Pharmacological Treatment of Major Depressive Episodes with Mixed Features: A Systematic Review

Abstract

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 ClinicalTrials.gov 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.

The Korean Medication Algorithm Project for Bipolar Disorder (KMAP‐BP): Changes in preferred treatment strategies and medications over 16 years and five editions

“…The KMAP‐BP has gradually come to view AAPs as primary drugs rather than just as adjunctive agents to MSs. AAPs are efficacious for difficult cases of depression, cases showing mixed features, and those with rapid cycling, as well as classical mania 4,5,35,38,39 . However, the preferred AAP differs depending on the KMAP‐BP edition and type of episode.…”

Diagnostic Issues of Depressive Disorders from Kraepelinian Dualism to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition

“…[22][23][24] Moreover, recent studies have reported that major depressive episode (MDE) mixed features are characterized by a low prevalence, the predominance of anxious distress, the prevalence of cluster B personality disorders, and pharmacological treatment with antipsychotics. [25][26][27] Thus, as shown in Figure 1, the specifier "with mixed features" may indicate quantitative but not qualitative overlapping symptoms from one pole to the opposite pole in the dichotomization of mood disorders into bipolar and depressive disorders.…”

Ecological momentary assessment of mood and movement with bipolar disorder over time: Participant recruitment and efficacy of study methods

“…See et al, 2021). This allows us to measure mixed depression and hypo/ mania symptoms, common to most BD mood episodes (Shim et al, 2018). Developing measures specifically for EMA is ideal; most researchers instead cherry-pick items from existing measures with limited pilot testing (i.e., psychometric properties untested ;Trull & Ebner-Priemer, 2020).…”