Major depressive disorder (MDD) is a chronic mental illness with a considerable lifetime prevalence in adult men and women. Only a third of MDD patients remit following adequate antidepressant treatment, while most suffer from significant core depressive or residual symptoms during their clinical course. Augmentation treatment with second-generation antipsychotics (SGAs) has been one of the suggested approaches to overcome this shortage of efficacy of antidepressant therapy.

To review the role of SGAs as an augmentation strategy to antidepressant therapy in MDD.

A search of the MEDLINE/Pubmed database was conducted for articles from 2010 to 2015, using the MeSH terms “antypsichotics”, “depression” and “treatment”.

There is a general consensus in the literature that antidepressant augmentation treatment with SGAs is more effective than placebo in the management of patients with MDD who failed to respond adequately to antidepressant therapy alone. The majority of studies found no significant differences between the different studied drugs (namely, aripiprazole, quetiapine, olanzapine and risperidone). On the other hand, discontinuation rates due to adverse effects are also higher with SGAs versus placebo. However, it remains unclear if augmentation with SGAs is more effective than other therapeutic strategies, such as combination or switching to other antidepressant or augmentation with other psychotropics.

There is strong evidence that SGAs augmentation is an effective and generally safe therapeutic approach to patients with MDD who respond poorly to antidepressants. Nevertheless, more studies are needed to understand the efficacy of this treatment comparing other therapeutic approaches.

The authors have not supplied their declaration of competing interest.