Elsevier

Journal of Affective Disorders

Volume 164, 1 August 2014, Pages 14-18
Journal of Affective Disorders

Research report
Koukopoulos׳ diagnostic criteria for mixed depression: A validation study

https://doi.org/10.1016/j.jad.2014.03.054Get rights and content

Abstract

Background

Mixed depression (MxD) is one subtype of depressive experiences within the depressive spectrum. MxD definition is debated among experts. Koukopoulos׳ proposed diagnostic criteria focused primarily on psychic agitation, marked irritability, and intense mood lability as markers of a mixed depressive episode. The present study validates Koukopoulos׳ criteria as diagnostic for MxD.

Methods

A sample of 435 patients from the International Mood Network (IMN), multi-center, international network of sites, and the Centro LucioBini of Rome was analyzed. Koukopoulos׳ criteria were assessed in all patients.

Results

The most prevalent MxD criteria were “absence of psychomotor retardation” (84%), “mood lability or marked reactivity” (78%), and “psychic agitation or inner tension” (75%). Multivariable predictors of a MxD (+) diagnosis were: higher current CGI (OR=1.23, 95% CI 1.23, 2.84), lower rates of previous bipolar type I diagnosis (OR=0.54, 95% CI −3.28, −0.13), mixed symptoms on the index episode (OR=10.02, 95% CI 2.32, 24.12), rapid cycling course (OR=2.6 95% CI 1.45, 3.56), past substance abuse (OR=3.02, 95% CI 2.01, 5.67) and lower education status (OR=0.44, 95% CI −3.23, −0.98). This model showed a sensitivity of 76.4%, specificity of 86.3%, negative predictive value of 75%, and positive predictive value of 86%.

Limitations

An external validation of these criteria in an independent sample is warranted.

Conclusion

A broad definition of mixed depression was internally validated with multiple diagnostic validators and was sensitively and specifically predicted. Contrary to DSM-5, Koukopoulos׳ broad criteria include agitation, irritability and mood lability as core features.

Introduction

Depression is defined as a state of dampened mood and energy, and reduction in motor and psychic activity. Yet some patients have many other depressive features, such as sad mood and diminished interest in activities, along with other features of psychomotor excitation. In the past, this presentation has been called agitated depression, and in the post DSM-III nosology, it has been seen as part of major depressive disorder (MDD). Agitated depression contrasts in phenomenology with what has traditionally been called melancholia—highly retarded psychomotor function and anhedonic depression in the absence of any irritability or mood lability. Yet both conditions are given the same post DSM-III diagnosis—MDD.

Psychomotor agitation is present in many cases, but not in all. In cases without psychomotor agitation, a depressed and anxious mood with inner, psychic agitation dominates the clinical picture. Koukopoulos first suggested that this depression combined with features of psychic excitation should be called “mixed depression” (MxD), and he postulated that it was different than other kinds of depressive syndromes (Koukopoulos et al., 1992).

Recently, some investigators have in part endorsed this position, suggesting that the term “mixed depression” be applied to the mixture of severe depression with some manic symptoms (Akiskal, 1992, Benazzi, 2000, Benazzi, 2003, Angst et al., 2011).

The DSM-5 definition of MxD is broader than the DSM-IV definition, and focuses on the presence of non-overlapping manic symptoms during a major depressive episode. However, this clinical picture seems to be rare (as ever present) and leaves a vast majority of patients undiagnosed and mistreated. Thus, our group has recently challenged this DSM-based view of MxD, highlighting its lack of clinical utility and scientific weakness (Koukopoulos and Sani, 2014, Koukopoulos et al., 2013).

Koukopoulos׳ perspective is broader, though, capturing not only DSM-based manic symptoms, but also psychic excitation in general (Koukopoulos and Koukopoulos, 1999, Koukopoulos et al., 2006). This proposal for the diagnosis of depressive mixed states focuses on psychic agitation, marked irritability, and marked mood lability, with or without the presence of other excitatory symptoms.

In this paper, we provide the first empirical examination of the potential nosological validity of this clinical definition of mixed depression based on criteria proposed by Koukopoulos et al. (2007) (see Table 1).

Section snippets

Participants

Subjects were enrolled in the study if they were diagnosed with a major depressive episode using DSM-IV-TR criteria (American Psychiatric Association, 2000) and confirmed through the Structured Clinical Interview (SCID-I) for DSM-IV-TR (First et al., 2002).

Any patient with at least three of the eight criteria (Table 1) during any major depressive episode over the course of his or her illness was considered “mixed depression positive” (MxD (+)). Patients were recruited through the International

Results

Of 435 patients (224 from the International Mood Network and 211 from the Centro Lucio Bini), 221 patients (50.8%) were mixed depression positive (MxD (+)) and 214 (49.2%) were mixed depression negative (MxD (−)).

No patients diagnosed with MxD met criteria for mania according to DSM-IV-TR; thus they were not diagnosable with a mixed episode according to DSM-IV-TR. Furthermore, no patients met criteria for depression with mixed features according to DSM-5.

Females comprised 61% of the subject

Discussion

This study tested Koukopoulos׳ broad criteria for mixed depression (MxD). The definition of MxD was validated using diagnostic validators, many of which were usually associated with a broad MxD definition. The most common MxD criteria were psychic agitation, marked irritability and mood reactivity, with an absence of psychomotor retardation. MxD (+) patients were male, younger, less educated, more likely to have a history of substance abuse and likely to have received psychiatric treatment at

Conclusion

In sum, Koukopoulos׳ definition of mixed depression (MxD)—identifying mixed depressive features such as agitation, irritability and mood lability—was internally validated in this sample using multiple course validators. These data show that “overlapping” symptoms of excitement and depression are specific and may be valid symptoms of MxD. New MxD diagnostic criteria are internally validated in this sample. Further validation work in other samples will be needed to replicate and reevaluate these

Role of funding source

Nothing declared.

Conflict of interest

In the past two years, Dr. Paolo Girardi has received research support from Lilly, Janssen, and Springer Healthcare, and has participated in Advisory Boards for Lilly, Otsuka, Pfizer, Schering, and Springer Healthcare and received honoraria from Lilly and Springer Healthcare. In the past 12 months, Dr. Nassir Ghaemi has received research grants from Pfizer and Takeda. Neither he nor his family holds equity positions in pharmaceutical corporations. All other authors declare that they have no

Acknowledgments

None.

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