Mixed-up about how to diagnose and treat mixed features in major depressive episodes

Abstract

The classical point of view—that major depressive episodes (MDEs), no matter what additional symptoms are present, should be treated first line with antidepressants—is now giving way to new a notion. The idea is that MDEs mixed with a few symptoms of mania/hypomania should be viewed very differently in terms of their natural history, clinical outcome, and treatment, and perhaps certain antipsychotics should be given as first-line treatment rather than antidepressant monotherapy.

Chris Cornell, the Black Hole Sun, and the Seasonality of Suicide

“…Of note is that this seasonally responsive central thermostat governs the sensitivity of certain brain dopamine-2 (D 2 ) receptors [74], which are the therapeutic mood-stabilizing neuroreceptor targets for the atypical antipsychotic medications that are effective for mixed depressive states [17]. Further, genetic variations affecting central D 2 receptor function regulate variations in habitual sleep duration in humans [75], while striatal extracellular dopamine concentrations and striatal D 2 receptors modulate the activity-rest ratio in mice [76].…”

“…Given that treatments for mixed depression versus unipolar depression are very different and may even be dangerous if misapplied [17], raising the awareness of clinicians and patients regarding this diagnostic distinction remains an ongoing and crucial matter. Also in this regard, it would be important to encourage the use a reliable and valid self-administered rating scale [83] for the better detection of mixed mood states, and to more fully explore the degree of mood conflict and suicidal ideation in patients with mixed mood episodes.…”

“…Controversy exists, however, regarding how many and what kind of depressive and manic symptoms may combine to constitute a nosologically and pathophysiologically meaningful entity of the mixed mood state [17-19]. Interestingly, mixed mood states are also most likely to occur in the spring, at the height of the seasonal suicide risk rhythm [20-23].…”

The relationship between depression with anxious distress DSM-5 specifier and mixed depression: a network analysis

“…Notably, epidemiological and clinical characteristics of MDE with ADS are quite similar to those of mixed depression (MXD) (for a review of the different diagnostic criteria for MXD see Malhi et al 9 ): the prevalence of MXD ranges from 20% to 80% (depending on setting, samples and diagnostic criteria used), [10][11] and patients with this diagnosis share the same features as mentioned above. [10][11][12][13][14] This evidence suggests at least a partial overlap between MDE with ADS and MXD, but, to the best of our knowledge, no research study examined how these conditions might be interrelated.…”

“…[15][16][17][18] The rationale behind the exclusion of these symptoms has been that they are unspecific, because they recur in pure (hypo) mania, depression, and anxiety disorders. As a consequence of this exclusion, DSM-5 criteria for MDE with MF have a highest specificity (100%), but a low sensitivity (5.1%), 14 and delineate a psychopathological condition that is extremely rare in clinical settings, with a prevalence ranging between 0% and 7.5%, 5,13,16,[19][20] although in a large naturalistic study it reached 31%. 4 Among the potential alternatives to DSM criteria for MXD proposed by many research groups (for a review see Malhi et al 9 ), Koukopoulos' criteria have been validated 21 and extensively used in the clinical practice since 1992.…”