Atypical Antipsychotic Augmentation in Major Depressive Disorder: A Meta-Analysis of Placebo-Controlled Randomized Trials

Abstract

Atypical antipsychotics are effective augmentation agents in major depressive disorder but are associated with an increased risk of discontinuation due to adverse events.

Augmentation Treatments with Second-generation Antipsychotics to Antidepressants in Treatment-resistant Depression

“…The meta-analysis by Nelson and Papakostas [5] examined the pooled odds ratios (ORs) of 16 studies including 3,480 subjects and using four SGAs (olanzapine, risperidone, quetiapine and aripiprazole). Among the studies, the pooled OR of augmentation versus placebo response rate was 1.69 [95 % confidence interval (CI) 1.46 to 1.95, p \ 0.00001], the NNT was nine, and there was no heterogeneity among studies.…”

“…Two meta-analyses have reviewed SGA efficacy as an augmentation therapy with antidepressant medications in TRD patients [5,6]. In 2009, Nelson and Papakostas [5] performed a meta-analysis of four of 10 SGAs used in 16 acute-phase (up to 12 weeks), parallel-group, double-blind, placebo controlled trials involving the random assignment of a total of 3,480 patients to adjunctive treatment with an SGA (n = 2,014) or a placebo (n = 1,466).…”

“…In 2009, Nelson and Papakostas [5] performed a meta-analysis of four of 10 SGAs used in 16 acute-phase (up to 12 weeks), parallel-group, double-blind, placebo controlled trials involving the random assignment of a total of 3,480 patients to adjunctive treatment with an SGA (n = 2,014) or a placebo (n = 1,466). Here, patients had to have nonpsychotic MDD that was considered treatment resistant either by history or as determined by a prospective trial.…”

“…The pooled OR for three studies (n = 1,065) in which subjects taking aripiprazole were compared with subjects taking a placebo in conjunction with antidepressants showed a significant benefit for the aripiprazole group in response rate (OR = 2.07, 95 % CI 1.58 to 2.72, NNT = 7, p \ 0.00001) and remission rate (OR = 2.09, 95 % CI 1.55 to 2.81, NNT = 8, p \ 0.00001) [5]. The mean difference in the MADRS score at endpoint was -3.04 (95 % CI -4.09 to -2.00, p \ 0.00001), showing a significant benefit for the aripiprazole group [6].…”

“…The efficacy of antipsychotics in treating depressive symptoms has previously been confirmed [4] but tolerability issues such as extrapyramidal side effects and over-sedation have limited the use of such drugs when treating MDD. Recently, however, the introduction of second-generation antipsychotics (SGAs), with varied neuropharmacological profiles with improved efficacy and fewer side effects relative to conventional antipsychotics, has rekindled interest in the use of this class of drugs to treat mood and anxiety disorders, including as an adjunctive therapy [5,6]. Therefore, this study reviews the efficacy and tolerability of SGA augmentation in conjunction with antidepressant therapy for treatment-resistant depression (TRD) in acute-phase studies published to date.…”