To review the diagnostic validity and utility of mixed depression, i.e. co-occurrence of depression and manic/hypomanic symptoms.
PubMed search of all English-language papers published between January 1966 and December 2006 using and cross-listing key words: bipolar disorder, mixed states, criteria, utility, validation, gender, temperament, depression-mixed states, mixed depression, depressive mixed state/s, dysphoric hypomania, mixed hypomania, mixed/dysphoric mania, agitated depression, anxiety disorders, neuroimaging, pathophysiology, and genetics. A manual review of paper reference lists was also conducted.
By classic diagnostic validators, the diagnostic validity of categorically-defined mixed depression (i.e. at least 2-3 manic/hypomanic symptoms) is mainly supported by family history (the current strongest diagnostic validator). Its diagnostic utility is supported by treatment response (negative effects of antidepressants). A dimensionally-defined mixed depression is instead supported by a non-bi-modal distribution of its intradepression manic/hypomanic symptoms.
Categorically-defined mixed depression may have some diagnostic validity (family history is the current strongest validator). Its diagnostic utility seems supported by treatment response.
"As a consequence, the selection of medication is usually based on individual factors and short and long-term safety and tolerability. It is largely recognized, however, that mixed manic/depressive presentations in BD have a poorer pharmacological response compared with pure episodes (Benazzi, 2008; Cassidy et al., 2008; Gonzalez-Pinto et al., 2011), and combination therapy is often required (Gonzalez-Pinto et al., 2007). In their metaanalysis , Yildiz et al. (2011) found that mixed features predicted poorer response to both active treatment and placebo. "
[Show abstract][Hide abstract] ABSTRACT: The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) nomenclature for the co-occurrence of manic and depressive symptoms (mixed states) has been revised in the new DSM-5 version to accommodate a mixed categorical-dimensional concept. The new classification will capture subthreshold non-overlapping symptoms of the opposite pole using a "with mixed features" specifier to be applied to manic episodes in bipolar disorder I (BD I), hypomanic, and major depressive episodes experienced in BD I, BD II, bipolar disorder not otherwise specified, and major depressive disorder. The revision will have a substantial impact in several fields: epidemiology, diagnosis, treatment, research, education, and regulations. The new concept is data-driven and overcomes the problems derived from the extremely narrow definition in the DSM-IV-TR. However, it is unclear how clinicians will deal with the possibility of diagnosing major depression with mixed features and how this may impact the bipolar-unipolar dichotomy and diagnostic reliability. Clinical trials may also need to address treatment effects according to the presence or absence of mixed features. The medications that are effective in treating mixed episodes per the DSM-IV-TR definition may also be effective in treating mixed features per the DSM-5, but new studies are needed to demonstrate it.
"The current study aims to explore the constructs of melancholic and non-melancholic depression and how they differ from one another drawing on both clinical and neuropsychological data. While current classifications suggest major depressive disorder (MDD) is a homogeneous disorder that changes on an index of severity (Benazzi, 2008; Judd, Schettler & Akisal, 2002; Sadek & Bona, 2000; Shankman & Klein, 2002), subtypes of depression are also diagnosed on the basis of certain symptoms being present in one subtype but not other. For instance, psychomotor retardation is characteristic of melancholic depression (see Parker, 2007). "
[Show abstract][Hide abstract] ABSTRACT: Major depressive disorder is often considered to be a homogenous disorder that changes in terms of severity; however, the presence of distinct subtypes and a variety of presenting symptoms suggests much heterogeneity. Aiming to better understand the relationship between heterogeneity and diagnosis we used an exploratory approach to identify subtypes of depression on the basis of clinical symptoms and neuropsychological performance. Cluster analysis identified two groups of patients distinguished by level of cognitive dysfunction with the more severe cluster being associated with melancholic depression. While the relationship between cluster and subtype was significant, only 58% of melancholic patients were assigned to cluster 1 (the more severe cluster) and 66% of non-melancholic patients assigned to cluster 2. Subtypes also displayed a distinctive profile of impairment such that melancholic patients (n = 65) displayed more variability in attention while non-melancholic patients (n = 59) displayed memory recall impairment. While melancholia and non-melancholia are associated with a more severe and less severe form of depression respectively, findings indicate that differences between melancholia and non-melancholia are more than simple variation on severity. In summary, findings provide support for the heterogeneity of depression.
Journal of the International Neuropsychological Society 03/2012; 18(2):361-9. DOI:10.1017/S1355617711001858 · 2.96 Impact Factor
"(2011), doi:10.1016/j.jad. Studies have found that such patients with mixed depres - sion appear to have different clinical course and treatment outcomes , compared to MDEs without manic symptoms ( pure depression ) ( Dilsaver and Benazzi , 2008 ; Dodd et al . , 2010 ; Keller et al . "
[Show abstract][Hide abstract] ABSTRACT: Mixed depression reflects the occurrence of a major depressive episode with subsyndromal manic symptoms. Not recognized in DSM-IV, it is included in the proposed changes for DSM-5. Observational and cross-sectional studies have suggested that mixed depression is present in up to one-half of major depressive episodes, whether in MDD or bipolar disorder. Based on observational studies, antidepressants appear to be less effective, and neuroleptics more effective, in mixed than pure depression (major depressive episodes with no manic symptoms). In this report, we examine the specific manic symptoms that are most present in mixed depression, especially as they correlate with prospectively assessed treatment response.
In 72 patients treated in a randomized clinical trial (ziprasidone versus placebo), we assessed the phenomenology of manic symptom type at study entry and their influence as predictors of treatment response.
The most common symptom presentation was a clinical triad of flight of ideas (60%), distractibility (58%), and irritable mood (55%). Irritable mood was the major predictor of treatment response. DSM-based diagnostic distinctions between MDD and bipolar disorder (type II) did not predict treatment response.
In this prospective study, mixed depression seems to be most commonly associated with irritable mood, flight of ideas, and distractibility, with irritability being an important predictor of treatment outcome with neuroleptic agents. If these data are correct, in the presence of mixed depression, the DSM-based dichotomy between MDD and bipolar disorder does not appear to influence treatment response.
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