Clinical differences between bipolar and unipolar depression

It is commonly – but wrongly – assumed that thereare no important differences between the clinical presentationsof major depressive disorder and bipolar depression. Here wecompare clinical course variables and depressive symptom profilesin a large sample of individuals with major depressive disorder(n=593) and bipolar disorder (n=443). Clinical characteristicsassociated with a bipolar course included the presence of psychosis,diurnal mood variation and hypersomnia during depressive episodes,and a greater number of shorter depressive episodes. Such featuresshould alert a clinician to a possible bipolar course. Thisis important because optimal management is not the same forbipolar and unipolar depression.

INTRODUCTION

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INTRODUCTION

Distinguishing between major depressive disorder and bipolardisorder is important because there are differences in theoptimal management of these conditions. Antidepressant treatmentof bipolar depression can adversely affect long-term prognosisby causing destabilisation of mood and more frequent depressiveepisodes, and can lead to the development of treatment resistance.¹Most people with bipolar disorder experience depression ratherthan mania as their first episode of illness. It is clinicallydesirable to recognise, or at least to suspect, bipolar depressionat an early stage of a bipolar illness. Here, we compare theclinical course and depressive symptoms of the two forms of depression by analysing phenotypic data for over 1000 patientswho were recruited to our genetic epidemiological studies ofmood disorders.

Method

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Method

The sample comprised 443 individuals with type I bipolar disorderand 593 with recurrent major depressive disorder. Participantswere recruited systematically from the case-loads of communitymental health teams, and non-systematically from advertisementsplaced in local general practices and local media. Patientswere excluded from the original genetic studies if they: hada lifetime diagnosis of injecting drug dependency; had onlyexperienced affective illness as a result of alcohol or substancedependence; had only experienced affective illness secondaryto medical illness or medication; or were biologically relatedto another study participant. In addition, people with majordepressive disorder were excluded if they had a first- or second-degreerelative with a clear diagnosis of bipolar disorder or schizophrenia,schizotypal disorder, persistent delusional disorder, acuteand transient psychotic disorders or schizo-affective disorder,or had ever experienced mood-incongruent psychosis or psychosisoutside of mood episodes.

Participants completed the Beck Depression Inventory (BDI)²and were interviewed using the Schedules for Clinical Assessmentin Neuropsychiatry (SCAN),³ which provides detailed informationabout lifetime psychopathology. Psychiatric and general practicecase notes were reviewed. These data were combined to form a written case vignette. Based on this vignette, best-estimatelifetime diagnoses were made according to DSM–IV criteria.⁴Vignettes were also used to rate key clinical variables (suchas age at onset, and number and severity of episodes of illness).The operational criteria (OPCRIT) symptom checklist was usedto rate presence or absence of depressive, manic and psychoticsymptoms on a lifetime-ever basis.^5,6 Each participant wasdiagnosed and had key clinical variables rated independentlyby at least two members of the research team, and a consensus was reached. Team members involved in the interview, ratingand diagnostic procedures were either fully trained researchpsychologists or psychiatrists. Interrater reliability wasassessed using joint ratings of 20 cases with a range of mooddisorder diagnoses. Mean overall kappa was 0.85 for DSM–IV diagnoses. Mean kappa statistics and intraclass correlationcoefficients for other key clinical variables were in the range0.81–0.99 and 0.85–0.97 respectively. This studyreceived all necessary multiregion and local research ethicscommittee approval, and all participants gave written informedconsent.

Forward stepwise likelihood ratio binary logistic regressionwas performed using the Statistical Package for the SocialSciences, SPSS version 12 for Windows, to identify variablessignificantly predictive of bipolar disorder v. major depressivedisorder classification.

Results

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Results

The proportions of women in the major depression group and thebipolar group were 70.2% and 71.3% respectively. The medianage at interview was 49 years for the major depression groupand 47 years for the bipolar group. Forty-six per cent of themajor depression group were recruited systematically, comparedwith 37% of the bipolar group. The median illness durationwas 19 years for the major depression group and 20 years forthe bipolar group. The major depression group had a medianBDI score at interview of 16, compared with 8 in the bipolargroup.

Forward stepwise logistic regression was used to establish thebest depression-related predictors of bipolar v. unipolar group membership. All lifetime variables relating to depressive episodesthat were significant at the 1% level in univariate analysescomparing the two groups were entered into the regression.To control for sample differences in recruitment and currentmental state, BDI score at interview and method of recruitmentwere included in the regression. Gender was also included inthe logistic regression analysis. Significant predictors ofdiagnosis are shown in Table 1.

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Table 1 Lifetime clinical characteristics predicting bipolar v. unipolar group membership

Although there were, of course, similarities between unipolarand bipolar depression, we found important clinical differences:characteristics that best predicted bipolar rather than unipolardepression were the presence of psychosis, diurnal mood variationand hypersomnia during depressive episodes, a greater numberof depressive episodes and a shorter duration of the longest depressive episode. Participants with major depressive disorderwere characterised by the presence of excessive self-reproach,loss of energy and diminished libido.

Discussion

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Discussion

Our results are consistent with, and extend the findings of,previous studies that have shown that ‘atypical’depressive features (such as hypersomnia and weight gain) maybe more common in bipolar disorder than in major depression.^7–9 Compared with previous studies, our study has several advantages,including the large number of participants and the high degreeof consistent and comprehensive clinical data collected.

Distinguishing between bipolar disorder and major depressivedisorder is of great clinical importance because optimal managementof the two conditions is very different. For example, anti-depressantsshould be used with caution in bipolar depression because ofthe risk of precipitating mood switches, cycling, or mixedor agitated states.¹⁰ It is desirable that clinicians useall available information to guide management (including choiceof treatment, advice to patient and intensity of monitoring).The clinical features of depression are not a definitive guideto diagnosis but can help to alert the clinician to a possiblebipolar course. These findings also have important implicationsfor future research on type II bipolar disorder and sub-thresholdbipolar disorders. Evidence suggests that 25–50% of individualswith recurrent major depression (particularly those withinatypical, early-onset or treatment-refractory subgroups) mayin fact have a broadly defined bipolar disorder.¹¹ We currentlyknow little about how best to treat such patients. Future studies will need to move beyond strict diagnostic categories and examinesubgroups of patients defined by extended phenotypic measuressuch as dimensional assessments of bipolar features, bipolarsymptom clusters and longitudinal illness course variables.

An important limitation of our study is that there might havebeen differences between the two groups of participants thatwe were not able to examine, such as subtle differences intreatment regimens or patterns of comorbid illness. We alsonote that although the proportion of women in the major depressivedisorder sample is typical of studies of this nature, the proportionof women in the bipolar disorder sample is higher than is typically reported (nearly three-quarters compared with a half) and thatthis may limit the generalisability of our findings. A furtherlimitation was the use of retrospective rather than prospectiveassessments, even though we used an in-depth semi-structuredclinical interview supplemented by case-note review. Prospectiveratings, though preferable, can be prohibitively expensive.

REFERENCES

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