A Double-Blind, Placebo-Controlled Study of Aripiprazole Adjunctive to Antidepressant Therapy among Depressed Outpatients with Inadequate Response to Prior Antidepressant Therapy (ADAPT-A Study)
ABSTRACT We assessed the efficacy of low-dose aripiprazole added to antidepressant therapy (ADT) in major depressive disorder (MDD) patients with inadequate response to prior ADT.
As per the sequential parallel comparison design, 225 MDD subjects were randomized to adjunctive treatment with aripiprazole 2 mg/day or placebo across two 30-day phases, with a 2:3:3 randomization ratio to drug/drug (aripiprazole 2 mg/day in phase 1; 5 mg/day in phase 2), placebo/placebo (placebo in both phases), and placebo/drug (placebo in phase 1; aripiprazole 2 mg/day in phase 2). Eligible subjects were patients whose MDD was independently deemed 'valid' with SAFER criteria. Subjects had been receiving ADT for ≥8 weeks, and had inadequate response to ≥1 and <4 adequate ADTs in the current episode, as defined by the Antidepressant Treatment Response Questionnaire.
The pooled, weighted response difference between aripiprazole 2 mg/day and placebo in the two phases was 5.6% (p = 0.18; NS). The aripiprazole 2 mg/day-placebo difference on the Montgomery-Asberg Depression Rating Scale pooled across the two phases was -1.51 (p = 0.065; NS). Other secondary endpoint analyses showed nonsignificant pooled differences favoring aripiprazole over placebo. Of the 225 randomized subjects in phase 1, 2 dropped out in both arms, while in phase 2, of 138 phase 1 placebo nonresponders, 9 dropped out on aripiprazole and 5 on placebo. There were only minimal differences in adverse event rates between treatments, except for constipation, weight gain, and dry mouth, more common on aripiprazole.
This study provides clear support for the tolerability of low-dose aripiprazole as an ADT-augmenting agent, with marginal efficacy.
- SourceAvailable from: Chi-Un Pae[Show abstract] [Hide abstract]
ABSTRACT: There has been no studies comparing the clinical benefits of aripiprazole augmentation (AT), antidepressant combination (AC), and switching to a different antidepressant (SW) in patients with major depressive disorder (MDD) patients partially or not responding to an initial antidepressant. AT, AC, or SW was chosen by patients. The primary efficacy measure was the proportion of patients showing an improvement in the Clinical Global Impression-Clinical Benefit (CGI-CB) score at week 8. Secondary efficacy measures included changes in CGI-CB, CGI-Severity (S) and subjective satisfaction scores. Remission and responder analysis were also employed. A total of 295 patients were enrolled. The most preferred strategy was AT (n = 156, 52.9%), followed by AC (n = 93, 31.5%) and SW (n = 46, 15.6%). The improver was significantly higher in AT (74.1%) compared with AC (48.1%; p < 0.001) and similar to SW (73.5%, p = 0.948), whereas no significant difference was found between AC and SW. Similar results were also found in the most secondary endpoint measures proving a superiority of AT over AC without differences between AT and SW. Tolerability profiles were similar across the three groups; however, the mean weight gain for SW (-0.1 kg) was significantly less than that for AC (1.3 kg, p < 0.05). Patients preferred AT to AC or SW when an antidepressant was ineffective in treating their depression. Among the three treatment strategies, overall AT yielded greater clinical benefit than did AC and SW. Adequately powered, well-controlled clinical trials are strongly warranted to confirm our findings due to methodological shortcomings.Journal of Psychiatric Research 11/2013; 49. DOI:10.1016/j.jpsychires.2013.11.001 · 4.09 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: This randomized, placebo-controlled study evaluated the efficacy and safety of a fixed dose (3mg/day) and flexible dose (3-15mg/day) schedule of aripiprazole as augmentation therapy in Japanese patients with inadequate response to antidepressant therapy (ADT). During an 8-week prospective treatment phase, patients experiencing a major depressive episode received clinicians' choice of ADT. Subjects with inadequate response to ADT were randomized to receive adjunctive treatment with placebo (n=195), fixed dose aripiprazole (n=197) or flexible dose aripiprazole (n=194) for 6 weeks. The primary efficacy endpoint was mean change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from the end of prospective treatment (baseline) to the end of randomized treatment. More than 90% of patients in all treatment groups completed the 6-week double-blind treatment phase. Mean MADRS total score was improved to a significantly greater extent with fixed dose aripiprazole and flexible dose aripiprazole (-10.5 and -9.6, respectively) than with placebo (-7.4). Aripiprazole was well tolerated. The incidence of akathisia observed in the flexible dose group may relate to a higher prevalence of the CYP2D6(*)10 allele in Asian populations. Six weeks of adjunctive treatment is insufficient to draw conclusions about the long-term benefits of aripiprazole. Exclusion of patients with established medical comorbidities does not reflect real-world practice. Aripiprazole augmentation at a fixed or flexible dose was superior to ADT alone and was reasonably well tolerated in Japanese patients with inadequate response to ADT. ClinicalTrials.gov identifier NCT00876343.Journal of Affective Disorders 08/2013; 151(3). DOI:10.1016/j.jad.2013.07.035 · 3.71 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Nonresponse or a partial response to 1 or more antidepressants is a common and significant problem in clinical practice. Adjunctive therapy with atypical antipsychotics is considered as 1 of the next treatment options for such inadequate responses. The present trial evaluated the efficacy and the safety of aripiprazole as an augmentation to ongoing antidepressant monotherapy for patients with major depressive disorder (MDD) who have previously exhibited an inadequate clinical response. This was a 6-week prospective, multicenter, open-label study with flexibly dosed adjunctive aripiprazole. The 86 participants with MDD showed inadequate responses to more than 8 weeks of standard antidepressant treatment. The primary outcome was the mean change in Montgomery-Asberg Depression Rating Scale total score from baseline to the end point (week 6). The mean daily dose of aripiprazole at the end point was 6.9 mg. The Montgomery-Asberg Depression Rating Scale total score was significantly decreased with adjunctive aripiprazole during the study period (by 14.0 points, P = 0.000). At the end point, the response rate was 52.3% and the remission rate was 39.8%. Adjunctive aripiprazole produced a significant response and remission from week 1 through the end point. The study completion rate was 73.9%, and adverse events included sedation (n = 11), akathisia (n = 9), headache (n = 6), tremor (n = 6), and increased appetite (n = 5). Of the discontinuations, only 5.7% were due to adverse events. Adjunctive aripiprazole in patients with MDD who had previously exhibited an inadequate response to standard antidepressant therapy was efficacious and well tolerated. A low daily dose of aripiprazole would be more acceptable in the clinical setting.Clinical neuropharmacology 09/2013; 36(5):157-161. DOI:10.1097/WNF.0b013e3182a31f3d · 1.84 Impact Factor