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Copyright ª Blackwell Munksgaard 2008

Bipolar Disorders 2008: 10: 144–152

BIPOLAR DISORDERS

Review Article

Diagnostic guidelines for bipolar depression: a
probabilistic approach
Mitchell PB, Goodwin GM, Johnson GF, Hirschfeld RMA. Diagnostic
guidelines for bipolar depression: a probabilistic approach.
Bipolar Disord 2008: 10: 144–152. ª Blackwell Munksgaard, 2008

Philip B Mitchella, Guy M Goodwinb,
Gordon F Johnsonc and Robert MA
Hirschfeldd
a

Objectives: There are currently no accepted diagnostic criteria for bipolar
depression for either research or clinical purposes. This paper aimed to
develop recommendations for diagnostic criteria for bipolar I depression.

Methods: Studies on the clinical characteristics of bipolar and unipolar
depression were reviewed. To identify relevant papers, literature searches
using PubMed and Medline were undertaken.
Results: There are no pathognomonic characteristics of bipolar I
depression compared to unipolar depressive disorder. There are, however,
replicated findings of clinical characteristics that are more common in both
bipolar I depression and unipolar depressive disorder, respectively, or which
are observed in unipolar-depressed patients who ÔconvertÕ (i.e., who later
develop hypo ⁄ manic symptoms) to bipolar disorder over time. The following
features are more common in bipolar I depression (or in unipolar ÔconvertersÕ
to bipolar disorder): ÔatypicalÕ depressive features such as hypersomnia,
hyperphagia, and leaden paralysis; psychomotor retardation; psychotic
features, and ⁄ or pathological guilt; and lability of mood. Furthermore,
bipolar-depressed patients are more likely to have an earlier age of onset of
their first depressive episode, to have more prior episodes of depression, to
have shorter depressive episodes, and to have a family history of bipolar
disorder. The following features are more common in unipolar depressive
disorder: initial insomnia ⁄ reduced sleep; appetite, and ⁄ or weight loss;
normal or increased activity levels; somatic complaints; later age of onset
of first depressive episode; prolonged episodes; and no family history of
bipolar disorder.
Conclusions: Rather than proposing a categorical diagnostic distinction
between bipolar depression and major depressive disorder, we would
recommend a ÔprobabilisticÕ (or likelihood) approach. While there is no
Ôpoint of rarityÕ between the two presentations, there is, rather, a differential
likelihood of experiencing the above symptoms and signs of depression.
A table outlining draft proposed operationalized criteria for such an
approach is provided. The specific details of such a probabilistic approach
need to be further explored. For example, to be useful, any diagnostic
innovation should inform treatment choices.

School of Psychiatry, University of New South
Wales, Sydney, Australia, bDepartment of
Psychiatry, Oxford University, Oxford, UK,
c
Discipline of Psychological Medicine, University of
Sydney, Sydney, Australia, dDepartment of
Psychiatry and Behavioral Sciences, University of
Texas Medical Branch, Galveston, TX, USA

Key words: bipolar depression – bipolar disorder
– diagnostic – nosology
Received 23 January 2007, revised and accepted
for publication 3 September 2007
Corresponding author: Professor Philip Mitchell,
School of Psychiatry, University of New South
Wales, Prince of Wales Hospital, Randwick, NSW
2031, Australia. Fax: +61 2 93828151;
e-mail: phil.mitchell@unsw.edu.au

PBM has received remuneration for lectures or advisory board membership from AstraZeneca, Eli Lilly & Co., GlaxoSmithKline, Janssen-Cilag, or
Lundbeck in the last 5 years. GMG (as of September 12, 2007) has an interest in relation to one or more organizations that could be perceived as a
possible conflict of interest in the context of the subject of this work. The relationship(s) include: grants: Sanofi-Aventis, Servier; honoraria: AstraZeneca,
Bristol-Myers Squibb, Eisai, Lundbeck, Sanofi-Aventis, Servier; paid positions: University of Oxford, Oxfordshire & Buckinghamshire NHS Mental
Healthcare Trust; advisory boards: AstraZeneca, Bristol-Myers Squibb, Eli Lilly & Co., Lundbeck, P1Vital, Sanofi-Aventis, Servier, and Wyeth. GFJ
has been (or is)* an advisory board member, clinical trial investigator, or consultant to AstraZeneca, Bristol-Myers Squibb, Eli Lilly & Co.,
GlaxoSmithKline, Novartis, Pfizer, Janssen-Cilag, Sanofi Aventis, Servier*, Organon Roche, Wyeth Pharmaceuticals, the Commonwealth Government
Pharmaceutical Benefits Advisory Committee, and the Australian Drug Evaluation Committee*. RMAH has served as a consultant ⁄ advisory board
member for Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Cephalon, Forest Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, Jazz
Pharmaceutical, KV Pharmaceutical, Ortho McNeil, Eli Lilly & Co., Novartis, Organon, Pfizer, Solvay Pharmaceuticals, and Wyeth-Ayerst.

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appear to be any significant differences in the severity of depression between bipolar. agitation. Depressive episodes in the course of bipolar disorder Bipolar disorder presents initially with a depressive episode in at least 50% of patients. after logistic regression. There were no differences in agitation items. bipolar-depressed patients were significantly more likely to demonstrate psychomotor disturbance (particularly retardation) and pathological guilt. had a greater delay in responding verbally. however. These data sets comprised 83 bipolar disorder and 904 unipolar patients assessed in detail whilst depressed. however. Cuellar et al. Phenomenology of bipolar depression There have now been a relatively large number of studies comparing the clinical characteristics of bipolar and unipolar depression.and unipolar-depressed subjects (13. ÔMelancholiaÕ was defined using several diagnostic systems [DSM-III. Conversely. Furthermore. There are currently no accepted diagnostic criteria for bipolar depression for either research or clinical purposes. CORE-I or II (21. with most studies reporting that a majority of subjects first present in this phase of the illness (9). and operationalized clinical diagnoses]. CORE (59% versus 33%). These studies have been the focus of a series of recent review articles (15–19).and unipolar-depressed patients. Table 1 details the clinical differences which have been reported in these comparisons of bipolar and unipolar depressive subjects. noting that many of the primary data investigations have not controlled for potentially critical confounding variables such as medications or demographic factors such as age or gender. were observed in the objective features of depressive psychomotor disturbance as rated by the CORE scale (20). and the tendency to blame others. Mitchell et al. Patients with bipolar disorder tend to experience more depressive episodes over a lifetime than those with unipolar depression (10–12). The age of onset of the first depressive episode in bipolar disorder has been found in many studies to be earlier than that found in unipolar depression (10. syndromal or subsyndromal depression is now recognized to comprise the predominant cumulative affect over time. 22). and noninteractiveness. Most studies have not corrected for multiple testing. Most studies have described samples that would now be recognized as fulfilling criteria for bipolar I disorder. they were less likely to manifest tearfulness. We examine the literature on bipolar depression – particularly focusing on its clinical aspects – then propose guidelines for its diagnosis. In one of these reviews. (20) examined the relative prevalence of melancholic syndromes in bipolar and unipolar depression.Diagnostic guidelines for bipolar depression While pathologically elevated mood is the hallmark characteristic of bipolar disorder. Recent studies of the phenomenology of bipolar depression We review here studies of bipolar I (or predominantly bipolar I) data sets. before focusing on potential distinguishing characteristics that may assist in the diagnosis of bipolar I depression. and clinical (70% versus 29%) systems. they were more likely to report worthlessness. (23) undertook a Ôfine grainedÕ analysis of the more recent (third) of these data sets. In 2000. and hypersomnia. 11). These bipolar-depressed patients were initially compared with 39 unipolar-depressed subjects matched for age. The aim of this study was to identify particular symptomatic differences between bipolar. found that bipolar disorder subjects were significantly more likely than unipolar patients to be diagnosed as melancholic by each of the DSM (69% versus 37%). (16) undertook a detailed methodological critique. restlessness. This paper aimed to develop recommendations for diagnostic criteria for bipolar I depression. III-R. anhedonia. Parker et al. 14). In a second paper from the same group. sex and the presence or absence of DSM-IV melancholia. Although there was no difference in severity of depression (assessed by the Hamilton Rating Scale for Depression). There do not. The most striking differences. This paper used three large depressive data sets recruited over a 15-year period. and demonstrated more slowed movement. Bipolar patients scored higher on both the 145 . With regard to current symptomatology.) Bipolar patients were less emotionally reactive. The sample comprised 270 inpatients and outpatients with a current DSM-IV major depressive episode (MDE). Thirty-nine of the patients had DSM-IV bipolar I disorder. and to make a major contribution to the disability related to this condition (1–8). we will first overview some of the more recent studies. As the older studies have been discussed in detail in previous reviews. anxiety. (This is an 18-item scale with subscales for retardation. leaden paralysis. the latter being a proxy for cognitive dysfunction. those with bipolar depression were significantly more likely to have had a past psychotic depressive episode. Parker et al. or DSM-IV.

BP > UP UP > BPI UP > BPI BPI > UP BPI > UP BPII > UP BP > UP UPs who Ôconverted toÕ BPI > UP BPI > UP BPII > UP BPI > UP BP > UP UPs who Ôconverted toÕ UP > BPI BP > UP BPI > UP UP > BPI UP > BPI UP > BPI n. (48) Mitchell et al. (49) Akiskal et al. (26. SAD sample) Coryell et al. (23) Benazzi (50) Mitchell et al. (49) Mitchell et al. hypersomnia) Serretti et al. (25) Mitchell et al. (28) Benazzi (51) Brockington et al. (49) Olfson et al. (23) Andreasen et al. (23. (23) Goel et al. (11) UP UP UP UP UP UP UP Katz et al. (33) Perlis et al. primary care sample) Perlis et al. BPI > UP BPI > UP UPs who Ôconverted toÕ BPII > UP BPII > UP BPII > UP UP > BPI UPs who Ôconverted toÕ UP > BPI Inconsistent findings BP > UP BPI > UP > > > > > > > BP BP BPI BPI BPI BP BP BPI BPI BPI BPII BPI . (10) Solomon et al. (24.s. SAD sample) Perlis et al.Mitchell et al. BP > UP BPII > UP BPI > UP BPI > BPII > UP BPII > UP UP > BP UPs who Ôconverted toÕ BPII > UP UP > BPI BPII > UP BPI > UP n. primary care sample) Andreasen et al. Table 1. UP > BPI BP > UP BPII > UP UP > BPI BPII > UP UP > BPI n. (23) Papadimitriou et al. (25) Simon et al. (11) Abrams and Taylor (46) Coryell et al. (54) Brockington et al. (27) Perlis et al. leaden paralysis. (33) Mitchell et al. (10) Benazzi (50) Abrams and Taylor (46) Benazzi (50) Papadimitriou et al. (10) Benazzi (50) Mitchell et al. (25) Mitchell et al. (24. (49) Coryell et al. primary care sample) Coryell et al. (52) Abrams and Taylor (46) Brockington et al. (34) Benazzi (50) Benazzi (50) Benazzi (50) Beigel and Murphy (53) Coryell et al. (23) Perlis et al. (27) Olfson et al. (24. (33) Brockington et al. (25) Benazzi (50) Brockington et al. (25) Andreasen et al. (47) Mitchell et al. (23) Benazzi (50) Olfson et al.s. Studies of illness characteristics of bipolar (BP) and unipolar (UP) depression Variable Course of illness Age of onset Duration of episode Number of prior depressive episodes Symptomatology Severity of depression Unvarying depression Worthlessness Low self-esteem Pessimistic thoughts Anticipatory anhedonia Irritability Subjective restlessness Social withdrawal Suicidal Tearfulness Initial insomnia Reduced sleep Increased sleep Weight loss Weight gain Appetite loss Appetite disturbance Increased eating ÔAtypical featuresÕ Muddled thoughts ⁄ thinking difficulties Difficulty concentrating Distractibility Depression worse in morning Mania score Lability of mood Racing thoughts More talkative Increased risky and goal-directed behaviors Anxiety Comorbid panic disorder or GAD Derealization 146 Study Finding Andreasen et al.s. (23) Mitchell et al.s. (23) Brockington et al. (25) Brockington et al. (26. (10) Solomon et al. (23) Goel et al. (49) UP > BPI n. (33) Benazzi (51) Perlis et al. (49) Parker et al. (49) Mitchell et al.

with respect to symptoms. n. (20) Mitchell et al.s.s. (BP II v UP) UP > BPI BPI > UP BPI > UP n.s. (33) Strober and Carlsson (58) Akiskal et al. (10) Coryell et al.s. n. (26.s. (48) Abrams and Taylor (46)a Abrams and Taylor (55) Mitchell et al. (63) Katz et al. n. (56) Perlis et al. (23) Guze et al. Mitchell et al. Continued Variable Current alcohol use disorder Somatic complaints ÔSomething wrong with bodyÕ Pathologic guilt Tendency to blame others Psychotic features Ideas of reference Auditory or visual hallucinations Auditory hallucinations Loss of insight Mental state signs Activity Agitation ÔObserved anxietyÕ Retardation Anger ⁄ aggression ÔHaughty attitudeÕ Family history of bipolar disorder Study Finding Olfson et al.s. (49) Parker et al. a Correlation with bipolar disorder. (23) Brockington et al.s. (32) UP > BPI UP > BPI UP > BPI BPI > UP n. n. (48) Abrams and Taylor (55) Dunner et al. (11) Coryell et al.and sex-matched melancholic unipolar patients. (24. (60) Endicott et al. (59) Geller et al. BPI > UP UP > BP BP > UP UP > BP UP > BP Beigel and Murphy (53) Kupfer et al. (24. 67). BP > UP BPII > UP UP > BPI BPI > UP BP > UP n. (33) Strober and Carlson (58) Akiskal et al. SAD sample) Benazzi (50) Brockington et al. (49) Dunner et al. (48) Popescu et al. BP > UP BP > UP UPs who Ôconverted toÕ BPI UPs who Ôconverted toÕ BP UPs who Ôconverted toÕ BP toÕ toÕ toÕ toÕ toÕ BPI BP BP BP BP GAD ¼ generalized anxiety disorder. then compared the 20 bipolardepressed patients with DSM-IV-defined melan- cholia against age. 147 . (49) Dunner et al. (10) Perris (64) Katz et al. (61) Beigel and Murphy (53) Black and Nasrallah (62) Mitchell et al. (23. SAD sample) Benazzi (29) Beigel and Murphy (53) Abrams and Taylor (46)a Brockington et al. n. (25) Brockington et al. (26. UP > BPI BPI > UP BPI > UP UP > BPI BPI > UP BP > UP UPs who Ôconverted UPs who Ôconverted UPs who Ôconverted UPs who Ôconverted UPs who Ôconverted BPI > UP n. (32) Goldberg et al. (49) Olfson et al.s.s. retardation subscale and total CORE score. (20) Mitchell et al. (49) BP > UP UP > BPI UP > BPI n.Diagnostic guidelines for bipolar depression Table 1.s. primary care sample) Brockington et al. First. BPI > UP BPI > UP BPI > BPII n. bipolar disorder patients reported more anhedonia. (49) Brockington et al. (23) Goel et al. (56) Andreasen et al. (65) Kuhs and Reschke (66) Mitchell et al. SAD ¼ seasonal affective disorder. n.s. n. primary care sample) Beigel and Murphy (53) Katz et al.s. (67) Parker et al. (57) Andreasen et al.s. (23) Goel et al. Updated from Mitchell et al. (56) Andreasen et al. (10) Solomon et al.

respectively. with differing raters and sites. ÔatypicalÕ depressive symptoms such as hypersomnia and leaden paralysis. the Montgomery-Asberg Depression Rating Scale and the Hamilton Anxiety Rating Scale. Those with bipolar depression were significantly more likely than those with unipolar depression to report hallucinations.82 in the index bipolar I disorder sample. (11) recently used data from the NIMH Collaborative Program on the Psychobiology of Depression cohort to develop a clinical screening instrument to screen for bipolar disorder in patients presenting with a current MDE. All assessments were performed using a variety of patient selfreport measures. and hypersomnia. and low self-esteem.Mitchell et al.. acknowledged that these features reflected differing group means and were not pathognomonic of bipolar depression. Bipolar II depression Benazzi has undertaken similar studies with bipolar II-depressed patients. Again. cognitive difficulties. persistence of depressed mood.72 in the bipolar I disorder crossvalidation sample. but in contrast to the bipolar I studies. (24) studied characteristics of depression in a low-income primary care clinic. the authors first investigated the most discriminating of 59 socio-demographic and clinical variables in a comparison of an index bipolar I sample compared to major depressive disorder. then tested them in a second and separate bipolar I disorder sample (the Ôbipolar I disorder cross-validationÕ sample). The sensitivity of the instrument was 0. i. Reports from other recent studies include: more psychomotor agitation and social withdrawal in bipolar I depression than major depressive disorder in a group with seasonal affective disorder (26).27. With regard to specific items from the rating scales. and (iii) family history of major depression or mania.58 in the bipolar II disorder cross-validation sample. (ii) number of prior episodes of major depression. bipolar patients reported more fears. and lacked other measures of depressive phenomenology. and tearfulness. the tendency to blame others. 0. These three questions comprised what the authors termed the ÔScreening Instrument of Depression Polarity (SAD-P)Õ. This pattern suggests that the clinical presentation of bipolar I depression is distinct from the ÔpureÕ atypical depression of. predominantly in a private practice outpatient context. n = 1. with findings of 0. Twenty-five percent of depressed patients were assessed as suffering from bipolar disorder according to the MDQ. he has reported an increased prevalence of ÔatypicalÕ features in bipolar II compared with unipolar-depressed patients. and marked anhedonia.Õ These were: signs of psychomotor retardation. The strength of this report is the large numbers involved (n = 477 in bipolar depression trial. found bipolar depression to be associated with a family history of 148 bipolar disorder. a greater frequency of appetite loss in unipolar depression (27). and somatic symptoms. The paper reported on items from two measures common to these studies. and more atypical but less melancholic symptoms in bipolar disorder when assessed retrospectively using the Ôoperationalized criteria checklistÕ system (28). they had significantly higher scores on the retardation subscale of this instrument. whereas unipolar patients more commonly experienced sadness. Using a split-sample data analytic procedure. bipolar disorder patients were rated on the CORE scale as demonstrating more facial immobility. melancholic symptoms such as worthlessness. (25) used three large data sets (two unipolar and one bipolar depressed) that had been recruited for pharmaceutical studies. slower movement. initial insomnia. and 0. atypical. seasonal affective disorder or the ÔpureÕ melancholic presentation of some patients with severe unipolar depression. Perlis et al. earlier age of onset. for example. unvarying mood. The limitations were that the original studies were distinct. however. They selected the three most distinguishing variables. with bipolar patients identified using the Mood Disorder Questionnaire (MDQ). The studies of Mitchell and Parker suggest that bipolar I depression is characterized by an admixture of melancholic. a past history of psychotic depression. and more prior depressive episodes. The three variables were: (i) presence of delusions at baseline assessment. but less initial insomnia and anxiety. and a greater delay in initiating motor activity.29 and 0. Olfson et al. but were less likely to acknowledge disturbed appetite (decreased or increased). has found no difference in . 0. current suicidal ideation. A logistic regression including these various symptoms correctly classified 87% of subjects. The positive predictive value of the screening instrument was low. and a bipolar II disorder cross-validation sample. and (less commonly) psychotic features.074 for the major depressive disorder trials). insomnia. Perlis et al. As in a number of the studies of bipolar I-depressed patients described above. Mitchell et al.e. These findings suggested features with potential clinical utility for diagnosing bipolar depression which were described by the authors as a Ôbipolar depression signature.36. Secondly. Solomon et al. and the absence of anxiety.

talkativeness. Burt et al. inability to concentrate. and increased risky and goal-directed activities. irritability. racing thoughts. Studies of clinical characteristics of ÔconvertersÕ from unipolar depression to bipolar disorder Another means of defining the characteristics of bipolar depression is identifying apparent ÔunipolarÕ patients who on long-term follow-up ÔconvertÕ to bipolar I or II disorder. however. Strober et al.Diagnostic guidelines for bipolar depression rates of psychomotor retardation (51). In a follow-up study of inpatient adolescents with major depression. For more detailed discussion of bipolar II depression. hypersomnia and motor retardation. Drawing on the various studies outlined in this paper. hypersomnia. These reports by Benazzi suggest both commonalities and distinctions between bipolar I and II depression. In 1983. The pattern of executive function is broadly similar to that found in unipolar depression. without any independent ratings. but rather some provisional evidence of dimensional differences. and psychomotor agitation were independent predictors of BP-II disorder. (40) found bipolar depression to be associated with worse memory as indicated by the California Verbal Learning Test. social withdrawal. there are no apparent pathognomonic neuropsychological characteristics of bipolar depression. In unipolar depression both semantic and phonemic deficits contribute to a reduction in verbal fluency (44). (35) found that those who later developed bipolar disorder were more likely to have evidenced psychosis and psychomotor retardation at the index assessment. whereas in bipolar depression the deficit appears to be more selective with only semantic categories being affected (45). replicated findings of clinical characteristics that are more common in both bipolar depression and major depressive disorder. psychomotor agitation. problem solving. as with the phenomenological studies described in previous sections. and decision making (41–43). those clinical features that have been most commonly and consistently reported to be more common in those with bipolar depression (or unipolar-depressed ÔconvertersÕ to bipolar disorder) are: 149 . and feelings of inadequacy and discouragement. worthlessness. Those who switched to bipolar I disorder were more likely to have been psychotic or hospitalized at the index depressive assessment. Bipolar I ÔconvertersÕ also rated worse on psychic anxiety. medicationprecipitated manic episodes. though there is some evidence of greater impairment in bipolar disorder. a family history of bipolar disorder. and postpartum depression. The features that were more common in the bipolar IIdepressed patients were: weight gain. with some evidence of worse executive functioning in bipolar-depressed subjects (36). Akiskal et al. Benazzi has reported on a comparison of the symptoms of depression in 379 bipolar II-depressed and 271 major depressive disorder outpatients (29). racing thoughts. Multiple logistic regression showed that hypersomnia. compared with those who continued to have a diagnosis of major depressive disorder (33). Patients with bipolar depression have impaired sustained attention and poor immediate and delayed verbal recall which is greater than that found in unipolar-depressed subjects and controls (37–39). They are limited in deriving from only one researcher. In a more recent paper (it is not clear if the sample overlaps with prior reports from this researcher). Mood lability in the depressive state was the most specific predictor of switching to bipolar II disorder (34). ÔInside-MDE hypomanicÕ symptoms that were more common in BP-II were distractibility. please refer to the paper by Vieta and Suppes in this special issue (30). The NIMH Collaborative Programme on the Psychobiology of Depression 11-year prospective follow-up found that 4% ÔconvertedÕ to bipolar I disorder and 9% to bipolar II disorder. with bipolardepressed subjects performing poorly on tests of concept formation. Overall. Angst and Preisig (31) have reported that about 1% of patients with unipolar depression initially identified while hospitalized convert from depression to bipolar I disorder each year. and a diminished ability to concentrate. increased eating. irritability. or are observed in unipolar-depressed patients who ÔconvertÕ to bipolar disorder over time. Neuropsychological differences between bipolar depression and unipolar depression The neuropsychological profiles of bipolar and unipolar depression overlap. There are. (32) reported that the predictors of a later emergence of bipolar disorder in unipolar patients were: onset of depression prior to 25. respectively. Both groups of patients have been found to be predominantly impaired in the domains of memory and executive functioning. A proposed ÔprobabilisticÕ approach to the diagnosis of bipolar I disorder It is apparent that there are no pathognomonic characteristics of bipolar depression compared to unipolar depression (major depressive disorder).

hyperphagia ⁄ weight gain. hypersomnia. This table is premised on a current MDE in patients with no clear prior episodes of hypo ⁄ mania. Thus. those clinical features that have been most commonly and consistently reported to be more common in those with unipolar depression are: • • • • Course of illness: later age of onset. we have considered these to be of low diagnostic specificity. and social withdrawal) are common in depression.Mitchell et al. there is a pressing need to understand treatment response to different classes of treatment in relation to diagnostic ⁄ dimensional extremes and along the bipolar ⁄ unipolar continuum. low self-esteem. rather. Ôatypical featuresÕ (such as leaden paralysis). for example in existing or future prospective longitudinal data sets. social withdrawal. While there is no Ôpoint of rarityÕ between the two presentations. a Confirmation of the specific numbers to be used requires further study and consideration. we would recommend a ÔprobabilisticÕ (or likelihood) approach. and psychotic features Mental state signs: psychomotor retardation ⁄ lower activity levels Family history: positive for bipolar disorder Conversely. and more prior episodes Symptomatology: worthlessness. • • • • Course of illness: earlier age of onset. lability of mood. The actual number of features specified have been determined on the basis of both the literature reviewed in this paper and Ôclinical reasonability. Table 2. appetite loss ⁄ weight loss. respectively. . As some of these features (such as worthlessness. low selfesteem. Furthermore. We specify particular number of features required to indicate the greater likelihood of bipolar depression or unipolar depression. and somatic complaints Mental state signs: higher activity levels Family history: negative for bipolar disorder Rather than proposing a categorical diagnostic distinction between bipolar depression and major depressive disorder.Õ Confirmation of the specific numbers to be used requires further study and consideration. there is. shorter duration of episodes. 150 The draft operationalized criteria for such an approach are detailed in Table 2. and have therefore not included these in the final ÔprobabilisticÕ approach to the diagnosis of bipolar depression. We have utilized specific depressive clinical signs or symptoms (as well as characteristics of illness course and family history). rather than proposing a requirement for particular syndromal presentations of depression such as ÔatypicalÕ or ÔmelancholicÕ depression. any diagnostic innovation should inform treatment choices either with respect to efficacy or adverse effects such as switch to hypo ⁄ mania. Acknowledgement Some of the material included in this paper has been adapted from Mitchell and Malhi (15). and less prior episodes Symptomatology: initial insomnia. A proposed ÔprobabilisticÕ approach to the diagnosis of bipolar I depression in a person experiencing a major depressive episode with no clear prior episodes of mania The greater likelihood of the diagnosis of BIPOLAR I DEPRESSION should be considered if ‡ 5 of the following features are presenta Symptomatology and mental state signs Hypersomnia and ⁄ or increased daytime napping Hyperphagia and ⁄ or increased weight Other ÔatypicalÕ depressive symptoms such as Ôleaden paralysisÕ Psychomotor retardation Psychotic features and ⁄ or pathological guilt Lability of mood ⁄ manic symptoms Course of illness Early onset of first depression (< 25 years)a Multiple prior episodes of depression (‡ 5 episodes)a Family history Positive family history of bipolar disorder The greater likelihood of the diagnosis of UNIPOLAR DEPRESSION should be considered if ‡ 4 of the following features are presenta Initial insomnia ⁄ reduced sleep Appetite and ⁄ or weight loss Normal or increased activity levels Somatic complaints Later onset of first depression (> 25 years)a Long duration of current episode (> 6 months)a Negative family history of bipolar disorder See original study data in Table 1. longer duration of episodes. We acknowledge the limitation of this somewhat arbitrary specification and would recommend that the specific details of such a probabilistic approach need to be further explored. a differential likelihood of experiencing the above symptoms and signs of depression. to be useful.

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