Early antipsychotic response to aripiprazole in adolescents with schizophrenia: predictive value for clinical outcomes.

OBJECTIVE: In adults with chronic schizophrenia, most symptom decreases occur in the first few weeks of antipsychotic treatment, and nonresponse at week 2 predicts a later nonresponse. The trajectory of antipsychotic response and the predictive value of early antipsychotic effects were investigated for ultimate outcome in adolescent schizophrenia, where such data are still lacking. METHOD: This post hoc analysis of a 6-week, randomized, double-blinded trial of aripiprazole (n = 196) versus placebo (n = 98) evaluated if adolescents 13 to 17 years old with schizophrenia exhibited substantial symptomatic improvement to aripiprazole in the first few treatment weeks and whether early response (ER) versus early nonresponse (ENR) predicted clinically relevant outcomes. ER decreased at least 20% and ENR decreased less than 20% in Positive and Negative Syndrome Scale (PANSS) total score at week 2 (ER2/ENR2) or 3 (ER3/ENR3). Ultimate response decreased at least 40% in PANSS score. RESULTS: Nearly 50% of the PANSS decrease was achieved by week 2 and up to 75% by week 3. ER2/ER3 subjects showed significantly greater improvement than ENR subjects in PANSS total score, PANSS positive and negative subscale scores, and functionally relevant outcomes. In general, ER3 had better sensitivity, specificity, and positive and negative predictive values than ER2 for predicting ultimate response. ER2 subjects were 8.8 times (95% confidence interval 4.0-19.4) and ER3 subjects were 8.6 times (95% confidence interval 4.5-16.6) more likely to achieve remission at week 6 (p < .0001) than ENR2 and ENR3 subjects, respectively, although adverse events were similar. CONCLUSIONS: Like adults with chronic schizophrenia, adolescents with early-phase schizophrenia exhibited most symptomatic improvement early during aripiprazole treatment, with week 3 improvements having the best predictive power. Although requiring extension, these results may inform clinical decision making. Clinical trial registration information-Aripiprazole in Adolescents with Schizophrenia, http://clinicaltrials.gov/, NCT00102063.

Respondent and item level patterns of response of aripiprazole in the acute treatment of pediatric bipolar I disorder.

BACKGROUND: Few studies have evaluated the value of a parent- and subject-rated scale in detecting symptom change in response to pharmacologic treatment. METHODS: This was a post-hoc analysis of data from a 4-week, randomized, double-blind, placebo-controlled study to evaluate which informants detect response to treatment with aripiprazole in pediatric subjects experiencing a mixed or manic episode associated with bipolar I disorder. Efficacy assessments included clinician-rated scales and the parent- and subject-rated 10-item General Behavior Inventory Mania (GBI-M10) and Depression (GBI-D10) scales. Cohen's d quantified effect sizes for total scale scores and individual line items. RESULTS: Parent-GBI-M10 total, clinician-rated Young Mania Rating Scale (YMRS) total, and Clinical Global Impression-Bipolar Disorder (CGI-BP) Mania scores produced similar effect sizes, suggesting that the parent-GBI-M10 is sensitive to treatment-related improvements in manic symptoms. Aripiprazole improved a broad spectrum of parent-rated mania symptoms; six parent-GBI-M10 line item effect sizes were moderate (>0.5) in at least one of the two aripiprazole treatment arms (10 or 30 mg/day). Subject-completed GBI-M10 line item effect sizes were consistently smaller, indicating that the subjects' experience of treatment effects were less pronounced. LIMITATIONS: Study inclusion/exclusion criteria may limit generalizability of these findings. CONCLUSIONS: Parent ratings of mania severity were in agreement with clinician ratings, indicating that parent-rated assessments can be valuable in detecting symptom change over the course of treatment. These data support the use of the parent-GBI-M10 as an outcome measure in research and clinical settings.

The neurocognitive effects of aripiprazole: an open-label comparison with olanzapine.

RATIONALE: Cognitive deficits are a core feature of schizophrenia. As a target of intervention, improvements in cognition may lead to improvements in functional outcome. OBJECTIVES: The present paper is the first report, to our knowledge, on the neurocognitive effects of aripiprazole. Unlike other second-generation antipsychotics, aripiprazole is a D(2) and D(3) receptor partial agonist. It is unknown what effects this unusual pharmacological profile may yield on neurocognition. MATERIALS AND METHODS: The present open-label study included data on 169 patients with schizophrenia or schizoaffective disorder who were randomly treated with aripiprazole or olanzapine. Subjects received a neurocognitive battery at baseline, week 8, and 26. RESULTS: The aripiprazole group had a significantly greater dropout rate than the olanzapine group. Neurocognitive data were reduced through a principal components analysis that yielded a three-factor solution. The factors were general cognitive functioning, executive functioning, and verbal learning. For general cognitive functioning, both groups improved from baseline and the effects were relatively stable over the 26-week protocol. There were no differential treatment effects. For executive functioning, neither group improved significantly from baseline. For verbal learning, the aripiprazole group improved significantly from baseline to the 8th and 26th week of assessment, and there was a between-group effect favoring aripiprazole over olanzapine that was largely attributable to the differences in performance within the 8th week. Separate analyses were conducted for a measure of sustained attention (Continuous Performance Test-Identical Pairs). There were no differential treatment effects on this measure. CONCLUSIONS: The findings from this open-label study suggest that the neurocognitive effects of aripiprazole are at least as good as those of olanzapine.

A comparison of weight change during treatment with olanzapine or aripiprazole: results from a randomized, double-blind study.

BACKGROUND: Weight gain is a side effect of therapy with many atypical antipsychotics and may have important clinical repercussions with respect to long-term health and treatment compliance. The primary objective of this double-blind study was to compare the safety and tolerability of aripiprazole and olanzapine in patients with schizophrenia as evidenced by the percentage of patients exhibiting significant weight gain. METHOD: This was a 26-week, multicenter, randomized, double-blind, active-controlled trial in patients with DSM-IV schizophrenia who were in acute relapse and required hospitalization. Significant weight gain was defined as a > or = 7% increase in body weight from baseline. Body weight, Positive and Negative Syndrome Scale, and Clinical Global Impressions-Improvement scale (CGI-I) assessments were performed at baseline and at regular intervals during the study. The study period was from April 2000 through June 2001. RESULTS: 317 patients were randomly assigned to aripiprazole (N = 156) or olanzapine (N = 161). Compared with those treated with aripiprazole, a greater proportion of patients treated with olanzapine exhibited clinically significant weight gain during the trial. By week 26, 37% of olanzapine-treated patients had experienced significant weight gain compared with 14% of aripiprazole-treated patients (p < .001). Statistically significant differences in mean weight change were observed between treatments beginning at week 1 and sustained throughout the study. At week 26, there was a mean weight loss of 1.37 kg (3.04 lb) with aripiprazole compared with a mean increase of 4.23 kg (9.40 lb) with olanzapine among patients who remained on therapy (p < .001). Changes in fasting plasma levels of total cholesterol, high-density lipoprotein cholesterol, and triglycerides were significantly different in the 2 treatment groups, with worsening of the lipid profile among patients treated with olanzapine. There was a consistent and sustained improvement in symptoms in patients who remained on therapy with either olanzapine or aripiprazole as assessed by CGI-I scores and responder rates throughout the study. CONCLUSION: Olanzapine had a greater impact on patients' weight than aripiprazole. Significant differences in favor of aripiprazole were also observed in the effects of therapy on plasma lipid profile. Both treatment groups achieved comparable clinically meaningful improvements on efficacy measures. The observed effects on weight and lipids indicate a potentially lower metabolic and cardiovascular risk in patients treated with aripiprazole compared with those treated with olanzapine.