Multivariate analysis of bipolar mania: Retrospectively assessed structure of bipolar I manic and mixed episodes in randomized clinical trial participants

University of Texas, Houston Health Science Center, Houston, TX, USA.
Journal of Affective Disorders (Impact Factor: 3.38). 08/2012; 144(1-2). DOI: 10.1016/j.jad.2012.05.061
Source: PubMed


BACKGROUND: Manic episodes are heterogeneous. Mixed states may differ in important clinical characteristics from other manic episodes. However, it has not been established whether mixed states are a distinct type of episodes, or a common basic structure exists across manic episodes. METHODS: Using 2179 well-characterized subjects in the pretreatment phase of six randomized, clinical trials, we conducted rotated factor analysis followed by cluster analysis, using all items from the Young Mania Rating Scale and the Montgomery-Åsberg Depression Scale. Analyses were conducted for all subjects (n=2179) and for those in Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition (DSM-IV) mixed (n=644) and non-mixed (n=1535) episodes separately. RESULTS: There were five factors characterized (in order of variance accounted for) as depression, mania, sleep disturbance, judgment/impulsivity and irritability/hostility. Cluster analysis identified five clusters. Three were predominately manic, with depression scores below average for the overall group. Two had high average depression scores; these clusters differed in irritability/hostility. Judgment/impulsivity scores were similar across factors. Essentially identical factors and clusters existed whether analyses were done in all subjects or only in subjects classified by DSM-IV as mixed or non-mixed. LIMITATIONS: Exclusion criteria of studies may limit generalizability of findings. DISCUSSION: All manic episodes, whether mixed or non-mixed, shared a similar structure according to factor/cluster analysis. Patients with high depression factor scores were heterogeneous with respect to irritability. These data suggest that depressive symptoms should be considered a dimensional property across manic episodes, rather than as defining a specific type of episode.

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    • "In that study, mixed patients in the dysphoric cluster had higher scores for anger, worry, and irritability. Swann et al. (2013) identified five clusters of patients with bipolar disorder (BD), and confirmed that depressive–manic states are heterogeneous. "
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    ABSTRACT: The aim of the present study was to determine the distinct clusters of subtypes among patients with bipolar disorder (BD) and the relationship between the clinical features of BD patients, particularly substance use disorders (SUDs) and the clusters. The present study initially assessed 96 inpatients who were hospitalized in the psychiatric clinic of Bakırköy Prof. Mazhar Osman Training and Research Hospital for Psychiatry and Neurology, for a BD manic episode. All patients were evaluated during the initial 3 days of their admission using the Young Mania Rating Scale (YMRS), the Montgomery-Asberg Depression Rating Scale (MADRS),the Scale for the Assessment of Positive Symptoms (SAPS), the Michigan Alcoholism Screening Test (MAST) and a sociodemographic questionnaire. The factor structures of the psychopathological scale items were determined with factor analyses and based on the factor loadings, cluster analyses were performed. The relationships among the clusters and the clinical variables were then evaluated. The factor analyses generated three factors: increased psychomotor activity, dysphoria, and psychosis. A hierarchical cluster analysis was applied to the three factor loadings, and revealed that factor 1 (increased psychomotor activity) was high in cluster 1 and that the effects of factors 2 (dysphoria) and 3 (psychosis) were high in cluster 2. Within cluster 1 (Psychomotor elevation), 39% of patients were diagnosed with an alcohol use disorder while 31.6% of patients in the cluster 2 (dysphoric-psychotic) were diagnosed with both alcohol and cannabis use disorders. Within cluster 2 (dysphoric-psychotic), 47.4% of patients had one suicide attempt and 21.1% of patients had two or more attempts during their lifetime. There was a significant difference in the presence of SUDs between patients with psychomotor elevation and patients in dysphoric-psychotic cluster. This may be point out that pure manic patients with BD self-medicate using the sedative effects of alcohol and the causal relationship between cannabis and psychosis. Using a dimensional approach to study BD may enhance detection of the biological correlates of BD and improve the treatment and outcomes of the disorder. Copyright © 2014 Elsevier B.V. All rights reserved.
    Full-text · Article · Dec 2014 · Journal of Affective Disorders
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    • "Conversely, antidepressant treatment to treat only depressive symptoms can induce a manic switch (Baldessarini et al., 2012; Fornaro et al., 2012; Pacchiarotti et al., 2011a; Valenti et al., 2011). The drugs that showed positive effects in the subset of patients with mixed mania as defined in DSM-IV in placebocontrolled trials (asenapine, olanzapine, and valproate) (Azorin et al., 2013; Baker et al., 2003; Nivoli et al., 2012; Swann et al., 1997; Yatham et al., 2013), and to some extent those that showed separation from placebo in pooled analysis (aripiprazole and ziprasidone) (Stahl et al., 2010; Suppes et al., 2008), may be the best candidates for the treatment of the newly defined DSM-5 mixed states. Of note, there are very few data on the use of quetiapine in acute mixed states but positive adjunctive longterm data (Vieta et al., 2012), and ziprasidone (Patkar et al., 2012) has been tested in depressive mixed states (which did not exist in the DSM-IV). "
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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.
    Full-text · Article · Apr 2013 · Journal of Affective Disorders
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    ABSTRACT: BACKGROUND: To describe the frequency of mixed specifier as proposed in DSM-5 in bipolar I patients with manic episodes, and to evaluate the effect of mixed specifier on symptom severity and treatment outcome. METHODS: This post-hoc analysis used proxies for DSM-5 mixed features specifier by using MADRS or PANSS items. RESULTS: Of the 960 patients analysed, 34%, 18% and 4.3% of patients, respectively, had ≥3 depressive features with mild (score ≥1 for MADRS items and ≥2 for PANSS item), moderate (score ≥2 MADRS, ≥3 PANSS) and severe (score ≥3 MADRS, ≥4 PANSS) symptoms. In patients with ≥3 depressive features and independent of treatment: MADRS remission (score ≤12) rate decreased with increasing severity (61-43%) and YMRS remission (score ≤12) was similar for mild and moderate patients (36-37%), but higher for severe (54%). In asenapine-treated patients, the MADRS remission rate was stable regardless of baseline depressive symptom severity (range 64-67%), whereas remission decreased with increasing severity with olanzapine (63-38%) and placebo (49-25%). Reduction in YMRS was significantly greater for asenapine compared with placebo at day 2 across the 3 severity cut-offs and continued to decrease throughout the treatment period. The difference between olanzapine and placebo was statistically significant in mild and moderate patients. LIMITATIONS: Results are from post-hoc analyses. CONCLUSIONS: These analyses support the validity of proposed DSM-5 criteria. They confirm that depressive features are frequent in bipolar patients with manic episodes. With increasing baseline severity of depressive features, treatment outcome was poorer with olanzapine and placebo, but remained stable with asenapine.
    No preview · Article · May 2013 · Journal of Affective Disorders
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