Efficacy Of Adjunctive Aripiprazole Research Articles

Efficacy of adjunctive aripiprazole in patients with major depressive disorder whose symptoms worsened with antidepressant monotherapy.

Efficacy of depression treatments, including adjunctive antipsychotic treatment, has not been explored for patients with worsening symptoms after antidepressant therapy (ADT). This post-hoc analysis utilized pooled data from 3 similarly designed, randomized, double-blind, placebo-controlled trials that assessed the efficacy, safety, and tolerability of adjunctive aripiprazole in patients with major depressive disorder with inadequate response to ADT. The studies had 2 phases: an 8-week prospective ADT phase and 6-week adjunctive (aripiprazole or placebo) treatment phase. This analysis focused on patients whose symptoms worsened during the prospective 8-week ADT phase (worsening defined as >0% increase in Montgomery-Åsberg Depressive Rating Scale [MADRS] Total score). During the 6-week, double-blind, adjunctive phase, response was defined as ≥50% reduction in MADRS Total score and remission as ≥50% reduction in MADRS Total score and MADRS score ≤10. Of 1065 patients who failed to achieve a response during the prospective phase, 160 exhibited worsening of symptoms (ADT-Worseners), and 905 exhibited no change/reduction in MADRS scores (ADT-Non-worseners). Response rates for ADT-Worseners at endpoint were 36.6% (adjunctive aripiprazole) and 22.5% (placebo). Similarly, response rates at endpoint for ADT-Non-worseners were 37.5% (adjunctive aripiprazole) and 22.5% (placebo). Remission rates at endpoint for ADT-Worseners were 25.4% (adjunctive aripiprazole) and 12.4% (placebo). For ADT-Non-worseners, remission rates were 29.9% (adjunctive aripiprazole) and 17.4% (placebo). These results suggest that adjunctive aripiprazole is an effective intervention for patients whose symptoms worsen during antidepressant monotherapy. The results challenge the view that benefits of adjunctive therapy with aripiprazole are limited to partial responders to ADT.

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

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. 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. 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). 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. ClinicalTrials.gov identifiers: NCT00095823, NCT00095758, and NCT00105196.

P01-186 - Efficacy of adjunctive aripiprazole to lithium or valproate in the long-term treatment of mania in subjects with bipolar i disorder (CN138–189)

ObjectivesTo evaluate the long-term safety and efficacy of adjunctive aripiprazole (ARI) to lithium (LI) or valproate (VAL) in delaying time to relapse in bipolar I disorder.MethodsBipolar I disorder subjects with a current manic or mixed episode received LI or VAL for at least 2 weeks; inadequate responders (YMRS score ≥ 16 and ≤35% decrease from baseline at 2 weeks) received adjunctive ARI. Subjects maintaining mood stability (YMRS and MADRS ≤ 12 for 12 consecutive weeks) were randomised 1:1 to double-blind ARI (10 to 30 mg/day) or placebo (PBO) plus LI or VAL. Relapse was monitored up to 52 weeks.Results337 subjects were randomised to continuation of mood stabiliser plus adjunctive ARI or PBO; 61.3% and 52.7%, respectively, completed the study. Adjunctive ARI significantly delayed the time to any relapse, hazard ratio = 0.544 (95% CI: 0.33, 0.89, log-rank p = 0.014). Overall relapse rates at 52 weeks were 14.9% and 25.4% in ARI vs PBO subjects. A superior reduction in CGI-BP Mania Severity of Illness from baseline at 52 weeks was also observed (0.3 vs. 0.0, respectively, p = 0.01). Adverse events generally were as expected per known drug and illness profiles with no significant difference in mean change in body weight between adjunctive PBO (0.60 kg) and adjunctive ARI (1.07 kg) (p = 0.49 Week 52, LOCF).ConclusionContinuation of aripiprazole treatment increased time to relapse to any mood episode compared with placebo plus LI/VAL over 1 year, indicating a long-term benefit in continuing adjunctive aripiprazole to a mood stabiliser after sustained remission is achieved.

P01-38 - Efficacy of adjunctive aripiprazole in patients with major depressive disorder: pooled analysis of subgroup data from three clinical trials

AimsTo conduct a subgroup analysis of the efficacy of adjunctive aripiprazole as treatment in patients with major depressive disorder (MDD) who demonstrated an inadequate response to standard antidepressant therapy (ADT).MethodsData were pooled from three identical, short-term, double-blind, placebo-controlled studies (CN138-139, CN138-163, CN138-165) with an 8-week phase of placebo plus ADT and a 6-week double-blind phase with ADT plus adjunctive placebo or aripiprazole. Only MDD patients without psychotic features were eligible for entry. The primary efficacy endpoint was the mean change in the Montgomery Asberg Depression Rating Scale (MADRS) total score in the double-blind phase. Subgroup analyses of the primary efficacy endpoint were performed for age, race, ethnicity, MADRS response, number and choice of previous ADTs, episode duration, and use of selective serotonin re-uptake inhibitors (SSRI).ResultsCompared with the adjunctive placebo group, adjunctive aripiprazole was associated with greater reductions in MADRS total score in all subgroups. Mean change in MADRS total score ranged from -10.71 to -5.89 with adjunctive aripiprazole and -7.57 to -4.10 with adjunctive placebo. No statistically significant treatment-by-subgroup interaction effects were observed for any subgroup except gender (p=0.039). This difference is, however, primarily because of results from study CN138-139 results; consistent results between men and women were reported in CN138-163 and CN138-165.ConclusionsPooled data indicate that in patient populations with similar baseline characteristics, treatment with adjunctive aripiprazole and ADT is efficacious in improving the symptoms of MDD in subgroups of patients having an inadequate response to ADT.