The acute efficacy of aripiprazole across the symptom spectrum of schizophrenia: a pooled post hoc analysis from 5 short-term studies.
ABSTRACT To evaluate the efficacy of aripiprazole across a range of symptoms-positive, negative, disorganized thought, depression/anxiety, and hostility-in schizophrenia and schizoaffective disorder.
Pooled data were analyzed from 5 short-term, double-blind, multicenter studies (published between 1997 and 2007) involving patients hospitalized with acute exacerbation of schizophrenia (5 studies) or schizoaffective disorder (2 studies) and randomly assigned to aripiprazole (N = 875), haloperidol (N = 193), risperidone (N = 95), or placebo (N = 406). Aripiprazole doses ranged from 2 to 30 mg/day. Patients receiving the ineffective 2-mg dose were excluded from the primary analyses presented here. Factor analysis of Positive and Negative Syndrome Scale (PANSS) data was used to evaluate changes from baseline with aripiprazole on 5 symptom factors-positive, negative, disorganized thought, depression/anxiety, and hostility-in 2 population subsets-schizophrenia and schizoaffective disorder. Pairwise comparisons were made as follows for schizophrenia: aripiprazole versus placebo in all 5 studies; aripiprazole, haloperidol, and placebo in 3 studies; and aripiprazole, risperidone, and placebo in 1 study. Patients with schizoaffective disorder in 2 studies were included in the comparison of aripiprazole and placebo.
Aripiprazole was significantly better than placebo in improving all 5 PANSS factor scores from baseline (each p < .001) in the schizophrenia dataset. In schizoaffective disorder, aripiprazole was significantly better than placebo for the improvement of positive (p <or= .05) and hostility (p <or= .01) factor scores. Analysis of the 3 studies involving haloperidol showed that aripiprazole was significantly better than placebo in improving all 5 factors (p <or= .01), whereas haloperidol produced significantly greater improvements than placebo in 3 factors (positive, disorganized thought, and hostility) (each p < .001). There was no difference between aripiprazole and haloperidol on any factor. Analysis of the study involving risperidone showed that both drugs were better than placebo for all 5 factors with the exception of the depression/anxiety factor, in which only risperidone separated from placebo. There was no difference between aripiprazole and risperidone on any factor.
In this large dataset, aripiprazole was associated with improvements in a broad range of symptom domains in the short-term treatment of schizophrenia and schizoaffective disorder.
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ABSTRACT: The PANSS is a valid instrument assessing schizophrenia symptom severity. Analyses have identified a five-factor solution. The negative symptom factor (NSFS) is robust, having been replicated in multiple analyses. The score has superior content validity versus the negative subscale. Aspects of validity in patients with predominant negative symptoms have yet to be established. The present data are from a Phase IIb study of add-on bitopertin therapy in schizophrenia outpatients with prominent negative or disorganized thought symptoms treated with antipsychotics. Analyses were conducted to evaluate reliability, validity and sensitivity to change. Test-retest screening to baseline was high (ICC=0.93). This was maintained in-study, for patients with no change in CGI negative symptom severity (CGI-S-N). Internal consistency at baseline was adequate (α=0.71) and increased at later assessments. Pearson correlation at baseline showed a good association between NSFS and CGI-S-N (0.63), but not overall CGI-S (0.31). Association with PSP at baseline was moderate (−0.39) and for change at Week 8 good (−0.65). NSFS responders (≥20% improvement) at Week 8 showed a significant improvement in function. The analyses demonstrated reliability, validity and ability to detect change of the NSFS, in schizophrenia patients with prominent negative or disorganized thought symptoms.Psychiatry Research. 08/2014;
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ABSTRACT: The Positive and Negative Syndrome Scale (PANSS) Pentagonal (PM) and Van der Gaag (VDG) 5-factor models were compared on a range of change-over-time statistical indicators. PANSS data from a randomized, controlled trial for 108 adults diagnosed with schizophrenia were re-analyzed to calculate five factor scores for each model. Random effects regression was used to determine their relative performance in modeling change-over-time, determining covariance structure, and achieving goodness of fit. Performance of the 10 factors in estimating change-over-time was similar, as were significant covariates for the factor dyads: age, gender, chronicity/acuity, and anticholinergic medication. The PM model factors demonstrated the best "goodness of model fit" to the data on all five of the factor dyads. Correlation analyses indicated significantly high, positive correlations between the five factor dyads: Positive and Negative factors for the PM and VDG models, the PM Activation and VDG Excited factors, the PM Dysphoric Mood and the VDG Emotional Distress factors, and the PM Autistic Preoccupation and the VDG Disorganized factors, although the PANSS items on each factor differed somewhat. These results extend previous findings and indicate several important performance differences between the PM and VDG models in their parsimonious representation of the syndromes of schizophrenia and estimating change-over-time.Psychiatry research. 01/2013; 207(1-2).
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ABSTRACT: Using symptom factors derived from two models of the Positive and Negative Syndrome Scale (PANSS) as covariates, change over time in consumer psychosocial functioning, medication adherence/compliance, and treatment satisfaction outcomes are compared based on a randomized, controlled trial assessing the effectiveness of antipsychotic medications for 108 individuals diagnosed with schizophrenia. Random effects regression analysis was used to determine the relative performance of these two 5-factor models as covariates in estimating change over time and the goodness of fit of the regression equations for each outcome. Self-reported psychosocial functioning was significantly associated with the relief of positive and negative syndromes, whereas patient satisfaction was more closely and significantly associated with control of excited/activation symptoms. Interviewer-rated psychosocial functioning was significantly associated with relief of positive and negative symptoms, as well as excited/activation and disoriented/autistic preoccupation symptoms. The VDG 5-factor model of the PANSS represents the best "goodness of fit" model for assessing symptom-related change associated with improved psychosocial outcomes and functional recovery. Five-factor models of the syndromes of schizophrenia, as assessed using the PANSS, are differentially valuable in determining the predictors of psychosocial and satisfaction changes over time, but not of improved medication adherence/compliance.Schizophrenia research and treatment. 01/2013; 2013:705631.