nicotinic receptors, has shown mixed effects on cognitive impairments in patients with schizophrenia. Given these mixed results we examined whether galantamine compared to adjunctive placebo may improve cognitive functions in patients treated concomitantly with a long acting atypical antipsychotic. Method The parent study was a 52-week double-blind, randomized study of treatment with long-acting injectable risperidone 25 mg or 50 mg every two weeks. Adjunctive galantamine or placebo treatment was administered from Month 6 to 12. Outcome measures were neurocognitive, psychopathology, social and quality of life functions. Patients were randomized to blinded galantamine up to 24 mg/day or matching placebo tablets. All patients were maintained on their randomized long-acting injectable risperidone regimen for the duration of the trial. Results 32 patients were included in the intent-to-treat analysis. No statistically significant differences were found for Attention Vigilance, Declarative Memory, Processing Speed, Reasoning/Problem Solving, Working Memory domains and the Neurocognitive Composite Score. Group specific analysis showed a statistically significant group interaction ( p = 0.043) with the Social Cognition domain showing in the galantamine group significantly lower scores at endpoint than placebo patients. The PANSS general psychopathology subscale showed significantly higher scores in the galantamine group at endpoint ( p = 0.05). ANCOVA model for within treatment group comparisons showed a significant increase of 7.3 points for the total PANSS score for the galantamine group. Conclusion Galantamine showed no ameliorative effects on cognitive measures in this 6 month, double-blind study of patients with schizophrenia treated with an assured and stable antipsychotic medication delivery system. Galantamine may not be an appropriate augmentation agent for cognitive impairments in patients with schizophrenia at the dose used.

It is generally accepted that between 10 and 60% of patients with schizophrenia respond poorly or only partially to antipsychotic treatment, even if they take their antipsychotic medication reliably.

Objective: Obesity is increasing at an alarming rate in the United States, as is the obesity rate in patients with schizophrenia. Our study retrospectively evaluated the effectiveness of the Solutions for Wellness and Team Solutions programs, 2 structured educational patient programs, and evaluated the effects on obesity and other metabolic markers in a large, naturalistic inpatient sample. Method: Between September 18, 2006, and September 15, 2007, 275 inpatients with DSM-IV TR-diagnosed chronic mental illness admitted to a tertiary care psychiatric facility were included in the 36-week comprehensive and manualized educational program for healthy lifestyles for patients with chronic mental illness incorporating psychoeducational small-group curricula. Patients were tested before and after each of three 12-week group periods by 30 knowledge-assessment questions, and metabolic markers were recorded at baseline, midpoint, and endpoint. Results: Of the 275 included inpatients, 50.5% completed more than 5 modules, 20.4% completed less than or equal to 2 or fewer modules, and 5.1% completed all 11 modules. Significant increases in scores were observed for 7 of the 11 modules in the knowledge assessments (P

Background Comparisons of diabetic potential, glucose related metabolic levels, and insulin resistance between olanzapine and risperidone have produced variable results in cross-sectional and epidemiologic studies. Randomized prospective studies of metabolic effects during treatment with these drugs may provide results that are more informative. Method Hospitalized patients with chronic schizophrenia (DSM-IV), most of whom had been treated with multiple antipsychotics in the past, were randomly assigned to treatment with a single antipsychotic, olanzapine or risperidone, for a period of 5 months. At baseline and every treatment month thereafter, fasting glucose, insulin, insulin-related metabolic measures, and prolactin were assessed, and an oral glucose tolerance test (OGTT) was performed during baseline and months 1, 2, and 5 of treatment. Weight was assessed monthly, and waist and hip measures were taken at baseline and month 5. Data were analyzed on 23 patients randomly assigned to risperidone and 23 patients randomly assigned to olanzapine. The study was conducted from February 2003 to August 2007. Results Most patients were overweight or obese at baseline (mean body mass index [BMI] = 29.4), but there were no differential drug effects on weight change and no differences between drug groups at the 5-month time point. There were no overall drug treatment differences in fasting glucose or glycohemoglobin or 2-hour glucose levels in OGTT and no differences between the two drug groups at the 5-month time point. There were no consistent drug treatment differences in the number of patients who developed borderline or diabetic glucose levels. Olanzapine-treated patients showed a significantly greater increase than risperidone-treated patients in a fasting measure of insulin resistance (P = .041), and olanzapine patients showed greater decreases in insulin sensitivity during OGTT (P = .023) compared to risperidone-treated patients. Olanzapine-treated patients had a significantly greater increase in 1-hour glucose and insulin levels during OGTT in subsequent months compared to baseline and greater increase in glucose and insulin area under the curve over time than the risperdone-treated patients. Prolactin levels decreased in olanzapine patients and increased in risperidone patients (P values approximately .02). There were no significant drug treatment differences in C-peptide levels or 2 indices proposed as measures of insulin secretion or beta-cell function (homeostasis model assessment of beta-cell function [HOMA-B], BIGTT-acute insulin response surrogate measure [BIGTT-AIR]). Changes in insulin resistance over time were not strongly related to changes in BMI or waist circumference during study drug treatment. Conclusions The increase in insulin levels during olanzapine treatment may compensate for the increase in insulin resistance and serve to reduce fasting and postprandial glucose levels. This may contribute to the lack of differences between olanzapine and risperidone in indices of diabetic or prediabetic glucose levels or glycohemoglobin. How many years this compensatory mechanism will persist needs further investigation. Periodic OGTT tests measuring glucose and insulin levels would be helpful in assessing the status of beta-cell insulin reserve in patients treated with olanzapine and other second-generation antipsychotics and assessing an individual patient's risk for conversion to type 2 diabetes. Trial registration clinicaltrials.gov Identifier NCT00287820.

A key problem in schizophrenia research is how to assess the effects of treatment interventions given the spectrum of schizophrenia symptoms and patients' functioning. Measuring symptoms is complex, because these symptoms cover a wide variety of psychopathologic domains. The commonly recognized domains are the positive, negative, cognitive, excitement, and depression domains. This article critically reviews some of the available assessment tools of these domains together with other associated syndromes. The instruments discussed cover the broad range of psychopathology found in patients who have schizophrenia.

Treatment of patients with schizophrenia can be improved by precise administration of rating scales. The Positive and Negative Syndrome Scale (PANSS) is a commonly used tool to assess symptoms of schizophrenia. In order to develop a participatory learning program that aims to enhance raters training and increase inter-rater reliability we trained five actors to serve as standardized patients (SP). A training program for SPs was constructed using a narrative analysis scheme in the following manner: 1) Seven transcripts of SCI-PANSS interviews were analyzed and subdivided into thematic chapters including: symptom frequency, intensity, complexity, interference and impairment; 2) Script/story analysis of transcribed interviews were conducted where we identified scripted elements common among all seven interviews and storied elements that deviate from the script and have a function to individuate each of the interviews; 3) Linguistic markers (words, phrases, or discursive patterns indicative of symptoms and their severity) that are often seen as hallmarks of aetiology of schizophrenia were identified; 4) Symptoms were divided into two severity levels, moderate and severe, and three full SCI-PANSS interview scripts were built; 5) A workshop for five professional actors was conducted under the supervision of an expert PANSS interviewer. By studying the development of this program knowledge can be gained about a number of aspects related overall psycho-social functioning of individuals diagnosed with schizophrenia, such as the impact of semantic and discursive practices on interpersonal interactions and their further effect on the progress of the illness.

The pharmacological choices for the treatment of schizophrenia have been greatly expanded with the availability of the atypical compounds clozapine (Clozaril, Novartis), risperidone (Risperdal, Janssen-Cilag), olanzapine (Zyprexa, Eli Lilly & Co.), quetiapine (Seroquel, AstraZeneca), ziprasidone (Geodon, Pfizer Inc.) and aripiprazole (Abilify, Otsuka Pharmaceutical Co. Ltd). In this article, the effects of the newer antipsychotics and their side effects are reviewed. Key issues in acute and maintenance treatment, often lifelong, will be reviewed. Side-effect management to ensure adherence to an optimal treatment regimen will be discussed. Coexisting syndromes must be treated in concordance with the patient's clinical presentation. For treatment-resistant patients, atypical compounds are generally more effective than their typical counterparts but medication augmentation strategies are frequently recommended. Finally, the results of recent meta-analyses comparing the effects of atypical versus typical compounds will be critically reviewed and remaining gaps in the current pharmacotherapy of schizophrenia will be explored.

Objectives The PANSS is utilized in clinical trials for assessment of psychopathology. In order to determine the status of a patient, comparisons within a general population are necessary. If several groups of patients are to be compared, gender, age, co-morbid diagnoses, and other factors affecting clinical status are not identically distributed. Aims 1) Phase 1: To establish the initial psychometric properties of the PANSS-Ru. 2) Phase 2: To establish normed-reference data for the PANSS-Ru. Methods Phase 1: 40 patients with schizophrenia and other psychotic disorders. Phase 2: 375 individuals (n = 250 patients; n = 125 controls). Responses were assessed for internal consistency, stability, reliability, discriminative validity, and construct validity. Fifth percentile norms are presented as step functions. Data were compared to US norms. Results 40 subjects enrolled for Phase 1. Alpha coefficient of 0.88 verified good internal consistency. Test-retest comparisons verified time stability ( r = 0.67 to 0.92). Correlation between subscale and the total scores ranged from 0.76 to 0.86, compared to > 0.83 for US norm studies. Internal consistencies were α > 0.745. Mean subscale/ total score were equivalent to US population norms within 13%. However, there was a difference of > 5 norm-based points for mean general psychopathology subscale. Norms had a sensitivity of 85% and specificity of 89%. Conclusions Preliminary results show that different dimensions of symptom presentations in the Russian population may help to improve symptom-specific treatments, and will also provide comparison data for a Russian population. Further normative studies are warranted in other populations.

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.

Background Patients with schizophrenia are known to have higher rates of mortality and morbidity when compared to the general population. Suicidality is a major contributor to increased mortality. The International Suicide Prevention Trial (InterSePT) Scale for Suicidal Thinking (ISST) is a validated tool to assess current suicidal ideation in patients with schizophrenia. The aims of the study were to culturally adapt the Arabic translation of ISST and to examine the psychometric characteristics of the Arabic version of the ISST among patients with schizophrenia in Qatar. Methods ISST was translated and adapted into formal Arabic using the back translation method. Patients diagnosed with schizophrenia were randomly recruited from the department of Psychiatry, Rumailah Hospital, Doha, Qatar. Healthy controls were randomly recruited from two primary health care centers in Doha, Qatar. The Arabic version of Module B for suicidality in Mini International Neuropsychiatric Interview was used as the gold standard to which the Arabic ISST was compared. Results The study sample (n = 199) was composed of 100 patients diagnosed with schizophrenia (age 35.30 ± 10.04 years; M/F is 2/1) and 99 controls (age 33.98 ± 8.33 years; M/F is 2/3). The mean score on the ISST was 3.03 ± 4.75 vs. 0.47 ± 1.44 for the schizophrenia and control groups, respectively. Inter-rater reliability coefficient was 0.95, p > 0.001. The overall Cronbach’s alpha was 0.92. Principal Component Analysis produced 3 factors explaining a total of 73.8% of variance. Conclusions This is the first study in the Arab countries to validate the Arabic version of the ISST. The psychometric properties indicate that the Arabic ISST is a valid tool to assess the severity of suicidal ideation in Arabic patients with schizophrenia.