Sustained Treatment Response and Global Improvements With Long-term Valbenazine in Patients With Tardive Dyskinesia.

PURPOSE/BACKGROUND: Using data from KINECT® 4, a phase 3, 48-week study of valbenazine, post hoc analyses were conducted to assess long-term outcomes that are relevant to the real-world management of tardive dyskinesia (TD). METHODS/PROCEDURES: Post hoc analyses of the participants of the KINECT 4 study who completed 48 weeks of open-label valbenazine (40 or 80 mg) treatment were conducted. Valbenazine effects on TD were evaluated using the Abnormal Involuntary Movement Scale (AIMS), Clinical Global Impression of Change-TD (CGI-TD), and Patient Global Impression of Change (PGIC). FINDINGS/RESULTS: Of 103 participants completing 48 weeks of treatment, 55% experienced clinically meaningful improvement (defined as ≥2-point reduction in AIMS total score [sum of items 1 - 7, evaluated by site raters]) by week 4; at week 48, 97% met this threshold. The percentage of completers who achieved AIMS total score response thresholds of ≥10% to ≥90% increased over time, with 86% of completers reaching ≥50% improvement. Of the 40 (39%) completers with AIMS ≥50% response at week 8, 38 (95%) sustained this response at week 48; 81% of those who did not meet this threshold at week 8 had achieved it by week 48. At week 48, more than 85% of completers achieved CGI-TD and PGIC ratings of "much improved" or "very much improved." IMPLICATIONS/CONCLUSIONS: The majority of participants who completed 48 weeks of treatment with once-daily valbenazine experienced substantial clinically meaningful and sustained TD improvements. These findings indicate that valbenazine can be a highly effective long-term treatment in patients with TD.

A long-term, open-label study of valbenazine for tardive dyskinesia.

BACKGROUND: Individuals with tardive dyskinesia (TD) who completed a long-term study (KINECT 3 or KINECT 4) of valbenazine (40 or 80 mg/day, once-daily for up to 48 weeks followed by 4-week washout) were enrolled in a subsequent study (NCT02736955) that was primarily designed to further evaluate the long-term safety of valbenazine. METHODS: Participants were initiated at 40 mg/day (following prior valbenazine washout). At week 4, dosing was escalated to 80 mg/day based on tolerability and clinical assessment of TD; reduction to 40 mg/day was allowed for tolerability. The study was planned for 72 weeks or until termination due to commercial availability of valbenazine. Assessments included the Clinical Global Impression of Severity-TD (CGIS-TD), Patient Satisfaction Questionnaire (PSQ), and treatment-emergent adverse events (TEAEs). RESULTS: At study termination, 85.7% (138/161) of participants were still active. Four participants had reached week 60, and none reached week 72. The percentage of participants with a CGIS-TD score ≤2 (normal/not ill or borderline ill) increased from study baseline (14.5% [23/159]) to week 48 (64.3% [36/56]). At baseline, 98.8% (158/160) of participants rated their prior valbenazine experience with a PSQ score ≤2 (very satisfied or somewhat satisfied). At week 48, 98.2% (55/56) remained satisfied. Before week 4 (dose escalation), 9.4% of participants had ≥1 TEAE. After week 4, the TEAE incidence was 49.0%. No TEAE occurred in ≥5% of participants during treatment (before or after week 4). CONCLUSIONS: Valbenazine was well-tolerated and persistent improvements in TD were found in adults who received once-daily treatment for >1 year.

Persistent Barriers to the Use of Long-Acting Injectable Antipsychotics for the Treatment of Schizophrenia.

PURPOSE/BACKGROUND: One of the major challenges in the treatment of schizophrenia is nonadherence, defined as the failure to take medications as prescribed. Nonadherence is a strong predictor of symptom relapse, hospital readmission, and poorer long-term outcome. Although long-acting injectable antipsychotics (LAIs) have been found to be superior to their oral analogs at reducing relapse in large-scale meta-analyses, their prevalence seldom exceeds 30% even in populations with a history of nonadherence. We review multiple barriers to the use of LAI utilization and suggest strategies to address them. METHODS/PROCEDURES: We searched for the following terms: long-acting injectable/depot antipsychotics, schizophrenia, barriers, and attitude/perception in both the PubMed search index and Google scholar from 1995 to 2018. A total of 329 studies were selected, of which data from 13 were reviewed for this article. Only peer-reviewed studies, randomized controlled trials, systematic reviews, and meta-analyses that describe barriers to using LAIs were included. FINDINGS/RESULTS: Several barriers to using LAIs were identified. These are organized into 3 overarching categories: those related to the clinician; those related to the patient; and systems barriers. Clinician factors include the perception of LAIs as coercive, fears of not being able to control the dose, as well as current practice patterns and guidelines. Patient factors include perception of the injection as painful or intrusive, general lack of knowledge, and a sense of coerciveness. For each identified barrier, we propose potential solutions. IMPLICATIONS/CONCLUSIONS: We identified multiple barriers to using LAIs in patients with schizophrenia. Specific strategies are suggested for overcoming each of these barriers.

A Phase 3, 1-Year, Open-Label Trial of Valbenazine in Adults With Tardive Dyskinesia.

PURPOSE/BACKGROUND: Valbenazine is approved to treat tardive dyskinesia (TD) in adults. KINECT 4 (NCT02405091) was conducted to explore the long-term effects of once-daily valbenazine in patients with TD. METHODS/PROCEDURES: The study included a 48-week, open-label treatment period and 4-week washout. Dosing was initiated at 40 mg/d, with escalation to 80 mg/d at week 4 based on efficacy and tolerability. Standard safety methods were applied, including treatment-emergent adverse event (TEAE) reporting. Valbenazine effects on TD were assessed using the Abnormal Involuntary Movement Scale (AIMS), Clinical Global Impression of Change-TD, and Patient Global Impression of Change. FINDINGS/RESULTS: After week 4, <15% of all participants had a serious TEAE (13.7%) or TEAE leading to discontinuation (11.8%). Participants experienced TD improvements during long-term treatment as indicated by mean change from baseline to week 48 in AIMS total score (sum of items 1-7, evaluated by site raters) with valbenazine 40 mg/d (-10.2 [n = 45]) or 80 mg/d (-11.0 [n = 107]). At week 48, most participants had ≥50% improvement from baseline in AIMS total score (40 mg/d, 90.0%; 80 mg/d, 89.2%), Clinical Global Impression of Change-TD rating of much or very much improved (40 mg/d, 90.0%; 80 mg/d, 95.9%), and Patient Global Impression of Change rating of much or very much improved (40 mg/d, 90.0%; 80 mg/d, 89.2%). No dose effects were apparent by week 36. Week 52 results indicated some loss of effect after washout. IMPLICATIONS/CONCLUSIONS: Valbenazine was generally well tolerated, and no new safety concerns were detected. Substantial clinician- and patient-reported improvements were observed in adults with TD who received once-daily valbenazine for up to 48 weeks.

Paliperidone Palmitate Once-Monthly Injectable Treatment for Acute Exacerbations of Schizoaffective Disorder.

The optimal treatment for schizoaffective disorder (SCA) is not well established. In this initial 6-month open-label treatment period of a large, multiphase, relapse-prevention study, the efficacy and safety of paliperidone palmitate once-monthly (PP1M) injectable were evaluated in subjects with symptomatic SCA. Subjects with acute exacerbation of SCA (ie, with psychotic and either depressive and/or manic symptoms) were enrolled and treated with PP1M either as monotherapy or in combination with antidepressants or mood stabilizers (combination therapy group). After flexible-dose treatment with PP1M for 13 weeks, stabilized subjects continued into a 12-week fixed-dose PP1M treatment period. A total of 667 subjects were enrolled; 320 received monotherapy and 347 received PP1M as combination therapy; 334 subjects completed the entire 25-week treatment. Statistically significant and clinically meaningful improvements from baseline were observed for all efficacy measures in psychosis (per Positive and Negative Syndrome Scale), mood symptoms (per Young Mania Rating Scale and Hamilton Depression Rating Scale-21 items), and functioning (per Personal and Social Performance Scale) from week 1 to all time points during the 25-week treatment period (P < 0.001). Similar improvements in efficacy measures were observed between subjects receiving monotherapy or combination therapy. Efficacy benefits persisted throughout the 25-week period. The most common adverse events were akathisia (11.1%), injection-site pain (10.6%), and insomnia (10.0%). Paliperidone palmitate once-monthly administered as monotherapy or in combination with mood stabilizers or antidepressants in patients with an acute exacerbation of SCA provided rapid, broad, and persistent reduction in psychotic, depressive, and manic symptoms, as well as improved functioning.

Computerized cognitive and social cognition training in schizophrenia for impulsive aggression.

BACKGROUND: Schizophrenia is associated with an elevated risk for impulsive aggression for which there are few psychosocial treatment options. Neurocognitive and social cognitive deficits have been associated with aggression with social cognitive deficits seemingly a more proximal contributor. The current study examined the effects of combining cognitive and social cognition treatment on impulsive aggression among inpatients with chronic schizophrenia and schizoaffective disorder and a history of aggression compared to cognitive remediation treatment alone. METHODS: The two-center study randomized 130 participants to receive 36 sessions of either a combination of cognitive remediation and social cognition treatment or cognitive remediation plus a computer-based control. Participants had at least one aggressive incident within the past year or a Life History of Aggression (LHA) score of 5 or more. Participants completed measures of neurocognition, social cognition, symptom severity, and aggression at baseline and endpoint. RESULTS: Study participants were mostly male (84.5 %), had a mean age 34.9 years, and 11.5 years of education. Both Cognitive Remediation Training (CRT) plus Social Cognition Training (SCT) and CRT plus control groups were associated with significant reductions in aggression measures with no group differences except on a block of the Taylor Aggression Paradigm (TAP), a behavioral task of aggression which favored the CRT plus SCT group. Both groups showed significant improvements in neurocognition and social cognition measures with CRT plus SCT being associated with greater improvements. CONCLUSION: CRT proved to be an effective non-pharmacological treatment in reducing impulsive aggression in schizophrenia inpatient participants with a history of aggressive episodes. The addition of social cognitive training did not enhance this anti-aggression treatment effect but did augment the CRT effect on cognitive functions, on emotion recognition and on mentalizing capacity of our participants.

Advances in Cognitive Remediation Training in Schizophrenia: A Review.

Cognitive Remediation Training (CRT) in schizophrenia has made great strides since its introduction in the 1990s. CRT was developed with the aim of improving the everyday functioning of individuals living with cognitive impairment. MEDLINE, PsychINFO, and Google Scholar were searched to extract peer-reviewed randomized controlled trials to produce the current review article. The aim of the present review is to summarize CRT effects on addressing cognitive changes in patients undergoing CRT as defined by the Cognitive Remediation Experts Workshop and to describe the areas of greatest impact in specific cognitive domains. Another area of this review aims to summarize the modalities of intervention (paper and pencil; computerized; home bound), the persistence of improvements, and their generalization to other domains of functioning. Finally, this review delineates barriers for wider dissemination of CRT, such as the transfer of research findings into clinical everyday practice and future developments of CRT.

Participant Engagement and Symptom Improvement: Aripiprazole Tablets with Sensor for the Treatment of Schizophrenia.

Purpose: A recent, phase 3b, mirror-image clinical trial of outpatients with schizophrenia found that use of aripiprazole tablets with sensor (AS; Abilify MyCite®, comprising an ingestible event-marker sensor embedded in aripiprazole tablets, wearable sensor patches, and a smartphone application) reduced the incidence of psychiatric hospitalizations relative to oral standard-of-care antipsychotics. This analysis explored the relationship between AS engagement by participants and changes in participant performance and symptom-severity measures assessed by clinical raters. Participants and Methods: This post hoc analysis used prospectively collected clinical data from a phase 3b clinical trial (NCT03892889). Outpatients had schizophrenia, were aged 18-65 years, and had ≥ 1 psychiatric hospitalization in the previous 48 months. Participants were grouped by study completion status and a k-means clustering algorithm based on AS utilization, resulting in 3 groups: discontinued (discontinued AS before month 3 of the study); moderate engagement (completed 3 months, used AS intermittently); and high engagement (completed 3 months, used AS regularly). Baseline to end-of-study differences for the Clinical Global Impression Scale (Severity of Illness and Improvement of Illness scales), Personal and Social Performance Scale, and Positive and Negative Syndrome Scale were calculated. Results: A total of 277 outpatients were enrolled (discontinued, n = 164; moderate engagement, n = 63; high engagement, n = 50). All groups experienced symptom improvement from baseline to end-of-study, with significant changes in the more-engaged groups. Highly engaged participants showed significant improvement for all clinical scores and subscores (all P < 0.05) and demonstrated significantly more improvement in symptoms than participants with less engagement. Conclusion: Participants who completed 3 months of the study and had higher AS engagement experienced significantly greater improvement in their end-of-study clinical assessments versus participants who did not complete 3 months. Improvement may be related to more-consistent medication intake and better engagement with a digital health system.

Healthcare Provider Engagement with a Novel Dashboard for Tracking Medication Ingestion: Impact on Treatment Decisions and Clinical Assessments for Adults with Schizophrenia.

Purpose: Schizophrenia is a severe, chronic condition accounting for disproportionate healthcare utilization. Antipsychotics can reduce relapse rates, but the characteristics of schizophrenia may hinder medication adherence. A phase 3b open-label clinical trial used aripiprazole tablets with sensor (AS; includes pills with ingestible event-marker, wearable sensor patches and smartphone application) in adults with schizophrenia. This post hoc analysis explored how healthcare providers' (HCPs) usage of a dashboard that provided medication ingestion information impacted treatment decisions and clinical assessments. Patients and Methods: Participants used AS for 3-6 months. HCPs were instructed to check the dashboard regularly, identify features used, and report impact on treatment decisions. After stratifying HCPs by frequency of dashboard checks and resulting treatment decisions, changes from baseline were calculated for Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI)-Severity of Illness and CGI-Improvement (CGI-I), and Personal and Social Performance (PSP), and compared using Mann-Whitney U-tests and rank-biserial correlation coefficient (r) effect sizes. Results: To ensure sufficient opportunity for AS engagement, 113 participants who completed ≥3 months on study were analyzed. HCPs most often accessed dashboard data regarding medication ingestion and missed doses. HCPs recommended adherence counseling and participant education most often. Participants whose HCPs used the dashboard more and recommended adherence counseling and participant education (n=61) improved significantly more than participants with less dashboard-active HCPs (n=49) in CGI-I mean score (2.9 versus 3.4 [p=0.004]), total PANSS (mean change: -9.2 versus -3.1 [p=0.0002]), PANSS positive subscale (-3.2 versus -1.5 [p=0.003]), PANSS general subscale (-4.3 versus -1.2 [p=0.02]), and Marder factor for negative symptoms (-1.9 versus 0.0 [p=0.03]). Most HCPs found the dashboard easy to use (74%) and helpful for improving conversations with participants about their treatment plan and progress (78%). Conclusion: This provider dashboard may facilitate discussions with patients about regular medication-taking, which can improve patient outcomes.

Association Between the Use of Psychotropic Medications and the Risk of COVID-19 Infection Among Long-term Inpatients With Serious Mental Illness in a New York State-wide Psychiatric Hospital System.

Importance: Individuals with serious mental illness are at increased risk of severe COVID-19 infection. Several psychotropic medications have been identified as potential therapeutic agents to prevent or treat COVID-19 but have not been systematically examined in this population. Objective: To evaluate the associations between the use of psychotropic medications and the risk of COVID-19 infection among adults with serious mental illness receiving long-term inpatient psychiatric treatment. Design, Setting, and Participants: This retrospective cohort study assessed adults with serious mental illness hospitalized in a statewide psychiatric hospital system in New York between March 8 and July 1, 2020. The final date of follow-up was December 1, 2020. The study included 1958 consecutive adult inpatients with serious mental illness (affective or nonaffective psychoses) who received testing for SARS-CoV-2 by reverse transcriptase-polymerase chain reaction or antinucleocapsid antibodies and were continuously hospitalized from March 8 until medical discharge or July 1, 2020. Exposures: Psychotropic medications prescribed prior to COVID-19 testing. Main Outcomes and Measures: COVID-19 infection was the primary outcome, defined by a positive SARS-CoV-2 reverse transcriptase-polymerase chain reaction or antibody test result. The secondary outcome was COVID-19-related death among patients with laboratory-confirmed infection. Results: Of the 2087 adult inpatients with serious mental illness continuously hospitalized during the study period, 1958 (93.8%) underwent testing and were included in the study; 1442 (73.6%) were men, and the mean (SD) age was 51.4 (14.3) years. A total of 969 patients (49.5%) had laboratory-confirmed COVID-19 infection that occurred while they were hospitalized; of those, 38 (3.9%) died. The use of second-generation antipsychotic medications, as a class, was associated with decreased odds of infection (odds ratio [OR], 0.62; 95% CI, 0.45-0.86), whereas the use of mood stabilizers was associated with increased odds of infection (OR, 1.23; 95% CI, 1.03-1.47). In a multivariable model of individual medications, the use of paliperidone was associated with decreased odds of infection (OR, 0.59; 95% CI, 0.41-0.84), and the use of valproic acid was associated with increased odds of infection (OR, 1.39; 95% CI, 1.10-1.76). Clozapine use was associated with reduced odds of mortality in unadjusted analyses (unadjusted OR, 0.25; 95% CI, 0.10-0.62; fully adjusted OR, 0.43; 95% CI, 0.17-1.12). Conclusions and Relevance: In this cohort study of adults hospitalized with serious mental illness, the use of second-generation antipsychotic medications was associated with decreased risk of COVID-19 infection, whereas the use of valproic acid was associated with increased risk. Further research is needed to assess the mechanisms that underlie these findings.

Phase 3b Multicenter, Prospective, Open-label Trial to Evaluate the Effects of a Digital Medicine System on Inpatient Psychiatric Hospitalization Rates for Adults With Schizophrenia.

Objective: Inpatient psychiatric admissions drive the financial burden of schizophrenia, and medication adherence remains challenging. We assessed whether aripiprazole tablets with sensor (AS; system includes ingestible event-marker sensor, wearable sensor patches, and smartphone application) could reduce psychiatric hospitalizations compared with oral standard-of-care (SOC) antipsychotics.Methods: This phase 3b, mirror-image clinical trial was conducted from April 29, 2019-August 11, 2020, in adults with schizophrenia with ≥ 1 hospitalization in the previous 48 months who had been prescribed oral SOC for the preceding 6 months (retrospective phase). All participants used AS for at least 3 months and up to 6 months. Primary endpoint was the inpatient psychiatric hospitalization rate in the modified intent-to-treat (mITT; n = 113) population during prospective months 1-3 versus retrospective phase. Proportion of days covered by medication was the secondary endpoint. Safety endpoints included adverse events related to the medication or patch and suicidality.Results: AS significantly reduced hospitalizations during prospective months 1-3 (-9.7%) and months 1-6 (-21.3% [P ≤ .001 for all comparisons]) in the mITT population versus the corresponding retrospective phase. AS use improved confirmed medication ingestion by 26.5 percentage points in prospective months 1-3 (P ≤ .001) and reduced PANSS scores. Patches were well-tolerated, and no participant reported changes in suicide risk.Conclusions: Compared with oral SOC, AS reduced inpatient psychiatric hospitalization rates for adults with mild-to-moderate schizophrenia. The AS system may aid medication ingestion and is associated with improvements in symptoms, potentially reducing acute-care needs among patients with schizophrenia.Trial Registration: ClinicalTrials.gov identifier: NCT03892889.

SIBAT-A Computerized Assessment Tool for Suicide Ideation and Behavior: Development and Psychometric Properties.

Objective: Most assessments of suicidal ideation and behavior (SIB) are limited by reliance on a single assessor, typically a clinician or patient, with scant detail on patient-related drivers of SIB and inability to detect rapid change in SIB. Furthermore, many techniques do not include a semistructured interview, increasing rater variability. The Suicide Ideation and Behavior Assessment Tool (SIBAT) addresses these limitations. Design: More than 30 experts in scale development, statistics, and clinical management of suicidal patients collaborated over a greater than four-year period to develop the SIBAT. Input for content and validity was received from patients, clinicians, and regulatory authorities in the United States (US) and Europe. Psychometric properties of the SIBAT were evaluated in validation studies. Results: The SIBAT is organized into eight independent patient- or clinician-rated modules with branching logic and scoring algorithms, which necessitates computerization. Patient-reported information is first captured in Modules 1 to 5. Thereafter, an experienced clinician reviews the patient's report, conducts a semistructured interview (Module 6), and assesses the patient's suicide risk (Module 7) and optimal antisuicide management (Module 8). Input from cognitive interviews of diverse adult, adolescent, and clinician participants was incorporated into the final version of the SIBAT. Psychometric testing demonstrated good inter-rater reliability (intraclass coefficient range: 0.68-0.82), intra-rater reliability (weighted-kappa range: 0.64-0.76), and concurrent validity with other instruments for assessing SIB. Conclusion: Patient- and clinician-based assessments and the psychometric studies summarized in this report support the validity and reliability of the SIBAT for capturing critical information related to assessment of SIB in adolescents and adults at risk for suicide.

Efficacy of Transcranial Direct Current Stimulation to Improve Insight in Patients With Schizophrenia: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND AND HYPOTHESIS: Impaired insight into the illness and its consequences is associated with poor outcomes in schizophrenia. While transcranial direct current stimulation (tDCS) may represent a potentially effective treatment strategy to relieve various symptoms of schizophrenia, its impact on insight remains unclear. To investigate whether tDCS would modulate insight in patients with schizophrenia, we undertook a meta-analysis based on results from previous RCTs that investigated the clinical efficacy of tDCS. We hypothesize that repeated sessions of tDCS will be associated with insight improvement among patients. STUDY DESIGN: PubMed and ScienceDirect databases were systematically searched to identify RCTs that delivered at least 10 tDCS sessions in patients with schizophrenia. The primary outcome was the change in insight score, assessed by the Positive and Negative Syndrome Scale (PANSS) item G12 following active tDCS sessions as opposed to sham stimulation. Effect sizes were calculated for all studies and pooled using a random-effects model. Meta-regression and subgroup analyses were conducted. STUDY RESULTS: Thirteen studies (587 patients with schizophrenia) were included. A significant pooled effect size (g) of -0.46 (95% CI [-0.78; -0.14]) in favor of active tDCS was observed. Age and G12 score at baseline were identified as significant moderators, while change in total PANSS score was not significant. CONCLUSIONS: Ten sessions of active tDCS with either frontotemporoparietal or bifrontal montage may improve insight into the illness in patients with schizophrenia. The effect of this treatment could contribute to the beneficial outcomes observed in patients following stimulation.

A randomized, double-blind, parallel-group, fixed-dose, clinical trial of quetiapine at 600 versus 1200 mg/d for patients with treatment-resistant schizophrenia or schizoaffective disorder.

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.

Use of non-parametric item response theory to develop a shortened version of the Positive and Negative Syndrome Scale (PANSS).

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.

Paliperidone ER and oral risperidone in patients with schizophrenia: a comparative database analysis.

BACKGROUND: To compare the efficacy and tolerability of paliperidone extended-release (ER) with risperidone immediate-release using propensity score methodology. METHODS: Six double-blind, randomized, placebo-controlled, short-term clinical trials for acute schizophrenia with availability of individual patient-level data were identified (3 per compound). Propensity score pairwise matching was used to balance observed covariates between the paliperidone ER and risperidone patient populations. Scores were generated using logistic regression models, with age, body mass index, race, sex, baseline Positive and Negative Syndrome Scale (PANSS) total score and baseline Clinical Global Impressions-Severity (CGI-S) score as factors. The dosage range of paliperidone ER (6-12 mg/day) was compared with 2 risperidone dosage ranges: 2-4 and 4-6 mg/day. The primary efficacy measure was change in PANSS total score at week 6 end point. Tolerability end points included adverse event (AE) reports and weight. AEs with rates ≥ 5% and with a ≥ 2% difference between paliperidone ER and risperidone were identified. RESULTS: Completion rates for placebo-treated subjects in paliperidone ER trials (n = 95) and risperidone trials (n = 122) groups were 36.8% and 51.6%, respectively; end point changes on PANSS total scores were similar (p = 0.768). Completion rates for subjects receiving paliperidone ER 6-12 mg/day (n = 179), risperidone 2-4 mg/day (n = 113) or risperidone 4-6 mg/day (n = 129) were 64.8%, 54.0% and 66.7%, respectively (placebo-adjusted rates: paliperidone ER vs risperidone 2-4 mg/day, p = 0.005; paliperidone ER vs risperidone 4-6 mg/day, p = 0.159). PANSS total score improvement with paliperidone ER was greater than with risperidone 2-4 mg/day (difference in mean change score, -6.7; p < 0.05) and similar to risperidone 4-6 mg/day (0.2; p = 0.927). Placebo-adjusted AEs more common with paliperidone ER were insomnia, sinus tachycardia and tachycardia; more common with risperidone were somnolence, restlessness, nausea, anxiety, salivary hypersecretion, akathisia, dizziness and nasal congestion. Weight changes with paliperidone ER and risperidone were similar (paliperidone ER vs risperidone 2-4 mg/day, p = 0.489; paliperidone ER vs risperidone 4-6 mg/day, p = 0.236). CONCLUSIONS: This indirect database analysis suggested that paliperidone ER 6-12 mg/day may be more efficacious than risperidone 2-4 mg/day and as efficacious as risperidone 4-6 mg/day. The AE-adjusted incidence rates suggest differences between treatments that may be relevant for individual patients. Additional randomized, direct, head-to-head clinical trials are needed to confirm these findings.

Noninvasive direct current stimulation for schizophrenia: a review.

PURPOSE OF REVIEW: To provide an update of recent studies describing the effects of transcranial direct current stimulation (tDCS) on patients with schizophrenia, with particular focus on auditory verbal hallucinations (AVH), cognitive deficits, and negative symptoms. RECENT FINDINGS: As a low-cost, easy-to-use neuromodulation technique, tDCS may have clinical implications for those suffering from treatment-persistent AVH, negative symptoms, and cognitive symptoms in schizophrenia. Over the past decade, tDCS has shown no effects for negative symptoms, except when used at a high frequency of sessions, and inconclusive results for AVH and cognitive symptoms. The treatment has little to no adverse effects. SUMMARY: The studies reviewed here support the need for further investigation and empirical data regarding the use of tDCS. The underlying mechanisms of tDCS as well as the most effective stimulation parameters must be better understood. Findings support the need for increased duration and frequency of tDCS sessions. One of the next steps is the investigation of effects of concomitant nonpharmacological treatments with tDCS.