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Efficacy of adjunctive aripiprazole in major depressive disorder: a pooled response quartile analysis and the predictive value of week 2 early response.

ABSTRACT: OBJECTIVE:To assess varying levels of response to aripiprazole adjunctive to standard antidepressant therapy (ADT) and the predictive value of an early response for a sustained response. METHOD:This post hoc analysis of 3 similarly designed randomized, double-blind, placebo-controlled phase 3 studies investigated the efficacy and safety of adjunctive aripiprazole to standard ADT in patients with major depressive disorder (DSM-IV-TR criteria) who had a prior inadequate response to 1-3 ADTs (CN138-139 [September 2004-December 2006], CN138-163 [June 2004-April 2006], and CN138-165 [March 2005-April 2008]). Response levels were defined as percent decreases from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score after 6 weeks of treatment, with a ? 25% decrease for minimal, > 25 to < 50% decrease for partial, ? 50% to < 75% decrease for moderate, and ? 75% decrease for a robust response to treatment. RESULTS:More patients receiving adjunctive aripiprazole exhibited a partial (23.9% vs 17.9%, P = .017), moderate (23.1% vs 15.0%, P < .001), and robust response (14.3% vs 7.4%, P < .001) compared with adjunctive placebo. Adjunctive aripiprazole treatment compared with adjunctive placebo treatment was associated with a significantly greater proportion of patients achieving an early response (week 2, ? 50% reduction in MADRS total score, n = 110/539 vs n = 47/525, P < .001, number needed to treat = 9) and an endpoint response (relative risk = 1.7, 95% CI = 1.4-2.0, P < .001, number needed to treat = 7). A univariate logistic regression analysis revealed that an early response was a significant predictor of endpoint remission (P < .001). CONCLUSIONS:Aripiprazole augmentation was associated with a significantly greater proportion of patients achieving a partial, moderate, or robust response to treatment compared with ADT alone. Patients showing an early response (week 2) to augmentation maintained their response through endpoint, suggesting that clinicians may make clinically meaningful decisions early during treatment. TRIAL REGISTRATION:ClinicalTrials.gov identifiers: NCT00095823, NCT00095758, and NCT00105196.

SUBMITTER: Casey DE

PROVIDER: S-EPMC3466032 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Efficacy of adjunctive aripiprazole in major depressive disorder: a pooled response quartile analysis and the predictive value of week 2 early response.

Casey Daniel E DE Laubmeier Kimberly K KK Marler Sabrina Vogel SV Forbes Robert A RA Baker Ross A RA

The primary care companion for CNS disorders 20120531 3

<h4>Objective</h4>To assess varying levels of response to aripiprazole adjunctive to standard antidepressant therapy (ADT) and the predictive value of an early response for a sustained response.<h4>Method</h4>This post hoc analysis of 3 similarly designed randomized, double-blind, placebo-controlled phase 3 studies investigated the efficacy and safety of adjunctive aripiprazole to standard ADT in patients with major depressive disorder (DSM-IV-TR criteria) who had a prior inadequate response to ...[more]

PMID: 23106023

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Project description:BackgroundPatients with major depressive disorder (MDD) who fail to achieve complete remission with antidepressant therapy may benefit from augmentation therapy with an atypical antipsychotic.MethodA pooled analysis was performed on 2 identical 14-week studies (8-week prospective antidepressant therapy treatment phase followed by 6-week randomized double-blind phase) evaluating the efficacy of adjunctive aripiprazole (2-20 mg/day) in DSM-IV-TR-defined MDD patients with an inadequate response to antidepressant therapy. Primary efficacy endpoint was the mean change in Montgomery-Asberg Depression Rating Scale (MADRS) total score from end of the prospective phase (week 8) to end of randomized phase (week 14, last observation carried forward). Subgroup analyses were performed. The key secondary endpoint was mean change in Sheehan Disability Scale (SDS) mean score.ResultsAt endpoint, mean change in MADRS total score was significantly greater with adjunctive aripiprazole (-8.7) than with adjunctive placebo (-5.7; p < .001). Except for a differential treatment-by-sex interaction, change in MADRS total scores were consistently greater with adjunctive aripiprazole than with adjunctive placebo, regardless of race, age, episode duration, prior antidepressant therapy response, number of historical treatment failures, severity of depressive symptoms, and antidepressant. At endpoint, MADRS remission rates were significantly greater with adjunctive aripiprazole than with placebo (25.7% vs. 15.4%; p < .001). Adjunctive aripiprazole also demonstrated significantly greater improvements in mean change from baseline in SDS total score than adjunctive placebo (-1.2 vs. -0.6; p = .001).ConclusionAugmentation of antidepressant therapy with the atypical antipsychotic aripiprazole resulted in significant efficacy benefits across a range of subgroups of patients with MDD. Further study of a treatment-by-sex interaction is needed.Trial registrationwww.clinicaltrials.gov Identifiers: NCT00095823 and NCT00095758.

Project description:ObjectiveTo evaluate the safety and tolerability of aripiprazole adjunctive to standard antidepressant therapy (ADT) for patients with major depressive disorder (DSM-IV-TR criteria).MethodData from 2 identical studies of aripiprazole augmentation (8 weeks of prospective ADT treatment followed by 6 weeks of randomized double-blind adjunctive treatment) were pooled. The incidence of treatment-emergent adverse events (TEAEs) and weight, electrocardiogram (ECG), and laboratory measurements were assessed during the 6-week phase, including time course, severity, resolution, and predictors. The studies were conducted from June 2004 to April 2006 and September 2004 to December 2006.ResultsThe safety analysis included 737 outpatients (aripiprazole, n = 371; placebo, n = 366). The majority of patients completed the trials (aripiprazole, 86%; placebo, 88%). Common TEAEs (≥ 5% and twice the placebo rate) with aripiprazole were akathisia (25%), restlessness (12%), insomnia (8%), fatigue (8%), blurred vision (6%), and constipation (5%). Most TEAEs were of mild to moderate severity (aripiprazole, 89%; placebo, 95%). TEAE rates in the aripiprazole and placebo groups were not affected by ADT, age, or gender. Discontinuation due to TEAEs was low (aripiprazole, 3%; placebo, 1%). Mean weight change was higher with aripiprazole versus placebo (1.73 kg vs 0.38 kg, P < .001). At endpoint, clinical laboratory parameters, vital signs, and ECG indices (including QT(c) interval) were similar between groups. Akathisia with aripiprazole generally occurred in the first 3 weeks (76%), was of mild to moderate severity (92%), and led to discontinuation in 3 patients (0.8%). Within the aripiprazole group, age (18-40 years) was the only positive predictor for akathisia.ConclusionsIn this short-term post hoc analysis, aripiprazole as augmentation to ADT demonstrated a safety and tolerability profile similar to that in monotherapy studies in other psychiatric populations. Controlled long-term safety and efficacy data of aripiprazole as adjunctive to ADT are warranted.Trial registrationclinicaltrials.gov Identifiers: NCT00095823 (CN138-139) and NCT00095758 (CN138-163).

Project description:OBJECTIVE:The present study aimed to evaluate the efficacy and safety of adjunctive aripiprazole treatment in schizophrenia patients with risperidone-induced hyperprolactinemia. METHODS:One hundred and thirteen patients who were receiving a stable dose of risperidone were randomly assigned to either adjunctive aripiprazole treatment (10 mg/day) (aripiprazole group) or no additional treatment (control group) at a 1:1 ratio for 8 weeks. Schizophrenia symptoms were measured using the Positive and Negative Syndrome Scale (PANSS). Rating scales and safety assessments (RSESE, BARS, UKU) were performed at baseline and at weeks 4 and 8. Serum levels of prolactin were determined at baseline and at weeks 2, 4, 6 and 8. Metabolic parameters were determined at baseline and again at weeks 4 and 8. RESULTS:One hundred and thirteen patients were enrolled in this study, and 107 patients completed the study (54 in the aripiprazole group, and 53 in the control group). PANSS-total scores in the aripiprazole group decreased significantly at week 4 (P = 0.003) and week 8 (P = 0.007) compared with the control group. PANSS-negative scores in the aripiprazole group also decreased significantly at week 4 (P = 0.005) and week 8 (P< 0.001) compared with the control group. Serum levels of prolactin in the aripiprazole group decreased significantly at week 2 (P< 0.001), week 4 (P< 0.001), week 6 (P< 0.001) and week 8 (P< 0.001) compared with the control group. There were no significant differences in changes of Fasting Plasma Glucose, Total cholesterol, Triglycerides and High Density Lipoprotein within each group at week 4 and 8 execpt low density lipoproteins. There was no significant difference in the incidence of adverse reactions between the two groups. CONCLUSIONS:Adjunctive aripiprazole treatment may be beneficial in reducing serum levels of prolactin and improving negative symptoms in schizophrenia patients with risperidone-induced hyperprolactinemia. TRIAL REGISTRATION:chictr.org ChiCTR-IOR-15006278.

Project description:To investigate the specific effect of adjunctive aripiprazole on sexual function in patients with major depressive disorder and a history of an inadequate response to antidepressant medication by controlling for improvement in depressive symptoms as measured by improvement in Montgomery-Asberg Depression Rating Scale (MADRS) total scores. For this post hoc analysis, data were pooled from 3 multicenter, randomized, double-blind, placebo-controlled aripiprazole augmentation studies (CN138-139: June 2004-April 2006; CN138-163: September 2004-December 2006; and CN138-165: March 2005-April 2008). Outpatients who met DSM-IV-TR criteria for a major depressive episode that had lasted ≥8 weeks with an inadequate response to prospective antidepressant treatment were randomized to adjunctive aripiprazole or placebo for 6 weeks. Sexual functioning was assessed using the Massachusetts General Hospital Sexual Functioning Inventory (MGH-SFI). To assess whether adjunctive aripiprazole improves sexual functioning directly, rather than as an indirect effect of improvement in depression symptoms, the mean change in MGH-SFI item scores and overall improvement scores was assessed using analysis of covariance, with double-blind baseline and change in MADRS total score as covariates. Correlations between MGH-SFI items and MADRS total score and prolactin levels were also assessed. The analysis included 1,092 subjects (n=737 female and n=355 male). In the total population, adjunctive aripiprazole demonstrated statistically significant greater improvements versus placebo on the MGH-SFI item "interest in sex" (-0.34 vs -0.18, P<.05). In males, no significant treatment differences were observed. In females, improvements in sexual functioning with adjunctive aripiprazole versus placebo were found on the MGH-SFI items "interest in sex" (-0.41 vs -0.21, P<.05) and "sexual satisfaction" (-0.44 vs -0.25, P<.05). Aripiprazole adjunctive to antidepressant treatment can have some beneficial effects on sexual functioning in patients with major depressive disorder who respond inadequately to standard antidepressant treatment; the benefits in women were specific to sexual interest and satisfaction and were independent of the improvement in depressive symptoms. clinicaltrials.gov Identifiers: NCT00095823, NCT00095758, and NCT00105196.

Dataset Information

Efficacy of adjunctive aripiprazole in major depressive disorder: a pooled response quartile analysis and the predictive value of week 2 early response.

Publications

Efficacy of adjunctive aripiprazole in major depressive disorder: a pooled response quartile analysis and the predictive value of week 2 early response.

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