Pharmacological Treatment of Major Depressive Episodes With Mixed Features: A Systematic Review
In Hee Shim 1, Won-Myong Bahk 2*, Young Sup Woo 2, Bo-Hyun Yoon 3
1Cancer center, Dongnam Institute of Radiological & Medical Sciences, Busan, Republic of Korea , 2College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea , 3Naju National Hospital, Naju, Republic of Korea
Received: March 6, 2018; Accepted: March 12, 2018; Published online: March 12, 2018.
© The Korean College of Neuropsychopharmacology. All rights reserved.

Objectives: 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).
Methods: 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.
Results: 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 RCTs. 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.
Conclusion: 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: antipsychotics, bipolar disorder, major depressive disorder, mixed features, pharmacological treatment