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: 5.5). 12/2008; 70(1):25-35. DOI: 10.4088/JCP.08m04310
Source: PubMed


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.
    Full-text · Article · Dec 2013
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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.
    Full-text · Article · Jan 2013
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    • "Patients diagnosed as schizophrenics, in fact, show distinct antipsychotic response and social functioning in relation to clinical presentation.3 In line with this approach, in the last years several trials have studied the relation between the predominant symptoms and the antipsychotic response in patients affected by schizophrenia.4-6 "
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    ABSTRACT: Preliminary data indicate that predominant positive symptoms are predictive of subsequent treatment response, while negative and cognitive symptoms are associated with poor outcome. Purpose of the present study was to investigate the relation between the predominant clinical dimension, duration of illness and acute antipsychotic response in a sample of schizophrenic inpatients. Fifty-one schizophrenic inpatients, receiving an antipsychotic mono-therapy, were dimensionally assessed at the admission in the Acute Psychiatric Unit of the University of Milan. Treatment response was selected as parameter of outcome and defined as a reduction >50% of baseline total The Positive and Negative Syndrome Scale (PANSS) score. Demographic and clinical variables between responders and non-responders were compared using one-way analysis of variance for continuous variables and χ(2) test for dichotomous ones. Binary logistic regression was performed to find if dimensional scores and duration of illness were associated with acute antipsychotic response. A longer duration of illness was found in non-responders respect to responders (15.61 years vs. 8.28 years)(F=4.98, p=0.03). Higher scores on PANSS positive sub-scale (OR=1.3, p=0.03), lower scores on cognitive PANSS scores (OR=0.75, p=0.05) and shorter duration of illness (OR=0.93, p=0.04) were found to be predictive of acute antipsychotic response. These preliminary results show that a long duration of illness as well as a more severe cognitive impairment is predictive of treatment non-response, indicating a worse outcome for chronic patients with predominant cognitive symptoms.
    Full-text · Article · Dec 2012 · Psychiatry investigation
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