Posted by jrbecker on February 11, 2005, at 12:41:00
In reply to Bipolar II Series - differences in +mania+ by dx, posted by jrbecker on February 11, 2005, at 12:35:06
Journal of Affective Disorders
Volume 84, Issues 2-3 , February 2005, Pages 107-115
Bipolar Depression: Focus on Phenomenologydoi:10.1016/j.jad.2004.06.003
Copyright © 2004 Elsevier B.V. All rights reserved.
Introcduction
The dark side of bipolarity: detecting bipolar depression in its pleomorphic expressions
Hagop S. Akiskal ,VA Psychiatry Service (116A), International Mood Center, University of Caifornia, 3550 La Jolla Village Drive, San Diego, CA 92161, USA
Received 15 March 2004. Available online 1 September 2004.
Abstract
The depressive expressions of bipolar disorders have long been neglected. Current data, from both clinical and epidemiologic studies, indicate that such expressions far exceed the manic forms in both cross-section and during follow-up course. Thus, mania occurs in 1% of the population at large; bipolar depression afflicts at least 5 times more people. Much of the new literature on this subject has emphasized its high prevalence, morbidity, and mortality. There has been relatively less attention paid to the phenomenology of bipolar depression as it presents clinically. This special issue (volume 84/2–3, 2005) is devoted to a systematic data-based in-depth examination of the different clinical expressions of bipolar depression including, among others, retarded depression, agitated and/or activated depression, mood-labile depression, irritable-hostile depression, atypical depression, anxious depression, depressive mixed state, and resistant depression. Both bipolar I (BP-I), and the more prevalent yet relatively understudied bipolar II (BP-II), are covered. We trust that this extensive coverage of the “darker” side of bipolarity will set the stage for a much needed renaissance in its complex phenotypic expressions—and its delimitation from unipolar depression (UP).
The phenomenology of BP-I depression ranges from depressive stupor to agitated psychosis, whereas UP depression expresses itself in psychic anxiety, and insomnia, as well as retardation. BP-II compared with UP is more likely to have atypical features, mood lability, hostility, activation, biographical instability, multiple anxiety comorbidities, suicidal tendencies, and to be rated as less “objectively” depressed. These findings are complex and do not fully agree with the conventional characterization of BP as retarded and UP as anxious and agitated. The inconsistency between the conventional and the phenomenology described herein is largely due to depressive mixed states, which tend to destabilize BP-II, and may account for the “contradictory” relationships of affect, sleep, drive, and psychomotor activity in mood disorders.
Keywords: Bipolar I; Bipolar II; Atypical depression; Mixed state; Retarded depression; Agitated depression
1. Introduction
Although much has been published about the clinical features of mania, there has been a comparative paucity of research on the depressive phase of bipolar disorder. This paper provides an overview of recent developments on the clinical features of the depressive phase of bipolar disorder. We term it the “dark side” of bipolarity because it is often missed in diagnostic assessments and has long been neglected. Such neglect, in turn, reflects the complexities of its clinical presentation and the instability, lability, and mixity of its clinical phenomenology in the BP-II subtype (Akiskal et al., 2003a). Such patients may be regarded as less depressed on clinician versus self-evaluation (Dunner et al., 1976a). Tragically, the dark side of these patients may lead to suicide (Rihmer and Pestality, 1999).
There is considerable confusion in the current literature about the clinical portrait of bipolar depression (Beigel and Murphy, 1971, Dunner et al., 1976a, Akiskal et al., 1983, Akiskal et al., 1995, Joffe et al., 1999 and Mitchell et al., 2001). In particular, it is uncertain whether bipolar depression manifests with psychomotor retardation or agitation. Indeed, both have been reported. Table 1 summarizes what we know from the literature about the validating differential features of bipolar and unipolar disorders in their depressive phases (Goodwin and Jamison, 1990 and Akiskal, 2000). To be further discussed in the present review is to what extent these features pertain to bipolar II (BP-II), the more common form of bipolar disorder (Akiskal et al., 2000). The present introductory review is undertaken as background material for the new data-based reports compiled for the present special issue.2. Bipolar I depression
It is generally believed that bipolar I (BP-I) disorder, the prototype of bipolar disorder, exemplifies the classical features listed in Table 1. This traditional view is supported in its main elements by two prospective studies, one in adolescents (Strober and Carlson, 1982), the other in adults (Akiskal et al., 1983). However, temperament was not tested in these two studies. Prospective assessment of temperamental attributes in the NIMH Collaborative Depression Study (Akiskal et al., 1995) has actually shown that MDE patients who switch to BP-I are more likely to be “sanguine” compared to those who do not switch; the latter tend to be anxious-neurotic (i.e. dysthymic). Similar findings have been reported by Angst and Clayton (1986) from the Zurich cohort. Such data suggest that most BP-I are not cyclothymic—this is certainly the case for BP-I with euphoric mania. However, BP-I with dysphoric mania may arise from depressive and cyclothymic temperaments (Perugi et al., 1997 and Akiskal et al., 1998).
Psychomotor retardation with hypersomnia (Detre et al., 1972, Himmelhoch, 1998 and Mitchell et al., 2001), touted as “pathognomonic” for bipolar illness, is characteristic of the “pure” depressive phase of the illness. Psychotic, agitated-irritable depression, the hallmark of bipolar mixed depression, is not uncommonly observed in BP-I (Perugi et al., 2001). Contrary-wise, as to be discussed later in this paper, anxious agitation in “unipolar” depression might be due to contamination by bipolar II mixed states.
Thus, the phenomenology of BP-I depression ranges from depressive stupor to agitated psychosis, whereas unipolar depression (UP) expresses itself in guilt and insomnia, as well as retardation (Allilaire et al., 2001). To further complicate matters, agitation can coexist with retardation (Greden and Carroll, 1981), a phenomenon which might be more characteristic of bipolar disorder. Such “paradoxical” coexisting psychomotor phenomenology is perhaps best understood when one considers that it is acceleration, not agitation, which is the opposite of retardation.
In conclusion, the distinguishing features of full-blown bipolar (BP-I) from UP depressions shown in Table 1 are largely accurate except for the foregoing qualifications for temperament and psychomotor activity.
3. The clinical spectrum of bipolarity
Current data indicate that classical manic-depressive illness (BP, type I) involves 1% of the population. These patients reach the threshold of mania, typically a condition which requires hospitalization; much of the course of BP-I, however, is dominated by depressive episodes and/or subthreshold depression (Judd et al., 2002). Bipolar type II is characterized by alternation of depression with more subtle periods of excitement known as hypomania which, by itself, does not warrant hospitalization (Dunner et al., 1976b); depression dominates its course. Type II, which is 5 times more common than type I, is poorly recognized by both researchers and clinicians (Akiskal et al., 2000), which explains the relative paucity of research on it.
Recent research has nonetheless shown reliable methods of clinical ascertainment in public, private, and national samples (Hantouche et al., 1998 and Benazzi and Akiskal, 2003). There is indeed a “hidden epidemic” in the making, consisting of major depressive disorders whose bipolar nature is unrecognized (Akiskal and Pinto, 1999). Failure to recognize the bipolar nature of bipolar II and its variants often leads to inappropriate treatments of the depression—and long delays in instituting effective treatments.
A new paradigm of bipolar spectrum is shaping up in the research literature and in clinical practice (Akiskal, 2002). It represents a partial return to the Kraepelinian (1921) broad concept of manic depression which included many recurrent depressions. Although bipolar I, bipolar II, and cyclothymia are now part of the official nomenclature of DSM-IV, the breadth of bipolarity is not represented in this manual. Old and new evidence indicate that the most common form of bipolar II is characterized by hypomanias of shorter duration than the arbitrary threshold of 4 days (Akiskal et al., 2000), and that cyclothymic depressions (major depressions arising from a cyclothymic baseline) represent a prevalent variant of the bipolar II pattern. Furthermore, evidence is now compelling that hypomania in association with antidepressant treatments (bipolar III) requires familial bipolar diathesis for bipolar disorder (Akiskal et al., 2003b). There also exist clinical depressions superimposed on hyperthymic temperament (bipolar IV), referring to individuals with subthreshold hypomanic traits rather than episodes (Akiskal, 1992 and Cassano et al., 1992). Given emerging data for a population prevalence of at least 5% for a broadly conceived bipolar spectrum (Akiskal and Mallya, 1987, Angst, 1998, Szadoczky et al., 1998, Judd and Akiskal, 2003 and Hirschfeld et al., 2003)—and 6% for the cyclothymic temperament (Placidi et al., 1998)—we estimate that 1 of 10 individuals in the community either has bipolar disorder or is at risk for it.
A provocative new development is the emergence of extensive clinical and research evidence for the comorbidity of panic, social phobic, and related anxiety states with bipolar, especially bipolar II, disorder (Perugi et al., 1999). In addition, prevalent mixed states beyond dysphoric mania have been described, consisting of hypomanic intrusions into major depressive states (Akiskal and Benazzi, 2003 and Sato et al., 2003).
The net effect of the broadened boundaries of bipolarity is encroachment into the terrain of so-called “unipolar” anxious depressions and that of axis II cluster B personality disorders predicted by us as early as the early 1980s (Akiskal, 1983). This is an evolving reformulation of the subclassification of affective disorders, validated on the basis of phenomenology, comorbidity, epidemiology, course, family history, twin studies, and molecular genetics and an evolutionary perspective (Akiskal, 2002). These considerations—especially the fact that depression is the most prevalent expression of the bipolar spectrum—have major implications for clinical practice, methodology of genetic investigations, pharmaceutical trials of putative bipolar agents in affective disorders, and public health.
Because bipolarity impacts on all aspects of life, the spectrum would be of great interest to all mental health clinicians, general practitioners, nurses, educators, and public health officials.
4. Prevalence of bipolar II in major depression
The clinical diagnosis of bipolar II is crucial, not only for psychopathology and its therapeutic implications, but also for prognostic reasons (e.g., high suicidality; Rihmer and Pestality, 1999). Accordingly, it is gratifying that a great deal of recent research has been conducted on the clinical prevalence of bipolar II among patients presenting with major depressive disorder in various psychiatric clinics—both public and private—worldwide (summarized in Akiskal et al., 2000). These data show that up to 50% of all major depressions conform to bipolar II or its variants. Simpson et al (1993) stated this fact most eloquently: bipolar II represents the most common phenotype of bipolar disorder. Recent epidemiologic studies both in the U.S. (Judd and Akiskal, 2003 and Hirschfeld et al., 2003) and Europe (Angst, 1998 and Szadoczky et al., 1998) have extended these findings to the community.
The French EPIDEP study (Hantouche et al., 1998), based on a representative national clinical sample, has provided the most compelling data on the high prevalence of bipolar II among major depressive patients. The overarching purpose of this study was to assist practicing psychiatrists to recognize bipolarity in all of its varieties. The main finding was that at index interview, 22% of major depressive patients could be diagnosed as bipolar II based on history of hypomania; a month later, upon reinterview, 40% of patients were diagnosed as bipolar II on the basis of more in-depth evaluation and collateral information from significant others, as well as observed hypomania by the clinician. These figures must be contrasted with the 6% at both index and follow-up for BP-I (which remained stable because it depends on history of manic episodes, readily available from past patient records).
To recapitulate, the EPIDEP study demonstrated that clinicians in diverse practice settings can document the diagnosis of BP-I with relative ease; however, they required the institution of systematic assessment methods to recognize bipolar II and its variants. Thus, specialized training can lead to changes in diagnostic practice at the national level.
5. Assessing hypomania
Bipolar II patients present with a major depressive episode, and upon further inquiry, history for hypomanic episodes is elicited. Accurate diagnostic subtyping then depends on the vagaries of the patient's memory and how systematically the clinician pursues lead questions about hypomania and whether relatives are interviewed.
Rice et al (1986), reporting from the NIMH collaborative study of depression, found low reliability of the bipolar II diagnosis. However, all such diagnoses occurred in pedigrees with bipolar disorder, suggesting that once history for hypomania was obtained, it did carry significant diagnostic specificity. In practice, then, the diagnosis of bipolar II requires repeated evaluation at different time points to obtain more reliable history for hypomania. Dunner and Tay (1993) found that clinicians specifically trained to recognize bipolar II outperformed those using structured instruments such as the SADS or the SCID in the diagnosis of bipolar II disorder. This finding has been replicated (Brugha, 2003). Although the foregoing consideration runs against the usual tenets in the literature on structured diagnostic interviewing, they are consistent in suggesting that the proper identification of bipolar II requires a sophisticated approach in the clinical evaluation of these patients.
Among the major reasons for diagnostic inconsistency in bipolar II is the underlying cyclothymic dysregulation, resulting in clinical presentations of a labile-variable nature, which can be confusing in cross section (Akiskal et al., 2003a). That is, these patients could present with cross-sectional features of atypical depression and lifelong history of anxiety states, bulimia, substance abuse, and cluster B personality disorder such as “borderline” (Perugi et al., 1999). A prospective study has also demonstrated that atypical depressions more often than not progress to bipolar spectrum disorders (Ebert et al., 1993). Hypersomnia, weight gain, and related atypical features then represent an important clinical marker of bipolar II, observed in cross-sectional studies as well; such features may actually serve as a clinical marker for bipolar II (Benazzi, 2000 and Akiskal and Benazzi, 2005, this issue).
Recent work has shown that the stem question on mood (euphoric or irritable) in the SCID and the DSM-IV is not understood by patients, either because it reflects the way they usually feel or they do not believe that there is anything wrong with it. In a study in the Ravenna–San Diego Collaboration, we found that bypassing this question and inquiring first about the behavioral or activation signs and symptoms of hypomania can better accomplish the diagnosis of bipolar II (Benazzi and Akiskal, 2003). After such activation symptoms are elicited, the patient can then be queried about their moods, who better remember that they were irritable or euphoric during such an activated period, thereby supporting a bipolar II diagnosis.
Another interesting development in the complexity of bipolar II is panic attacks. There have been stronger lod score estimates in molecular linkage in bipolar II patients with familial panic versus those without (MacKinnon et al., 1998). Thus, the affective dysregulation of bipolar disorder extends beyond elation and depression—to include, among others, such negative affective arousal states as panic, irritability, and mood lability (Akiskal et al., 1995).
6. The specificity of mood lability and related life disruptions in bipolar II
Analyses from the NIMH Collaborative Depression Study on 559 “unipolar” patients showed that 48 converted to bipolar II during a prospective observation period of 11 years. What characterized these bipolar II converters at entry were early age at onset of first depression, recurrent depression, high rates of divorce or separation, high rates of scholastic and/or job maladjustment, isolated “antisocial acts,” and drug abuse—in brief, a more tempestuous affective and life history. In addition, the index depressive episode was further characterized by such features as phobic anxiety, interpersonal sensitivity, obsessive-impulsive symptoms, somatization (often with subpanic symptoms), worse in evening, self-pity, demandingness, subjective or overt anger, jealousy, suspiciousness, and ideas of reference—again testifying to a broad mélange of “atypical” depressive symptoms with “borderline” features. Temperamental attributes obtained at index interview proved decisive (sensitivity=91%) in identifying those who switched from depression to hypomania: these attributes consisted of trait “mood lability,” “energy activity,” and “daydreaming”—all characteristic of Kretschmer's (1936) description of the cyclothymic temperament; mood lability was the most specific predictor (specificity=86%) of which depressions will prospectively transform to bipolar. This study testifies to the fact that bipolar II is a complex affective disorder with biographical instability—deriving from an intense temperamental dysregulation. Mood lability—with rapid shifts, often in a depressive polarity—was the hallmark of “unipolar” patients who switched to bipolar II. Unfortunately, our formal diagnostic systems (e.g., ICD-10 and DSM-IV) are symptom-oriented and do not consider extreme temperamental dispositions in clinical evaluation. Instead—and regrettably this is particularly true for the DSM-IV schema—such patients often get labeled “borderline.”
7. Bipolar II depressive mixed states
Because history for hypomanic episodes often proves difficult to obtain from a depressive patient, one may examine hypomanic features during a depressive phase. Hypomanic symptoms such as racing and grandiose thoughts, sexual arousal, and psychomotor acceleration have been described in major depressive episodes in contemporary psychiatry, thereby testifying to Kraepelin's diagnostic acumen—yet, the number of studies reporting on “bipolar depressive mixed states” are too few (reviewed in Akiskal and Benazzi, 2003). A recent study by Benazzi (2000) demonstrated that irritability, distractibility, and racing thoughts were the most common hypomanic features during depression, mostly among bipolar II depressives. Unfortunately, such studies have not commanded sufficient interest in official nosologic systems nor in the clinical literature. The nonrecognition of depressive mixed state is nothing short of a clinical tragedy because these are the very “unipolar” depressive patients who are likely to do poorly on antidepressants and require mood stabilizers, antipsychotics, or electroconvulsive therapy (Akiskal and Mallya, 1987 and Akiskal and Benazzi, 2003). Koukopoulos and Koukopoulos (1999) have recently written a superb clinical article on agitated depression as a mixed state. This is an instance where clinical acumen has outpaced the conventional scientific literature. Validation of the bipolar nature of agitated depression represents a new frontier (Akiskal and Benazzi, 2005 and Benazzi et al., 2004).
8. Characterizing the phenomenology of bipolar II depression
In the French national collaborative study on depression (EPIDEP. Hantouche et al., 1998 and Allilaire et al., 2001), analyses in midstream demonstrated that hypersomnia and suicidal ideation were more common in bipolar II (BP-II) versus unipolar (UP) disorder, which had more insomnia. In the most recent analyses based on dimensional measures in the entire sample of 493 patients, the differential features of the two disorders emerged more clearly (see Hantouche and Akiskal, 2005, this issue):
• BP-II depressives were rated higher on suicidal thoughts, guilt, depersonalization, and derealization, and yet, despite hypersomnia and weight gain, had high ratings on psychomotor activation, suggesting the picture of an activated or mixed depressive state. These findings, in turn, showed why BP-II patients were deemed as less “objectively” depressed, revealing greater discrepancy between clinician versus self-rated measures of depression.
• Strictly UP major depressives did have more psychic anxiety and insomnia on various self-assessment [including Multiple Analog Visual Scale for bipolar on the Ahearn-Carroll scale (1996)] and were higher on slow thinking, anergia, feeling worst, avoiding risks, life dull, and dreary. Indeed, “psychomotor retardation” was highest in UP, and this difference appeared most significant when compared with cyclothymic BP-II.
9. Diagnostic implications for the clinician
Depression is the more common expression of the bipolar spectrum. Bipolar II is actually the most common clinical phenotype of this disorder.
Apart from demographic, familial, and course differences between unipolar and bipolar disorders, the literature has emphasized differences in psychomotor function. Most studies have reported higher psychomotor retardation in bipolar than unipolar disorder. However, this depends on whether mixed features are permitted in bipolar depression and whether or not the comparison with unipolar is between bipolar I or bipolar II. The data overall indicate that in bipolar II depression, irritability, distractibility, racing thoughts, and mood lability are quite common, despite the presence of hypersomnia. Once bipolar II is properly diagnosed and excluded from broadly defined unipolar major depression, not only are atypical features less common in strictly defined unipolar patients, but also the mixed features documented above become the clinical signature of bipolar II. It is therefore not surprising that psychomotor retardation per se might be more marked in unipolar depressive patients once BP-II are excluded from it.
On the other hand, psychic anxiety and insomnia, long known for their state association with unipolar disorder (Beigel and Murphy, 1971), continue to accompany this subtype of depression. The situation, however, is more intricate because of increasing reports about high prevalence of multiple comorbid anxiety states during the course of bipolar II (Perugi et al., 1998 and Rihmer et al., 2001). This means that the presence of anxiousness and/or anxiety comorbidity does not automatically suggest unipolarity. Such comorbidity appears to be a marker of even childhood onset bipolar disorder (Masi et al., 2001). These conclusions are complex and suggest that heterogeneity of depressive states, particularly in bipolar II, should be taken into consideration in describing the differentiating characteristics of unipolar and bipolar disorders.
This special issue provides an in-depth data-based collection of reports that expand upon and go beyond the present introductory review. DSM-IV is not of great help in the differential diagnosis of bipolar from major depressive disorders. This cannot be merely achieved in cross-sectional symptomatologic basis or past episodes of mania or hypomania. The clinician must also consider, among other validators, family history, temperament, switching on antidepressants, cyclicity, mixity, and seasonal patterns (Akiskal, 2002).
On the basis of the foregoing validators, the “depressive” presentations listed in Table 2 should be considered as putative soft bipolar disorders. These conditions are not officially recognized as bipolar. They are often misconstrued as recurrent major depressive in nature. The author submits that they have affinity to bipolar disorder, yet are not listed in the bipolar NOS category in DSM-IV. I would like to highlight recent evidence that anxious inhibition may partly replace the depressive phase in certain patients with cyclothymic tendencies (Perugi et al., 1999), resulting in social phobic, panic, and obsessive-compulsive variants of bipolarity; these patients are often considered to have anxious depressions with mood instability and, regrettably, more often than not, delegated to cluster B erratic personality disorders.
It is important to consider soft bipolarity in the listed conditions because such patients often show mediocre response to monotherapy; indeed, they often fail multiple (≥3) antidepressants from different classes (Akiskal and Mallya, 1987). This is upheld by clinical experience in specialized mood and bipolar clinics (Akiskal and Pinto, 1999 and Ghaemi and Goodwin, 2001). In particular, activated depressions respond poorly to antidepressants (Caligiuri et al., 2003). We obviously need more rigorous studies to demonstrate the efficacy of mood stabilizer augmentation in such patients.
10. Concluding remarks
The concept of a bipolar spectrum is a heuristic concept that is rooted in the descriptive clinical tradition and is validated by a new wave of epidemiologic studies demonstrating the high prevalence of subthreshold cases, familial aggregation studies, high-risk offspring studies, analysis of monozygotic “discordance,” and molecular linkage studies (Akiskal, 2002).
Family history for bipolar disorder, cyclothymic temperament, and switching on antidepressants represent the most useful validating principles in clinical practice when examining depressed patients without antecedent frank hypomania. Early age at onset, postpartum onset, mixity, high rate of recurrence, cyclicity, and seasonality can also serve as clinical validators. Specific comorbid patterns of depression with alcohol and multiple drug abuse, as well as social phobic, panic, and obsessive-compulsive disorder, should also raise clinical suspicion of a bipolar diathesis. The thrust of arguments made in this report suggests that the clinical management of affective disorders will not improve significantly until there is recognition that most depressions presenting clinically are, at some level, bipolar. As counterintuitive as this suggestion might be, there is increasing evidence in its support.
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