The Efficacy and Safety of Aripiprazole as Adjunctive Therapy in Major Depressive Disorder

Bristol-Myers Squibb, Wallingford, CT 06492, USA.
Journal of Clinical Psychopharmacology (Impact Factor: 3.24). 05/2008; 28(2):156-65. DOI: 10.1097/JCP.0b013e31816774f9
Source: PubMed


Nonresponse to one or more antidepressants is common and an important public health problem. This study evaluated the efficacy and safety of adjunctive aripiprazole or placebo to standard antidepressant therapy (ADT) in patients with major depressive disorder who showed an inadequate response to at least 1 and up to 3 historical and 1 additional prospective ADT. The study comprised a 7-28-day screening, an 8-week prospective treatment, and a 6-week randomization phase. During prospective treatment, patients experiencing a major depressive episode (17-item Hamilton Rating Scale for Depression total score >18) received single-blind adjunctive placebo plus clinicians' choice of ADT (escitalopram, fluoxetine, paroxetine controlled-release, sertraline, or venlafaxine extended-release). Subjects with inadequate response were randomized to adjunctive placebo (n = 190) or adjunctive aripiprazole (n = 191) (starting dose 5 mg/d, dose adjustments 2-20 mg/d, mean end-point dose of 11.0 mg/d). The primary efficacy endpoint was the mean change in Montgomery-Asberg Depression Rating Scale total score from end of prospective treatment phase to end of randomized treatment phase (last observation carried forward). Mean change in Montgomery-Asberg Depression Rating Scale total score was significantly greater with adjunctive aripiprazole than placebo (-8.5 vs -5.7; P = 0.001). Remission rates were significantly greater with adjunctive aripiprazole than placebo (25.4% vs 15.2%; P = 0.016) as were response rates (32.4% vs 17.4%; P < 0.001). Adverse events occurring in 10% of patients or more with adjunctive placebo or aripiprazole were akathisia (4.2% vs 25.9%), headache (10.5% vs 9.0%), and fatigue (3.7% vs 10.1%). Incidence of adverse events leading to discontinuation was low (adjunctive placebo [1.1%] vs adjunctive aripiprazole [3.7%]). Aripiprazole is an effective and safe adjunctive therapy as demonstrated in this short-term study for patients who are nonresponsive to standard ADT.

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Available from: Madhukar H Trivedi, Oct 10, 2015
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    • "After screening 5 259 citations (Figure 1), 17 articles were included in this review (Shelton et al., 2001, 2005; Corya et al., 2006; Khullar et al., 2006; Mattingly et al., 2006; Berman et al., 2007, 2009; Mahmoud et al., 2007; McIntyre et al., 2007; Thase et al., 2007; Marcus et al., 2008; Reeves et al., 2008; Bauer et al., 2009; Keitner et al., 2009; El-Khalili et al., 2010; Fava et al., 2012; Kamijima et al., 2013) comprised of 18 RCTs with a total of 4 422 patients treated with seven different types (and dosages) "
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    • "The 11 trials included one trial with risperidone (Mahmoud et al., 2007), three with quetiapine (Garakani et al., 2008; Bauer et al., 2009; El-Khalili et al., 2010), two with an olanzapinefluoxetine combination (Thase et al., 2007), and five with aripiprazole (Berman et al., 2007, 2009; Marcus et al., 2008; Lin et al., 2011; Kamijima et al., 2013). Two trials investigated the efficacy of atypical antipsychotics in the non-TRD population (Garakani et al., 2008; Lin et al., 2011), and the remaining nine trials did so in the TRD population. "
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    • "Aripiprazole, a D2R/D3R partial agonist, has demonstrated to be clinically effective enhancing the effects of standard antidepressant drugs in core depressive symptoms of treatment-resistant depressed patients [32] [62] [63]. Another pharmacological evidence supporting the antidepressant effect of D3R activation is given by pramipexole, a D3R preferring D2R/D3R agonist. "
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