Diagnostic and Therapeutic Considerations in Depressive Mixed State

Abstract

Although the definition of depressive mixed state, more commonly known as mixed depression, is still controversial, about one-third of major depressive episodes are held to contain mixed components. The most frequent manifestations of mixed depression are irritability, distractibility and psychomotor agitation, although these symptoms are not included in the mixed features during a major depressive episode according to the DSM-5 criteria, which is therefore unlikely to cover the full scope of mixed depression in real-world settings. Mixed depression often accompanies risky behavior including impulsive suicide attempts. The early detection and treatment of these unstable conditions is therefore necessary. Also, sufficiently sensitive and specific screening methods for depressive mixed state are needed to avoid both under-and over-diagnosis. Antidepressants should be avoided since these drugs often worsen irritability, agitation and impulsivity, and increase risky behavior. Instead, combination therapy with mood stabilizer(s) to prevent the relapse of the depressive mixed state and atypical antipsychotics for rapid stabilization in the acute phase should be considered. Because there is very little evidence for effective pharmacotherapy in mixed depression, the efficacy of various mood-stabilizing agents, either as monotherapy or in combination therapies, should be extensively examined in the future using quantitative assessments of the psychopathology of mixed depression in patients with confirmed diagnoses of mixed depression.

The prevalence and diagnostic classification of mixed features in patients with major depressive episodes: A multicenter study based on the DSM‐5

“…In contrast with a previous study, which predicted an increase in prevalence when comparing the DSM-IV-TR with the DSM-5, the prevalence of mixed features did not significantly increase after applying the DSM-5 in this study (McIntyre et al, 2015;Shim, Woo, & Bahk, 2015). Nevertheless, the prevalence of mixed states satisfying the RBDC was nearly identical to that in the existing data (Kondo et al, 2016). This means that the DSM did not identify patients who met the RBDC for mixed states as having mixed features.…”

“…When the RBDC were applied, the overall prevalence of mixed states increased to 31.7%: 61.8% in BD and 19.0% in MDD. The results of the present study resemble those of an earlier study reporting that the prevalence of mixed states in those with depression was much higher according to research‐based than DSM‐based criteria (Kondo, Shinzato, & Koda, ). Although the prevalence of mixed states in those with depression differs among studies due to differences in the definition used, the rate has been estimated at 62.0–66.4% in BD and 12.8–32.5% in MDD, reflecting a significantly higher rate of mixed states in BD than in MDD (Benazzi, ; Takeshima & Oka, ).…”

The 12-item self-rating questionnaire for depressive mixed state (DMX-12) in relation to categorical diagnoses of mixed depression and mixed features

“…The DMX-12 questionnaire in Japanese was developed by us (Appendix 1) [16], according to previously reported core features for DMX such as distractibility, irritability and psychomotor agitation (inner tension and restlessness) and racing/crowded thought [3,14] as well as other prevalent mixed symptoms, e.g., mood lability, overreactivity, impulsivity, aggression and risk-taking behavior, pointed out from previous researches [7,17]. This scale was also translated into English and was again back-translated into Japanese by two native speakers for both English and Japanese, followed by confirmation from all the authors (Appendix 2) [16].…”

“…Manifestation of DMX is mainly characterized by dysphoric/irritable mood with inner agitation, racing/ crowded thought despite dysfunctional thought content and impulsive/risky behavior together with restlessness [2]. However, spontaneous verbalization of DMX symptoms is usually difficult for patients whereas clinicians interview them mainly focusing on typical depressive symptoms, which may easily lead to underdiagnosis of DMX despite the necessity for urgent management of DMX and deliberate pharmacotherapy different from usual treatment of depression [3,4].…”

“…Furthermore, such criteria are unlikely to be suitable for correct assessment of severity of DMX. Recently, we proposed a postulated model for depressive psychopathology structured by static/ dynamic and internalized/externalized dimensions together with its plausible treatment options and suggested the necessity of dimensional approaches to assess various types of depressive symptomatology such as melancholic depression, psychotic depression and mixed depression [3]. Thereafter, we have developed the 12-item questionnaire for screening and quantification of DMX (DMX-12), covering non-specific but frequent mixed symptoms [16].…”