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Section 17
The Need
for a Bipolar Depression Rating Scale
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Bipolar disorder is characterized by periods of mania and ⁄ or
hypomania, generally interspersed between episodes of depression. The latter
is its predominant mood state conferring the bulk of its associated burden
and risk of suicide and yet diagnostic distinction is still based on the presence
of mania. Like major depression, bipolar disorder is a common psychiatric illness
that has been estimated in previous studies to have a lifetime prevalence of
less than 1%, but recent studies indicate a lifetime prevalence closer to 6.4%
(using criteria that include subsyndromal manic or hypomanic symptoms. However,
it is often undetected with a third of patients waiting more than a decade
after the onset of the illness before seeking help, and even then almost 70%
are repeatedly misdiagnosed. The delay in detection and diagnosis occurs most
commonly because of a misdiagnosis of unipolar depression. This is consistent
with the fact that most patients with
bipolar disorder first present in the depressive phase of their illness. Although
such misdiagnoses are understandable, its consequences both for the individual
and those around them are costly. Therefore clinically it is important to be
able to detect bipolar depression and discriminate between it and unipolar
illness.
Increasingly, bipolar disorder is viewed as
a spectrum that comprises a variety of overlapping syndromes. Patients with
bipolar disorder that initially present with depressive episodes and are consequently
incorrectly diagnosed as having unipolar disorder are often called “converters”.
These patients tend to have a more volatile illness than unipolar patients,
with only brief periods of being well. Furthermore, they are more likely to
have a history of temperamental instability, a younger age of onset, an unstable
interpersonal and occupational history and to have suffered postnatal episode.
Thus a patient presenting with these clinical features should signal the possibility
of bipolarity. Additional features that are thought to indicate bipolar depression
include a family history of bipolar disorder, a premorbid hyperthymic personality,
the occurrence of atypical depressive features, psychotic episodes, antidepressant-induced
mania ⁄ hypomania,
antidepressant wear-off and a lack of response to three or more antidepressant
treatment trials. In practice, mixed states form a large subgroup of patients
within bipolar disorder. However, despite the potential clinical significance
of mixed features in cohorts with predominantly depressive presentations, there
is little prevalence data for this subgroup. Like bipolar disorder, mixed states
form a spectrum that extends from depressive features within mania to manic
features within depression, with admixtures in between. The Diagnostic and
Statistical Manual of Disorders, 4th edition (DSMIV), defines mixed states
as the concurrent presence of a full manic and depressive syndrome, most likely
the least common subtype. Indeed the most common manifestation of mixed states
is the presence of a few features of one pole of the illness during the polar
opposite phase further highlighting the restrictive nature of DSM-IV criteria.
The emergence of manic features in a dominantly depressive
presentation is difficult to diagnose. Here there is an overlap with the concept
of agitated depression. Patients with depressive mixed states tend to have
low scores on mania rating scales and the hyperactivity they experience tends
not to be goal-directed. Clinically meaningful signs and symptoms, such as
changes in energy, neurovegetative symptoms and distorted cognitions tend to
characterize the manic or hypomanic component of such mixed presentations.
Conventional depression rating scales make no attempt to detect and measure
these symptoms. Clinically the phenomenological separation of unipolar and
bipolar depression should be underpinned by differences across other domains.
The neuropsychological profiles for instance overlap considerably with patients
in both groups demonstrating memory and executive functioning impairment. However,
patients with bipolar depression have impaired sustained attention and poor
immediate and delayed verbal recall, greater than that found in unipolar depressed
patients. Similarly, preliminary functional neuroimaging studies are differentiating
patterns of activation in unipolar and bipolar-depressed patients and across
the phases of bipolar disorder. However, most of the findings are as yet tentative
and await replication.
Depression rating scales
In order to be responsive to the needs of individuals with bipolar depression
a well-devised scale must be used that is sensitive to the specific symptoms
they experience. Existing scales can be categorized along a number of parameters
including syndrome vs. symptom, diagnosis vs. severity, brief vs. comprehensive,
Likert vs. visual analogue or other measurement styles, and trained observer
vs. self-rating scales. In this paper we will focus briefly on the use of
self-report scales with depressed individuals and then examine in greater
detail the strengths and limitations of observer rating scales as it is the
latter that has greater utility in treatment studies.
Self-report scales
Self-report scales like the Beck Depression Inventory (BDI) the Zung Self Rating
Scale and the Internal State Scale allow the assessment of depressive symptoms
in bipolar disorder. These are widely used, and are simple to administer
across a number of clinical and subclinical populations. Unfortunately, self-report
scales can lack reliability and have limited usefulness in patients with
diminished concentration, poor motivation, fatigue, advanced age or limited
reading skills. Factor analytic studies have found that the structure of
the BDI is influenced by socio-economic and diagnostic characteristics of
the patient sample. For instance, depressed subjects tend to exaggerate their
negative feelings and somatic symptoms, a tendency that is more prominent
in some subtypes of depression. In particular, patients that have been depressed
for a long time have difficulty comparing their emotions when depressed to
their feelings when well, as they may no longer have a benchmark for normality.
In bipolar depression perhaps more so than unipolar disorder, insight is
often compromised, further limiting the usefulness of self-report methodology.
Self-report scales also suffer from inaccuracy because of interpretive errors
and non-response. However, perhaps most significant of all is the fact that
opportunities that emerge for discussion during an observer-rated interview
are inevitably lost during self-report assessment. For these reasons in the
present study the rationale for development of a clinician-rated measure for
bipolar depression is discussed.
Observer-rated scales
Of the observer-rated scales, two of the best known are the Hamilton Depression
Rating Scale and the Montgomery-Asberg Depression Rating Scale (MADRS). The
17-item Hamilton Depression Rating Scale (HAM-D) was developed in the 1960s
so as to provide a structured measure of depression severity. Since then
it has been adopted universally and is widely considered to be the “gold
standard” of clinician-rated depression scales. Numerous studies have
assessed its psychometric properties and confirmed its role with respect
to rating depressive symptoms that are typical of unipolar depression. Not
surprisingly it has also undergone several modifications with 21-item and
31-item versions attempting to capture a broader range of depressive symptomatology.
However, the longer a scale becomes the more cumbersome it is to administer
and score. This then detracts from its appeal and ultimately limits its utility.
This is indirectly borne out by the MADRS, a 10-point observer rated scale
designed to reflect change in the severity of depression especially during
treatment. It too is easy to administer and score, and like the HAM-D against
which it was validated, it has become a global standard. Total MADRS scores
when assessing depressed patients demonstrate strong positive correlation
with a number of other established instruments such as the Clinical Global
Impressions Rating Scale for Severity and Improvement, and the Symptom-Checklist-90.
However despite their ubiquitous use these scales have important limitations,
particularly in bipolar disorder, that warrant careful consideration.
Firstly, these scales do not evaluate all aspects of depression
and unfortunately some of the aspects omitted are particularly relevant to
the assessment of bipolar disorder. For example the MADRS does not assess worthlessness,
motor retardation or loss of pleasure ⁄ interest. The utility of these
scales in the assessment of bipolar depression is hence diminished, especially
as the construct of depression itself is not that of a homogeneous entity.
Depression is clearly heterogeneous and multifaceted and the factors brought
together to measure and evaluate depression vary from scale
to scale. Strong convergent validity across scales only indicates that they
are measuring the same constructs, not that the full scope of constructs are
covered, or that these are all of the most clinically relevant constructs.
Importantly, there is no means of gleaning the clinical salience of the measure.
For example, features that are not mood-specific, such as functional, genital
or gastrointestinal-related symptoms, can contribute to a significant proportion
of the total HAM-D score. This means that in some cases the severity of depression
can be determined by items that may in fact be associated with something other
than depression, resulting perhaps in total scores being a misleading index
of severity, and even to misclassification. Weight loss for example does not
necessarily equate with depression severity just as a reduced anxiety does
not connote diminished suicidality. Discriminant validity is further confounded
by comorbidity as shown in a study of elderly patients in which investigators
found that high scores on eight somatic items from the HAMD exaggerated the
total scores of depression when in fact these symptoms were evidence of concurrent
medical illness. Scales weighted towards somatic symptoms risk reflecting side-effect
profiles of, for example, the atypical agents, reflecting items measuring appetite,
weight and sleep. Scales weighted to core symptomatology may be better able
to track true change.
Another limitation is that atypical depressive
symptoms such as hyperphagia and hypersomnia are not included in the 17- item
HAM-D or the MADRS. These symptoms are disproportionately common in bipolar
disorder, and the HAM-D only provides unidirectional measures of sleep and
appetite, and is excessively weighted with regard to the former. The pertinence
of these symptoms to the diagnosis of atypical depression is in itself a topic
of some discussion however, such omissions clearly have implications for delineating
depressive subtypes and capturing depressive symptomatology across phenotypes.
In patients with bipolar disorder mixed states are relatively common with up
to a third meeting criteria for a mixed episode and almost half having a lifetime
history of mixed episodes. Of particular interest in the latter study is the
finding that HAM-D rating failed to discriminate, both on individual items
and total score, patients with a mixed episode from those with depression alone.
None of the unipolar rating scales have any items that identify mixed state
constructs, despite the frequency with which they occur and their clinical
significance. The lack of a recognized instrument that measures depressive
mixed episodes may add to their misidentification. Constructs including irritability,
lability, increased speech and motor drive and agitation are typical of mixed
states and merit concurrent assessment. Clearly, the HAM-D is not a “one
size fits all” instrument and its use as such raises serious concerns
as regards its symptom sensitivity and phenotype specificity. Items such as
hypochondriasis and insight have been criticized in their ability to gauge
depression severity and are not symptoms commonly described in bipolar cohorts.
Furthermore, the value of rating weight loss in hospitalized patients has been
questioned as hospital staff routinely strive to prevent weight loss. Indeed
it is weight gain that is more frequently present in atypical depression and
is more frequent in bipolar than unipolar individuals. Such contextual elements
are also important in the rating of items such as sexual interest, which patients
tend to underrate when away from their partners. Despite the introduction of
structured guidelines, interrater reliability in the HAM-D has been found to
be problematic with raters at different facilities being trained using separate
guidelines and versions. Items such as those involving subjective evaluation
are inherently difficult to interpret even for trained observers and the scoring
of items is somewhat idiosyncratic. For instance, depressed mood rates a maximum
of 4 compared
to 6 points for sleep disturbance.
Naturally, the robustness of the MADRS in rating overall depression
and in particular change in total score is achieved at the expense of specificity
for symptoms and its brevity that makes it so easy to administer sacrifices
comprehensiveness. In common with the HAM-D the validity of some MADRS items
has been questioned, namely sleep disturbance, reduced appetite and suicidal
ideation. The MADRS also lacks discriminant validity to the extent that total
scores equating to a diagnosis of Major Depression have been described when
rating patients with bulimia nervosa. Recently it has been suggested that because
the MADRS was developed to be maximally sensitive to change in treatment following
the administration of older antidepressants (amytryptiline, clomipramine, mianserin
and maprotiline) it cannot be assumed to be as sensitive to changes that occur
in response to the newer classes of antidepressants. Clearly this has significant
implications for its use in pharmaceutical research especially as there is
little consensus with respect to a normative cut-off score for defining remission.
Similar problems exist with the HAM-D resulting in different cut-off points
being suggested for different disorders including stroke, Parkinson’s
Disease and Alzheimer’s
Disease. This further compounds the problem of interrater reliability. It seems
that Hamilton’s instructions indicating that the scale was devised solely
for the assessment of primary depressive illness have been largely forgotten.
As awareness of differences between unipolar and bipolar depression increases
it highlights the necessity of being aware of the limitations of commonly used
assessment tools.
Conclusion
Continued investigation of the symptoms that individuals experience has allowed
diagnosis and treatment of depression to progress, and the continuing expansion
of the DSM and ICD classifications attests to the growing knowledge base
underpinning the differentiation of subcategories of disorders. It is therefore
necessary that more sophisticated means of assessing these symptom differences
and their respective responses to change be developed. Scales developed specifically
for particular populations are likely to better identify and weight symptoms
that characterize that disorder, and to accurately track change. As discussed,
bipolar patients often first present with depressive symptoms, which can
be readily mistaken for unipolar depression. The corollary of this is that
medication appropriate to unipolar depression is initiated and this is often
detrimental to patients with bipolar disorder. Antidepressant treatment is
generally less effective and risks precipitating mania, mixed states and
rapid cycling as well as the additional burden of misdiagnosis for both patient
and practitioner alike. A specific instrument more sensitive to the array
of bipolar depressive symptoms would advance both research and clinical goals.
With this in mind, we are currently developing and validating a new Bipolar
Depression Rating Scale (BDRS), which will assess aspects of bipolar depression
and mixed phase presentations.
- Berk, M et al; Scale Matters: The Need for a Bipolar Depression
Rating Scale; Acta Psychiatrica Scandinavica; Sep2004 Supplement 422,
Vol. 110, p 39
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Personal
Reflection Exercise #3
The preceding section contained information
about the need for a bipolar depression rating scale. Write
three case study examples regarding how you might use the content of this section
in your practice.
QUESTION
17
According to Berk, what is the main disadvantage caused by not having a
universal bipolar depression rating scale? Record the letter of the correct answer
the Answer
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Answer
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