Personal And Social Performance Scores Research Articles

F233. NEGATIVE SYMPTOMS ARE INDEPENDENT MODERATOR FACTORS OF TREATMENT RESISTANT SCHIZOPHRENIA EFFECTS ON MULTIPLE CLINICAL, PSYCHOPATHOLOGICAL, COGNITIVE AND PSYCHOSOCIAL VARIABLES

BackgroundNegative symptoms (NSs) are more severe in Treatment Resistant Schizophrenia (TRS) than Antipsychotic Responder Schizophrenia (ARS) patients. NSs are predictors of outcomes of neurological soft signs and functional capacity in TRS but not in ARS patients. The scope of this work is to clarify whether NSs effects are integral to or independent from the TRS diagnosis in our sample of patients.Methods70 out of 206 eligible putative TRS and ARS patients were included (enrollment still ongoing). Patients were tested by the Neurological Evaluation Scale (NES); the CGI-S; the PANSS; the Heinrichs’ Quality of Life Scale (QLS); the UCSD Performance-Based Skills Assessment (UPSA); the Personal and Social Performance (PSP) scale and Specific Level of Functioning (SLOF). Patients were subdivided in NSHigh (severe NSs) and NSLow (mild NSs) based on ROC curve-derived cut-off.ResultsAt the Student’s t test, NSHigh had significantly lower scores than NSLow patients on: Verbal Fluency; QLS score; PSP score; UPSA Financial, Communication, and Family Skills; UPSA total score; all SLOF areas (except Area4). NSHigh patients had significantly higher scores than NSLow patients on CGI-S; PANSS Positive and General Psychopathology Subscale scores; and NES score.Distribution of NS patients was significantly different between TRS/ARS diagnostic groups, as NSHigh patients were significantly more frequent in the TRS group (Pearson chi square: □1=5.51, p=.001). Notably, mean PANSS Negative Subscale scores were significantly higher in TRS compared to ARS patients (Student’s t: F1,58=2.84, p=.006).Since multiple variables found to be significantly different in NSHigh vs. NSLow patients were also significantly different between TRS and ARS patients, the question arises whether the significant differences found between diagnostic groups may depend on the higher percentage of patients with more severe NSs in the TRS group. Therefore, a two-way ANOVA was carried out with dichotomous NS and Diagnosis variables as the independent variables. Outcomes on multiple clinical variables were significantly different among groups. A NS*Diagnosis interaction effect was found for NES score (F1,58=4.32, p=.042, Visuospatial Memory, UPSA Transportation skills, and SLOF Area1. In all these cases, NSHigh/TRS patients performed significantly worse than the other patient groups; in the case of NES score, NSHigh/TRS patients score significantly higher than the other groups. Independent effect of either NSs or Diagnosis were also found for multiple variables, suggesting that NSs and Diagnosis may interact but their effects are not completely overlapping. To have a more deepen comprehension of NS effects on diagnosis, we carried out a moderator regression analysis and an ANCOVA analysis that further confirmed the finding that NSs’ mediate Diagnosis effects on a number of clinical outcomes.Given that NSs largely affect clinical variables, we asked which distinct symptom may exert the greater impact on each of these variables. Therefore, we carried out a including the seven PANSS Negative Subscale items as the independent variables. The items that explained the highest variance in clinical variables were mostly Stereotyped Thinking (N7), Passive Social Withdrawal (N4), and Difficulty in Thinking (N5).DiscussionThese data suggest that NSs are both independent determinants and moderators of TRS/ARS diagnosis effect on multiple psychopathology, cognitive, and psychosocial factors. More impaired functions attributed to non-response to antipsychotics may depend on more severe NSs. However, only a subset of NSs appears to exert this action, possibly related to the multidimensional construct of these symptoms.

Once-monthly paliperidone palmitate in early stage schizophrenia - a retrospective, non-interventional 1-year study of patients with newly diagnosed schizophrenia.

BackgroundLong-acting antipsychotic therapy may be best suited for patients in the early stage of schizophrenia, when the most can be done before disease progression associated with poor adherence occurs. We explored the patterns of use of once-monthly paliperidone palmitate (PP1M), concomitant medication use, hospitalization, and clinical outcomes of adult, newly diagnosed patients with schizophrenia receiving continuous treatment with PP1M for at least 12 months.MethodsThis was an international, multicenter, exploratory, retrospective chart review of medical records of adult patients who were newly diagnosed (not more than 1 year before initiation of PP1M treatment) with schizophrenia and who had received continuous treatment with PP1M for ≥12 months in naturalistic clinical settings.ResultsA total of 84 (93.3%) patients were included in the analysis. All but one patient (98.8%, n=83) had received oral antipsychotic medication at least during the last month before the first PP1M administration. Three patients (3.6%) were newly hospitalized during the 12-month documentation period. The reason for hospitalization for all three was management of episode/relapse. A total of 79.2% of patients had a ≥20% improvement and 47.2% had a ≥50% improvement in Positive and Negative Syndrome Scale total score from baseline to endpoint. Half of patients (53.3%) showed a significant improvement, as reflected by an increase in Personal and Social Performance (PSP) total score of at least 7 points from baseline to endpoint (mean [SD] 11.9 [15.0] points; P<0.001). One quarter of patients (24.4%, n=11) moved from a PSP score of 31–70 (ie, moderate to marked functional impairment) at baseline to a PSP score of mild to no functional impairment (PSP score ≥71) at endpoint. Most adverse drug reactions were mild or moderate in severity.ConclusionContinuous treatment with PP1M over 12 months was associated with statistically significant and clinically meaningful improvements in psychotic symptoms, disease severity, and functional outcomes in patients with schizophrenia.

Paliperidone palmitate once-monthly maintains improvement in functioning domains of the Personal and Social Performance scale compared with placebo in subjects with schizoaffective disorder

ObjectiveEvaluate the effect of paliperidone palmitate once-monthly (PP1M) injectable on the specific functioning domains of the Personal and Social Performance (PSP) scale in patients with schizoaffective disorder (SCA) participating in a long-term study. MethodsThis study (NCT01193153) included both in- and outpatient subjects with SCA experiencing an acute exacerbation of psychotic and mood symptoms. Subjects were treated with PP1M either as monotherapy or in combination with antidepressants or mood stabilizers during a 25-week open-label (OL) phase. Stabilized subjects were randomly assigned 1:1 (PP1M or placebo) into a 15-month double-blind (DB) relapse-prevention period. Functioning of the randomized subjects during OL and DB phases was evaluated using the PSP scale (four domains: socially useful activities, personal/social relationships, self-care, and disturbing/aggressive behaviors). Three statistical approaches were utilized to analyze PSP scores to assess robustness and consistency of findings. No adjustments were made for multiplicity. Results334 of 667 enrolled subjects were stabilized with PP1M, randomly assigned to PP1M (n=164) or placebo (n=170) in the DB phase, and included in this analysis. Improvements in all PSP domain scores were observed during the OL phase and were maintained during the DB phase with PP1M, but decreased with placebo. Differences compared to placebo were significant in all four PSP domains during the DB phase (P≤0.008). ConclusionThe analysis in this study showed that PP1M improves functioning, as measured by the four PSP domain scores, in symptomatic subjects with SCA. Functioning was maintained compared with placebo.

Treatment satisfaction with paliperidone extended-release tablets: open-label study in schizophrenia patients dissatisfied with previous antipsychotic medication.

ObjectiveThe aim of this study was to evaluate the changes in treatment satisfaction after switching to paliperidone extended-release (ER) in Chinese schizophrenia patients dissatisfied with their previous antipsychotic treatment.MethodsIn this 8-week, open-label, single-arm, multicenter, prospective study, 1,693 patients dissatisfied with previous antipsychotic medication were enrolled and switched to paliperidone ER tablets (3–12 mg/d) based on clinical judgment. The primary efficacy end point was change in Medication Satisfaction Questionnaire (MSQ) score from baseline to week 8. The secondary end points included percentage of patients with MSQ score ≥4, as well as changes in Clinical Global Improvement-Severity (CGI-S) and Personal and Social Performance (PSP) scores.ResultsMSQ scores increased significantly from baseline (mean [standard deviation {SD}]: 2.48 [0.55]) to week 8 (5.47 [0.89], P<0.0001; primary end point, full analysis set). The percentage of patients with MSQ score ≥4 was 95.9% at week 8, indicating that most of the patients were satisfied with their treatment. Significant (P<0.0001) improvements from baseline to week 8 were noted in CGI-S score (2.37 [1.20]) and PSP score (25.5 [15.0]). A total of 174 (10.28%) patients experienced adverse events (AEs). The most common (>10 patients) events were extrapyramidal disorder (n=84, 4.96%), poor quality sleep (n=18, 1.06%) and akathisia (n=13, 0.77%). The majority of AEs were mild to moderate in severity. No deaths occurred.ConclusionTreatment satisfaction improved after switching to paliperidone ER from the previous antipsychotic in Chinese patients with schizophrenia.

SA83. Brain Glutamate Levels and Antipsychotic Response in Schizophrenia

Background: There is considerable interest in identifying biomarkers of antipsychotic response in schizophrenia, and brain glutamate is one key candidate. Methods: In a series of 1H-MRS studies, we have investigated the relationship between brain glutamate and antipsychotic response. This includes cross-sectional studies in patients with early psychosis,1 and chronic schizophrenia.2,3 Longitudinally, within the OPTiMiSE consortium, we examined whether glutamate levels in first-episode psychosis (FEP; n = 72, <2 weeks antipsychotic medication) predict psychopathology after subsequent administration of oral amisulpride for 4 weeks. Finally, in an ongoing study in treatment-resistant schizophrenia, we investigate whether glutamate levels prior to clozapine initiation predict the degree of symptomatic response after 12 weeks of clozapine treatment. Results: The cross-sectional study in early psychosis1 found elevated glutamate in the anterior cingulate cortex (ACC) in patients who had reached remission compared to those who had not (T(30) = 3.02; P = .005). ACC glutamate level was positively associated with the severity of negative symptoms (r = .42; P = .017) and negatively associated with of global functioning (r = .47; P = .007). Our first cross-sectional study in chronic schizophrenia2 detected an elevation in ACC glutamate in treatment-resistant schizophrenia (TRS) compared to healthy volunteers (T(14) = 2.80, P = 0.01), which was not apparent in treatment responders (T(16) = 0.29, P = .77). The subsequent larger study3 found higher ACC glutamate levels in TRS than in treatment-responsive patients (T(35) = 2.34, P = .025). In the OPTiMiSE FEP cohort at baseline (prior to amisulpride treatment), ACC glutamate was positively correlated with the PANSS general score (r = .26; P = .03) and negatively correlated with the personal and social performance (PSP) score, (r = −.34; P = .006). Baseline glutamate in the ACC (r = −.38; P = .004) and thalamus (r = −.42; P = .003) were negatively correlated with PSP score after 4 weeks amisulpride. Baseline thalamic glutamate negatively correlated with the longitudinal reduction in the PANSS positive (r = −.35; P = .009) and total (r = −.28; P = .04) scores after 4 weeks amisulpride. An interim update on the ongoing clozapine study will also be provided. Conclusion: This series of studies has returned consistent findings that elevated ACC glutamate is associated with poor response to antipsychotics, more severe symptoms, and social dysfunction. Brain glutamate may relate to the magnitude of response to subsequent antipsychotic treatment.

Structured Walking and Chronic Institutionalized Schizophrenia Inmates: A pilot RCT Study on Quality of Life.

Background:Lifestyle moderate-intensity physical activity can lower the risk of over twenty chronic health conditions, whilst inactivity reduces daily functioning and physical health of individuals living with schizophrenia. This study conducted in 2014 examines the effect of structured walking participation on QOL, psychosocial functioning and symptoms in Hospital Permai, one of the largest psychiatry institution in AsiaMethod:Chronic patients with schizophrenia (n=104) who met inclusion criteria were randomised to either a 3-month structured walking intervention or a treatment-as-usual arm. The Positive and Negative Syndrome Scale (PANSS), global functioning (PSP) and QOL (SF-36) were measured at baseline and after the 3-month interval.Results:At 3 month follow-up, there were significant within group differences in QOL (SF-36), psychiatric symptoms (PANSS), and personal and social performance (PSP). There were statistically significant increase in the median SF-36 scores, with increases shown in physical functioning (p<.001), physical role limitations (p<.05), social functioning (p<.01) in the intervention group compared to treatment-as-usual group. Statistically significant reduction of median PANSS score of the intervention group were noted in positive (p<0.001) and negative (p<0.01) symptom, and general psychopathology (p<0.01) scales. Statistically significant increase in the median PSP score (p<0.01) was found in the intervention group compared with the treatment-as-usual group. Between-group differences at post intervention (favouring Intervention) were significant for PANSS positive and SF36 PhysicalConclusion:In long stayed chronic inmates, a simple but consistent, organized walking intervention has the potential to bring improvement in functioning, reduction in psychiatric symptoms and quality of Life. The emphasis of rehabilitation should target at lifestyle redesign intervention.

UCSD Performance-Based Skills Assessment (UPSA): validation of a Brazilian version in patients with schizophrenia

The UCSD Performance-based Skills Assessment (UPSA) is a measure of Functional Capacity and assesses skills involved in community tasks. It has good psychometrics properties, and is currently recommended as a co-primary assessment of cognition in the MATRICS Project. To our knowledge so far, there are no studies in western developing countries concerning Functional Capacity in Schizophrenia. The aims of this study were to translate, culturally adapt and validate the UPSA to assess Functional Capacity in community-dwelling patients with Schizophrenia living in Brazil. Eighty-two subjects (52 patients, 30 controls) were evaluated using: the Brazilian version of the UPSA (UPSA-1-BR), PANSS, Personal and Social Performance (PSP) and Global Assessment of Functioning (GAF). In the reliability test, UPSA-1-BR showed good Internal Consistency (Cronbach’s alpha of 0.88) and strong correlation between test and retest (4-month gap; r = 0.91; p < 0.01). Spearman’s rho values showed a moderate correlation between UPSA-1-BR and both PSP (0.50; p < 0.01) and GAF (0.46; p < 0.01) scores. UPSA-1-BR is capable of differentiating people with and without Schizophrenia. Patients scored lower than controls (58.9 versus 79.1), with an AUC of 0.79 (95%IC: 0.69–0.89). Sensitivity and specificity values of 0.71 and 0.70, respectively, were found in the cut-off point of 73.5, for separation of patients and controls, with predictive values of 80% (positive) and 58% (negative). UPSA-B-BR was also evaluated. UPSA-1-BR and its brief version presented adequate psychometric properties and proved to be valid and reliable instruments in the assessment of Functional Capacity in subjects with Schizophrenia.

An open-label, flexible-dose study of paliperidone extended-release in Chinese patients with first-onset psychosis

BackgroundAntipsychotic medications facilitate the improvement of psychotic symptoms in patients with first-episode psychosis. Paliperidone extended-release (pali-ER), an atypical antipsychotic, was assessed for efficacy and safety in Chinese patients with first-episode psychosis.MethodsIn this 8-week, open-label, single-arm, multicenter study, patients with first-episode psychosis (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) and a Positive and Negative Syndrome Scale (PANSS) total score ≥70 were treated with flexible-dose pali-ER tablets (3–12 mg/day). The primary efficacy endpoint was the percentage of patients with an increase of ≥8 points in Personal and Social Performance (PSP) score from baseline to day 56 (8 weeks). Secondary endpoints included reduction in PANSS total score, improvement in Clinical Global Impression-Severity score, PSP score, Subjective Well-being under Neuroleptics Scale score, and relationship between duration of untreated psychosis and PANSS or PSP. Incidences of treatment-emergent adverse events were used to evaluate safety.ResultsOverall, 283 of 294 patients (96%) achieved a ≥8-point increase in PSP (primary endpoint, analysis set). For the secondary efficacy endpoints, 284/306 patients (93%) had a ≥30% reduction in PANSS total score; 266/306 patients (87%) achieved a ≤3 Clinical Global Impression-Severity scale score, and 218/294 patients (74%) had a PSP score ≥71. The Subjective Well-being under Neuroleptics Scale score was improved from a baseline mean of 72.7 to 94.7 at endpoint. There was a negative correlation between duration of untreated psychosis and posttreatment PSP score and a positive correlation with posttreatment PANSS total score. The most common treatment-emergent adverse events were extrapyramidal symptoms (12%), and agitation, somnolence, and xerostomia (4% each).ConclusionAn 8-week, flexible-dose (3–12 mg/day) treatment with pali-ER resulted in significant improvements in psychotic symptoms and social functioning in Chinese patients with first-episode psychosis and was generally tolerable.

Correlation between the Personal and Social Performance scale (PSP) and the Positive and Negative Syndrome Scale (PANSS) in a Greek sample of patients with schizophrenia.

BackgroundPsychosocial dysfunction is one of schizophrenia’s core features, often leading to a deprecation of independent living and significant failure to maintain a competent quality of life. Cognitive and occupational performance as well as psychosocial functioning is moreover recognized as determinants of treatment response. Therefore, the elaboration of measures regarding social performance besides scales that assess psychopathology is essential. The Personal and Social Performance (PSP) scale has been found to be as much valid as reliable for assessing social functioning in the acute and stable stage of schizophrenia. The aim of this study was to estimate the correlation between the PSP and Positive and Negative Syndrome Scale (PANSS) (convergent validity) in patients with schizophrenia during routine clinical practice.MethodsA longitudinal study with a six-month follow-up is presented. Correlation between the PSP scale and the Positive and Negative Syndrome Scale (PANSS) was conducted in a Greek sample of 2010 patients with schizophrenia in outpatient setting in two successive visits. PANSS and PSP scales were used for the assessment of psychopathological symptoms and social and personal functioning.ResultsThe PSP subscales scores were well correlated with each other with Spearman correlation coefficients (r) ranging from 0.56 to 0.76 on both visits in three out of the four main areas, whereas in the category of “disturbing and aggressive behavior” the correlations were lower but still significant. Furthermore, total PSP score showed high association to PANSS total score in the first (r = -0.59) as well as in the second visit (r = -0.50). Regression analysis showed that one point decrease of PANSS’s total score is associated with a 0.42 points increase on the PSP scale. PSP and PANSS scales exhibited high convergent validity.ConclusionsThe PSP could provide additional valuable information in the assessment of schizophrenia related social functioning and treatment response.

Reliability and validity of the Personal and Social Performance scale in patients with schizophrenia

ObjectiveThe construct validity and test–retest reliability of the Personal and Social Performance (PSP) scale were used to assess social functioning in a cohort of ethnically diverse UK patients with schizophrenia. MethodsA total of 73 patients with schizophrenia took part in the study. At baseline, the PSP, two symptomatology scales and two other functioning scales were administered. A subset of the sample (N=40) took part in a retest where the Clinical Global Impression—Severity (CGI-S) and PSP scales were administered 8–10days later. ResultsPSP significantly correlated with all other measures, Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF) and Quality of Life Scale (QLS) at baseline (p<0.02) and with CGI-S at follow-up (p<0.01). In addition, the PSP scale was moderately sensitive to the severity of illness. Test–retest reliability for the PSP score was 0.45 and the scale was able to discriminate between known groups (mild and severe patients). ConclusionThe PSP was easy to administer in this predominantly inpatient cohort and was moderately correlated with all other functioning measures tested. Due to patient homogeneity, the test–retest reliability statistic of the PSP was lower than that observed in other studies.

Effects of paliperidone extended release on the symptoms and functioning of schizophrenia

BackgroundWe aimed to explore relations between symptomatic remission and functionality evaluation in schizophrenia patients treated with paliperidone extended-release (ER), as seen in a normal day-to-day practice, using flexible dosing regimens of paliperidone ER. We explored symptomatic remission rate in patients treated with flexibly dosed paliperidone ER by 8 items of Positive and Negative Syndrome Scale (PANSS) and change of Personal and Social Performance (PSP) scale.MethodThis was a 12-week multicenter, open-label, prospective clinical study conducted in in-patient and out-patient populations. Flexible dosing in the range 3-12 mg/day was used throughout the study. All subjects attended clinic visits on weeks 0, 4, 8, and 12 as usual clinical practice for the 12-week observation period. Data were summarized with respect to demographic and baseline characteristics, efficacy measurement with PANSS scale, PSP, and social functioning score, and safety observations. Descriptive statistics were performed to identify the retention rate at each visit as well as the symptomatic remission rate. Summary statistics of average doses the subjects received were based on all subjects participating in the study.ResultsA total of 480 patients were enrolled. Among them, 426 patients (88.8%) had evaluation at week 4 and 350 (72.9%) completed the 12-week evaluation. Patients with at least moderate severity of schizophrenia were evaluated as "mild" or better on PANSS scale by all 8 items after 12 weeks of treatment with paliperidone ER. There was significant improvement in patients' functionality as measured by PSP improvement and score changes. Concerning the other efficacy parameters, PANSS total scale, PSP total scale, and social functioning total scale at the end of study all indicated statistically significant improvement by comparison with baseline. The safety profile also demonstrated that paliperidone ER was well-tolerated without clinically significant changes after treatment administration.ConclusionsAlthough the short-term nature of this study may limit the potential for assessing improvements in function, it is noteworthy that in the present short-term study significant improvements in patient personal and social functioning with paliperidone ER treatment were observed, as assessed by PSP scale.Trial RegistrationClinical Trials. PAL-TWN-MA3

Intercorrelations Between the Personal and Social Performance Scale, Cognitive Function, and Activities of Daily Living

The aim of this study was to evaluate the intercorrelation between the Personal and Social Performance (PSP) score, cognitive function, and activities of daily living (ADLs). Twenty patients with chronic schizophrenia were recruited; the PSP and ADL scales and psychological assessments including the Wisconsin Card Sorting Test, the Wechsler Memory Scale-Revised (WMS-R), and the Continuous Performance Test (CPT) were administered. Positive correlations between the total PSP scale score and performance in the WMS-R, CPT, and ADL scores were identified. The PSP score was found to be of good reliability for cognitive function and ADL evaluation.

Validation of the Spanish Personal and Social Performance scale (PSP) in outpatients with stable and unstable schizophrenia

IntroductionThe main long-term therapeutic goals of schizophrenia should go beyond the symptoms and include the improvement of patients’ psychosocial functioning and quality of life. The aim of this study was to validate the Personal and Social Performance (PSP) scale in Spanish outpatients with schizophrenia. Materials and methodsNaturalistic, 6-month follow-up, multicentre study. 244 patients and 76 controls were evaluated using the PSP, the Social and Occupational Functioning Assessment Scale (SOFAS), and the Clinical Global Impression–Severity (CGI-S) and Change (CGI-C) scales. ResultsInternal reliability = 0.87. Test-retest reliability = 0.98. Construct validity = 1 component that explained 73.2% of the variance. Convergent validity: Pearson correlation coefficient between PSP and SOFAS= 0.95 (p<0.0001), between PSP and CGI-S=−0.88 (p<0.0001). Discriminant validity: the PSP discriminates between patients and controls [50.3 versus 91.9, p<0.0001] and among patients with mild, moderate, and severe schizophrenia according to CGI-S scores [73 versus 56.6 versus 37.5, p<0.0001]. Area under the curve = 0.986. A cut-off point of 79 on the PSP scale provided good sensitivity (94.3%) and specificity (96.1%) for identifying patients and controls according to their level of functioning. At month 6 significant improvements (p<0.0001) were seen in PSP, SOFAS, and CGI-C scores. The PSP was sensitive to improvement; a score of very much improved in the CGI-C corresponds to a improvement of 34 points in the PSP. ConclusionThe Spanish PSP is a reliable, valid and sensitive instrument for measuring functioning in outpatients with schizophrenia. As a brief, clinician-rated instrument, the PSP scale seems to be appropriate for use in everyday clinical practice as a mean of identifying and monitoring changes in patient's functioning.

Onset of efficacy with acute long-acting injectable paliperidone palmitate treatment in markedly to severely ill patients with schizophrenia: post hoc analysis of a randomized, double-blind clinical trial

BackgroundThis post hoc analysis (trial registration: ClinicalTrials.gov NCT00590577) assessed onset of efficacy and tolerability of acute treatment with once-monthly paliperidone palmitate (PP), a long-acting atypical antipsychotic initiated by day 1 and day 8 injections, in a markedly to severely ill schizophrenia population.MethodsSubjects entering the 13-week, double-blind trial were randomized to PP (39, 156, or 234 mg [25, 100, and 150 mg eq of paliperidone, respectively]) or placebo. This subgroup analysis included those with a baseline Clinical Global Impressions-Severity (CGI-S) score indicating marked to severe illness. PP subjects received a 234-mg day 1 injection (deltoid), followed by their assigned dose on day 8 and monthly thereafter (deltoid or gluteal). Thus, data for PP groups were pooled for days 4 and 8. Measures included Positive and Negative Syndrome Scale (PANSS), CGI-S, Personal and Social Performance (PSP), and adverse events (AEs). Analysis of covariance (ANCOVA) and last-observation-carried-forward (LOCF) methodologies, without multiplicity adjustments, were used to assess changes in continuous measures. Onset of efficacy was defined as the first time point a treatment group showed significant PANSS improvement (assessed days 4, 8, 22, 36, 64, and 92) versus placebo, which was maintained through end point.ResultsA total of 312 subjects met inclusion criterion for this subgroup analysis. After the day 1 injection, mean PANSS total scores improved significantly with PP (all received 234 mg) versus placebo at day 4 (P = 0.012) and day 8 (P = 0.007). After the day 8 injection, a significant PANSS improvement persisted at all subsequent time points in the 234-mg group versus placebo (P < 0.05). PANSS improvements were greater from day 36 through end point in the 156-mg group (P < 0.05) and only at end point in the 39-mg group (P < 0.05). CGI-S and PSP scores improved significantly in the 234-mg and 156-mg PP groups versus placebo at end point (P < 0.05 for both, respectively); improvement in the 39-mg group was not significant. The most common AEs for PP-treated subjects (≥10%, any treatment group) were headache, insomnia, schizophrenia exacerbation, injection site pain, and agitation.ConclusionsIn this markedly to severely ill population, acute treatment with 234 mg PP improved psychotic symptoms compared with placebo by day 4. After subsequent injections, observed improvements are suggestive of a dose-dependent effect. No unexpected tolerability findings were noted.

Measuring social functioning with the personal and social performance scale in patients with acute symptoms of schizophrenia: Interpretation of results of a pooled analysis of three Phase III trials of paliperidone extended-release tablets

Background: The safety and efficacy of paliperidone extended-release tablets (paliperidone ER) in patients with acute symptoms of schizophrenia have been described in 3 randomized, double-blind, 6-week, placebo-controlled, fixed-dose, Phase III clinical trials. The validity and reliability of the Personal and Social Performance (PSP) scale, both in patients with acute symptoms of schizophrenia and those with stabilized symptoms, have also been reported. Objective: The aim of this work was to estimate the treatment benefit of paliperidone ER compared with placebo in terms of improvements in personal and social functioning as measured by the PSP scale in 3 controlled clinical trials. Methods: Data were derived from 3 paliperidone ER multicenter Phase III pivotal studies of patients with acute symptoms of schizophrenia. Each study included a randomized, double-blind, placebo- and active-controlled, parallel-group, 6-week treatment period with an open-label extension of paliperidone ER treatment. Patients were randomized to receive paliperidone ER, olanzapine 10 mg, or placebo once daily. Paliperidone ER doses were 3, 9, and 15 mg/d in 1 study; 6, 9, and 12 mg/d in another; and 6 and 12 mg/d in the third. Collectively, 1306 intent-to-treat patients received placebo or paliperidone ER in these 3 trials. Most (61.7%) were white; 21.6% were black, 8.8% were Asian, and 7.9% were of another race. The mean age ranged from 36.3 to 39.4 years across treatment groups. Multiple analyses were applied to PSP data (for which higher scores indicate better personal and social functioning) from these paliperidone ER studies: between-group minimum important difference (MID) estimates; responder analyses; between-group cumulative frequency comparisons of PSP change from baseline to end point; and number-needed-to-treat (NNT) estimates. Results: Standardized differences and effect sizes between paliperidone ER and placebo in PSP mean change from baseline to end point ranged from 0.52 to 0.85 for all paliperidone ER doses. Observed between-group differences (paliperidone ER minus placebo) in PSP mean change from baseline to end point exceeded the between-group MID of 7 points at all paliperidone ER doses. The percentage of patients achieving at least one 10-point category improvement in the PSP was higher with all paliperidone ER doses (range, 49.6%–63.6%) than placebo (33.1%) ( P < 0.005). Across the distribution of all possible PSP scores, the percentage of patients achieving any level of change appeared to be greater for paliperidone ER than for placebo at all doses. Derived NNTs for improved personal and social functioning based on paliperidone ER trials ranged from 3.3 to 6.1. The improvement in personal and social functioning achieved by patients receiving paliperidone ER during the double-blind studies was maintained throughout the 52-week, open-label extension studies, as assessed using multiple definitions of response; subjects in the placebo arm during doubleblind treatment appeared to achieve and maintain improved functioning when switched to paliperidone ER for the extension studies. Conclusion: These results suggest that paliperidone ER had a meaningful treatment benefit with respect to improving personal and social functioning in these patients with acute symptoms of schizophrenia.

Paliperidone extended‐release tablets in patients with recently diagnosed schizophrenia

Effective early and persistent antipsychotic treatment in recently diagnosed schizophrenia may positively impact long-term outcomes. Paliperidone extended-release (ER) was assessed in this population. Post hoc analysis of pooled data from three 6-week, double-blind (DB), placebo-controlled, and three 1-year open-label (OL) studies of paliperidone ER in schizophrenia patients. Data stratified by time since diagnosis (< or =3 vs. >3 years). At DB (n = 1193) and OL baselines (n = 744), 259 (21.9%) and 188 (25.3%) patients were diagnosed < or =3 years. At DB end point, both populations improved with paliperidone ER versus placebo on Positive and Negative Syndrome Scale (PANSS) total, Clinical Global Impressions-Severity and Personal and Social Performance (PSP) scale scores (all P < 0.05). At OL end point, there were significant improvements from DB baseline in both populations on these scales (P < 0.0001), with greater improvement in the < or =3-year population on PANSS total (P < 0.001) and PSP (P < 0.001) scores. During DB treatment, only the < or =3-year population reported adverse events (AEs) in > or =5% (placebo-adjusted rate) of subjects receiving paliperidone ER: akathisia, extrapyramidal disorder not otherwise specified and somnolence. During OL treatment, akathisia and somnolence occurred more frequently (> or =5%) in the < or =3- versus >3-year population. OL study completion rates were 51.1% in < or =3-year, and 48.2% in >3-year subjects. Paliperidone ER significantly improved symptoms and functioning in schizophrenia patients, regardless of time since diagnosis. Recently diagnosed patients who continued treatment exhibited greater symptom reduction and functional benefit over the long term. Results also suggest that these patients may be more susceptible to certain AEs.

Efficacy and safety of paliperidone extended-release in schizophrenia patients with prominent affective symptoms

Background This post-hoc analysis evaluated the effects of paliperidone extended-release (ER) in patients with schizophrenia and prominent affective symptoms. Methods Pooled data from three 6-week, randomized, double-blind, placebo-controlled studies were analyzed. Subjects received fixed doses of paliperidone ER 3–12 mg/day or placebo. Prominent affective symptoms were defined as depressive (Positive and Negative Syndrome Scale [PANSS] depression item score of ≥ 5 [moderately severe]) and/or manic (PANSS grandiosity score of ≥ 4 [moderate], plus a score of ≥ 4 [moderate] on at least 1 PANSS item for excitement, hostility, uncooperativeness, or poor impulse control). Assessments included PANSS, Clinical Global Impressions-Severity (CGI-S), Personal and Social Performance (PSP) scale, and adverse events (AEs). Results Among 193 patients with prominent affective symptoms, 140 received paliperidone ER and 53 received placebo. Paliperidone ER showed significant mean (SD) improvements vs. placebo in PANSS total (− 20.5 [23.8] vs. − 6.3 [27.2]; p < 0.001, respectively) and all factor scores ( p < 0.01). Significant mean (SD) improvements were observed in PSP (7.2 [15.8] vs. 0.4 [14.6]; p = 0.004) and CGI-S (− 0.9 [1.2] vs. − 0.3 [1.2]; p < 0.001) scores. Most common AEs with paliperidone ER vs. placebo: headache (16.4% vs. 13.2%), insomnia (7.9% vs. 9.4%), akathisia (7.1% vs. 1.9%), sedation (7.1% vs. 3.8%). Limitations These studies were not designed to examine patients with prominent affective symptoms. Authors' clinical judgment was used to define prominent affective symptoms, using relevant PANSS items. Conclusions Paliperidone ER was well tolerated and associated with significantly greater improvements in symptomatology, functioning, and overall clinical status vs. placebo in patients with schizophrenia and prominent affective symptoms.

Validity of the Spanish version of the Personal and Social Performance scale in schizophrenia

Background The Personal and Social Performance (PSP) scale is a reliable and valid instrument that utilizes objective parameters for the assessment of social functioning in patients with schizophrenia. Objective The aim of this study was to determine the validity and reliability of the Spanish version of the PSP scale. Method In total, 100 patients with DSM-IV diagnoses of schizophrenia and schizoaffective disorder were recruited and assessed with the PSP, the GAF, the PANSS, and the CGI. Internal consistency for the PSP was obtained and discriminant validity was assessed by comparing PSP scores between inpatients and outpatients; correlations between PSP scores, the GAF, and the five factors of the PANSS were used to evaluate the convergent validity of the scale; reliability was evaluated with intra-class correlation coefficients and temporal stability was obtained using correlation coefficients between the PSP and CGI scores on a follow up assessment. Results The Cronbach's alpha coefficient of the PSP was 0.843. Inpatients showed lower scores on the PSP than did outpatients. Patients with low scores on the PSP reported fewer years of education, were more frequently unemployed, had a longer duration of illness, and had a shorter duration of antipsychotic treatment. The PSP scores showed a positive correlation with the GAF and a negative correlation with the cognitive, negative, and positive factors derived from the PANSS. The PSP scores showed significant correlations with the severity and improvement CGI scores at follow-up. Good inter-rater reliability was obtained. Conclusion These findings support the Spanish version of PSP to be a reliable and valid instrument for the assessment of social functioning in patients with schizophrenia.

The Impact of Insight on Functioning in Patients With Schizophrenia or Schizoaffective Disorder Receiving Risperidone Long-Acting Injectable

This post hoc analysis explored the role of insight as a mediator of functioning in a 52-week, double-blind, international trial of 323 patients with schizophrenia or schizoaffective disorder receiving risperidone long-acting injectable. Measures included the Positive and Negative Syndrome Scale (PANSS) insight item, PANSS factors, Clinical Global Impressions-Severity (CGI-S), Strauss-Carpenter Levels of Functioning (LOF), Personal and Social Performance (PSP) scale, and a cognitive test battery. Correlation/regression analyses examined associations between demographic and clinical characteristics, including insight, and functional measures. Insight scores correlated significantly with CGI-S, PANSS subscales, PSP, LOF, and several cognitive measures. Regression models demonstrated that changes in insight, changes in negative symptoms, and study duration were significantly associated with PSP and LOF total change scores. Findings identified important variables to consider for intervention to improve functioning in schizophrenia.