Download Dysphoric mania, mixed states, and mania with mixed features

CNS Spectrums (2017), 22, 170–176. © Cambridge University Press 2016
doi:10.1017/S1092852916000717
REVIEW ARTICLE
Dysphoric mania, mixed states, and mania with mixed
features specifier: are we mixing things up?
Susan L. McElroy* and Paul E. Keck Jr.
Lindner Center of HOPE, Mason, Ohio, USA; Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine,
Cincinnati, Ohio, USA
Various terms have been used to describe mania when it is accompanied by depressive symptoms. In this article, we
attempt to define and discuss 3 of these terms: dysphoric mania, mixed state, and mania with mixed features specifier.
We conclude that whatever term is used, it is important to be aware that mania is more often unpleasant than pleasant,
and that the unpleasantness is not limited to depression.
Received 27 April 2016; Accepted 8 September 2016; First published online 21 November 2016
Key words: Depression, dysphoric mania, mania, mixed features specifier, mixed states.
Introduction
It is well established that manic and depressive symptoms
combine in many ways in persons with bipolar disorder,
and when they combine there are important diagnostic
and treatment implications.1–9 Various terms have been
used to describe such combinations of manic and
depressive symptoms. In this article, we attempt to
define and discuss 3 of these terms: dysphoric mania,
mixed state, and mania with mixed features specifier.
Dysphoric Mania
As the precise meaning of dysphoria is unclear, so is the
meaning of the term dysphoric mania. In its glossary, the
Diagnostic and Statistical Manual of Mental Disorders,
Fifth Edition (DSM-5)10 defines dysphoria as “a condition in which a person experiences intense feelings of
depression, discontent, and in some cases indifference to
the world around them” (p 821). Using this definition of
dysphoria, dysphoric mania is simply another term for
mania with prominent depressive symptoms, also called
mixed mania, depressive mania, or, in DSM-5, mania
with mixed features.
However, the term dysphoria is also used more broadly
to denote unpleasant, negative, or uncomfortable affective states beyond depression.11,12 Webster’s Third New
* Address for correspondence: Dr. Susan L. McElroy, Lindner Center
of HOPE, 4075 Old Western Row Road, Mason, OH 45040, USA.
(Email: [email protected] or [email protected])
International Dictionary13 defines dysphoria as a
“generalized state of feeling unwell or unhappy,” as
“opposed to euphoria” (p 712). Medical dictionaries have
defined dysphoria as “a mood of general dissatisfaction,
restlessness, depression, and anxiety; a feeling of unpleasantness or discomfort”14; “an emotional state marked by
anxiety, depression, and restlessness”15; or “a disorder of
affect characterized by depression and anguish.”16
Indeed, Swann11 said dysphoria “can refer to many ways
of feeling bad” (p 325). Using this meaning of dysphoria,
dysphoric mania refers to unpleasant mania or mania
accompanied by negative or painful mood states such as
irritability, anger, or anxiety, as well as depression.
Dysphoric mania would thus include mixed (depressive)
mania, as well as paranoid-destructive mania, irritable
mania, and anxious mania. An advantage to this use of the
term dysphoric mania is that it stresses that mania is often
an unpleasant condition, and that the nature of the
unpleasantness is highly variable. In other words,
depression is not the only unpleasant mood state that
occurs in mania. For example, Cassidy et al17 rated 237
patients with Diagnostic and Statistical Manual of
Mental Disorders, Third Edition Revised (DSM-III-R)defined bipolar manic or mixed episodes on 15 classic
features of mania and 5 related to dysphoric mood, and
identified 5 clinically interpretable factors. The first and
strongest factor represented dysphoric mood and
included depressed mood, anxiety, guilt, mood lability,
and suicide. The other 4 factors were psychomotor
pressure, psychosis, increased hedonic function, and
irritable aggression.
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DYSPHORIC MANIA AND MIXED FEATURES SPECIFIER
However, several authors have conceptualized
dysphoria as a “third possibility of mood swing,” a “third
emotional field,” or a “third dimension” in addition to
mania and depression, and defined it as “a morose,
tense, and irritated mood.”12,18–20 Dayer et al19 argued
that dysphoria was a combination of irritability and
aggression, and proposed the dysphoric syndrome be
defined as the presence during at least 24 hours of overt
irritability with 2 of the following 4 criteria: expressed
(subjective) internal tension; expressed (subjective)
irritability or feelings of hostility in reaction to external
stimuli; aggressive or destructive behaviors; and suspiciousness. Starcevic12 argued that dysphoria was “a
complex emotional state, consisting of intense unhappiness and irritability” (p 12). Bertschy et al20 defined
dysphoria as 3 of the following 4 symptoms: inner
tension, irritability, aggressive behavior, and hostility.
They evaluated the presence of dysphoria in 165 patients
hospitalized for Diagnostic and Statistical Manual of
Mental Disorders, Fourth Edition (DSM-IV)-defined21
manic or major depressive episodes and found that when
defined this way, dysphoria occurred in 17.5% of the
group with pure depression, 22.7% of the pure mania
group, and 73.3% of the mixed episode group. The rate
of dysphoria increased from 14.3% to 69.2% (p = 0.057)
when the member of depressive symptoms in manic
patients increased from 2 to 3. The authors concluded
that dysphoria is strongly, but not necessarily, associated
with mixed states, for which it might serve as a marker.
Dilsaver et al22 suggested that dysphoric mania was a
third type of manic episode, distinct from euphoric
mania and depressive mania. They conducted a factor
analysis of 37 behavior rating items from the Schedule of
Affective Disorders and Schizophrenia in 105 inpatients
meeting DSM-III-R23 criteria for mania; 57 (54%)
patients had a clinical diagnosis of mixed mania while
48 (46%) had non-mixed mania. Four factors were found,
described as manic activation, depressed state, sleep
disturbance, and irritability/paranoia. Cluster analysis
separated the patients into 2 groups that differed with
respect to depressed mood. Forty-five (94%) of the
patients with non-mixed mania and 30 (53%) of the
patients with mixed mania were in the manic-activation
cluster, while 27 (47%) mixed and 3(6%) non-mixed
patients were in the depressed-state cluster. Non-mixed
patients from the manic-activation cluster appeared to be
experiencing predominantly euphoric-grandiose manic
episodes; they had low scores for depressed state and
irritability/paranoia. Patients in the depressed-state
cluster appeared to be experiencing depressive mania
and had high scores for all factors. Clinically mixed
patients from the manic-activation cluster, however,
differed from non-mixed patients by having lower scores
for manic activation and higher scores for depressed
state and irritability/paranoia. They differed from
171
depressed-state cluster patients by having lower scores
for both depression and mania. The authors concluded
that there were 3 types of manic episodes: pure or
euphoric mania, depressive mania, and dysphoric mania.
In the latter subtype, mania scores were lower than those
in the other 2 subtypes, while depression scores were
intermediate.
An important caveat is that many of these studies were
cross sectional, and naturalistic studies have suggested
that an individual manic episode has different levels of
severity over time. In a study evaluating 20 patients who
had at least 1 complete manic episode in which they
proceeded from a normal or depressed mood state
through mania, returned to a normal or depressed state,
and were often off medication, Carlson and Goodwin24
documented 3 stages of mania. Mood was qualitatively
different during these 3 stages, being predominantly
euphoric in Stage 1, predominantly angry and irritable in
Stage 2, and extremely dysphoric, with panic-level
anxiety, in Stage 3. Importantly, as manic episodes
progressed, ratings of mania and dysphoria (and
psychosis) increased in parallel. In cross-sectional
studies of the phenomenology of mania, therefore, mood
differences might be due to the stage of mania rather
than episode subtype.
Mixed State
Mixed state is a broad term that connotes some
combination of manic/hypomanic and depressive symptoms occurring together over a period of time.1,5,7–9
Alternatively, mixed states are conditions resulting from
the combination of 2 dimensions, a manic dimension
with a depressive dimension (see Figure 1). The term
mixed state is often used as the opposite of pure state,2,6
which means the occurrence of only 1 dimension over a
period of time—of only manic/hypomanic symptoms or of
only depressive symptoms.
Pure
Mania
Increasing
severity of
manic
symptoms
Pure
Hypomania
Mixed
Mania
Mixed
Hypomania
Mixed
Depression
Pure Dysthymia
No mood
symptoms
(Euthymia)
DSM-IV
Mixed Episode
Pure Depression
Increasing severity of depressive
symptoms
FIGURE 1. Two Dimensional Model of Mixed States.
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172 S. L. MCELROY AND P. E. KECK
More precise definitions of mixed states vary regarding the number and type of required manic and
depressive symptoms, the temporal relationship between
manic and depressive symptoms (occurring simultaneous and/or rapidly alternating), and the duration of
co-occurrence. Thus, in DSM-III,25 DSM-III-R,23 and
DSM-IV,21 there was only 1 type of mixed state, each
requiring at least 5 symptoms of a major depressive
episode during a full manic episode. In DSM-III, mixed
bipolar disorder was defined as the current or most
recent episode involving “the full symptomatic pictures
of both manic and depressive episodes,” with the
depressive symptoms being “prominent” and lasting
“at least a full day” (p 217).25 In DSM-III-R, mixed
bipolar disorder was similarly defined, except the
depressive symptoms did not have to occur for 2 weeks
and the manic and depressive symptoms were “intermixed or rapidly alternating every few days” (p 226).23 In
DSM-IV, a mixed episode was defined as “a period of
time (lasting at least 1 week) in which the criteria are met
for a both a Manic Episode and for a Major Depressive
Episode nearly every day” (p 333).21 In DSM-5,10 3 types
of mixed states are recognized based on coupling episode
type with the mixed features specifier: a manic episode
with mixed features, a hypomanic episode with mixed
features, and a depressive episode with mixed features.
There are 4 mixed states if mixed depression is further
categorized as bipolar or unipolar. Mixed features, in
turn, are defined as at least 3 of 6 specific depressive
symptoms for mania and hypomania, and at least 3 of 7
specific manic/hypomanic symptoms for depression (see
below). These “opposite polarity” symptoms must be
“present during the majority of days” of the episode.
In contrast, Kraepelin1 defined 6 mixed states
according to increases (excitation) or decreases (inhibition) in 3 psychological dimensions (mood, thought, and
activity), and differentiated them from pure states, where
mood, thought, and activity were all increased or excited
(mania) or all decreased or inhibited (depression).
According to his classification, there were 6 different
types of mixed states: depressive or anxious mania,
excited depression, unproductive mania, manic stupor,
depression with flight of ideas, and inhibited mania (see
Table 1). In later work, Kraepelin and his apprentice
TABLE 1. Kraepelinian definitions of mixed states
Mixed state
Mood
Motor activity
Thought
Depressive mania
Excited depression
Mania with poverty of thought
Manic stupor
Depression with flight of ideas
Inhibited mania
Depressed
Depressed
Manic
Manic
Depressed
Manic
Manic
Manic
Manic
Depressed
Depressed
Depressed
Manic
Depressed
Depressed
Depressed
Manic
Manic
Wilhelm Weygandt extended this three-dimensional
model of the psyche to a multidimensional one, and
broadened the concept of mixed states to “the infinite
possibilities” of the co-existence of manic and depressive
symptoms.8 That there are in fact an infinite number of
mixed states seems possible when looking at Figure 1:
every possible point of intersection between a mania
dimension and a depression dimension could reflect a
discrete mixed state.
However, there is disagreement in the field as to how
much depression or how many depressive symptoms are
needed for a manic episode to be mixed. Thus, most
authors do not view mania with 1 symptom of depression
(even if it is suicidal ideation) as a mixed state.26 Some
have argued that the presence of 2 depressive symptoms is
enough for a mixed state, as mania with at least 2
depressive symptoms, as compared to mania with no
depressive symptoms or 1 depressive symptom, has been
associated in some studies with female preponderance,
lower frequency of core manic symptoms, higher prevalence of psychotic features, and better response to
valproate over lithium.27–30 Our group,3 Swann et al,31
and DSM-510 have argued that the number of depressive
symptoms required for a manic episode to be definitely
mixed should be at least 3. Our group further suggested
that mania with 2 depressive symptoms could be
considered probable mixed mania, while mania with 1
depressive symptom be considered possible mixed mania.3
There is also disagreement as to which particular
depressive symptoms may count toward a mixed state.
Some proposed definitions of mixed states suggest that
only certain core depressive symptoms be allowed to
count toward a mixed manic state. Our group proposed
that mixed mania be defined as mania with 3 or more of
the following: depressed mood; markedly diminished
interest or pleasure in all, or almost all, activities;
substantial weight gain or increase in appetite; hypersomnia; psychomotor retardation; fatigue or loss of
energy; feelings of worthlessness or inappropriate guilt;
feelings of helplessness or hopelessness; or recurrent
suicidal ideation, a suicide attempt, or a specific plan for
committing suicide.3 We proposed not to include
insomnia, reduced appetite, psychomotor agitation, or
diminished ability to concentrate because of the difficulty in reliably determining if these symptoms are
primarily manic or depressed. As discussed later, a manic
episode with mixed features is defined in the DSM-5 as
syndromal mania with at least 3 of the following
symptoms: prominent dysphoria or depressed mood;
diminished interest in all, or almost all, activities;
psychomotor retardation; fatigue or loss of energy;
feelings of worthlessness or excessive or inappropriate
guilt; and recurrent thoughts of death, recurrent suicidal
ideation, a suicide attempt, or a specific plan for
committing suicide.10 In contrast, Cassidy et al28
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DYSPHORIC MANIA AND MIXED FEATURES SPECIFIER
evaluated 237 manic patients and identified the
following 6 symptoms as best defining mixed bipolar
episodes: depressed mood, anhedonia, guilt, suicide,
fatigue, and anxiety. Thus, criteria sets for mixed
episodes usually include depressed mood, anhedonia,
fatigue, and suicidal ideation but differ regarding
inclusion of anxiety and changes in appetite or weight.
Yet another unresolved issue is how severe a particular depressive symptom must be in ordered to be
considered present in mania. McIntyre et al32 conducted
a post-hoc analysis in 900 bipolar manic patients using
different levels of severity (mild, moderate, and severe)
of certain Montgomery–Åsberg Depression Rating Scale
(MADRS) and Positive and Negative Symptom Scale
(PANSS) items as a proxy for DSM-5 with mixed features.
They found that rates of mixed features decreased as
required severity of depressive symptoms increased.
Specifically, 34%, 18%, and 4.3% of manic patients had
3 or more depressive symptoms of mild, moderate, and
severe intensity, respectively.
But this leaves many unanswered questions. Is 1
depressive symptom during mania enough to be a mixed
state if it is severe and clinically relevant, such as suicidal
ideation or delusional guilt?26 Should other negative or
uncomfortable symptoms that often occur with depression, but are not necessarily considered “core” depressive symptoms, be allowed to count toward a mixed state,
such as irritability, anxiety, obsessions, panic attacks,
hypochondriasis, or binge eating? In other words, should
mixed states denote the co-occurrence of discordant
psychiatric target symptoms, such as manic symptoms
with anxiety, eating, or impulse control disorder
symptoms, as well as core depression symptoms?
This in turn raises the question of what exactly is a
manic versus a depressive symptom. Like the term
bipolar, the term mixed implies that manic and depressive symptoms differ and are even polar opposites. Some
manic and depressive symptoms do in fact appear to be
polar opposites, such as euphoria versus sadness,
increased energy versus fatigue, increased interest and
motivation versus anhedonia and reduced motivation,
increased sex drive versus decreased sex drive, elevated
self-esteem or grandiosity versus reduced self-esteem or
feelings of worthlessness, racing thoughts versus slow
thoughts, and reduced need for sleep versus hypersomnia. These polar opposite symptoms are often viewed as
core symptoms specific to mania (elevated or euphoric
mood, increased energy, grandiosity, and increased sex
drive) or depression (depressed mood, anhedonia, low
energy, hopelessness, guilt, and suicidality). However,
there is considerable overlap between manic and
depressive symptoms. Indeed, manic and depressive
symptoms are generally positively correlated in persons
experiencing both sets of symptoms.33,34 Symptoms that
occur in both mania and depression to considerable
173
degrees are irritability, anxiety, impaired thinking or
concentration, psychomotor agitation, and insomnia.
As a result, these symptoms are sometimes referred
to as nonspecific symptoms. Few definitions of mixed
states include these symptoms, but they are often
included in definitions of dysphoric mania. Mixed states,
however, are frequently characterized by these symptoms, especially irritability, anxiety, and psychomotor
agitation.7,28,35,36 For example, Cassidy et al35 rated 316
bipolar inpatients with mania or mixed episodes on 20
signs and symptoms, and found dysphoric mood, mood
lability, anxiety, guilt, suicidality, and irritability to be
more common in the mixed versus the manic group.
Indeed, several authors have argued that anxiety is a core
symptom of mixed mania.36,37
A mixed state, therefore, may not be 1 unique
condition but rather a group of heterogeneous clinical
entities that vary according to the selected defining
criteria. Different mixed states can be distinguished as to
preponderance of manic or depressive symptoms, or as
Kraepelin postulated, different combinations of manic
(or excited) versus depressive (or inhibitory) mood,
motor activity, or thought. In the first model, there are
at least 2, and possibly 3, mixed states: syndromal mania
with subsyndromal or syndromal depressive symptoms;
syndromal depression with subsyndromal manic symptoms; and the combination of subsyndromal manic and
subsyndromal depressive symptoms. In Kraeplinian
models, there are at least 6 mixed states and perhaps an
infinite number.
Mania with Mixed Features Specifier
A manic episode with mixed features is defined in the
DSM-5 as a full manic episode with at least 3 of the
following depressive symptoms present during the
majority of days of the manic episode: prominent
dysphoria or depressed mood; diminished interest in
all, or almost all, activities; psychomotor retardation;
fatigue or loss of energy; feelings of worthlessness or
excessive or inappropriate guilt; and recurrent thoughts
of death, recurrent suicidal ideation, a suicide attempt,
or a specific plan for committing suicide.10,38,39
The occurrence of mania with syndromal depression
is considered a manic episode with mixed features,
rather than a depressive episode with mixed features
(as in DSM-5) or a mixed episode (as in DSM-IV).
Several empirical studies have compared prevalence
rates of DSM-5 mania with mixed features with DSM-IV
mixed bipolar disorder. Shim et al40 reviewed the medical
records of 331 inpatients with bipolar I disorder, bipolar
II disorder, or bipolar disorder not otherwise specified by
DSM-IV criteria and reclassified them into 4 groups
based on the DSM-5 definition of mixed features.
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174 S. L. MCELROY AND P. E. KECK
Rates of DSM-5 mixed episodes were threefold
higher than DSM-IV mixed episodes. McIntyre et al41
evaluated 255 patients with bipolar I disorder and found
that 20.4% had mania/hypomania with mixed
features compared with 12.9% meeting criteria for a
DSM-IV-defined mixed episode. Thus, as expected,
both studies found that DSM-5 mania with mixed
features was more common than DSM-IV mixed bipolar
disorder.
Several studies have empirically compared manic
patients with and without the DSM-5 mixed feature
specifier. Vieta et al42 gave an online survey consisting of
a 54-item questionnaire to 700 people with bipolar
disorder to examine the phenomenology of mania,
including 4 of the 6 DSM-5-defined mixed features.
During a past manic episode, 39% participants reported
3 or more DSM-5 depressive symptoms. Patients with at
least 3 depressive symptoms had a markedly lower
prevalence of typical manic manifestations and greater
anxiety associated with irritability/agitation. Tohen
et al43 pooled data from 3 placebo-controlled studies of
olanzapine in 447 bipolar I patients with manic or mixed
episodes. Patients were re-categorized into those with
(28%) or without (72%) DSM-5 mixed features, determined by an item score ≥ 1 on 3 or more of 6 Hamilton
Depression Rating Scale (HAM-D) items. Compared with
non-mixed patients, mixed patients had higher total
HAM-D scores and earlier age of onset, and were more
likely to meet DSM-IV criteria for a mixed episode, have
a rapid-cycling course, and were more likely to be
Caucasian. They had similar total Young Mania Rating
Scale (YMRS) scores and rates of psychotic features.
Young and Eberhard44 evaluated 1035 bipolar patients
with a manic episode, and found that 34% met criteria
for DSM-5 mixed features. Bipolar manic patients with
mixed features had more severe symptoms of anxiety,
irritability, and agitation, and a higher incidence of
suicide attempts compared with patients with 2 or fewer
depressive symptoms. Reinares et al45 found that 27% of
169 adult patients with mania had DSM-5 mixed features.
Number of episodes and rates of suicidal ideation, rapid
cycling, and personality disorders were greater in mixed
patients. Seo et al46 retrospectively assessed 334
hospitalized bipolar patients and found the presence of
DSM-5 mixed features to be strongly related to suicidal
behavior. Finally, 2 studies performed post hoc pooled
analyses exploring the presence of DSM-5 mixed features
and pharmacotherapy response. In the first,43 olanzapine was superior to placebo for reducing manic
symptoms in manic patients with and without mixed
features. In the second,32 a pooled analysis of 960
patients with bipolar mania showed that increasing
baseline severity of depressive features was associated
with poorer outcome for olanzapine and placebo but
remained stable for asenapine. All of these studies
concluded that their findings supported the validity of
the DSM-5 mixed features specifier.
Virtually every symptom of depression can occur in
mania. The DSM-5 does not provide a rationale for why
certain depressive symptoms were not included in the
mixed features specifier for mania (or hypomania). Thus,
significant weight loss or weight gain, decreased or
increased appetite, and insomnia or hypersomnia were
not listed as potential mixed symptoms, even though they
are criteria for the diagnosis of a depressive episode.
Perhaps these symptoms were considered nonspecific or
non-polar opposite symptoms, but empirical data to
support this possibility are lacking. Indeed, Malhi47 has
argued that the symptoms of the DSM-5 mixed features
specifier are themselves nonspecific. Moreover, DSM-5
has other specifiers that contain primarily depressive
symptoms, including melancholic and atypical features.
While atypical features can be applied only to a major
depressive episode, this is not the case for melancholic
features, which include depression that is regularly worse
in the morning, marked psychomotor agitation, and
significant anorexia or weight loss. As these symptoms
are not included in the mixed features specifies, it is
possible that a patient can have mania with melancholic
features and not meet criteria for mixed features.
The DSM-5 mixed feature specifier also does not
capture the importance of anxiety as a core symptom of
mixed states. Rather, there is a separate specifier for
“anxious distress,” which is to be used if 2 of the
following 5 symptoms are present: feeling keyed up or
tense, feeling unusually restless, difficulty concentrating
because of worry, fear that something awful will happen,
and feeling like the individual will lose control of him- or
herself (p 149). Thus, although mania with 2 depressive
symptoms and 1 anxious distress symptom might best be
viewed clinically as a mixed state, it would not be
classified as such by DSM-5.
Therefore, instead of specifying a certain number of
certain types of depressive symptoms be present, it might
be better to use scales, including self-report tools, to
measure severity of depressive (and other unpleasant)
symptoms in patients with mania—without regard
to whether symptoms are primarily manic or
depressed.48–50 In one study, 94 inpatients with DSMIV-defined mania were evaluated with the HAM-D and
the self-rated Carroll Depression Scale.50 Self-rated
depressive symptoms were highly concordant with
observer-rated depressive symptoms. Eight dysphoric
symptoms discriminated mixed from pure episodes on
both scales: depressed mood, pathological guilt, suicidal
tendency, anhedonia, psychomotor agitation, psychic
anxiety, somatic anxiety, and general somatic symptoms
(fatigue). The authors concluded that patient self-report
rating was another way to recognize depressive symptoms during mania.
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DYSPHORIC MANIA AND MIXED FEATURES SPECIFIER
Conclusion
The terms dysphoric mania, mixed state, and mania with
mixed features are overlapping constructs that have
subtle yet important differences. All describe the
co-occurrence of manic and depressive symptoms.
Dysphoric mania can refer to mania with prominent
depression (or mania with mixed features) or mania that
is unpleasant due to irritability, anxiety, or depression—
depending on how the term dysphoria is defined. Mixed
state is a broad term that usually means a period of mood
disturbance that has some combination of manic or
depressive symptoms. Most descriptions of mixed states
argue that there are there are different types. By contrast,
mania with mixed features (according to DSM-5) is a
manic episode with at least 3 of 6 specified depressive
symptoms; it is a type of mixed state, another term for
depressive mania, and depending on the definition of
dysphoria, is also another term for dysphoric mania.
However, it does not necessarily encompass other types
of unpleasant mania, such as mania with prominent
irritability and/or anxiety.
Some have argued that the DSM-5 mixed feature
specifier represents a nosological advance and that more
people with mixed states will be properly diagnosed.
Though it may be an advance over DSM-IV, it is not
necessarily an advance over historical (ie, Kraeplinian)
conceptualizations of mixed states. Moreover, the definition of both a manic episode and hypomanic episode in
DSM-5 is narrower than in DSM-IV because “persistently
increased goal-directed activity or energy” (p 124) is
required, as well as elevated, expansive, or irritable
mood.51 Retrospective analyses have found higher rates
of mania with mixed features than DSM-IV mixed bipolar
disorder, which suggests that the DSM-5 mixed specifier
will enable proper diagnosis of more patients.40,41
However, these studies did not re-evaluate whether their
bipolar patients’ abnormal moods were also associated
with increased goal-directed activity or energy. Thus, by
requiring an extra stem criteria for mania/hypomania, it
is unknown if the DSM-5 mixed features specifier will in
fact lead to greater recognition of mixed manic states.
Conversely, it has been argued that DSM-IV mixed
symptoms are nonspecific and will lead to falsely elevated
diagnosis of mixed states and additional diagnostic
uncertainty.47
Great strides have been made in recognizing, describing, and defining mixed states. The DSM-5 mixed features
specifier is likely a step forward, but further empirical
study is essential and further refinement is likely.
Potential limitations of the DSM-5 mixed features
specifier are that they do not account for data showing
that 2 symptoms of depression are enough to differentiate
mixed from manic states, and that key symptoms, such as
anxiety, are not included. Perhaps the 2 most important
175
concepts are that mania and depression are not polar
opposite states which can combine in various ways, and
that mania, like depression, is often unpleasant, and can
be unpleasant in a variety of ways. The attempt to define a
mixed state, therefore, should not become so precise that
it becomes artificial and excludes the innumerable mixed
states that occur in nature. Indeed, Akiskal et al27 noted
that depression during mania ran “along a spectrum that
is without firm cutoffs” (p 182).
Disclosures
Susan McElroy reports personal fees from Bracket,
personal fees from F. Hoffmann-La Roche, Ltd., grants
and personal fees from Myriad, grants and personal
fees from Naurex, personal fees from Novo Nordisk,
grants and personal fees from Shire, grants and personal
fees from Sunovion, grants from Agency for Healthcare
Research & Quality (AHRQ), grants from Alkermes,
grants from Cephalon, grants from Forest, grants from
Marriott Foundation, and grants from Takeda Pharmaceutical Company Limited, outside of the submitted
work. Paul Keck reports personal fees from Merck,
personal fees from ProPhase, grants and personal
fees from Shire, personal fees from Supernus, and
grants from Marriott Foundation, outside of the
submitted work.
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