Research reportKoukopoulos׳ diagnostic criteria for mixed depression: A validation study
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).
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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.
References (24)
- et al.
The evolving bipolar spectrum: prototypes I, II, III, and IV
Psychiatr. Clin. North Am.
(1999) - et al.
TEMPS-A: validation of a short version of a self-rated instrument designed to measure variations in temperament
J. Affect. Disord.
(2005) - et al.
TEMPS-A: progress towards validation of a self-rated clinical version of the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Auto questionnaire
J. Affect. Disord.
(2005) - et al.
Self-assessment and characteristics of mixed depression in the French national EPIDEP study
J. Affect. Disord.
(2012) Depressive mixed state: dimensional versus categorical definitions
Prog. Neuropsychopharmacol. Biol. Psychiatry
(2003)- et al.
Agitated depression as a mixed state and the problem of melancholia
Psychiatr. Clin. North Am.
(1999) - et al.
Endogenous and exogenous cyclicity and temperament in bipolar disorder: review, new data and hypotheses
J. Affect. Disord.
(2006) - et al.
Mixed depression: a study of its phenomenology and relation to treatment response
J. Affect. Disord.
(2012) - et al.
Treatment of mixed mania
J. Affect. Disord.
(1988) - et al.
Criteria for the “soft” bipolar spectrum: treatment implications
Psychopharmacol. Bull.
(1987)
The distinctive mixed states of bipolar I, II, and III
Clin. Neuropharmacol.
Diagnostic and Statistical Manual of Mental Disorders Text revision (DSM-IV-TR)
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