Second-generation antipsychotics in the treatment of major depressive disorder: Current evidence

Changsu Han, Sheng Min Wang, Masaki Kato, Soo Jung Lee, Ashwin A. Patkar, Prakash S. Masand, Chi Un Pae

    Research output: Contribution to journalReview articlepeer-review

    66 Citations (Scopus)


    Major depressive disorder (MDD) is a chronic and recurrent mental condition leading to huge impacts on direct and indirect personal and public medical costs. To overcome such a serious mental disorder, we currently have a number of different classes of antidepressants, such as selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, noradrenergic and specific serotonin receptor antagonists, dopamine and norepinephrine reuptake inhibitors, along with newly introduced antidepressants (e.g., vilazodone and agomelatine). However, a number of well-controlled clinical trials, meta-analyses and practical clinical studies have found that only a third of such MDD patients remit following adequate antidepressant treatment, while most MDD patients suffer from significant core depressive or residual symptoms during their clinical course. There have been some treatment approaches to overcome such a shortage of antidepressant efficacy, such as augmentation of psychotropics other than antidepressants, switching to a different antidepressant and combinations of different antidepressants. Among these different second treatment options, augmentation treatment has some favorable points compared with the combination and switching option (e.g., maintaining previous antidepressant partial response, synergistic effect between different pharmacological profile and no need to wash out previous antidepressants). Recently, second-generation antipsychotics (SGAs), olanzapine plus fluoxetine, quetiapine extended release and aripiprazole have clearly demonstrated efficacy in the treatment of MDD patients through a number of small-scale, open-label studies or randomized, placebo-controlled clinical trials. Eventually, in November 2007, aripiprazole was the first approved by the US FDA as an adjunctive treatment to antidepressants for treating MDD, followed by the approval of quetiapine and olanzapine plus fluoxetine at 2009. This comprehensive review provides an overview of the clinical trial data of SGAs for treating MDD and clinical issues raised in the use of SGA therapy in patients with MDD in clinical practice.

    Original languageEnglish
    Pages (from-to)851-870
    Number of pages20
    JournalExpert Review of Neurotherapeutics
    Issue number7
    Publication statusPublished - 2013

    Bibliographical note

    Funding Information:
    This study was supported by a grant from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A120004). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.


    • Antidepressant
    • Augmentation
    • Clinical trial
    • Major depressive disorder
    • Second-generation antipsychotic

    ASJC Scopus subject areas

    • General Neuroscience
    • Clinical Neurology
    • Pharmacology (medical)


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