Predominant previous polarity as an outcome predictor in a controlled treatment trial for depression in bipolar I disorder patients

doi:10.1016/j.jad.2009.02.028

Journal of Affective Disorders

Volume 119, Issues 1–3, December 2009, Pages 22-27

https://doi.org/10.1016/j.jad.2009.02.028 Get rights and content

Abstract

Introduction

We hypothesized that predominant episode-polarity would predict response to treatment of depressive episodes in bipolar I disorder (BPD) patients with treatment in a placebo-controlled trial, in the sense that patients with manic predominant polarity (PM) would respond better than patients with depressive predominant polarity (PD).

Method

This post-hoc analysis of a published trial examined outcomes of 788 depressed (MADRS score ≥ 20) adult BPD patients with baseline and follow-up assessments, according to their predominant polarity based on previous recurrences of mania-hypomania vs. depression in ≥ 2:1 excess. Patients (total = 833) were randomized to an 8-week trial of treatment with placebo (n = 377), olanzapine (5–20 mg/day; n = 370), or olanzapine/fluoxetine combination (OFC; 6/25, 6/50, or 12/50 mg/day; n = 86). Treatment response was based on improvement in Clinical Global Impression of depression severity (CGI-D). We analyzed for associations of this outcome with predominant lifetime illness-polarity, based on retrospective SCID-based assessment of individual clinical history.

Results

Predominant polarity could be demonstrated in 367/788 patients (46.6%), showing a 2.7-fold excess of predominant depressive over manic past-illnesses (34.1%/12.4%), with similar distribution by sex and among treatment-arms. Moreover, based on least-square change in CGI-D severity (based on a mixed model of repeated measures [MMRM]), predominant polarity has different impact in the treatment outcome for each gender. Men with predominantly manic polarity had statistically significant better improvement than men with predominantly depressive polarity. Such difference was not observed in the female population. Other outcome measures yielded similar conclusions.

Conclusions

Predominant previous depressive > manic episodes selectively yielded poorer responses of BPD to treatment for acute BP depression, particularly in men.

Section snippets

Subjects

Study subjects were adults (≥ 18 years) who met DSM-IV-TR (American Psychiatric Association (APA), 2000) criteria for type I BPD, and a current episode of major depression. For the original RCT (Tohen et al., 2003), a total of 833/1072 patients were recruited from inpatient and outpatient services from 84 study sites in 13 countries from June 2000 through December 2001. Diagnosis was confirmed by the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders,

Subject characteristics

Of the 833 subjects enrolled in the trial, 788 subjects had both baseline and follow-up ratings so as to allow outcome assessments; of these patients, 367/788 (46.6%) could be categorized as having had predominantly depressive (PD; 269/788; 34.1%) or predominantly manic polarity (PM; 98/788; 12.4%) whereas 53.4% had uncertain polarity (PU; 421/788). That is, somewhat less than half of type I BPD patients could be categorized by predominant episode polarity, and the PD pattern was 2.74-times

Discussion

To our knowledge this is the first attempt to analyze for potential effects of predominant past episode polarities in type-I BPD patients in a placebo-controlled RCT, in this instance, we used a trial of olanzapine or olanzapine/fluoxetine in BP major depression involving 833 patients, of whom 788 had baseline and follow-up assessments and 367 (46.6%) could be characterized by past history as PM or PD (18), or somewhat less than two previous experiences with the successful categorization of

Conclusions

Predominant polarity proved to be useful in predicting short-term outcome of depressive episodes, albeit only among men with BPD. A predominance of depressive recurrences was more common than manic recurrences among both men and women diagnosed with BPD, as expected from previous studies finding a great excess of depressive illness in treated BPD patients followed over time. An excess of depressive illness proved to be a useful predictor of inferior responses in acute depressive episodes, but

Role of funding source

Study funded by Lilly.

Conflict of interest

Dr. Vieta has received grants from Instituto Carlos III, CIBER-SAM, Spain, and has also received grants unrelated to this study and has acted as consultant for the following companies: Astra-Zeneca, Bristol-Myers-Squibb, Eli Lilly, Glaxo-Smith-Kline, Janssen-Cilag, Merck Sharp & Dohme, Novartis, Organon, Otsuka, Pfizer, Sanofi, and Servier. Dr. Berk has received Grant/Research Support from the Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Geelong Medical Research Foundation,

Acknowledgements

This study was supported by Eli Lilly and was based on data provided from Eli Lilly — supported randomized, controlled trials (to EV, MB and FC), and by a grant from the Ministerio de Educación y Ciencia, Madrid, Spain (to EV) and by Bruce J. Anderson Foundation and the McLean Private Donors' Research Fund (to RJB).

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Cited by (58)

Predominant polarity as a neurobiological specifier in bipolar disorder: Evidence from a multimodal neuroimaging study
2023, Progress in Neuro-Psychopharmacology and Biological Psychiatry
While predominant (PP) and onset polarity (OP) have considerable clinical and treatment implications in bipolar disorder (BD), the neurobiological underpinnings of PP and OP from a radiological perspective remain largely unknown. The main objective of this study is to investigate the neuroanatomical profile of polarity subphenotypes (PP and OP) in euthymic BD patients, using a standardized multimodal neuroimaging protocol to evaluate regional gray matter (GM) volumes, cortical thickness, as well as white matter (WM) integrity of major projection, commissural and association tracts.
Forty-two euthymic BD patients stratified for PP and OP and 42 healthy controls (HC) were included in this computational neuroimaging study to comprehensively characterize gray and white matter alterations. Univariate analyses of covariance (ANCOVAs) were conducted with Bonferroni corrections for each MRI modality and Cohen's d effect sizes were calculated for group comparisons.
Phenotype-associated cortical thickness abnormalities and volumetric alterations were identified, but no WM changes ascertained. Specifically, we found a main effect of OP on GM volume of left middle frontal gyrus and of OP and PP (either or both) on cortical thickness of various regions previously implicated in BD, i.e. inferior frontal gyrus-pars opercularis (left) and pars orbitalis (bilateral), left lateral orbitofrontal gyrus, bilateral medial segment of the superior frontal gyrus, left planum polare, right anterior cingulate gyrus, left anterior and posterior insula, bilateral frontal operculum (both OP and PP); left anterior and posterior orbitofrontal gyrus, left transverse temporal gyrus, right posterior insula (only OP); and right medial frontal cortex (only PP). Based on the magnitude of differences on pairwise comparisons, we found a large effect of OP on cortical thickness in a single region (left anterior orbitofrontal gyrus) (OP-M > OP-D), while PP subgroups showed large or medium effect size differences in cortical thickness (PP-M > PP-D) in a wider array of regions (right medial frontal cortex, left frontal operculum, left inferior frontal gyrus-pars opercularis, bilateral medial segment of the superior frontal gyrus). For most regions, PP-D patients showed the greatest decreases in cortical thickness compared to HC while PP-M showed the smallest, with PP-U showing an “unspecified” pattern mostly lying in-between PP-D and PP-M.
Our multimodal imaging findings suggest specific polarity BD subgroups with compromised cortical thickness; we recorded a greater impact of PP on brain structure compared to OP, which provides additional evidence that PP can be considered as a neurobiological specifier in BD.
Undetermined predominant polarity in a cohort of bipolar disorder patients: Prevalent, severe, and overlooked: Undetermined predominant polarity in bipolar disorder
2022, Journal of Affective Disorders
Predominant polarity (PP) is a concept used to define patients with bipolar disorder (BD) as presenting a tendency to manifest depressive (DPP) or manic (MPP) episodes. Still, the high percentage of patients with an undetermined PP (UPP), has been overlooked in most studies. Thus, we aimed to study UPP and outline its socio-demographic, clinical, and treatment-related features.
Patients were recruited from a BD specialized unit. The sample was divided into three groups according to PP and socio‐demographic and clinical variables were compared. Significant variables at univariate comparisons were included in multivariate logistic regression with UPP as the dependent variable.
A total of 708 BD patients were included, of which 437 with UPP (61.7%). UPP was associated with a higher number of affective relapses, when compared with DPP or MPP (χ2= 28.704, p<0.001). Mixed episodes (OR=1.398; CI=1.118–1.749), aggressive behaviour (OR=1.861; CI=1.190–2.913), seasonality (OR=2.025; CI= 1.289–3.501) and treatment with lamotrigine (OR= 2.101; CI=1.244–3.550) were significantly associated with UPP at the logistic regression.
Recall bias may have occurred due to mixed episode diagnostic criteria change over the years. No data on the patients’ follow-up has been reported on predominant polarity changes.
UPP is associated with a higher number of relapses, and different clinical variables related to a severe course of illness. Considering PP in patients with BD may guide the choice for differential treatment approaches having an impact on BD course of illness and patients' prognosis and recovery.
The biological basis of predominant polarity
2020, Neurobiology of Bipolar Disorder: Road to Novel Therapeutics
The concept of predominant polarity (PP) appears to be an important course specifier for bipolar disorder (BD). Despite this, it was not included in the DSM-5 as a specifier for BD. A unifying definition and conceptualization of PP is lacking. A PP is present in approximately half of BD patients. The depressive PP has been consistently associated with a depressive onset of illness, a delayed diagnosis of BD, type II BD, and higher suicidality. The manic PP is associated with a younger onset of illness, a first episode manic/psychotic and a higher rate of substance abuse. PP appears as a valid neurobiological endophenotype in the characterization of BD that provides relevant information for clinicians. Neurobiological research supports the potential utility of predominant polarity not only as a clinical but also as a neurobiological specifier in BD. Future research should clarify the potential use of predominant polarity as a biological marker.
Predominant polarity in bipolar disorder patients: The COPE bipolar sample
2019, Journal of Affective Disorders
Citation Excerpt :
The most recent and only review in the field by Carvalho et al. (2014) indicated differences between the two predominant polarities. A sample of exclusively type I BD patients showed more MPP (Vieta et al., 2009; Popovic et al., 2013); this pattern was reversed for samples of exclusively type II BD patients (Rosa et al., 2008; Vieta et al., 2009; Judd et al., 2003; Popovic et al., 2013). Studies have suggested that DPP was more closely associated with socio-demographic features such as being a woman (Popovic et al., 2014; Baldessarini et al., 2012) and being married (Baldessarini et al., 2012; Gonzalez-Pinto et al., 2010; Nivoli et al., 2014).
The concept of predominant polarity (PP) is defined as presenting more symptoms of one polarity. Previous studies have defined PP as one polarity (either a depression or mania episode) occurring during at least two-thirds of the lifetime.
We conducted an observational study with the COPE-BD (Clinical Outcome and Psycho-Education for Bipolar Disorder, Clinical Outcome Measures Section) dataset to identify the diagnostic and treatment differences between bipolar disorder (BD) patients with and without PP.
The final sample included 210 BD-I (59.0%) and 146 BD-II (41.0%) patients. Of these, 28.9% patients presented predominant polarity (PP): 62 (17.4%) of those patients were depressed polarity predominant (DPP), 41 (11.5%) were manic polarity predominant (MPP), and 253 (71.1%) met criteria for bipolar disorders but did not present with PP. In comparison to this group of BD patients with undetermined polarity, the group of BD patients with PP presented more rapid cycling.
Furthermore, in the undetermined polarity group, the onset of illness occurred earlier, and the duration of the illness was longer, with more hypomanic/manic and depressive episodes than patients who met the PP criteria.
This study has a naturalistic and retrospective design and does not allow a specific follow-up of polarity over time.
These different clinical characteristics underline the importance of considering PP in patients with BD, and justify the need for differential treatment approach which could have an impact on patients' prognosis. Yet, more independent and prospective research is needed to confirm these findings, especially with the new classification of DSM-5 concerning mixed states.
Predominant polarity in bipolar I and II disorders: A five-year follow-up study
2019, Journal of Affective Disorders
Patients with bipolar disorder (BD) differ in their relative predominance of types of episodes, yielding predominant polarity, which has important treatment implications. However, few prospective studies of predominant polarity exist.
In the Jorvi Bipolar Study (JoBS), a regionally representative cohort of 191 BD I and BD II in- and outpatients was followed for five years using life-chart methodology. Differences between depressive (DP), manic (MP), and no predominant polarity (NP) groups were examined regarding time ill, incidence of suicide attempts, and comorbidity.
At baseline, 16% of patients had MP, 36% DP, and 48% NP. During the follow-up the MP group spent significantly more time euthymic, less time in major depressive episodes, and more time in manic states than the DP and NP groups. The MP group had significantly lower incidence of suicide attempts than the DP and NP group, lower prevalence of comorbid anxiety disorders but more psychotic symptoms lifetime and more often (hypo)manic first phase of the illness than the DP group. Classification of predominant polarity was influenced by the timeframe used.
The retrospective counting of former phases is vulnerable to recall bias. Assignment of dominant polarity may necessitate a sufficient number of illness phases.
Predominant polarity has predictive value in predicting group differences in course of illness, but individual patients’ classification may change over time. Patients with manic polarity may represent a more distinct subgroup than the two others regarding illness course, suicide attempts, and psychiatric comorbidity.
Predominant polarity classification and associated clinical variables in bipolar disorder: A machine learning approach
2019, Journal of Affective Disorders
Bipolar disorder (BD) is a severe psychiatric disorder characterized by periodic episodes of manic and depressive symptomatology. Predominant polarity (PP) appears to be an important specifier of BD. The present study employed machine learning (ML) algorithms to accurately determine a patient´s PP without the inclusion of number and polarity of past episodes, while exploring associations between PP and demographic and clinical variables.
From a cohort of 148 BD patients, demographic and clinical variables were collected using a customized questionnaire and the SCID-CV. The algorithm employed was the Random-Forest method. The algorithm was programed to classify patients into either depressive or manic predominant polarities and to reveal which variables were associated to the specifier.
The algorithm attained an AUC ROC of 74.72% (95% CI = 72.29–77.15%) in classifying patients into either manic or depressive PP. The variables selected by the algorithm were: (1) age at first depressive episode; (2) number of hospitalizations; (3) BD Type II; (4) manic onset; (5) delusions; (6) psychotic features at onset; (7) tobacco addiction; (8) family history of BD; (9) hallucinations; and (10) comorbid anxiety disorders, (11) alcohol dependence, (12) eating disorders and (13) substance dependence.
The study is limited due to the small sample size, the inclusion of only self-reported and clinician-observed clinical variables and its cross-sectional design.
The results suggest that the ML approach could be effective in determining a patient´s PP. Furthermore, although not previously reported, some variables, such as tobacco use and comorbid eating disorders, appear to be closely associated with PP.

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Research reportPredominant previous polarity as an outcome predictor in a controlled treatment trial for depression in bipolar I disorder patients

Abstract

Introduction

Method

Results

Conclusions

Section snippets

Subjects

Subject characteristics

Discussion

Conclusions

Role of funding source

Conflict of interest

Acknowledgements

Biol. Psychiatry

J. Affect. Disord.

Compr. Psychiatry

Biol. Psychiatry

J. Affect. Disord.

J. Psychiatr. Res.

Psychiatry Res.

Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR)

The course of affective disorders. II. Typology of bipolar manic-depressive illness

Arch. Psychiatr. Nervenkr.

Morbidity from onset in first-episode bipolar i disorder patients: the international 300 study

Neuropsychopharmacology

Bipolar disorder

The road to DSM-V: bipolar disorder episode and course specifiers

Psychopathology

Episode sequence in bipolar disorder and response to lithium treatment

Am. J. Psychiatry

Structured Clinical Interview for DSM-IV® Axis II Personality Disorders (SCID-II)

Structured Clinical Interview for DSM-IV® Axis I Disorders (SCID-I)

Diagnostic guidelines for bipolar disorder: a summary of the International Society for Bipolar Disorders Diagnostic Guidelines Task Force Report

Bipolar Disord.

Research report
Predominant previous polarity as an outcome predictor in a controlled treatment trial for depression in bipolar I disorder patients

Structured Clinical Interview for DSM-IV^® Axis II Personality Disorders (SCID-II)

Structured Clinical Interview for DSM-IV^® Axis I Disorders (SCID-I)