1.
Mood disorders
This chapter discusses disorders characterized by abnormalities
of mood: namely, depression,
mania, or both. Included here are descriptions of a wide variety
of mood disorders that occur over a
broad clinical spectrum. Also included in this chapter is an
analysis of how monoamine
neurotransmitter systems are hypothetically linked to the
biological basis of mood disorders. The
three principal monoamine neurotransmitters are norepinephrine
(NE; also called noradrenaline or
NA), discussed in this chapter, dopamine (DA), discussed in ,
and serotonin (also calledChapter 4
5-hydroxytryptamine or 5HT), discussed in .Chapter 5
The approach taken here is to deconstruct each mood disorder
into its component symptoms,
followed by matching each symptom to hypothetically
malfunctioning brain circuits, each regulated by
one or more of the monoamine neurotransmitters. Genetic
regulation and neuroimaging of these
hypothetically malfunctioning brain circuits are also discussed.
Coverage of symptoms and circuits of
mood disorders in this chapter is intended to set the stage for
understanding the pharmacological
concepts underlying the mechanisms of action and use of
antidepressants and mood stabilizing
drugs, which will be reviewed in the following two chapters (
and ).Chapters 7 8
Clinical descriptions and criteria for how to diagnose disorders

2.
of mood will only be mentioned in
passing. The reader should consult standard reference sources
for this material.
Description of mood disorders
Disorders of mood are often called affective disorders, since
affect is the external display of mood,
an emotion that is felt internally. Depression and mania are
often seen as opposite ends of an
affective or mood spectrum. Classically, mania and depression
are "poles" apart, thus generating the
terms depression (i.e., patients who just experience the or
depressed pole) and unipolar down
(i.e., patients who at different times experience either the [i.e.,
manic] pole or the bipolar up down
[i.e., depressed] pole). Depression and mania may even occur
simultaneously, which is called a
mood state. Mania may also occur in lesser degrees, known as ,
or switch somixed hypomania
Figure 6-1. . Bipolar disorder is generally characterized by four
types of illness episodes: manic,Mood episodes
major depressive, hypomanic, and mixed. A patient may have
any combination of these episodes over the
course of illness; subsyndromal manic or depressive episodes
also occur during the course of illness, in which
case there are not enough symptoms or the symptoms are not
severe enough to meet the diagnostic criteria for
one of these episodes. Thus the presentation of mood disorders
can vary widely.
fast between mania and depression that it is called .rapid
cycling

3.
Mood disorders can be usefully visualized not only to contrast
different mood disorders from one
another, but also to summarize the course of illness for
individual patients by showing them mapped
onto a mood chart. Thus, mood ranges from hypomania to mania
at the top, to euthymia (or normal
mood) in the middle, to dysthymia and depression at the bottom
( ). The most common andFigure 6-1
readily recognized mood disorder is major depressive disorder (
), with single or recurrentFigure 6-2
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episodes. Dysthymia is a less severe but long-lasting form of
depression ( ). Patients with aFigure 6-3
major depressive episode who have poor inter-episode recovery,
only to the level of dysthymia,
followed by another episode of major depression are sometimes
said to have "double depression,"
alternating between major depression and dysthymia, but not
remitting ( ).Figure 6-4
Patients with bipolar I disorder have full-blown manic episodes
or mixed episodes of mania plus
depression, often followed by a depressive episode ( ). When
mania recurs at least fourFigure 6-5
times a year, it is called rapid cycling ( ). Patients with bipolar I
disorder can also haveFigure 6-6A
rapid switches from mania to depression and back ( ). By

4.
definition, this occurs at leastFigure 6-6B
four times a year, but can occur much more frequently than that.
Bipolar II disorder is characterized by at least one hypomanic
episode that follows a depressive
episode ( ). Cyclothymic disorder is characterized by mood
swings that are not as severeFigure 6-7
as full mania and full depression, but still wax and wane above
and below the boundaries of normal
mood ( ). There may be lesser degrees of variation from normal
mood that are stable andFigure 6-8
persistent, including both depressive temperament (below
normal mood but not a mood disorder)
and hyperthymic temperament (above normal mood but also not
a mood disorder) ( ).Figure 6-9
Temperaments are personality styles of responding to
environmental stimuli that can be heritable
patterns present early in life and persisting throughout a
lifetime; temperaments include such
independent personality dimensions as novelty seeking, harm
avoidance, and conscientiousness.
Some patients may have mood-related temperaments, and these
may render them vulnerable to
mood disorders, especially bipolar spectrum disorders, later in
life.
Figure 6-2. . Major depression is the most common mood
disorder and is defined by theMajor depression
occurrence of at least a single major depressive episode,
although most patients will experience recurrent
episodes.
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5.
distribution.
Figure 6-3. . Dysthymia is a less severe form of depression than
major depression, but long-lastingDysthymia
(over 2 years in duration) and often unremitting.
Figure 6-4. . Patients with unremitting dysthymia who also
experience the superimpositionDouble depression
of one or more major depressive episodes are described as
having double depression. This is also a form of
recurrent major depressive episodes with poor inter-episode
recovery.
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Figure 6-5. . Bipolar I disorder is defined as the occurrence of
at least one manic or mixedBipolar I disorder
(full mania and full depression simultaneously) episode.
Patients with bipolar I disorder typically experience
major depressive episodes as well, although this is not
necessary for the bipolar I diagnosis.
Figure 6-6
A. . The course of bipolar disorder can be rapid cycling, which
means that at least fourRapid cycling mania
episodes occur within a 1-year period. This can manifest itself
as four distinct manic episodes, as shown here.

6.
Many patients with this form of mood disorder experience
switches much more frequently than four times a year.
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B. . A rapid cycling course (at least four distinct mood episodes
within 1 year) can alsoRapid cycling switches
manifest as rapid switches between manic and depressive
episodes.
Figure 6-7. . Bipolar II disorder is defined as an illness course
consisting of one or moreBipolar II disorder
major depressive episodes and at least one hypomanic episode.
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Figure 6-8. . Cyclothymic disorder is characterized by mood
swings between hypomaniaCyclothymic disorder
and dysthymia but without any full manic or major depressive
episodes.
Figure 6-9. . Not all mood variations are pathological.
Individuals with depressive temperamentTemperaments
may be consistently sad or apathetic but do not meet the criteria

7.
for dysthymia and do not necessarily
experience any functional impairment. However, individuals
with depressive temperament may be at greater risk
for the development of a mood disorder later in life.
Hyperthymic temperament, in which mood is above normal
but not pathological, includes stable characteristics such as
extroversion, optimism, exuberance, impulsiveness,
overconfidence, grandiosity, and lack of inhibition. Individuals
with hyperthymic temperament may be at greater
risk for the development of a mood disorder later in life.
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Mood stabilizers
In this chapter, we will define mood stabilizers and will review
the various pharmacological
mechanisms of action proposed for mood stabilizers. We will
also discuss concepts about how to use
these drugs in clinical practice, including strategies for what to
do if initial treatments fail and how to
rationally combine mood stabilizers with another drug. Our
treatment of mood stabilizers in this
chapter is at the conceptual level, not at the pragmatic level.
The reader should consult standard
drug handbooks (such as the companion Stahl’s Essential
Psychopharmacology: the Prescriber’s
) for details of doses, side effects, drug interactions, and other

8.
issues relevant to theGuide
prescribing of these drugs in clinical practice.
Definition of a mood stabilizer: a labile label
"There is no such thing as a mood stabilizer" - FDA
"Long live the mood stabilizers" - prescribers
What is a mood stabilizer? Originally, a mood stabilizer was a
drug that treated mania and prevented
recurrence of mania, thus "stabilizing" the manic pole of bipolar
disorder. More recently, the concept
of mood stabilizer has been defined in a wide-ranging manner,
from "something that acts like
lithium," to "an anticonvulsant used to treat bipolar disorder,"
to "an atypical antipsychotic used to
treat bipolar disorder," with antidepressants considered as
"mood de-stabilizers." With all this
competing terminology, and with the number of drugs for the
treatment of bipolar disorder exploding,
the term has become so confusing that regulatory authorities
and some experts nowmood stabilizer
suggest that it is best to use other terms for agents that treat
bipolar disorder.
Rather than the term , some would argue that there are drugs
that can treat any ormood stabilizers
all of four distinct phases of the illness ( and ). Thus, a drug
can be "mania-minded"Figures 8-1 8-2
and "treat from above" to reduce symptoms of mania, and/or
"stabilize from above" to prevent
relapse and recurrence of mania ( ). Furthermore, drugs can be
"depression-minded" andFigure 8-1
"treat from
Figure 8-1. . Although the ideal "mood stabilizer" would treat

9.
both mania and bipolarMania-minded treatments
depression while also preventing episodes of either pole, in
reality there is as yet no evidence to suggest that
any single agent can achieve this consistently. Rather, different
agents may be efficacious for different phases of
bipolar disorder. As shown here, some agents seem to be
"mania-minded" and thus able to "treat from above"
and/or "stabilize from above" - in other words, to reduce and/or
prevent symptoms of mania.
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Figure 8-2. . Although the ideal "mood stabilizer" would treat
both mania andDepression-minded treatments
bipolar depression while also preventing episodes of either pole,
as mentioned for , in reality there isFigure 8-1
as yet no evidence to suggest that any single agent can achieve
this consistently. Rather, different agents may
be efficacious for different phases of bipolar disorder. As
shown here, some agents seem to be
"depression-minded" and thus able to "treat from below" and/or
"stabilize from below" - in other words, to reduce
and/or prevent symptoms of bipolar depression.
below" to reduce symptoms of bipolar depression, and/or
"stabilize from below" to prevent relapse
and recurrence of depression ( ). Not all drugs proven to work
in bipolar disorder have allFigure 8-2
four therapeutic actions. In this chapter, we will discuss agents
that have one or more of these

10.
actions in bipolar disorder, and for historical purposes and
simplification, refer to any of these agents
as "mood stabilizers."
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Bipolar Therapy
Client of Korean Descent/Ancestry
BACKGROUND INFORMATION
The client is a 26-year-old woman of Korean descent who
presents to her first appointment following a 21-day
hospitalization for onset of acute mania. She was diagnosed
with bipolar I disorder.
Upon arrival in your office, she is quite “busy,” playing with
things on your desk and shifting from side to side in her chair.
She informs you that “they said I was bipolar, I don’t believe
that, do you? I just like to talk, and dance, and sing. Did I tell
you that I liked to cook?”
She weights 110 lbs. and is 5’ 5”
SUBJECTIVE
Patient reports “fantastic” mood. Reports that she sleeps about 5
hours/night to which she adds “I hate sleep, it’s no fun.”
You reviewed her hospital records and find that she has been
medically worked up by a physician who reported her to be in
overall good health. Lab studies were all within normal limits.
You find that the patient had genetic testing in the hospital
(specifically GeneSight testing) as none of the medications that
they were treating her with seemed to work.

11.
Genetic testing reveals that she is positive for CYP2D6*10
allele.
Patient confesses that she stopped taking her lithium (which was
prescribed in the hospital) since she was discharged two weeks
ago.
MENTAL STATUS EXAM
The patient is alert, oriented to person, place, time, and event.
She is dressed quite oddly- wearing what appears to be an
evening gown to her appointment. Speech is rapid, pressured,
tangential. Self-reported mood is euthymic. Affect broad.
Patient denies visual or auditory hallucinations, no overt
delusional or paranoid thought processes readily apparent.
Judgment is grossly intact, but insight is clearly impaired. She
is currently denying suicidal or homicidal ideation.
The Young Mania Rating Scale (YMRS) score is 22
RESOURCES
§ Chen, R., Wang, H., Shi, J., Shen, K., & Hu, P. (2015).
Cytochrome P450 2D6 genotype affects the pharmacokinetics of
controlled-release paroxetine in healthy Chinese subjects:
comparison of traditional phenotype and activity score systems.
European Journal of Clinical Pharmacology, 71(7), 835-841.
doi:10.1007/s00228-015-1855-6
Select what the PMHNP should do:
Begin Lithium 300 mg orally BID
Begin Risperdal 1 mg orally BID
Begin Seroquel XR 100 mg orally at HS