Clinical and psychometric characterization of depression in mixed mania: A report from the French National Cohort of 1090 manic patients

Mood Center, Adult Psychiatry Department, Pitié-Salpêtrière Hospital, 47 Bd de l'Hôpital, 75013 Paris Cedex 13, France.
Journal of Affective Disorders (Impact Factor: 3.38). 01/2007; 96(3):225-32. DOI: 10.1016/j.jad.2005.01.005
Source: PubMed


Despite extensive research recently focused on mixed mania, it is uncertain as how best to define it clinically, psychometrically (which has major bearing on its prevalence), and the methodology needed for future research. This topic is also of historical interest, because Magnan (1890) [Magnan, V., 1890. La Folie Intermittente. G Masson, Paris.] suggested that "combined [mixed] states" linked Falret's "circular insanity" with Baillarger's "dual insanity" (both described in 1854). This work eventually led to the Kraepelinian synthesis of all manic, mixed, and depressive states into the unitary rubric of "manic-depressive insanity (1899/1921).
EPIMAN-II Thousand" (EPIMAN-II MILLE) is a French national collaborative study, which involved training 317 psychiatrists working in different sites representative of psychiatric practice in France. We recruited 1090 patients hospitalized for acute DSM-IV mania. assessed at index admission by the following measures: the Mania Rating Scale (MRS), the Beigel-Murphy Scale (MSRS), a newly derived checklist of depressive symptoms least contaminated by mania, MADRS for severity of depression, and the SAPS for psychotic features.
The rate of mixed mania, as defined by at least 2 depressive symptoms, was 30%. Even with this broad definition, we found significantly higher female representation. This clinical sub-type of mania was characterized by high frequency of past diagnostic errors, particularly those of anxiety and personality disorders. Refined definition of co-exiting depression was obtained from an abbreviated version of the MADRS (6 items), with distinct "emotional-cognitive" symptoms, and "psychomotor inhibition" factors, both of which were separable from an "irritable" factor linked to lability and poor judgment. Mixed mania was psychometrically best identified by a MADRS score of 6 (80% sensitivity, 94% specificity) and validated by a mixed polarity of first episodes, a higher rate of recurrence, psychotic features, and suicide attempts.
Cross-sectional study.
The data deriving from EPIMAN, the largest and only national study ever conducted on mania, provide definitive characterization of the clinical and psychotic structure of mixed mania, which accounts for 1 out of 3 patients who present with mania. This figure is more accurate than higher rates reported in the literature because, in describing "mixity", we eliminated depressive features that could be contaminated by mania. Despite the prominent affective features described herein, the bipolar nature of mixed mania is often missed, with the result that these patients are diagnosed as having anxiety and/or personality disorders. It is of great public health significance for psychiatrists to recognize the bipolar nature of this condition that has been known as a major phase of manic-depressive illness since at least Magnan, a disciple of Falret and Baillarger.

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    • "Regarding the age of onset, the majority of studies report that both mixed mania and mixed depression occur at a younger age than pure episodes (Azorin et al., 2012; Benazzi, 2008; Cassidy and Carroll, 2001; Goldberg et al., 2009; Gonzalez-Pinto et al., 2011; Perugi and Akiskal, 2005; Valenti et al., 2011), although similar or older ages have also been described (Benazzi, 2008; Hantouche et al., 2006; Perugi and Akiskal, 2005; Perugi et al., 2001). Compared to pure manic episodes, the clinical picture of mixed mania shows that patients tend to experience more episodes of illness, with episodes of longer duration (Martin- Carrasco et al., 2012) and more functional impairment (Rosa et al., 2009). "
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    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.
    Journal of Affective Disorders 04/2013; 148(1). DOI:10.1016/j.jad.2013.03.007 · 3.38 Impact Factor
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    • "The traditional categorical paradigm of the bipolar disorder spectrum (manic, depressive, and mixed states) has been recently completed by a dimensional paradigm with the description of a range of intermediate states (e.g., dysphoric mania and hypomania, mixed depression) which belong to a broad spectrum of mixed states [1,2]. One of the major issues in clinical practice is the accurate differential diagnosis between mixed states and depression, often leading to inappropriate prescriptions of antidepressants in mixed states, and as a consequence, increasing the risk of manic switch and suicide [3,4]. "
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    ABSTRACT: One of the major issues in clinical practice is the accurate differential diagnosis between mixed states and depression, often leading to inappropriate prescriptions of antidepressants in mixed states, and as a consequence, increasing the risk of manic switch and suicide. In order to better define the spectrum of mixed states, it may be useful to develop a dimensional approach. In this context, the MAThyS (Multidimensional Assessment of Thymic States) scale was built to assess activation/inhibition levels in all bipolar mood episodes, and to determine whether a clinical description in terms of activation/inhibition can help better define bipolar states with which both manic and depressive symptoms are associated. The aim of this paper is the validation of the MAThyS scale in 141 bipolar patients in acute states (manic, hypomanic, mixed, or depressive). The validation of the MAThyS scale was the primary outcome of this 24-week, phase III, open-label, olanzapine single-arm clinical trial. Principal component, factorial analysis, and Cronbach's coefficient calculation (internal consistency) were performed. Concurrent validity (correlations with 17-item Hamilton Depression Rating Scale [HAMD-17], Hamilton Anxiety Rating Scale [HAMA], and Young Mania Rating Scale [YMRS]) and responsiveness to the clinical intervention were assessed (change in MAThyS scale and effect size) at 6 and 24 weeks. Scree plot of eigenvalues identified a 2-dimension structure ("activation/inhibition level" and "emotional component"). Psychometric properties were good: Cronbach's coefficient was >0.9. Concurrent validity was good with low correlation (-0.19) with the HAMA scale and a higher correlation at baseline with the YMRS (0.72) and HAMD-17(-0.43). As expected, the activation state was predominant in manic, hypomanic, and mixed states while inhibition was predominant in depressive states. MAThyS score improvement was observed (effect size: -0.3 at 6 and 24 weeks). The MAThyS demonstrated good psychometric properties. The MAThyS scale may help clinicians to better discriminate and follow bipolar episodes, especially the broad spectrum of mixed episodes. registration identification number: NCT#002592722.
    BMC Psychiatry 03/2013; 13:79. DOI:10.1186/1471-244X-13-79 · 2.21 Impact Factor
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    • "The inclusion of the MADRS score in our analysis may explain our results. The MADRS item 'inability of feel', which was positively correlated with LOS in our study, has been considered as a core depressive symptom by some authors [35]. However, since some of the other MADRS items are susceptible to contamination by a manic state, such as sleep reduction, appetite reduction, concentration difficulties and inner tension, it could be thought that the effect of the MADRS score on LOS could be explained by the manic symptoms included in this scale. "
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    ABSTRACT: Few studies have analyzed predictors of length of stay (LOS) in patients admitted due to acute bipolar manic episodes. The purpose of the present study was to estimate LOS and to determine the potential sociodemographic and clinical risk factors associated with a longer hospitalization. Such information could be useful to identify those patients at high risk for long LOS and to allocate them to special treatments, with the aim of optimizing their hospital management. This was a cross-sectional study recruiting adult patients with a diagnosis of bipolar disorder (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) criteria) who had been hospitalized due to an acute manic episode with a Young Mania Rating Scale total score greater than 20. Bivariate correlational and multiple linear regression analyses were performed to identify independent predictors of LOS. A total of 235 patients from 44 centers were included in the study. The only factors that were significantly associated to LOS in the regression model were the number of previous episodes and the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at admission (P < 0.05). Patients with a high number of previous episodes and those with depressive symptoms during mania are more likely to stay longer in hospital. Patients with severe depressive symptoms may have a more severe or treatment-resistant course of the acute bipolar manic episode.
    Annals of General Psychiatry 03/2012; 11(1):7. DOI:10.1186/1744-859X-11-7 · 1.40 Impact Factor
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