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Mixed State.pptx
1. The concept of Mixed state in Bipolar disorder
From Kraepelin to DSM-5
The untold Story
BY
Mostafa Mahmoud Elsabban
ASS. Lecturer of Psychiatry
Al Azhar University
2. Methods
A search in MEDLINE and PUBMED
was performed using the
following keywords:
• Bipolar disorder,
• Mixed state/s,
• Mixed episode/s,
• Mixed mania,
• Dysphoric mania,
• Mixed depression,
• Agitated depression
3. Introduction
Mixed states, in which
symptoms of depression and
mania
combine, represent a complex
and often confusing aspect
of the clinical presentation of
bipolar illness.
Indeed, the risk of suicide is
particularly associated with
mixed states So, correct
identification of mixed states has
important clinical relevance
4. Introduction
• Mixed states are essentially considered the co-presence of symptoms of
opposite polarity.
• This apparently simple concept, however, in reality poses several problems in
terms of psychopathology and diagnostic categorization, due to high grades
of polymorphism of clinical features of mixed states.
• In contrast, the inability to recognize this clinical entity which is
frequent may lead to worsening of symptoms due to
inappropriate therapy.
5. “Pre-Kraepelinian” authors
Textbook of Disturbances of
Mental Life
“Mixed states of exaltation
and depression”
• Melancholia with
destructive impulses.
Griesinger
1868
Heinroth
1818
Falret
1854
• la folie circulaire.
• Noted depressive Sx often
observed before, during,
and after manic episodes.
6. Kraepelin (1921) and the later periods
• The origin of the
concept of mixed
states belongs to the
German psychiatrist
Emil Kraepelin
• Kraepelin viewed
mixed states as a
‘Third polarity’ of
manic-depressive
disorder
7. Kraepelin(1921)
Kraepelin identified 6
basic types of mixed
states depending on
combination of 3
different domains
• The three domains
consisted of :
1. Mood,
2. Course of thought
and
3. Psychomotor
changes.
Kraepelin conceptualized mixed states as
primarily transitional phenomena
9. Kraepelin criteria for mixed states
1. “Depressive mania” (depressed mood, flight of ideas and hyperactivity),
2. “Excited depression” (depressed mood, inhibition of thought and
hyperactivity),
3. “Unproductive mania” (euphoria, inhibition of thought and
hyperactivity),
4. “Manic stupor” (euphoria, inhibition of thought and apathy),
5. “Depression with flight of ideas” (depressed mood, flight of ideas and
apathy) and
6. “Inhibited mania” (euphoria, flight of ideas and apathy).
Manic stupor, according to Kraepelin’s student and colleague Weygandt is
the most important of the mixed states which is characterized by
psychomotor retardation (specifically stupor) as the prominent feature.
10. Kraepelin criteria for mixed states
• Later, Kraepelin and Weygandt
recognized 2 basic types of
mixed states:
1. “Transitional” forms and
2. “Autonomous” forms
• According to Kraepelin, the
latter form characterized by:
1. The most unfavorable form of
manic-depressive disorder,
2. Presenting with a lengthy
course and
3. The tendency to become
chronic.
11. Criticism to Kraepelin criteria for mixed states
Described ‘mixed melancholia’,
characterized as a “Querulant
mania” or “Nagging depression”
Negated the existence of this
diagnostic category, viewing it
as a simple transitional phase
Karl Jaspers 1913 Kurt Schneider 1967
12. Current classification systems
• The concept of Mixed episode in both
systems is the combination of manic and
depressive symptoms for 1 week.
• This means that the presence of subthreshold of symptoms with opposite
polarity is not considered to diagnose mixed state.
• Lastly, diagnosis of a mixed episode is not considered if drug/substance
indued or due to general medical conditions is not allowed
13. Mixed Manic States
• Simultaneous presence of rapid cycling (within several
minutes) of a variable number of depressive symptoms in
the context of a (hypo)manic episode.
• The presence of symptoms for at least 24 hours is also
required to diagnose mixed mania.
• Different diagnostic thresholds:
1. Certain diagnosis of Mixed manic state( > 3 depressive
symptoms,
2. Probable diagnosis (presence of 2 symptoms) and
3. Possible diagnosis (1 symptom present) but not one of
the following Sx : psychomotor agitation, insomnia and
loss of appetite/ weight loss.
McElroy et al.,2005
proposed working
criteria for the
identification of
mixed mania
14. Mixed Manic states
Cassidy et al.,2000
distinguished mixed
mania from pure mania
according to the
presence of at least 2 of
6 depressive symptoms
• Depressed mood,
• Anhedonia,
• Anxiety,
• Guilt,
• Suicidal ideation and
• Low energy.
15. Mixed Manic States
Akiskal et al., 1998 published a
study that compared the prevalence
of mixed states in patients
recruited according to DSM-IV
criteria to that
observed using less restrictive
criteria (manic episode + at least 2
depressive Sx).
Results
They noted a substantial difference
between the two definitions, in
that the prevalence was 6.7% in
the former and 37.5% in the latter.
Akiskal
Akiskal proposed that mixed states arise when
temperament and episodes are opposite in polarity ie
1. Mixed mania arising from a depressive temperament and
2. Mixed depression arising from a hyperthymic
temperament.
16. Mixed Depressive States
It was concluded that the mixed state can be defined using 3 different
approaches:
1. From a categorical point of view through identification of at least 2
depressive Sx,
2. From a psychometric standpoint with a score >10 on the HDRS and
3. From a dimensional point of view through identification of a dominant
temperament.
Akiskal et al., 1998
Conclusion
1- Depressive temperament 2- Hyperthymic temperament
3- Cyclothymic temperament 4- A worrying temperament
Akiskal
17. The Role of Temperament
Temperament Affect
Type B-I Depressive Psychotic
Mania
Type B-II Cyclothymic MDE
Type B-III Hyperthymic MDE
Akiskal proposed 3 types
of mixed states
depending on the type of
interaction of
temperament/affective
interaction
18. Mixed Depressive States
Koukopoulos et al,
1999 suggested that all
types of agitated
depressions should be
called “mixed
depression.”
• They proposed that the
following diagnostic criteria be
used:
1. Major depressive episode and
2. At least 2 of the three
symptoms of :
Motor agitation,
Psychic agitation or intense
inner tension, and
Racing or crowded thoughts.
Koukopoulos
19. Mixed Depressive States
Koukopoulos
The Primacy
of Mania
• Koukopoulos (2006) has made a novel suggestion about
the relationship between mania and depression that may
explain the occurrence and frequency of mixed states.
• According to his hypothesis, mania is primary, with
depression being the consequence of a preceding mania.
21. DSM-5 & DSM 5 TR
• Eliminate the category “Mixed Episode”.
• Replace it with the specifier “with mixed features”….
with at least 3 symptoms with opposite polarity
(Contra polar)
However, the diagnostic criteria for mixed features
diagnosis exclude “overlapping symptoms” of :
• Irritability & Distractibility for ME
• Insomnia & Psychomotor agitation for MDE
as defining of the opposite polarity due to the presence
of these symptoms in both mania and depression.
22. The exclusion of overlapping symptoms increases the
specificity of the diagnosis at the expense of sensitivity
and possibly face validity insofar as most individuals
presenting with an MDE and mixed features do present
with “overlapping symptoms.”
23. ICD-11
• Similar to those in the DSM-5 (Contra Polar)
• But the term “Mixed episode” is maintained, which
is further divided into 2 subtypes depending on the
presence of psychotic symptoms.
• Very Rapid alternation of symptoms
26. Conclusions
• In the present review, the complex problem of diagnosis of mixed states was
examined in detail.
• Mixed states have now gained increased attention, and it should be kept in
mind that they are relevant for the clinical practice of every psychiatrist.
• Not all patients with depression (as part of bipolar disorder or major
depressive disorder) should be prescribed an antidepressant.
• All patients who receive antidepressants for an MDE should be monitored
for signs of abnormal behavioral activation or psychomotor acceleration.
