Safety and Tolerability of Adjunctive Aripiprazole in Major Depressive Disorder: A Pooled Post Hoc Analysis (studies CN138-139 and CN138-163)

Augmentation of antidepressant therapy (ADT) with an atypical antipsychotic is one treatment option for patients who do not obtain sufficient benefit from an adequate course of ADT.1,2 Aripiprazole is approved for use as an adjunctive treatment to ADT in adults with major depressive disorder (MDD) on the basis of results from 2 identical, large, multicenter, randomized, double-blind, placebo-controlled trials.3,4 These trials demonstrated the efficacy of adjunctive aripiprazole in patients with an inadequate response to a prospective 8-week trial of the same ADT and at least 1 historical ADT trial.3,4 Aripiprazole is a novel atypical agent with a unique pharmacologic profile that may make it particularly effective as an augmentation agent for the treatment of depression. Aripiprazole has potent partial-agonist activity at D2 and D3 receptors5,6 and demonstrates high affinity and partial-agonist activity at serotonin 5-HT1A receptors and antagonist activity at 5-HT2 receptors7,8—effects that may contribute to specific antidepressant action. Augmentation of standard ADTs has the potential to induce or exacerbate adverse events (AEs). Treatment-emergent AEs (TEAEs) common with adjunctive atypical antipsychotic use include weight gain, sedation, extrapyramidal symptoms, metabolic disturbances (eg, diabetes and hyperlipidemia), and hyperprolactinemia, although risk varies between agents.9–11 Consideration of the relative risks and benefits of these agents may influence treatment selection. Understanding safety and tolerability issues may be particularly important early in treatment in order to improve clinical management and to promote good adherence. Finally, identification of groups of patients at increased risk for particular AEs may also assist drug selection, enhanced monitoring, and patient education. This pooled analysis used data from 2 identical studies of aripiprazole augmentation3,4 to provide a more comprehensive assessment of the safety and tolerability of aripiprazole adjunctive to standard ADT for patients with MDD. Clinical Points ♦ Atypical antipsychotics as augmentation agents to antidepressant therapy can be used in patients with MDD who have an inadequate response to antidepressant monotherapy. ♦ The safety and tolerability profile of adjunctive aripiprazole in MDD is similar to that in monotherapy studies in other psychiatric populations. ♦ Akathisia was the most common side effect reported, usually of mild to moderate severity, and led to discontinuation in less than 1% of patients treated.