Clin Psychopharmacol Neurosci 2018; 16(4): 376-382  
Pharmacological Treatment of Major Depressive Episodes with Mixed Features: A Systematic Review
In Hee Shim1, Won-Myong Bahk2, Young Sup Woo2, Bo-Hyun Yoon3
1Department of Psychiatry, Cancer Center, Dongnam Institute of Radiological & Medical Sciences, Busan, 2Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, 3Department of Psychiatry, Naju National Hospital, Naju, Korea
Correspondence to: Won-Myong Bahk, MD, PhD
Department of Psychiatry, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 10 63-ro, Yeongdeungpo-gu, Seoul 07345, Korea
Tel: +82-2-3779-1250, Fax: +82-2-780-6577
Received: March 7, 2018; Accepted: March 12, 2018; Published online: November 30, 2018.
© The Korean College of Neuropsychopharmacology. All rights reserved.

This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
We reviewed clinical studies investigating the pharmacological treatment of major depressive episodes (MDEs) with mixed features diagnosed according to the dimensional criteria (more than two or three [hypo]manic symptoms+principle depressive symptoms). We systematically reviewed published randomized controlled trials on the pharmacological treatment of MDEs with mixed features associated with mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD). We searched the PubMed, Cochrane Library, and databases through December 2017 with the following key word combinations linked with the word OR: (a) mixed or mixed state, mixed features, DMX, mixed depression; (b) depressive, major depressive, MDE, MDD, bipolar, bipolar depression; and (c) antidepressant, antipsychotic, mood stabilizer, anticonvulsant, treatment, medication, algorithm, guideline, pharmacological. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We found few randomized trials on pharmacological treatments for MDEs with mixed features. Of the 36 articles assessed for eligibility, 11 investigated MDEs with mixed features in mood disorders: six assessed the efficacy of antipsychotic drugs (lurasidone and ziprasidone) in the acute phase of MDD with mixed features, although four of these were post hoc analyses based on large randomized controlled trials. Four studies compared antipsychotic drugs (olanzapine, lurasidone, and ziprasidone) with placebo, and one study assessed the efficacy of combination therapy (olanzapine+fluoxetine) in the acute phase of BD with mixed features. Pharmacological treatments for MDEs with mixed features have focused on antipsychotics, although evidence of their efficacy is lacking. Additional well-designed clinical trials are needed.
Keywords: Antipsychotic agents; Bipolar disorder; Major depressive disorder; Mixed features; Pharmacological treatment.

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