Efficacy of aripiprazole versus placebo as adjuncts to lithium or valproate in relapse prevention of manic or mixed episodes in bipolar I patients stratified by index manic or mixed episode.

BACKGROUND: Differences in response to treatment have been observed for bipolar disorder (BPD) patients with manic or mixed episodes. This post-hoc analysis examined the maintenance effect of aripiprazole in combination with lithium or valproate in subpopulations of patients entering a relapse prevention study with either manic or mixed bipolar episodes. METHODS: A long-term relapse prevention study of BPD patients with manic or mixed episodes included a single-blind stabilization phase, in which patients were stabilized with single-blind aripiprazole plus lithium or valproate (maintaining stability for 12 weeks), and a double-blind relapse assessment phase, where patients were randomized to aripiprazole or placebo plus lithium or valproate for up to 52 weeks. Lithium and valproate groups were pooled. RESULTS: The time to relapse of any mood episode was longer in the adjunctive aripiprazole group versus the lithium/valproate monotherapy group for the manic (p<0.01) but not mixed population (p=0.59). The LOCF analysis indicated a significantly greater reduction in YMRS total score from baseline with continued aripiprazole versus placebo at 52 weeks in both manic (treatment difference=-3.32, p<0.01) and mixed episode populations (treatment difference=-2.56, p=0.02). Overall, adverse event profiles were similar between the populations. LIMITATION: The lithium and valproate subgroups were combined. CONCLUSIONS: The continuation of aripiprazole in stabilized BPD patients treated with lithium or valproate increased the time to relapse of any mood episode for manic but not mixed patients; both groups achieved greater stability in YMRS total score with adjunctive aripiprazole. Thus, adjunctive aripiprazole may be more appropriate for stabilized patients with manic episodes.

Effect of aripiprazole 2 to 15 mg/d on health-related quality of life in the treatment of irritability associated with autistic disorder in children: a post hoc analysis of two controlled trials.

BACKGROUND: There are limited published data on the impact of treatment on the health-related quality of life (HRQOL) in individuals with autistic disorder. OBJECTIVE: The aim of this study was to evaluate the impact of aripiprazole on HRQOL in the treatment of irritability in pediatric patients (aged 6-17 years) with autistic disorder. METHODS: This post hoc analysis assessed data from two 8-week, double-blind, randomized, placebo-controlled studies that compared the efficacy of aripiprazole (fixed-dose study, 5, 10, and 15 mg/d; flexible-dose study, 2-15 mg/d) with placebo in the treatment of irritability associated with autistic disorder. HRQOL was assessed at baseline and week 8 using 3 Pediatric Quality of Life Inventory (PedsQL™) scales. Clinically relevant improvement in HRQOL was determined using an accepted distribution-based criterion-1 standard error of measurement. RESULTS: In total, 316 patients were randomly assigned to receive treatment with aripiprazole (fixed-dose study, 166; flexible-dose study, 47) or placebo (fixed-dose study, 52; flexible-dose study, 51). Aripiprazole was associated with significantly greater improvement than placebo in PedsQL combined-scales total score (difference, 7.8; 95% CI, 3.8-11.8; P < 0.001) and in 3 PedsQL scale scores (differences [95% CI]: Emotional Functioning, 7.8 [3.4-12.2]; Social Functioning, 6.2 [0.7-11.8]; Cognitive Functioning, 9.3 [3.8-14.9]; all, P < 0.05). Patients who received aripiprazole were significantly more likely than those who received placebo to have a clinically meaningful improvement on the combined-scales total score (odds ratio [OR] = 1.9; 95% CI, 1.0-3.3; P < 0.05), Emotional Functioning scale (OR = 2.2; 95% CI, 1.2-4.0; P < 0.05) and Social Functioning scale (OR = 2.2; 95% CI, 1.2-4.1; P < 0.05), and were significantly less likely to experience deterioration (OR: 0.3, 95% CI: 0.1-0.8; P < 0.05) when "Stable" was used as the reference group. CONCLUSIONS: The findings from the present post hoc analysis suggest that aripiprazole was associated with improved HRQOL, as assessed using 3 PedsQL scales, in pediatric patients with irritability associated with autistic disorder.

Improvement in functional outcomes with adjunctive aripiprazole versus placebo in major depressive disorder: a pooled post hoc analysis of 3 short-term studies.

OBJECTIVE: To evaluate the effect of adjunctive aripiprazole to antidepressant therapy (ADT) on functional outcomes, as assessed by the Sheehan Disability Scale (SDS). METHOD: A post hoc analysis of pooled data from 3 similarly designed randomized, placebo-controlled trials was conducted (CN138-139 [September 2004-December 2006], CN138-163 [June 2004-April 2006], and CN138-165 [March 2005-April 2008]). Patients with DSM-IV major depressive disorder who had a prior inadequate response to ADT received adjunctive aripiprazole or placebo to standard ADT. The change from baseline to endpoint on total SDS score and on individual SDS domains and the distributional categorical shifts of patient-reported severity of functional impairment on the SDS were assessed. RESULTS: Aripiprazole compared to placebo augmentation produced significant improvements in self-reported functioning levels in the SDS mean total score (-1.2 vs -0.7, P ≤ .001) and social life (-1.4 vs -0.7, P ≤ .001) and family life (-1.4 vs -0.7, P ≤ .001) domains. Additionally, a significant number of patients exhibited a shift from a severe/moderate level of impairment at baseline to a mild level of functional impairment after 6 weeks of adjunctive aripiprazole treatment compared with placebo in the SDS mean total score (P = .001) and social life (P ≤ .001) and family life (P = .001) scores. CONCLUSIONS: Aripiprazole augmentation of standard antidepressant therapy resulted in significant improvements in both total and individual domains of functioning, as assessed by the SDS, with significant categorical shifts from severe/moderate to mild levels of functioning compared with placebo augmentation. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT00095823, NCT00095758, and NCT00105196.

Time to psychiatric hospitalization in patients with bipolar disorder treated with a mood stabilizer and adjunctive atypical antipsychotics: a retrospective claims database analysis.

OBJECTIVE: This study compared the time to psychiatric hospitalization in commercially insured patients with bipolar disorder who were treated with a mood stabilizer plus adjunctive aripiprazole versus adjunctive ziprasidone, olanzapine, quetiapine, or risperidone. METHODS: This was a retrospective, propensity score-matched cohort study using the Ingenix I3/LabRx integrated insurance claims data set. Patients with bipolar disorder were included if they had >or=180 days of pre-index enrollment in the health plan without atypical antipsychotic exposure. Patients received mood stabilizers and subsequently received adjunctive atypical antipsychotic agents; they were then monitored for up to 90 days after the index antipsychotic prescription. The primary analysis was a Cox proportional hazards analysis to evaluate the time until psychiatric hospitalization comparing adjunctive aripiprazole with ziprasidone, olanzapine, quetiapine, or risperidone after adjusting for age, sex, and preindex hospitalization. RESULTS: Adjunctive aripiprazole was associated with a longer time until hospitalization than adjunctive ziprasidone, olanzapine, quetiapine, or risperidone (hazard ratios 1.7, 1.6, 1.5, and 1.5, respectively; all, P < 0.05). Mean initial and maximum doses of all drugs were below those recommended by the package insert or clinical practice guidelines. Sensitivity analyses suggested the robustness of the results in the general population of patients with bipolar disorder recently treated with atypical antipsychotics. CONCLUSIONS: This retrospective claims-data analysis suggests that in these adults with bipolar disorder treated with mood stabilizers, the addition of adjunctive aripiprazole was associated with a longer time to hospitalization than adjunctive ziprasidone, olanzapine, quetiapine, or risperidone during a 90-day follow-up period.

Predictors of aripiprazole treatment continuation in hospitalized patients.

OBJECTIVE: Aripiprazole is a second-generation antipsychotic that is increasingly prescribed in a variety of psychiatric disorders. The goal of this study was to investigate patient and treatment factors associated with aripiprazole treatment continuation on hospital discharge in psychiatric inpatients. METHOD: This was a retrospective cohort analysis of patients admitted to a psychiatric hospital between January 1, 2003, and June 30, 2006, and treated with aripiprazole. The goal was to determine factors associated with continuation of aripiprazole throughout the hospital stay and on discharge from the hospital. Covariates assessed included patient demographics, prior psychiatric hospitalizations, diagnoses, prior antipsychotic use, and concomitant psychotropic medications. Aripiprazole-specific covariates were starting and maximum dose and dose titration pattern. Diagnoses were identified using ICD-9-CM codes. RESULTS: There were 1957 aripiprazole-treated patients included in this study, and 1573 (80%) continued aripiprazole treatment at the time of hospital discharge. Median starting doses were lower (5 mg/day) for younger and older patients, and patients with psychotic disorders received higher doses than other patients. Approximately 58% of patients had at least 1 aripiprazole dose titration while hospitalized, and most (73%) of those patients had a dose titration within 3 days of admission. Predictors of treatment continuation in this broad patient population were younger age, a diagnosis of bipolar or major depressive disorder, higher maximum aripiprazole doses, and upward dose titration within 3 days of admission. Patients receiving concomitant anticholinergics or antipsychotics were less likely to continue treatment as were those receiving aripiprazole at the time of hospitalization. CONCLUSION: In this acute inpatient psychiatric setting, continuation of aripiprazole treatment on discharge was achieved in most patients. Demographic, diagnostic, and treatment factors predicting aripiprazole treatment effectiveness were identified.