The Acute Efficacy of Aripiprazole Across the Symptom Spectrum of Schizophrenia

Department of Psychiatry, Rush University Medical Center, Chicago, Illinoise 60612, USA.
The Journal of Clinical Psychiatry (Impact Factor: 5.14). 12/2008; 70(1):25-35. DOI: 10.4088/JCP.08m04310
Source: PubMed

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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    • "be more representative of the syndromes of schizophrenia [7– 9] than the original 3 subscales: positive, negative, and psychopathology [10], especially in a chronic course [11]. These five factors remain consistent whether patients are on or off medication [7] [12] and are consistently identified across subgroups of patients to include negative, positive, disorganized/autistic preoccupation, excited/activation (hostility/aggression ), and dysphoric mood/emotional distress (depression) [7–9, 11–13]. "
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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.
    12/2013; 2013:705631. DOI:10.1155/2013/705631
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    • "Many authors now recognize that the number of factors used when analyzing the PANSS can impact the identification of clusters of symptoms and their patterns of change-overtime , which may influence prognosis, therapeutic approaches, response to treatment, and prediction of related variables (Kay and Sevy, 1990; Cuesta and Peralta, 1995; Lindenmayer et al., 1995; Dollfus et al., 1996; Nakaya et al., 1999; Lancon et al., 2000; Emsley et al., 2003; Van den Oord et al., 2006; Van der Gaag et al., 2006a, 2006b). Five-factor models are thought to be more representative of the symptoms of schizophrenia, especially in the chronic course (Janicak et al., 2009), and their structure of symptoms remains consistent whether patients were on or off medication, explaining 50–60% of the variance (Lindenmayer et al., 1995; Dollfus et al., 1996). "
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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.
    01/2013; 207(1-2). DOI:10.1016/j.psychres.2012.12.010
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    • "Such an effect may provide an important advantage for patients in the early phase of their illness in the achievement of a greater degree of overall functional recovery. The efficacy of aripiprazole in improving social functioning is in addition to the known efficacy in treating a broad range of other symptoms (Janicak et al., 2009). Further analysis of the dataset presented herein confirmed that aripiprazole provides significantly greater improvement than haloperidol on the PANSS Total score, even when the Prosocial (−17.3 versus −12.2, p = 0.03) or Modified Prosocial items (−18.7 versus −13.5, p = 0.03) are excluded, confirming that efficacy is not restricted to those items. "
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    ABSTRACT: Improving social functioning is critically important in early-episode schizophrenia, if patients are to achieve functional recovery. This post-hoc, pooled analysis of two studies compared the effect of aripiprazole versus haloperidol on social functioning in early-episode schizophrenia. Data were pooled from two 52 week, randomized (2:1), double-blind, multicenter studies involving 1294 patients with chronic schizophrenia who were in an acute psychotic episode and had a history of positive antipsychotic response during previous episodes. The early-episode group was defined as patients who are <or=40 years of age with <or=5 years' duration of illness. Social functioning was assessed by mean change from baseline on the PANSS Prosocial subscale (ANCOVA and LOCF), comprising six PANSS items, and the Modified Prosocial subscale, comprising four PANSS items. Measurements were taken at approximately monthly intervals for up to 1 year. Aripiprazole (n=237) demonstrated significant improvement versus haloperidol (n=123) as early as Week 18 on both the Prosocial subscale (-4.75 versus -3.78, p<0.05) and on the Modified Prosocial subscale (-3.16 versus -2.28, p<0.05). Patients receiving aripiprazole continued to show similar significant improvement versus haloperidol at all remaining timepoints through Week 52 using the Modified Prosocial subscale, but less consistent improvement with the Prosocial subscale. Significant advantage for the aripiprazole-treated patients was observed at Weeks 46 and 52 (endpoint) with both subscales. In patients with early-episode schizophrenia, aripiprazole demonstrates greater improvement than haloperidol on PANSS items related to social functioning. The cognitive and functional implications of these findings remain to be clarified in future studies.
    Schizophrenia Research 07/2010; 120(1-3):199-203. DOI:10.1016/j.schres.2010.03.040 · 4.43 Impact Factor
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