Treatment recommendations for DSM-5–defined mixed features

Abstract

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) mixed features specifier provides a less restrictive definition of mixed mood states, compared to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), including mood episodes that manifest with subthreshold symptoms of the opposite mood state. A limited number of studies have assessed the efficacy of treatments specifically for DSM-5-defined mixed features in mood disorders. As such, there is currently an inadequate amount of data to appropriately inform evidence-based treatment guidelines of DSM-5 defined mixed features. However, given the high prevalence and morbidity of mixed features, treatment recommendations based on the currently available evidence along with expert opinion may be of benefit. This article serves to provide these interim treatment recommendations while humbly acknowledging the limited amount of evidence currently available. Second-generation antipsychotics (SGAs) appear to have the greatest promise in the treatment of bipolar disorder (BD) with mixed features. Conventional mood stabilizing agents (ie, lithium and divalproex) may also be of benefit; however, they have been inadequately studied. In the treatment of major depressive disorder (MDD) with mixed features, the comparable efficacy of antidepressants versus other treatments, such as SGAs, remains unknown. As such, antidepressants remain first-line treatment of MDD with or without mixed features; however, there are significant safety concerns associated with antidepressant monotherapy when mixed features are present, which merits increased monitoring. Lurasidone is the only SGA monotherapy that has been shown to be efficacious specifically in the treatment of MDD with mixed features. Further research is needed to accurately determine the efficacy, safety, and tolerability of treatments specifically for mood episodes with mixed features to adequately inform future treatment guidelines.

The clinical characterization of the adult patient with depression aimed at personalization of management

“…The presence of manic/hypomanic symptoms during a depressive episode is associated with a higher rate of anxiety and substance use disorders, increased suicidality, greater impairment in functioning, more frequent family history of bipolar disorder, and poorer response to treatment 62 . It has been suggested that patients with mixed features who are treated with antidepressants should be monitored closely because they are at greater risk for emergence of activation, hypomania and suicidality 64 . An expert panel of mood disorder researchers, while acknowledging the limited number of prospectively designed trials for depression with mixed features, recommended atypical antipsychotic medication as the first-line treatment 65 .…”

The effectiveness of ketamine on anxiety, irritability, and agitation: Implications for treating mixed features in adults with major depressive or bipolar disorder

“…Participants with comorbid psychiatric conditions were eligible for IV ketamine treatment if their primary diagnosis was MDD or BD, meeting Stage 2, or higher (inadequate response to at least two antidepressant trials), 27 criteria for TRD (inadequate response to at least two antidepressant trials). 28,29 A small subpopulation of participants had a primary diagnosis of OCD or PTSD (Table 1).…”

A pragmatic approach to the diagnosis and treatment of mixed features in adults with mood disorders

“…Available evidence suggests that conventional antidepressants prescribed for an MDE with MFS provide a less reliable therapeutic outcome, higher rates of non-remission, and intolerability. 19 Prospective data evaluating the course of illness in individuals experiencing MFS indicate that MFS has a much more pernicious illness trajectory (eg, earlier age at onset, greater episode frequency, higher rates of comorbidity and suicidality). Prescription data indicate that a significant percentage of individuals experiencing an MDE with MFS are treated with antipsychotic agents (first-and second-generations), as well as traditional mood stabilizers (eg, lithium).…”

“…Moreover, MFS has not been rigorously studied with sufficient randomized, double-blind, placebo-controlled trials. Available evidence suggests that conventional antidepressants prescribed for an MDE with MFS provide a less reliable therapeutic outcome, higher rates of non-remission, and intolerability 19 . Prospective data evaluating the course of illness in individuals experiencing MFS indicate that MFS has a much more pernicious illness trajectory (eg, earlier age at onset, greater episode frequency, higher rates of comorbidity and suicidality).…”