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
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- "arable to those with AC or SW . Moreover , augmentation did not cause significantly greater weight gain . These results may be attributable to the lower aripiprazole dose used in our study than in the three RCTs ( Berman et al . , 2009 , 2007 ; Marcus et al . , 2008 ) . The tolerability of low - dose AT has also been demonstrated in a recent RCT ( Fava et al . , 2012 ) . Our study has several strengths . First , this is the first patient preference - based study comparing the effectiveness and tolera - bility among three treatment strategies to overcome partial or non - response to current antidepressants carried out in routine practice . Moreover , the uniformly Korean population is another strengt"
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
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- "Interestingly, the findings revealed comparable clinical benefits between the fixed dose (3 mg/day) and flexible dose (3–15 mg/ day) schedule of aripiprazole in our patient population. This is contrary to what was expected but is supported by other successful clinical experiences of low-dose aripiprazole as an adjunctive agent for refractory depression in Asian populations (Chen et al., 2012; Lin et al., 2011; Terao, 2008) but not in Western populations (Fava et al., 2012; Mischoulon et al., 2012). The CYP2D6 * 10 allele, which decreases CYP2D6 enzyme activity, is known to be highly prevalent in Asian populations but rare in Caucasian populations (Ji et al., 2002); this may affect the pharmacokinetics of aripiprazole in Japanese patients (Suzuki et al., 2011) and impact on treatment response and risk of AEs. "
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
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ABSTRACT: The sequential parallel comparison design (SPCD) has been proposed to increase the likelihood of success of clinical trials in therapeutic areas where high-placebo response is a concern. The trial is run in two stages, and subjects are randomized into three groups: (i) placebo in both stages; (ii) placebo in the first stage and drug in the second stage; and (iii) drug in both stages. We consider the case of binary response data (response/no response). In the SPCD, all first-stage and second-stage data from placebo subjects who failed to respond in the first stage of the trial are utilized in the efficacy analysis. We develop 1 and 2 degree of freedom score tests for treatment effect in the SPCD. We give formulae for asymptotic power and for sample size computations and evaluate their accuracy via simulation studies. We compute the optimal allocation ratio between drug and placebo in stage 1 for the SPCD to determine from a theoretical viewpoint whether a single-stage design, a two-stage design with placebo only in the first stage, or a two-stage design is the best design for a given set of response rates. As response rates are not known before the trial, a two-stage approach with allocation to active drug in both stages is a robust design choice.Statistics in Medicine 10/2011; 30(23):2793-803. DOI:10.1002/sim.4292 · 2.04 Impact Factor