Download Bipolar Disorder CPM - Intermountain Healthcare

Care Process Model
M
MA
O RN CT HH
22001156
D
MEENNTT O
A FN D D E S I G N O F
M EAVNEALGOEPM
Care Process
Models
Bipolar
Disorder
2015
6 Update
This care process model (CPM) was developed by Intermountain Healthcare’s Behavioral Health Clinical Program as part of a care
management system for bipolar disorder. The CPM recommends screening, diagnosis, and treatment processes to improve care
and outcomes for patients with bipolar disorder. Related tools — including evaluation forms, reference tools, and patient education
handouts — support implementation of these recommended processes.
WHAT’S INSIDE?
Why Focus ON BIPOLAR DISORDER?
• High prevalence. A 2005 report on National Comorbidity Survey Replication
(NCS-R) data estimated that bipolar disorder affects about 5.7 million
American adults, or about 2.6% of the population 18 years and older (1-year
prevalence).KES1 The same study noted a lifetime prevalence of 3.9%, suggesting
the chronic nature of this illness.KES2
• Inadequate detection. Estimates from surveys of people who screen positive
for bipolar disorder note that clinicians misidentify their condition more
than half of the time.FRY1, SUP1 Patients may visit several clinicians before being
correctly diagnosed. Many suffer for a decade or more before being diagnosed
and appropriately treated.BIR Misidentification leads to increased hospitalization
and emergency room visits and higher healthcare costs.BIR, HIR1, PEE
• Inappropriate use of antidepressants. When providers mistake bipolar
depression for unipolar depression, they are likely to treat using only
antidepressants.FRY1, HIR1, PEE In patients with bipolar disorder, using antidepressants
alone (unopposed by mood-stabilizing medications) can induce mania, mixed
states, and more severe rapid cycling varieties of this disorder.EIMA, GYU Medications
with mood-stabilizing properties should be used to treat this illness.
• Poor treatment adherence. Patients with bipolar disorder typically have low
adherence to treatment; reported non-adherence for long-term prophylactic
pharmacotherapy is about 40%.LIN Psychosocial interventions can significantly
improve adherence.
• Risk of death. Bipolar disorder can be a debilitating disease with a high risk of
death by suicide (19%).GOO People with this disorder rate their illness as “severe”
83% of the time — much higher than they rate the severity of other mental
illnesses (22%) — and have trouble functioning in many areas of life.KES2, EIMA
Treatment can significantly reduce suicide rates, even in those who are more
severely ill.ANG
• Lost productivity. According to a recent study funded by the National
Institute of Mental Health (NIMH), bipolar disorder costs the U.S. workplace
$14.1 billion annually; this is nearly half as much as lost-productivity costs due
to unipolar depression, although unipolar depression is more than six times as
prevalent.KES3 Over the past 20 years, the World Health Organization (WHO)
has consistently rated bipolar disorder among the top 10 leading causes of
disability in the world.WHO
UNDERSTANDING BIPOLAR
DISORDER. . . . . . . . . . . . . . . . . . . . . 2
SCREENING AND DIAGNOSIS. . . . . . . 4
ALGORITHM 1: Diagnosis. . . . . . . . . . . 4
Discussion: The need for consistent
screening and diagnosis. . . . . . . . . . . . 5
TREATMENT FOR ADULTS. . . . . . . . 11
ALGORITHM 2: Treatment . . . . . . . . . 11
Medications. . . . . . . . . . . . . . . . . . . . . 12
Psychosocial Therapy . . . . . . . . . . . . . 19
Electroconvulsive Therapy (ECT). . . . . 20
Care Management . . . . . . . . . . . . . . . 20
FOLLOW-UP AND MAINTENANCE. . 21
Follow-up Schedule. . . . . . . . . . . . . . . 21
Remission and Maintenance. . . . . . . . 21
Outcomes Assessment Tools. . . . . . . . 22
BIPOLAR DISORDER IN CHILDREN
AND ADOLESCENTS. . . . . . . . . . . . . 24
Symptom expression. . . . . . . . . . . . . . 24
Differential diagnosis and
comorbidity. . . . . . . . . . . . . . . . . . . . . 25
Treatment guidelines. . . . . . . . . . . . . . 25
PATIENT AND FAMILY EDUCATION. . 28
RESOURCES AND REFERENCES. . . . 29
GOALS /MEASUREMENTS
• Improve identification of bipolar
disorder by promoting and measuring use
of validated screening tools such as the Mood
Disorder Questionnaire (MDQ).
• Improve treatment by reducing
the use of unopposed antidepressants and
increasing appropriate use of mood stabilizers.
• Improve outcomes assessment using
both symptom-specific and functional
measures to determine treatment impact.
Throughout this CPM, the icon at right
indicates an Intermountain measure.
MANAGEMENT OF BIPOL AR DISORDER
DIMENSIONS OF IMPAIRMENT
• Moods. Extreme mood episodes are the
hallmark of this disorder.
• Thoughts. Several studies detail cognitive
impairment in bipolar disorder—in
particular, problems with memory and
executive function, attention and verbal
skills.NOR
• Actions. Impulsivity and excessive
risk-taking are common, especially during
episodes of mania. People can find
themselves acting in ways that aren’t
characteristic for them and don’t represent
their personal values. Excessive spending,
sudden travel, uncharacteristic substance
abuse and sexual promiscuity are common
expressions of bipolar impulsivity.
MAJOR TYPES OF
BIPOLAR DISORDER
Bipolar I Disorder:
Diagnosis requires at least one lifetime
manic or mixed episode (causing significant
impairment); most people with bipolar I
have also had one or more episodes of
major depression.
Bipolar II Disorder:
Diagnosis requires at least one lifetime
episode of hypomania (causing less significant
impairment) and at least one episode of
major depression.
Cyclothymia:
Diagnosis requires at least 2 years (only
1 year in children and adolescents) of
clinically significant distress/impairment in
key areas of functioning (at work, at school,
at home, with friends, etc.). This period is
characterized by numerous periods where the
person experiences hypomanic and depressive
symptoms that fail to meet the full criteria of
either hypomania or major depression.
2 MARCH 2016
UNDERSTANDING BIPOLAR DISORDER
Bipolar disorder, previously called manic-depressive disorder, is a chronic biological
disease, not a character defect or moral failing. People with this illness experience
changes in their mood and ability to think and to function. At other times they can be
completely without signs or symptoms of their illness. Depression is the most common
mood in bipolar disorder but people also experience hallmark periods of euphoria and
irritability. It is not unusual for these mood states to overlap and profoundly disrupt a
person’s work, school, home, and social life. The risk of suicide for this illness is very
high but does decrease with treatment.ANG
Genetic basis
The exact cause of bipolar disorder is not known. Recent studies have identified that
a patient’s genetic predisposition to the disorder may derive from those genes that are
involved in hormone regulation, calcium channels, secondary messenger systems, and
glutamate signaling.NUR The risk of bipolar disorder increases if a parent or sibling suffers
from the disorder.CRA, LIC First-degree biological relatives of someone with bipolar I
disorder have a 4­– 24% chance of developing bipolar I disorder, a 1 – 5% chance of
developing bipolar II disorder, and a 4 – 24% chance of having unipolar depression.APA1
When one identical twin has bipolar disorder, the other twin is 7 – 8 times more likely
to have it than a fraternal twin.KIE, MCG
Bipolar depression versus unipolar depression
Depressive symptoms are the most common in bipolar disorder. They can appear
identical to those of a person with unipolar depression. More than 10% of patients with
depression will go on to experience a mania or hypomania episode in the next decade.
AKI
Unlike unipolar depression, which is more common in women than men, bipolar I
disorder is equally common in men and women.APA1
• Discriminators of unipolar versus bipolar depression: Factors suggestive of bipolar
depression include an onset before the age of 25, a parent or sibling with bipolar
disorder, a history of psychotic depression, postpartum depression, multiple recurrent
depressive episodes, or a history of mania or hypomania induced by antidepressants.
Further, bipolar depression is often associated with “atypical” symptoms including
hypersomnia and hyperphagia. Depression frequently occurs with partial or complete
mania symptoms such as racing thoughts, irritability, impulsivity, and psychosis.PER
• Predictors of progression from unipolar to bipolar I or II depression: Among patients
who have major depression and go on to develop bipolar disorder, a more acute,
severe, and psychotic episode predicts bipolar I disorder (about 4% of depressives
followed long term) and mood lability or temperamental instability predicts bipolar II
disorder (about 9% of depressives followed long-term).AKI
Bipolar spectrum
Bipolar disorder and unipolar depression seem to exist at two ends of a spectrum.
In the middle of the spectrum are patients with major depression and some symptoms
associated with bipolar disorder (e.g., racing thoughts). These patients have more risk
factors of bipolar disorder (e.g., early age of depression onset and family history) than
those suffering unipolar depression without those symptoms. If these patients do not
respond to standard depression treatment, clinicians should consider medications with
mood stabilizing properties.
Family history studies support this view of the bipolar spectrum. Patients with bipolar I
disorder may have offspring with bipolar I, bipolar II, or unipolar depression, whereas
patients with bipolar II disorder tend to have offspring with bipolar II or unipolar
depression.BEN
©2007–2016 INTERMOUNTAIN HEALTHCARE. ALL RIGHTS RESERVED.
MARCH 2016
MANAGEMENT OF BIPOL AR DISORDER
Variety in symptom expression
WHAT IS MANIA?
The average age of onset of bipolar disorder is in the teen years to early 20s.
The
first episode can be either a depressive or manic episode. Transitioning from a
manic/hypomanic episode to a depressive episode or from a depressive episode to a
manic/hypomanic is considered one “cycle” of bipolar disorder. The episodes in each
cycle can vary from mild to severe in intensity. They can be interspersed by long periods
of euthymic mood or be followed immediately by another mood cycle. Disability in
functioning is usually related to how frequently people cycle and how severe their
symptoms are during their cycle.
KES2
• Proportion of time spent in various mood states. People with bipolar disorder
suffer reoccurring mood symptoms throughout their life. One study tracked patients’
moods weekly for over a decade for the two major types of the illness (bipolar I
disorder and bipolar II disorder). In this study, most of the time symptomatic was
spent depressed and a minority of time was spent either manic or hypomanic.JUD1,JUD2
These results are shown below:
Cycling/Mixed
Manic/Hypomanic
(6%)
(1%)
Cycling/Mixed
(2%)
Manic/Hypomanic
(9%)
Asymptomatic
Asymptomatic
Depressed
(53%)
Depressed
(32%)
Bipolar I
146 patients
followed 12.8 years
(46%)
(50%)
Bipolar II
86 patients
followed 13.4 years
• Severity of symptoms. Over the long-term course, the majority of symptoms
are subsyndromal or not severe enough to diagnose as major depression or as overt
mania. Nevertheless, subsyndromal depressive symptoms can be significantly
disabling. Hypomanic episodes are often rated by patients as causing no disability
(and some feel it to be a state of superior functioning). Severe manic symptoms are as
disabling as severe depressive symptoms.
• Combinations of symptoms. It is common to have symptoms of mania/
hypomania and depression at the same time. An estimated 40% of manic episodes
and more than half of all hypomanic episodes are associated with significant
depressive symptoms.SUP2 Some people with bipolar disorder experience mixed
states — episodes in which they have symptoms that meet criteria for both mania
and depression nearly every day for a 1-week period or longer. Mixed episodes
are common and can be very severe. They are also associated with less frequent
remissions, poorer response to mood stabilizers, increased suicidal ideation/behavior,
and more comorbidities (including substance abuse). Use of antidepressants is also
associated with increased incidence of mixed episodes.HIR1, GOL1, PRI, SHA
• Frequency of episodes. Cycling varies from an average of 1 cycle every 3 years to
the severe variation called rapid cycling. Rapid cycling is when people cycle between
mood episodes four or more times a year. This variety can be either bipolar I or
bipolar II. The typical patient is bipolar II and female. In this variant, there appears
to be a continuous distribution from limited mood cycling to the extreme of intraday (ultraradian) cycling. This form of the illness may be less sensitive to the effects
of lithium carbonate. Factors associated with rapid cycling include the following:GOL1,
Mania is defined as a mental state
characterized by rapid thoughts, irritable/
euphoric mood, increased activity,
talkativeness, and/or impaired judgment.
Manic or hypomanic patients exhibit these
types of symptoms:
• Activity or stimulation: Symptoms
are similar to those experienced when
one takes excessive doses of stimulant
medications, such as euphoria and
irritability. Actions and feelings are also
stimulated: a manic patient may need
less sleep, have increased speed of
thoughts, speak faster or with pressure,
have increased focus on activities, and be
overtly agitated. Increased activity can
range from doing a routine task excessively,
such as doing housework all night long,
to becoming involved in uncharacteristic
activities, such as planning multiple risky
business ventures.
• Intensity: Mania symptoms are
experienced with heightened intensity.
They may be intensely pleasurable or
intensely dysphoric.
• Impaired judgment and thinking:
Behavior and actions are often
impulsive and pleasure-seeking. When
manic, patients can participate in
uncharacteristic overspending, promiscuity,
substance abuse, or other impulsive
behavior. Judgment may be affected by
perceptual disturbances such as auditory
hallucinations, thought problems such as
paranoia, flight of ideas (ideas that change
so rapidly that they are confusing), or false
beliefs (e.g., that one is more powerful,
famous, or successful than in reality). Over
half of patients who have bipolar disorder
experience psychotic symptoms at some
time during their illness.GOO
PRI, SHA, HIR2, SCHN
–– Female gender and early life trauma (more strongly associated with cycling
between mood states more than once a month)
–– Antidepressant use
–– Genetic susceptibility (higher prevalence of the double short allele of the serotonin
transporter protein)
–– Clinical or subclinical hypothyroidism
The variables noted above should be considered when diagnosing bipolar disorder — and
when treating it. Medication(s) can alter the expression of the disorder.
©2007–2016 INTERMOUNTAIN HEALTHCARE. ALL RIGHTS RESERVED.
3
MANAGEMENT OF BIPOL AR DISORDER
MARCH 2016
SCREENING AND DIAGNOSIS
ALGORITHM NOTES
(a) PHQ-2 Scoring
The PHQ-2 consists of the first two questions
in the PHQ-9 (see page 5) used as a first step
in screening patents for depression. Scoring
for each question is indicated below:
ALGORITHM 1: DIAGNOSIS
TABLE 1. PHQ-2 Scoring
ADMINISTER and SCORE the first two questions of
the Patient Health Questionnaire (PHQ-2) (a)
Score* based on patient response to
each item below:
Over the past 2 weeks, how often have
you been bothered by any of the following problems?
Item
Positive?
0–3
Feeling down, depressed or
hopeless
0–3
Total Score (Positive = ≥ 3)
0–6
The PHQ-9 (see page 5) uses both a symptom
score and a severity score. Scoring guidance
for each type is indicated below:
Positive?
Scoring Guidelines
Symptom Score
≥ 5 = Administer MDQ
(see page xx)
< 5 = Usual care; see
Depression cpm.
Severity Score
Suicidal Ideation
*NOTE: the score from the
Question 9
Positive?*
PHQ-9 does not override
clinical judgment.
no
TREAT per
Depression
CPM
• Question 2: Positive (yes) response
• Question 4: “moderate” or “serious”
response
4 Prevention CPM)
no
Positive?
Positive?
yes
ASSESS for comorbidities (see page 8)
(c) MDQ Scoring
• Question 1: 7 / 13 positive (yes) responses
ASSESS suicide risk and
DETERMINE associated
treatment
(see page 5 and Suicide
•• INTERVIEW patient to confirm specific DSM-5 diagnostic criteria.
•• USE SADFIGS mnemonic to aid diagnosis (see page 7).
•• RATE severity of illness with CGI Scale (see page 22).
If “yes” to question #9,
assess suicide risk.
For a positive screen, all three of the
following criteria must be met:
yes
PROVIDE usual care
ADMINISTER and SCORE(c) the Mood
Disorder Questionnaire (MDQ) (see page 6 (c)
≥ 9 = Administer MDQ
(see page xx)
< 9 = Usual care; see
Depression cpm.
Score the MDQ according to the criteria below
and guidance in the Scoring and Evaluating
Adult MHI Forms CPM.
no
yes
TABLE 2. PHQ-9 Scoring
Measure
PROVIDE usual care
ADMINISTER and SCORE the Patient Health
Questionnaire (PHQ-9) to identify and
diagnose major depression (see page 5) (b)
*Score based on the following: 0 = Not at all;
1 = Several Days; 2 = > Half the Days;
3 = Nearly Every Day
(b) PHQ-9 Scoring
no
yes
Score
Range*
Little interest or pleasure in
doing things
Patient appointment with
primary care provider
Patient appointment with
mental health specialist
Mental health specialist
Primary care provider
•• REFER to a mental health specialist if patient has
TREAT per
algorithm
on page 10
unmanageable conditions or behaviors such as significant
comorbidities, psychotic tendencies, suicidal ideation/behavior,
violence, or treatment failures.
•• START treatment (using a medication with mood-stabilizing
properties per algorithm on page 11) while awaiting mental
health referral or consultation.
•• DO NOT USE UNOPPOSED ANTIDEPRESSANTS.
©2007–2016 INTERMOUNTAIN HEALTHCARE. ALL RIGHTS RESERVED.
MARCH 2016
MANAGEMENT OF BIPOL AR DISORDER
Discussion:
The need for consistent screening and diagnosis
Patients with bipolar disorder may see multiple healthcare providers for as many
as 10 years or more before they receive the correct diagnosis. This is due in part to
these factors:
• People with bipolar disorder seek treatment more often when depressed, and thus
they are often treated for unipolar depression.
• Bipolar disorder is often comorbid with substance abuse and anxiety disorders,
which can mask and complicate symptoms. Thus, assessing for comorbidities is a
critical part of the screening process (see pages 9 – 10).
• There is often no consistent process for screening and diagnosis in various
care settings.
Primary care providers (PCPs) are generally the first care providers who see a patient
with bipolar disorder. Unfortunately, since patients often present with symptoms of
depression, bipolar disorder is often misdiagnosed as unipolar depression and treated
inappropriately with an unopposed antidepressant, which can make the illness worse.
Unopposed antidepressants may induce mania and mixed bipolar states, mood
instability, and rapid cycling.
Patients eventually diagnosed with bipolar disorder often experience multiple failed
antidepressant trials or the onset or worsening of agitation and anxiety while on
antidepressants.FRY1, SUP1, BIR, HIR1, PEE
You can download the PHQ-9
at: https://m.intermountain.net/forms/
Pages/Details.aspx?isForm=true&ncid=52
1377846&title=MHI PHQ-9 Patient Health
Questionnaire
To improve early identification
and treatment of bipolar disorder,
this CPM recommends a
consistent process for screening
and diagnosis in all treatment
settings. This includes use of
validated screening tools such as
the Patient Health Questionnaire
(PHQ-9) for depression and
suicidal ideation and behavior
(content appears at right) and
the Mood Disorder Questionnaire
(MDQ) for mania (content appears
on page 6).HIR3
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5
MANAGEMENT OF BIPOL AR DISORDER
MARCH 2016
Suicide assessment
As shown in the algorithm on the previous page, an assessment of suicide risk should be done for every patient who responds
positively to question 9 on the PHQ-9 or who has experienced suicidal ideation (thoughts of engaging in suicidal behavior).
Although suicide is a low-probability event, bipolar disorder is one of the most common psychiatric disorders associated with
suicide.PAL, SAR Patients with bipolar disorder have a high rate of lifetime suicide completion (about 19%).GOO
Intermountain uses the Columbia-Suicide Severity Rating Scale (C-SSRS) to standardize assessment of suicidal ideation and
behavior, determine levels of risk, and make clinical decisions about care. The Suicide Prevention CPM details the C-SSRS versions
used and suggested treatment approaches in each care setting. The table below (from page 3 of the Suicide Prevention CPM) provides
an overview of risk level (based on a positive response to each C-SSRS Quick Screen question and recommended actions to take in
each setting based on patient responses. See the Suicide Prevention CPM for detailed steps for asking these questions.
TABLE 3: Patient safety measures and response protocols based on Quick Screen responses
C-SSRS Quick Screen questions
(in the last month)
Question
“Yes”
Level of risk
indicates
LOW
Action if patient response “Yes”
Outpatient clinic
(non-BH)
ED at triage
•• Consider referral to
MHI or BH provider
•• Consider patient
education
•• Consider referral to
MHI or BH provider
at discharge from ED
•• Consider patient
education
•• Continue with
plan of care
For identified BH patients BH unit
1. Have you wished
you were dead or
wished you could
go to sleep and
not wake up?
Wish to
be dead
2. Have you actually
had any thoughts
of killing yourself?
Nonspecific
thoughts
3. Have you been
thinking about
how you might
kill yourself?
Thoughts
MODERATE
with method
(without
specific plan or
intent to act)
•• Assess risk factors
and either facilitate
evaluation for
inpatient admission
or complete Safety
Plan with follow-up
in 24 – 48 hours
•• Educate patient
•• Initiate nursing
interventions (e.g.,
secure belongings)
•• Order crisis
worker evaluation
•• Psychiatric consult
recommended
•• Continue with
plan of care
•• Initiate nursing interventions
4. Have you had
these thoughts
and had some
intention of acting
on them?
Intent
(without plan)
HIGH
•• Facilitate immediate
evaluation
•• Educate the patient
•• Initiate nursing
interventions
•• Order PSA until
crisis worker
evaluation complete
•• Notify ED physician
•• Order crisis worker
evaluation
•• Psychiatric consult
highly recommended
•• Notify charge nurse/shift
coordinator
•• Notify attending physician
•• Assess need for 1:1
•• Initiate nursing interventions
•• Administer C-SSRS Lifetime/
Recent Assessment
(Adult/Adolescent
or Pediatric)
>1 year ago: LOW
•• Consider referral to MHI or BH provider
•• Consider patient education
1 – 12 months ago:
MODERATE
•• Assess risk factors
and refer to MHI or
BH provider
•• Educate patient
5. Have you started
Intent
to work out or
with plan
worked out the
details of how to
kill yourself? Do
you intend to carry
out this plan?
6. Have you ever
done anything,
started to do
anything, or
prepared to do
anything to end
your life?
Behavior
Past 4 weeks, during •• Facilitate immediate
current inpatient stay,
evaluation for
since last assessment:
inpatient care
HIGH
•• Educate patient
6 Inpatient care
•• Continue with
plan of care
•• Notify charge
nurse/shift
coordinator
•• Notify attending
physician
•• Assess need
for 1:1
•• Order crisis worker
evaluation
•• Psychiatric consult
recommended
•• Assess risk factors and consider referral to MHI
or BH provider
•• Initiate nursing interventions
•• Order crisis worker
evaluation
•• Initiate nursing
interventions
•• Order PSA
•• Psychiatric consult
highly recommended
•• Notify charge nurse/shift
coordinator
•• Notify attending physician
•• Assess need for 1:1
•• Initiate nursing interventions
•• Notify charge
nurse/shift
coordinator
•• Notify attending
physician
•• Assess need
for 1:1
©2007–2016 INTERMOUNTAIN HEALTHCARE. ALL RIGHTS RESERVED.
MARCH 2016
MANAGEMENT OF BIPOL AR DISORDER
Mood Disorder Questionnaire (MDQ)
WHEN TO SCREEN
The Mood Disorder Questionnaire (MDQ) is a tool that screens specifically for
bipolar disorder. It is NOT a diagnostic instrument. Used alone in a population with
low rates of bipolar disorder (e.g., in primary care settings), it will produce significant
false positive results. Therefore, screening an enriched population, such as those who
meet diagnostic criteria for depression and/or have failed an antidepressant trial, or
Mental Health
Adult
those for whom the clinician intuits bipolar disorder, is likely to correctly identify
the most patients. Mood
(Note that
patients who have a negative result using the MDQ are
Disorder Questionnaire (MDQ) (page 1 of 1)
unlikely to have bipolar disorder.) Content of the MDQ form appears below; see the
Today’s Date:
Patient’s Name:
Date of Birth:
notes at right for tips on using and interpreting the tool.
• In primary care settings: Primary care
Integration
providers should screen all new patients
for depression with the PHQ; patients who
screen positive for depression should be
further screened with the MDQ.
• In mental health provider settings:
Mental health specialists should screen all
new patients with the MDQ.
INTERPRETING RESULTS
YES
NO
… you felt so good or so hyper that other people thought you were not your normal self,
or you were so hyper that you got into trouble?
…
…
For a positive screening, questions 1 and 2
must both be positive:
… you were so irritable that you shouted at people or started fights or arguments?
…
…
• For question 1, a positive result is 7 or
… you felt much more self-confident than usual?
…
…
… you got much less sleep than usual and found you didn’t really miss it?
…
…
… you were much more talkative or spoke much faster than usual?
…
…
… thoughts raced through your head or you couldn’t slow your mind down?
…
…
… you were so easily distracted by things around you that you had trouble concentrating
or staying on track?
…
…
… you had much more energy than usual?
…
…
… you were much more active or did many more things than usual?
…
…
… you were much more social or outgoing than usual; for example, you telephoned friends
in the middle of the night?
…
…
… you were much more interested in sex than usual?
…
…
… you did things that were unusual for you or that other people might have thought were
excessive, foolish, or risky?
…
…
… spending money got you or your family into trouble?
…
…
…
…
…
…
1 Has there ever been a period of time when you were not your usual self and…
2 If you checked YES to more than one of the above, have several of these ever happened during
the same period of time?
3 During the period of time indicated above, do you think any of these symptoms were brought on
by prescription or other drugs?
4 How much of a problem did any of these cause you — like being unable to work; having family, money, or legal troubles; or
getting into arguments or fights?
… no problem
… minor problem
… moderate problem
American Psychiatric Association.
/ 13
*50402*
When
a Intermountain
patientHealthcare.
screens
for bipolar disorder
using the MDQ:
©2004–2014
All rightspositive
reserved.
MHI Pack 50402
Patient and Provider Publications 801-442-2963 MHI019 - 10/14
• For question 2, a positive result
is “yes.”
• Question 3 measures potential for
medication-induced symptoms.
• Question 4 measures impairment.
A response of “moderate” or serious”
suggests bipolar I disorder, whereas a
response of “minor” or “no problem”
suggests bipolar II disorder. (See the
following page for more detail on
distinguishing these 2 bipolar variants.)
IMPROVING SENSITIVITY
Adding the following 2 sub-questions
to question 1 of the MDQ can improve
the sensitivity of the MDQ screening by
as much as 10% (as suggested by 2007
Intermountain Healthcare data):
• Have any close family members (parents,
siblings, children) ever been diagnosed with
bipolar disorder or manic depression?
… serious problem
For Office Use Only:
What
next?
Reprinted with
permission from the American Journal of Psychiatry, (Copyright 2000).
more of the 13 sub-questions answered
“yes.”
• Interview the patient to determine if the patient has had at least one lifetime
episode of depression and one lifetime episode of mania or hypomania.
• Did you have mood problems before the
age of 25?
When these two questions are added to the
13 items in section 1, patients who answer
“yes” to <6 of the 15 questions are very
unlikely to have bipolar disorder.
• Use DSM-5 diagnostic criteria to determine and confirm a diagnosis (see page 8).
©2007–2016 INTERMOUNTAIN HEALTHCARE. ALL RIGHTS RESERVED.
7
MANAGEMENT OF BIPOL AR DISORDER
A MNEMONIC TO AID
DIAGNOSIS:
SADFIGS
For confirmation of a lifetime episode of
mania or hypomania — and a bipolar
disorder diagnosis — a patient’s symptoms
must meet these criteria:
MARCH 2016
Diagnostic criteria
The table below provides an overview of key diagnostic criteria for bipolar 1 disorder,
bipolar II disorder, and cyclothymic disorder — the most prevalent bipolar disorder
diagnoses.
TABLE 4: Overview of Major1 Bipolar DiagnosesAPA1
Episode
Type(s)
• A consistently elevated, irritable, or
A
Agitation or increased
focused activity
D
Distractibility
F
Flight of ideas or racing thoughts
I
Impulsivity
G
Grandiosity
S
Speech, rapid or pressured
(ICD-10: FS31.81)
Sleep, less need
(ICD-10: FS34.0)
S
Bipolar I
(see box at bottom
of page for
ICD-10 codes)
following SADFIGS symptoms. If irritable
mood, at least four of the following
SADFIGS symptoms:
Bipolar II
• If elevated mood, at least three of the
Severity3
Manic
Lifetime
1 week; almost
daily; >50% of
each day
Impacts all key areas of
functioning, includes
psychotic features,
or necessitates
hospitalization
Hypomanic AND
major depressive
Lifetime
4 days; almost
daily; >50% of
each day
Functioning is not seen
as usual for patient by
others in key areas; no
psychotic features; no
hospitalization needed
Past 2 years
(1 year if child or
adolescent); 50%
of overall time;
symptom free
< 2 months within
time frame
Impacts key areas of
functioning and causes
considerable distress
(Required)1
Cyclothymia
expansive mood lasting at least 1 week
(or any duration if hospitalization is
required) for mania and at least 4 days
for hypomania.
Context1 Duration2
Symptoms related
Lifetime or
to hypomanic AND
past 2 years?
major depressive
BUT not meeting
full criteria for either
episode as defined by
DSM-5
1. For information related to other bipolar diagnoses (substance/medication-induced bipolar and related
disorders, bipolar and related disorders due to another medical condition, and other specified bipolar and
related disorders), see Diagnostic and Statistical Manual of Mental Disorders — Fifth Edition.APA1
2. Context: time frame in which symptomatic episode must have occurred (e.g., lifetime, past 2 years, etc.)
3. Duration: specific number of days that symptoms occurred; symptoms last for a specified time and
frequency during those days
4. Severity: symptoms are severe enough to cause patients considerable distress and impact their daily
functioning in key areas of their lives
ICD-10 CODING FOR BIPOLAR I
Diagnostic coding for bipolar I is typically based on current or most
recent episode and severity. General ranges appear in this box. For more
detailed coding instructions, refer to ICD10data.com.
F31.6 Bipolar disorder, current episode mixed (specify severity and
presence of psychotic features)
F31.0 Bipolar disorder, current episode hypomanic
F31.7_ Bipolar disorder, currently in remission (specify full or partial
remission and type of most recent episode)
F31.1_ Bipolar disorder, current episode manic without psychotic
features (specify severity)
F31.8 Other bipolar disorders (F31.81 Bipolar II disorders; F31.89 other
bipolar disorder)
F31.2 Bipolar disorder, current episode manic severe with psychotic
features
F31.9 Bipolar disorder, unspecified
F31.3_ Bipolar disorder, current episode depressed mild or moderate
severity (specify severity)
NOTE: ICD-10 codes do not correspond exactly to DSM-5
codes and explanations. Intermountain‑employed providers
F31.4 Bipolar disorder, current episode depressed, severe without
psychotic features
can access an online version of the DSM- through the eResources
page on IntermountainPhysician.org or Intermountain.net.
F31.5 Bipolar disorder, current episode depressed, severe with psychotic
features
8 ©2007–2016 INTERMOUNTAIN HEALTHCARE. ALL RIGHTS RESERVED.
MARCH 2016
MANAGEMENT OF BIPOL AR DISORDER
Comorbidities
OTHER COMORBIDITIES/
DIFFERENTIAL DIAGNOSES
Those with bipolar disorder typically suffer from at least one comorbid medical
or psychiatric disorder (some studies indicate a large number of patients having at
least three chronic medical conditions) as well as having higher lifestyle risk factors
that occur at a younger age.VA These comorbidities can confuse and confound
diagnosis and treatment and also make the disorder more severe and difficult to
treat. Comorbidities are associated with increased emergency room visits and
more hospitalizations.NOR, GOL2 The most common mental health comorbidities are
described below; medical comorbidities are discussed on page 10.
• Attention deficit hyperactivity
disorder
• Disruptive mood dysregulation
disorder
• Eating disorders
• Intermittent explosive disorder
• Major depressive disorder
Mental Health Comorbidities
• Personality disorders including borderline
personality disorder
The most common comorbid mental health conditions are anxiety disorders and
substance use disorder. When co-occurring major psychiatric illnesses and/or
significant suicidal ideation/behaviors or homicidality are present, clinical guidelines
emphasize the importance of referring these patients to specialty care (see also suicide
assessment information on page 6).VA
For complete differential diagnosis
information on these disorders, see the
Diagnostic and Statistical Manual of Mental
Disorders — Fifth Edition.APA1
Anxiety disorders. Anxiety disorders are the most common mental health
comorbidities in patients with bipolar disorder — nearly 75% of patients have
comorbid bipolar disorder and some type of anxiety disorder.KES4 Common features
of anxiety include panic attacks, fears, and worries. Somatic symptoms include
poor concentration, agitation, muscle tension, headache, and perspiration. It may be
difficult to differentiate agitation caused by mania from anxiety caused by a comorbid
anxiety disorder. Anxiety symptoms may be difficult to separate from symptoms of
agitation while a patient is experiencing mania.
What to do: Treat the bipolar disorder first; treatment may take care of
anxiety symptoms.
•
For men, ≥5 standard drinks* a day
For women, ≥4 standard drinks* a day
Daily or
Almost Daily
•
Weekly
Alcohol:
Monthly
In the past year, how often have you used the following?
Once or
Twice
Intermountain-Modified National Institute
on Drug Abuse (NIDA) Quick Screen
Never
Substance use disorder. Substance use
disorder is the second most common comorbid
diagnosis in bipolar disorder.KES4, WEI More
than half of patients with bipolar disorder will
have a substance use diagnosis in their lifetime.
Substance use disorder includes alcoholism,
tobacco use, prescription drug abuse, and “street
drug” abuse. Alcoholism is the most common of
the substance use comorbidities.WEI The incidence
of alcoholism in those with bipolar disorder
is 3 times higher for men and 7 times higher
for women.FRY2





What to do: Use the NIDA Quick Screen
Tobacco products (including e-cigarettes)





(download the full-size version of this tool here:
Intermountain-Modified NIDA Quick Screen to
screen for substance use disorder. If identified,
aggressively treat the substance use disorder
concurrently with bipolar disorder based on the
Substance Use Disorder CPM. Successful treatment
of bipolar disorder is unlikely with ongoing
substance-use problems. Avoid lithium as a
primary mood stabilizer in these patients, and use
habit-forming sedatives with caution.
Prescription medications for non-medical reasons





Prescription medications in amounts greater than
prescribed, for reasons other than prescribed, or that
weren’t prescribed to you





Illegal drugs (illicit, street drugs)





©2007–2016 INTERMOUNTAIN HEALTHCARE. ALL RIGHTS RESERVED.
Beer or cooler (5% alcohol): 12 ounces
Malt liquor (7% alcohol): 8–9 ounces
• Table wine (12% alcohol): 5 ounces
• 80-proof spirits (hard liquor) (40% alcohol): 1.5 ounces
•
*Definition of a “standard drink:”
•
9
MANAGEMENT OF BIPOL AR DISORDER
THE IMPORTANCE OF
INTERDISCIPLINARY
COLLABORATION
For patients with bipolar disorder and
other medical conditions, early and regular
screening for comorbidities and careful
medication management is crucial. For
example, corticosteroids used to treat
asthma and inflammatory disease and
stimulants can be associated with secondary
mania. Taking diuretics and angiotensincoverting enzyme inhibitors with lithium in
patients with kidney disease or hypertension
may complicate bipolar disorder treatment.
Careful consideration of medications
that tend to promote weight gain is also
important. Referrals to a registered dietitian
nutritionist (RDA) can be helpful in dealing
with dietary intake and glycemic load.
MARCH 2016
Medical comorbidities
Medical problems can not only cause mood episodes but can exacerbate the course of
bipolar disorder and complicate treatment in terms of greater illness severity, reduced
recovery, and increased or premature mortality. These comorbidities often accentuate
psychological stressors related to employment and disability reimbursement and
increase healthcare utilization.VA
Major medical comorbidities in patients with bipolar disorder include cardiovascular
disease, autoimmune diseases, cancer, and metabolic disorders. Of these, metabolic
disorders (especially diabetes and obesity) offer significant challenges, in part due to
the weight-gain side effects of many medications used to treat bipolar disorder. In
addition, there are significant challenges of care associated with comorbid diabetes,
including:VA
• Almost double the overall health care costs for bipolar patients who have diabetes
• Greater impairment in both physical and mental health
• Lower quality of life
• Less satisfaction with health
According to recent research, there is a bi-directional relationship between comorbid
metabolic disorders and bipolar disorder because those with bipolar disorder tend
to take in more calories with a higher glycemic load and are significantly more
sedentary than the general population.MAN In addition, a 2012 population-based
study of 800,000 people indicated that those with untreated type 2 diabetes had a
significantly increased risk of developing bipolar disorder and that treating diabetes
may prevent bipolar onset.MAN
Other medical comorbidities can include thyroid dysfunction, migraines, and
cardiovascular disease. Considerations include:
• Thyroid dysfunction. Hypothyroidism is associated with rapid cycling and
difficult-to-treat depression, and hyperthyroidism can produce agitation and
anxiety that can make the identification of mania more difficult.
• Other medical comorbidities lead to additional disability and mortality for bipolar
patients. Note that compared to people without bipolar disorder:CAS, ELM, MAH, SCHI, WEE
–– Incidence of migraines is 5 times higher.
–– Incidence of cardiovascular disease is 1.9 times higher.
What to do: Assessment for bipolar disorder must include assessment for the
medical the conditions above. Patients should be treated concurrently — and extra
monitoring may be necessary. Many medications used to treat this illness can
aggravate cardiovascular risk factors (cardiovascular disease is the leading cause
of death in patients with bipolar disorder).
10 ©2007–2016 INTERMOUNTAIN HEALTHCARE. ALL RIGHTS RESERVED.
MARCH 2016
MANAGEMENT OF BIPOL AR DISORDER
TREATMENT FOR ADULTS
Patients with bipolar disorder have better outcomes with aggressive, multimodal treatment that includes appropriate medication,
patient/family education, psychotherapy, and (when available) care management. The target for treatment is FULL REMISSION.
Patients who achieve remission will have lower rates of relapse. To assess progress toward this goal, providers should have a
consistent method — such as the CGI scores described on page 18 — to assess response to treatment. Note that because of limited
quality studies comparing treatment outcomes, the guidelines presented in this CPM are reasonably broad and focus primarily on
bipolar I disorder. There is little quality evidence to support specific treatments for bipolar II disorder, and no published research
for bipolar not otherwise specified (NOS). The algorithm below and the discussion and tables that follow present a recommended
approach to treatment based on the best available evidence, along with expert opinion from clinical practice.
ALGORITHM 2: TREATMENT
Patient diagnosed with bipolar I or bipolar II
*Note: In emergency situations with
acute symptoms, rapid titration and
more than one medication may be
necessary to reduce time to response.
However, lamotrigine should never be
rapidly titrated due to increased risk of
allergic rash.
START monotherapy with a medication
with mood stabilizing properties*
START with a mood stabilizer with “A” quality data for
treatment of the appropriate pole.
See the medication tables on pages 13 – 16 for details.
Bipolar depression:
START with ONE of these:
• Quetiapine
• Lamotrigine
• Lurasidone
• Olanzapine + fluoxetine
• PROVIDE
patient/family education (see pages 27 – 28)
for psychotherapy
• CONSIDER care management
Mania/mixed mania:
• REFER
START with:
• Lithium
carbonate (mania)
OR
Divalproex sodium (mania/mixed)
OR
• An atypical antipsychotic:
• Aripiprazole • Ziprasidone
• Olanzapine
• Lurasidone
• Quetiapine
• Asenapine
• Risperidone
FOLLOW UP in 1 – 2 weeks
as indicated by acuity and severity
Adequate response?
ADD a second mood stabilizer.
no
yes
(Somewhat or much improved CGI global improvement score 1 – 3)
For moderate to severe symptoms:
• COMBINE
lithium and valproic
acid with each other OR with an atypical antipsychotic
• CONSIDER
the combination of
olanzapine and fluoxetine
(Symbyax), which is FDA
approved for bipolar 1 depression.
FOLLOW UP in 4 weeks until remission. At every
follow-up visit:
• EVALUATE adherence
• ASSESS clinical response and side effects at current dose
• USE outcome measures to assess progress (see page 22)
• ASSESS educational needs
• ASSESS therapeutic alliance (see page 21)
• ASSESS for substance abuse (see page 9)
Improved?
Much improved
CGI score 1 – 2
• CONTINUE at present dosage(s).
• FOLLOW UP every 4 weeks until
remission (CGI severity score 1 – 2).
• When in remission, FOLLOW UP at least
every 6 months to monitor symptoms, lab
values, and functional outcomes.
Somewhat improved
CGI score 3
• RAISE dose of mood stabilizer
as tolerated.
OR
• ADD a second mood stabilizer
focused on specific symptoms
No improvement or worsening
CGI score 4 – 7
• RAISE dose as tolerated; if at
maximum dose, change to a
different primary mood stabilizer.
OR
• ADD a second mood stabilizer
focused on specific symptoms
• CONSIDER consultation/referral to
a mental health specialist
TARGET: FULL REMISSION
(CGI severity score 1 – 2)
©2007–2016 INTERMOUNTAIN HEALTHCARE. ALL RIGHTS RESERVED. 11
MANAGEMENT OF BIPOL AR DISORDER
THE 3 Ms OF MEDICATION
MANAGEMENT FOR BIPOLAR
DISORDER
Mood stabilizers
In general, people with bipolar disorder
should be treated with mood stabilizers
for extended periods of time (years). Other
medications are added when necessary,
typically for shorter periods, to treat episodes
of mania or depression that break through
despite the mood stabilizer.
NOTE: if antidepressants are
prescribed, mood-stabilizers must be
continued as well.
Multiple medications
Studies indicate that most patients will
need more than one medication to achieve
remission.GIT Expert consensus guidelines
suggest adding a second medication
after 1–2 weeks of inadequate response
to one medication or for moderate-tosevere symptoms.APA2, KEC Combining lithium
or divalproex sodium with an atypical
antipsychotic can be effective.MOL However,
mixing atypical antipsychotics has no clinical
research to support its efficacy and may
increase the impact of shared side effects.
Monitoring
Because using multiple medications increases
side effects, complicates treatment, and
worsens patient compliance, monitor
patients carefully for these problems. See
the treatment algorithm on page 10 and
the medication table at right for specific
considerations. In addition, monitoring
is especially warranted for patients
taking antidepressants due to the risk
of manic switch.
ADJUNCT MEDICATIONS
Benzodiazepines such as alprazolam,
clonazepam, and lorazepam are often useful
for treating insomnia, anxiety, and agitation.
Anticholinergics and beta-blockers are
used for patients at risk for or currently
experiencing medication-induced
extrapyramidal symptoms (EPS) such as
pseudo-Parkinsons, akathisia and acute
dystonia. Thyroid supplements may be
necessary for some patients on lithium
carbonate since it can interfere with thyroid
functioning.
12 MARCH 2016
Medications
Because bipolar disorder is a recurrent and chronic illness, long-term
pharmacotherapy is almost always indicated. Optimizing medication for people
with bipolar may require some trial-and-error to balance medication effectiveness
with the associated side-effect burden. Overall, this process should be driven by
the best scientific evidence possible — starting with FDA approved treatments or
treatments that have shown positive effects in large controlled trials. Medication
recommendations (detailed on pages 13 – 18) are based on the strength of evidence
derived from review of literature, product package inserts, and experience from
clinical practice.
Mood stabilizers
Medications with mood-stabilizing properties are the mainstay of treatment for
bipolar disorder. Mood stabilization happens when a medication effectively treats at
least one pole of bipolar disorder without worsening the opposite pole. Medications
with mood-stabilizing properties are a heterogeneous group that can be categorized
by drug class and by whether they best treat mania, depressive symptoms, or both.
The group includes the following:
• Anticonvulsants, including carbamazepine, divalproex, lamotrigine, and oxcarbazepine
• Lithium carbonate
• Atypical antipsychotics, including aripiprazole, asenapine, lurasidone, olanzapine,
quetiapine, risperidone, and ziprasidone
Providers should choose a mood-stabilizing medication based on whether the patient
presents with depression, mania, or a mixed state — and on the severity of symptoms.
Because of significant side effects, careful monitoring is important for patients taking
mood stabilizers. Tables 6A and 6B on page 16 detail recommended monitoring for
each medication/class. Preference should be given to a mood stabilizer intended for
maintenance; some medications are better at preventing mania and some are better at
preventing depressive relapse (see information on use in table 5 on pages 13 – 15).
Antidepressants
Although bipolar disorder is mostly a depressive illness, evidence indicates that
antidepressant monotherapy is no more effective than mood stabilizers at treating
bipolar depression — and lacks maintenance properties.GHA, WHE, SAC In fact,
unopposed antidepressants may actually induce or worsen mania, promote rapid
cycling between poles, and destabilize the course of bipolar treatment.EIMA, GYU, HSIN
Despite this, antidepressants remain the most widely prescribed medications for the
treatment of bipolar depression. Antidepressants should not be used without
mood-stabilizing medications to minimize a patient’s risk of switching to mania or
rapid cycling, which further increases the risk of future switches.
Bipolar II disorder (characterized by at least 1 depressive and 1 hypomanic episode
over the course of a lifetime) lacks clear treatment guidelines; however, interventions
are critical for these patients for treatment and prevention, especially due to suicide
risk. Internationally, patients with bipolar II experience similarly high rates of suicidal
ideation (50.6%) and attempted suicide (20.8%) as those with bipolar I disorder.HSIN
A review of recent, evidence-based treatment strategies for bipolar II depression
and bipolar depression with mixed features strongly recommends treatment with
quetiapine for acute therapy and lithium for maintenance therapy.HSIN
©2007–2016 INTERMOUNTAIN HEALTHCARE. ALL RIGHTS RESERVED.
MARCH 2016
TABLE 5. Medications
Class
MANAGEMENT OF BIPOL AR DISORDER
used to treat bipolar disorderKUP1,2; LEC1,2; LEX; POST; STA1,2; STO1,2
Medication
Use (strength
(common brands) of evidence1)
carbamazepine
(Carbatrol, Tegretol)
Mania (A), but
due to significant
side effects, use
only after trying all
other meds with (A)
strength evidence
Bipolar
depression (C)
Maintenance (B)
FDA-approved
valproate (or
divalproex
sodium)
(Depakote,
Depakote ER)
Anticonvulsants
NOTE: divalproex
is referred to
as valproate
throughout this
CPM.
lamotrigine
(Lamictal)
Dosage
guidelines2
Initiate:
at 200 mg/twice
daily; then increase by
200 mg/day at weekly
intervals
Range:
400 – 1600 mg/day
Target: serum level
4 – 12 mcg/mL
1
$$ – $$$
Initiate:
at 25 mg/kg/day in
divided doses
Bipolar
depression,
maintenance (A)
Mania (D); no
acute efficacy for
mania
Initiate:
at 25 mg once daily
•• Auto-inducer: Monitor and adjust serum levels due to liver
induction.
•• Agranulocytosis, aplastic anemia, thrombocytopenia, hepatic failure
and toxic dermal eruptions can rarely occur.
1
$$ – $$$
•• Common side effects include nausea, diarrhea, thrombocytopenia
and moderate weight gain.
Titrate: rapidly to
desired clinical effect
•• Dose range presented is for valproate (divalproex). May be given
as an extended release formula once daily instead; add 8 – 20% to
total daily dose (usual 250 – 500 mg).
Range:
750 – 3,000 mg/day
•• Agranulocytosis, aplastic anemia, hyperammonemia, hepatic failure
and toxic dermal eruptions can rarely occur.
Target: serum level
50 – 125 mcg/mL (mid
to upper range generally
required)
Titrate:
per set schedule:
•• 25 mg once daily x 2
wks
1
$ – $$
•• If taking with divalproex, halve titration doses; if taking with
carbamazepine, double titration doses (but no more than 100
mg/day increase).
•• May provoke toxic dermal eruptions (Stevens-Johnson Syndrome,
toxic epidermal necrolysis), but markedly reduced risk when titrated
as directed; patient should seek medical attention immediately if a
rash appears.
•• Common side effects include nausea and rash; if continuing
therapy despite rash, reduce dose and titrate more slowly once rash
resolves.
•• Further titrations
<100 mg per day at
weekly intervals
Initiate:
at 300 mg twice daily;
increase by 600 mg/day
at weekly intervals
Range:
600 – 2400 mg/day
divided
Usual Target:
1,200 mg/day
•• Do not titrate more rapidly than recommended dosing
schedule due to increased risk of potentially fatal rash.
•• Dose adjustment is needed if concomitant enzyme-inducing
antiepileptic medication or valproic acid is discontinued.
•• 50 mg once daily x 2
wks
•• 200 mg once daily
thereafter
Mania, bipolar
depression, and
maintenance (C)
Not FDAapproved
•• Strong inducer of CYP1A2, CYP2B6, CYP2C19, CYP2C8, CYP2C9,
and CYP3A4.
•• Common side effects include dizziness, headache, nausea,
moderate weight gain, sedation and ataxia.
•• 100 mg once daily
x 1 wk
oxcarbazepine
(Trileptal)
Side effects and other comments
(see page 16 for monitoring guidelines)
•• Prior to therapy, screen with HLA-B*1502 genotype.
Mania and
maintenance (A)
Bipolar
depression
(B) (Better
at preventing
manic episodes
than depressive
episodes)
FDA-approved
(for treatment of
mania)
FDA-approved
Tier/
Cost 3
•• Estrogen-containing oral contraceptives may decrease lamotrigine
levels by 50%.
1
•• Strong inducer of CYP3A4.
$$
•• Common side effects include dizziness, headache, nausea and
sedation.
•• Agranulocytosis, aplastic anemia, hepatic failure, hyponatremia and
toxic dermal eruptions can rarely occur.
•• May reduce effectiveness of contraceptives
•• Prior to therapy, screen for HLA-B*1502 genotype.
Strength of evidence key: (A) = Based on data from large controlled trials; (B) = Based on data from smaller controlled trials; (C) = Based on expert opinion, open-label data, or usualcare experience; (D) = No acute efficacy
1
2
Some dosage guidelines are based on usual care experience and may differ from manufacturer’s package data.
Tier 1 = Generic; Tier 2 = Preferred Brand; Tier 3 = Non-Preferred Brand. Cost is based on 30-day actual cost (not copay), and on generic, when available: $=$1 – 25; $$=$26 – 75;
$$$=$76 – 150; $$$$= > $1500
3
©2007–2016 INTERMOUNTAIN HEALTHCARE. ALL RIGHTS RESERVED.
13
MANAGEMENT OF BIPOL AR DISORDER
TABLE 5. Medications
used to treat bipolar disorder (continued)KUP1,2; LEC1,2; LEX; POST; STA1,2; STO1,2
Lithium Preparations
Medication
Class (common
Use (strength of evidence1)
brands)
lithium
carbonate
(Eskalith,
Eskalith CR,
Lithobid)
Mania, maintenance (A)
Bipolar depression (B)
Decreased efficacy in mixed
episodes, rapid cycling, and
comorbid substance abuse
FDA-approved for treatment of
acute mania and maintenance
Dosage guidelines2
Initiate:
at 300 mg twice daily;
increase by ≤ 300 mg/day
every 3 – 4 days
Range:
600 – 1500 mg/day
Acute Mania Target:
Serum level 1 – 1.5 mEq/L
Maintenance Target:
0.6 – 1.2 mEq/L
Side effects and other comments
Tier/
(see Table 6A on page 16 for
3
Cost
monitoring guidelines)
1
•• Effective for reducing suicide riskCIP
$ –$$
•• May be given once daily as tolerated;
immediate release formulations generally
given in doses divided 2–3 times/day
•• Multiple drug interactions (e.g., NSAIDs,
ACEIs, diuretics)
•• Moderate weight gain.
•• Common side effects include polydipsia,
polyuria, acne, GI discomfort, hand tremor;
most are serum-level related
•• No significant sedation or stimulation
lithium
citrate
aripiprazole
(Abilify)
8 mEQ/5mL solution
Mania, maintenance (A)
Bipolar depression (C)
FDA-approved (for acute
treatment of manic and mixed
episodes associated with bipolar 1
disorder)
Atypical Antipsychotics
MARCH 2016
Initiate: at 5 – 15 mg once
daily
Titrate: as tolerated to 30
mg/day, if clinically indicated
Range: 15 – 30 mg/day
asenapine
Mania (A)
Monotherapy —
(Saphris)
Bipolar depression,
maintenance (B)
Initiate: at 5 – 10 mg twice
daily by mouth
FDA-approved (for treatment
of acute mania or mixed episodes
associated with bipolar 1 disorder as
monotherapy or in combination with
lithium or valproate)
Combination
therapy —
Initiate: at 5 mg twice daily
lurasidone
Mania, maintenance (C)
(Latuda)
Bipolar depression (B)
Initiate: at 40 mg by mouth
once daily (increase as
clinically indicated)
FDA-approved (for treatment of
depressive episodes associated with
bipolar 1 disorder as monotherapy
or in combination with lithium or
valproate)
1
$$$$
3
$$$$
•• Common side effects include restlessness,
stimulation, and nausea
•• Minimal risk of extrapyramidal symptoms (EPS)
other than akathisia
•• Sublingual administration only; no eating or
drinking for 10 minutes after placing under
tongue
•• Common side effects include headache,
dizziness and oral hypoesthesia
•• Minimal risk of EPS other than akathisia
•• Minimal sedation and little to no weight gain
Titrate: to 10 mg twice daily
based on clinical response
Range: 20 – 120 mg/day
3
$$$$
•• Medication must be taken with food (at least
350 calories)
•• Common side effects include sedation, EPS,
and nausea
•• Little to no weight gain
Strength of evidence key: (A) = Based on data from large controlled trials; (B) = Based on data from smaller controlled trials; (C) = Based on expert opinion, open-label data, or usualcare experience; (D) = No acute efficacy
1
Some dosage guidelines are based on usual care experience and may differ from manufacturer’s package data.
2
Tier 1 = Generic; Tier 2 = Preferred Brand; Tier 3 = Non-Preferred Brand. Cost is based on 30-day actual cost (not copay), and on generic, when available: $=$1–25; $$=$26–75;
$$$=$76–150; $$$$= > $1500
3
4
Strength of evidence is based on use as an adjunct to lithium or divalproex.
14 ©2007–2016 INTERMOUNTAIN HEALTHCARE. ALL RIGHTS RESERVED.
MARCH 2016
MANAGEMENT OF BIPOL AR DISORDER
TABLE 5. Medications
used to treat bipolar disorder (continued)KUP1,2; LEC1,2; LEX; POST; STA1,2; STO1,2
Medication
Class (common
Use (strength of evidence1)
brands)
olanzapine
(Zyprexa, Zydis)
Mania, maintenance (A)
Bipolar depression (B)
4
FDA-approved (for treating bipolar 1
Atypical Antipsychotics, continued
disorder as follows):
•• Acute mania or mixed episodes as
monotherapy or in combination with
lithium or valproate
•• Maintenance treatment
Dosage
guidelines2
Initiate: at 10 mg at
bedtime
Titrate: by 5 mg
increments at daily
intervals
Range: 5 – 20 mg at
bedtime (may be split
twice daily)
olanzapine +
fluoxetine
(Symbyax)
•• Bipolar depression in combination with
fluoxetine
quetiapine
(Seroquel)
Mania, bipolar depression, and
maintenance (A)
Initiate: at 50 –
100 mg at bedtime
FDA-approved (for treating bipolar 1
Titrate: as clinically
indicated
disorder as follows):
•• Acute mania or mixed episodes as
monotherapy or in combination with
lithium or valproate
•• Maintenance treatment (in combination
with lithium or valproate)
•• Acute treatment of depressive episodes
(bipolar I and II disorder)
risperidone
(Risperidal)
Mania (A)
Bipolar depression (C)
Maintenance (B)
FDA-approved (for treatment of acute
mania or mixed episodes associated with
bipolar 1 disorder as monotherapy or in
combination with lithium or valproate)
ziprasidone
(Geodon)
Mania (A)
Bipolar depression (C)
Maintenance (B)5
FDA-approved (for treatment of acute
manic or mixed episodes associated
with bipolar disorder with or without
psychosis; for maintenance treatment
of bipolar disorder in combination with
lithium or valproate)
Tier/
Cost 3
Side effects and other
comments (see Table 6B
on page 16 for monitoring
guideines)
1
•• Significant sedation
$ – $$
•• Severe weight gain
•• Medium risk of extrapyramidal symptoms
(EPS)
•• Potential for dyslipidemia and
hyperinsulinemia, case reports of diabetes risk
•• IM formulation effective for acute agitation
1
$ – $$$
•• Significant sedation and moderate weight
gain; dry mouth
•• Lowest EPS risk of the atypical antipsychotics
Range: 300 –
400 mg/day; up to
800 mg/day may be
needed
May be given once
nightly as tolerated
Range: 1 – 2 mg at
bedtime
Titrate: by 1 mg
increments at daily
intervals
1
$
•• Moderate sedation and weight gain;
increases prolactin
•• Minimal risk of EPS below 4 mg daily
Range: 1 – 6 mg at
bedtime; may be split
to twice daily
Initiate: at 40 mg
twice daily with food
Titrate: to 60 –
80 mg twice daily
with food on day 2
Range: 40 – 80 mg
twice daily with food
1
$$-$$$$
•• Poor absorption without food; for best results
take once daily with evening meal (minimum
500 calories)
•• Minimal sedation at lower doses; little to no
weight gain
•• Moderate risk of EPS
•• Significant additional monitoring
requirements (see Table 6B on page 16)
IM formulation effective for acute agitation
Strength of evidence key: (A) = Based on data from large controlled trials; (B) = Based on data from smaller controlled trials; (C) = Based on expert opinion, open-label data, or usualcare experience; (D) = No acute efficacy
2
Some dosage guidelines are based on usual care experience and may differ from manufacturer’s package data. In patients with repeated compliance issues, consider a long-acting
injectable medication.
3
Tier 1 = Generic; Tier 2 = Preferred Brand; Tier 3 = Non-Preferred Brand. Cost is based on 30-day actual cost (not copay), and on generic, when available: $=$1 – 25; $$=$26 – 75;
$$$=$76 – 150; $$$$= > $1500
4
Strength of evidence is based on use as an adjunct to lithium or divalproex.
5
Grade A evidence based on use in combination with fluoxetine 1
©2007–2016 INTERMOUNTAIN HEALTHCARE. ALL RIGHTS RESERVED. 15
MANAGEMENT OF BIPOL AR DISORDER
MARCH 2016
Monitoring Guidelines for Anticonvulsants and Lithium —
­ Monitor (as clinically indicated)
AND: KUP1,2; LEC1,2; LEX; POST; STA1,2; STO1,2
TABLE 6A.
Anticonvulsants
Test
HLA-B*1502 genotype
CBC w/differential
carbamazepine
screening prior to
therapy1 FDA,CPIC
every 2 – 4 wks X 2 mos,
then every 3 – 6 mos
Hepatic Function
at baseline; then every
6 – 12 mos
Renal Function
divalproex
lamotrigine
oxcarbazapine
screening prior to
therapy1 FDA
at baseline; then 1 – 2 wks
after any dose change
at baseline; then every
6 – 12 mos
periodically
at baseline
at baseline
at baseline and yearly
at baseline;
then yearly
at baseline; every
6 mos
Thyroid Function
Pregnancy Test
Lithium
at baseline;
then yearly
at baseline
Fasting Lipids
Serum Sodium
at baseline
Serum Medication Level
(Trough)
3 – 4 wks after
any sustained dose
adjustment
at baseline; then
periodically during
first 3 mos of
therapy
Serum Ammonia
1 – 2 wks after any dose
change
10 – 12 hrs after last
dose, 4 – 5 days after
initiation or dose
change; then every
3 mos.
when clinically indicated2
ECG
at baseline and yearly
Electrolytes
at baseline
Urinalysis
at baseline
TABLE 6B.
Monitoring Guidelines for Atypical Antipsychotics — Monitor (as clinically indicated)3
AND:ADA, GOT
Pregnancy Test
at baseline, if indicated (see page 17)
Fasting Lipids
at baseline; at 12 weeks; then annually
BMI
initial measurement; then at 4, 8, and 12 weeks; then every visit
HgA1c/fasting plasma glucose
at baseline; at 12 weeks; then annually
Blood Pressure
at baseline; at 12 weeks; then annually
Extrapyramidal symptoms (EPS)
baseline, then at each visit
1
In patients of Asian descent, DO NOT USE if the HLA-B*1501 allele is present.
2
For unexplained lethargy, vomiting, or mental status changes
3
For ziprasidone (Geodon), also do baseline ECG if known heart disease, personal history of syncope, family history of early sudden death or congenital long QT syndrome. Also monitor ECGs
as clinically indicated for symptoms of prologed QT interval (e.g., syncope).
16 ©2007–2016 INTERMOUNTAIN HEALTHCARE. ALL RIGHTS RESERVED.
MARCH 2016
MANAGEMENT OF BIPOL AR DISORDER
TABLE 7. Medication
considerations for SPECIAL CIRCUMSTANCES HEN1-4; KUP1,2; LEC1; LEX; MAR; STA2
Circumstance
Medication Considerations
Acute illness
•• Lithium has been proven effective for reducing the risk of suicide in patients with acute illness.CIP
•• Titrate medication dosage rapidly (except for lamotrigine — never rapidly titrate lamotrigine).
•• Use respective adjunctive medications at beginning of treatment.
•• Start co-therapy with two primary mood stabilizers from separate classes at beginning of treatment.
Akathisia
•• Consider a cautious antipsychotic dose reduction
•• Use lorazepam 0.5 mg twice daily (B); titrate as needed to manage symptom severity.
•• Use propranolol 10 mg twice daily (C); gradually increase to 20 mg three times daily. Avoid in patients with asthma; watch for
bradycardia and hypotension.
•• Use benztropine 1 mg twice daily (C); increase to 2 mg twice daily as needed and tolerated.
Anxiety,
agitation, and/
or insomnia
•• Augment with a sedating atypical antipsychotic medication (see page 13), adjunctive sleeping pill, or sedative (benzodiazepine such
as clonazepam, lorazepam, alprazolam) 0.5 – 6 mg, in divided doses (A).
Bipolar II
disorder
•• The hypomanic state of bipolar type II is often experienced as a functional and non-pathologic state. Aggressive treatment of this
state may lead to patient non-compliance. The consequences of not treating hypomania are unknown.
Elderly patient
•• Consider half doses of medication. Older patients are more susceptible to lithium toxicity and suffer more side effects from
medication.
•• Suppression of manic symptoms, anxiety, or agitation with sedatives is a short-term solution. Avoid or use cautiously in patients
with a history of substance abuse.
•• Due to the possibility of lower manic conversion rates, antidepressant use may be less risky with this population compared to the
bipolar type I population. However, antidepressants should be avoided in patients who are rapid cycling.
•• Monitor for increased suicide risk, more accidents, and self-neglect.
•• Atypical antipsychotic medications may increase the risk of death in patients with dementia.
Female of
child-bearing
years
•• Use anticonvulsant mood stabilizers with caution — many are generally regarded as teratogens.
•• For patients that plan to become pregnant, consider lamotrigine as first-line therapy (C).
•• Failing lamotrigine, consider quetiapine or risperidone as second-line therapies (C). Lurasidone may also be considered as secondline therapy.
•• For treatment refractory patients, lithium is considered a reasonable option. While it is generally considered teratogenic (increased
risk for cardiac defects), the absolute risk is low.
•• Evaluate sexual activity, menstrual status, and birth control use at every visit for child-bearing age females on divalproex sodium,
lithium, or carbamazepine.
Insomnia
•• May be chronic in patients with bipolar disorder. Lack of adequate sleep may be both a sign of and a precipitant to relapse.
•• Use adjunct sleeping medications. Benzodiazepine and related sedatives are helpful as sleep aids as well as for treatment (with
mood stabilizer) of residual agitation and anxiety, though habit-forming sedatives should be avoided in patients with history of
substance abuse.
•• Educate patient on proper sleep hygiene: No evening caffeine or tobacco; no daytime napping; avoid reading and TV in bed; go to
bed when sleepy; get out of bed if unable to fall asleep in less than 30 minutes.
Pregnancy
Risk of relapse is high for those who discontinue mood stabilizers; near-term pregnant women are vulnerable to relapse.YON
For patients with bipolar depression:
•• Consider lamotrigine as first line therapy (C).
•• Consider quetiapine as second-line therapy (C). Lurasidone may also be considered as second-line therapy.
•• Treatment refractory patients are often treated with fluoxetine plus olanzapine, lamotrigine plus lithium, or electroconvulsive
therapy (ECT).
For patients with manic, hypomanic or mixed episodes:
•• First-generation antipsychotics (e.g. haloperidol) are the preferred first-line therapy (B).
•• Consider risperidone, quetiapine, or olanzapine (in that order) as second-line therapy (C).
•• Treatment-refractory patients are often treated with lithium, electroconvulsive therapy (ECT), or lithium plus an antipsychotic.
©2007–2016 INTERMOUNTAIN HEALTHCARE. ALL RIGHTS RESERVED. 17
MANAGEMENT OF BIPOL AR DISORDER
TABLE 7. Medication
MARCH 2016
considerations for SPECIAL CIRCUMSTANCES (continued) HEN1-4; KUP1,2; LEC1; LEX; MAR; STA2
Circumstance
Medication Considerations
Rapid cycling
(four or more mood cycles
per year)
For patients with bipolar depression:
•• Quetiapine is the preferred first-line therapy (C).
•• Consider lamotrigine, lithium, and fluoxetine plus olanzapine second-line agents, in order of preference (C).
•• Failing the above, treatment refractory patients should be referred to a psychiatrist and potentially considered for
electroconvulsive therapy (ECT), rather than additional pharmacotherapy trials (C).
For patients with manic, hypomanic or mixed episodes:
•• Consider risperidone, aripiprazole, or olanzapine monotherapy as first-line therapy (B).
•• Second-line agents include lithium, valproate, quetiapine, haloperidol or carbamazepine, in order of preference (C).
•• Failing the above, treatment refractory patients should be considered for combination therapy with either lithium or
valproate and a first-line atypical antipsychotic. Alternately, in cases of severe mania, consider combination therapy a
first-line option (C).
•• For severe mania unresponsive to a single trial of combination pharmacotherapy, consider addition medication
trials over electroconvulsive therapy (ECT). However, for severe mania unresponsive to 4 – 6 trials of combination
pharmacotherapy, consider referral to a psychiatrist for electroconvulsive therapy (ECT) rather than additional
pharmacotherapy trials (C).
For all patients:
•• Optimize thyroid function.
•• Augment with psychotherapy.
Side effects intolerable
prior to efficacy
•• Consider lower dose.
•• Change medications.
•• Treat with low dose of two primary mood stabilizers.
Switch to opposite pole or
mixed symptoms
•• Add mood stabilizer with efficacy for appropriate pole.
•• If depressed, raise lithium level to more than 0.8 mEq/L, add lamotrigine, quetiapine, OR add an antidepressant.
Avoid TCAs, venlafaxine, and duloxetine.
•• If manic or mixed, discontinue antidepressant (if that caused switch) or add a primary mood stabilizer for mania/
mixed mania.
•• Patients who have a history of manic conversion on antidepressants are at high risk of future conversion with
antidepressants.
Substance use disorder
•• Avoid lithium as a primary mood stabilizer in these patients.
•• Give appropriate referral and treatment for substance use issues.
•• Use habit-forming sedatives with caution
Thyroid dysfunction
•• Thyroid supplements may be necessary for some patients on lithium, since lithium carbonate can interfere with thyroid
functioning. Consider treating subclinical hypothyroidism in patients who have resistant depression or rapid cycling.
Weight gain >5% of initial
weight or weight gain
prevention
•• Modify treatment plan to include exercise and calorie restriction.
•• Follow weight, serum lipids, and fasting glucose.
•• Consider medication change — atypical antipsychotics may be associated with more weight gain than other mood
stabilizing agents.
•• Consider adjunctive use of metformin (B) or topiramate (B). Three small controlled studies showed diminished or
reversed weight gain with metformin in patients who were taking atypical antipsychotics. One large trial showed an
average three-year weight loss of 2.5% with metformin therapy, which was maintained over a 10-year observation
period. A meta-analysis of six trials showed an average 6-month weight loss of 6.5% with topiramate therapy.
Worsening mania
•• Assess medication adherence.
•• Raise dose of existing mood-stabilizing medications AND/OR add second mood stabilizer for mania.
•• Discontinue antidepressant if it is considered a precipitant.
Strength of evidence key: (A) = Based on data from large controlled trials; (B) = Based on data from smaller controlled trials; (C) = Based on expert opinion, open-label data, or usual-care
experience; (D) = No acute efficacy
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MARCH 2016
MANAGEMENT OF BIPOL AR DISORDER
Psychosocial therapy
Patients with bipolar disorder suffer a variety of psychosocial consequences —
stigmatization; interpersonal issues in marriage, family, childbearing, and parenting;
academic, occupational, legal, and social problems — related to acute episodes
(typically resulting from reckless and/or inappropriate behaviors or being withdrawn
or violent). The resultant stress of past episodes often sets these patients up for
ongoing vulnerability to future episodes. In addition, patients struggle to adhere to a
long-term pharmacological treatment regimen with frequently unpleasant side effects.
As a result, recent research-based clinical guidelines recommend that psychosocial
therapy be an essential part of a bipolar disorder treatment plan, especially for
maintenance treatment to: APA3, CAN, VA
ADJUNCTIVE PSYCHOSOCIAL
THERAPY GOALS APA3,CAN,MIK
Help patients better:
• Understand and accept the nature of their
chronic illness and treatments
• Adhere to medication regimens
• Recognize early warning signs of and
stressors that trigger relapse
• Regulate their emotions and improve
functioning
• Communicate and solve problems within
family relationships
• Reduce stress
• Increase patient functioning between episodes
• Decrease likelihood and severity of future episodes
• Regulate sleep/wake cycles and other
Treatment strategies vary in terms of format (individual, group, or family unit),
duration of treatment, patient cohort (in remission, recovering from an acute episode,
or both). As part of a treatment plan, therefore, psychosocial treatment strategies
should be individualized over time for each patient in terms of form, intensity, and focus.APA3
Help family members/caregivers:
Evidence-based adjunctive psychosocial treatments for bipolar disorder include:
daily routines
• Avoid substance misuse
• Increase illness management and their own
self-care skills
• Decrease their own depressive symptoms
• Decrease their health-risk behavior
• Individual cognitive-behavioral therapy (CBT) — Likely the most extensively
researched modality as adjunctive therapy, CBT research reflects varying protocols
and outcomes in comparison to other psychosocial treatments.MIK CBT is
recommended for those in remission from acute mania who have experienced fewer
than 12 previous acute episodes. With this treatment approach, patients learn about
their symptoms, course of illness, and treatments as well as techniques for cognitive
restructuring and problem-solving strategies for adapting activity levels to mood,
detecting early signs of relapse, and implementing prevention strategies. Providers
may want to consider booster sessions after 18 months to maintain treatment benefits.VA
• Individual and/or group psychoeducation — This treatment approach focuses on
helping patients become active partners in their treatment by learning:
–– The nature and course of the illness
–– Benefits/risks of treatment options
–– How to recognize early signs and stressors that may signal relapse
–– How sleep regulation and substance misuse impact likelihood of relapse
Psychoeducation can involve the patient’s family members/caregivers if the patient
agrees and providers should consider structured group psychoeducation, which has
been validated in two randomized trials as effective for reducing the duration of
patients’ manic episodes, lowering mania scores, and significantly improving patients’
social functioning and quality of life.MIK In addition, brief group psychoeducation
has been found to be as effective as longer-term individual CBT at a significantly
reduced cost (an 85% savings).PAR
• Interpersonal and Social Rhythm Therapy (IPSRT) — This treatment approach
addresses resolving patient-specific problems and focuses on stabilizing sleep/wake
rhythms as well as patterns of social routines and stimulation. IPSRT uses a selfreport tool, the Social Rhythm Metric, to track routines and mood. Designed for
use with patients in remission, the treatment homes in on individualized problem
resolutions and strategies for preventing problem recurrence. Some research
indicates that IPSRT may be associated with longer time between episodes, better
occupational functioning for those undergoing acute treatment, and even improved
depression scores when used as monotherapy for those with bipolar II disorder.MIK
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19
MANAGEMENT OF BIPOL AR DISORDER
THE ROLE OF FUNCTIONAL
REMEDIATION
Those with bipolar disorder struggle with
both social and occupational functioning
— challenges that represent both clinical
concerns as well as social and economic
burdens. Functional remediation programs
address struggles patients face with
attention, memory, and executive functioning
in their daily routines. Elements of IPSRT (see
page 19) also focus on functional remediation
by addressing stabilization of daily routines
and sleep/wake cycles.
Adjunctive psychosocial interventions
focused on functional remediation have been
associated with significant improvements in
occupational and interpersonal functioning
among patients with both bipolar I and II
disorder. In a 2-year study of patients with
bipolar I disorder, IPSRT combined with
medical management rapidly improved
occupational functioning as compared to
other psychosocial approaches (especially
among women), and these gains were
maintained for two years following the study.
FRA
A multicenter, randomized controlled
trial of 239 euthymic patients with bipolar
disorder compared functional remediation
with psychoeducation and treatment as usual
over 21 weeks. Results indicated significant
improvements in both occupational and
interpersonal functioning.TOR
MARCH 2016
• Family Focused Therapy (FFT) — Targeting couples and families of patients
stabilizing from acute episodes, this treatment approach includes both the patient
and the family members and offers an initial assessment followed by education about:
–– The illness, medication adherence, early warning signs of relapse, and relapse
prevention strategies
–– Communication and problem-solving skills to improve family relationships
While patients whose families experience more conflict and intensity of relationships
may benefit the most, research indicates that overall, patients involved in FFT
as an adjunct to pharmacotherapy may experience a 35 – 40% reduction in
recurrence rates over 2 years as compared to those undergoing brief psychoeducation
and pharmacotherapy.MIK In addition, FFT can help caregivers increase illness
management skills as well as their own self-care, which is associated with decreased
depressive symptoms and health-risk behavior among caregivers as well as decreased
depressive symptoms in patients.CAN
Electroconvulsive therapy (ECT)
With ECT, patients undergo a generalized cerebral seizure via administration of
low-level electrical current to the scalp while under general anesthesia and muscle
relaxation. Treatment usually requires 6 – 12 sessions over a 2- to 4-week period.
Although considered a standard treatment for unipolar depression, ECT has also
been proven effective for acute mania, bipolar depression, mixed affective states, and
especially for treatment-resistant bipolar disorder.LOO Other typical indications for
the use of ECT include multiple treatment failures, pregnancy, prior positive ECT
response, and patient preference. Studies also indicate that ECT may be effective as
a first-line treatment to achieve rapid clinical response in urgent cases where patients
present with severe suicidal ideation and behaviors, severe psychosis, malignant
catatonia, or with dangerous, depression-related refusal of fluid and food. APA4, HUS,
KEL1, KEL2
There are no absolute medical contraindications for using ECT; however, relative
risk may differ depending on a patient’s clinical situation.APA4 Because of potential
side effects, such as confusion and short-term memory loss (as well as side effects
associated with anesthesia), ECT has typically been considered with treatmentresistant bipolar disorder patients. However, recent research indicates that these
patients do not generally suffer adverse neurocognitive consequences and in fact,
ECT may also be associated with a favorable long-term influence on some cognitive
functions.KES, VER, BOD
Care management
With routine phone or clinic contact, care managers can educate patients regarding
their care, set expectations, assist with social emergencies, and direct patients to
return to the clinic sooner rather than later. Care managers offer both knowledge
and a supportive relationship to patients — both of which are necessary for success.
Patients who receive this type of care for depression have much better results than
those who don’t. Working inside and outside the clinic, a care manager can assist
with the following:
• Treatment adherence (medications and/or psychotherapy)
• Patient education, self-management, and reinforcement of ongoing physician,
patient, and family contact
• Communication and coordination between mental health and primary care
• Support with requests for consultation
• Improving timely contact with patients and monitoring their response
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MARCH 2016
MANAGEMENT OF BIPOL AR DISORDER
FOLLOW UP AND MAINTENANCE
Since bipolar disorder is a chronic and reoccurring illness, it usually requires regular
follow-up, lifetime maintenance pharmacotherapy, and ongoing, objective outcomes
assessment. Sustained remission lowers relapse risk.
Follow-up schedule
Multimodal treatment of this complex disorder demands regular, lifelong follow-up.
Objectives of follow-up include:
• Adjusting medications and addressing side effects
• Monitoring lab values (e.g., lithium serum levels) as indicated
• Managing comorbidities
• Continuing/coordinating therapy and education for patients and families
• Measuring outcomes
See below for a recommended follow-up schedule:
TABLE 8. Recommended follow-up schedule
When
Why
1 to 2 weeks after diagnosis and initial
medication therapy
•• Assess initial response to treatment, assess
outcome.
Every 4 weeks after diagnosis and initial
medication therapy until patient is much improved
(CGI global improvement score 1 – 2).
•• Achieve target doses.
•• Assess functional outcome (see page 18).
•• Monitor side effects and adherence.
•• Assess educational needs.
•• Assess therapeutic alliance (see sidebar).
THERAPEUTIC ALLIANCE
Clinicians should assess therapeutic alliance
on a routine basis. Therapeutic alliance
refers to how well the patient and clinician
are working together to manage the
patient’s illness. The patient’s perception of
this relationships is related to compliance
and outcome.
•• Assess for substance abuse (see page 8).
Even limited alcohol use can destabilize the
course of bipolar disorder.GOLD
At least every 6 months
•• Monitor symptoms, lab values, and functional
outcomes.
PRN
•• Respond to worsening of symptoms or side
effects, reinforce compliance.
STICK WITH WHAT WORKS
Remission and maintenance
Bipolar disorder is a recurrent illness. The goal of treatment is full, continuous
remission of symptoms. Nearly 3 in 4 patients will relapse within 5 years, and
many patients who do not have formal relapse will still exhibit significant residual
symptoms. More than 90% of patients who experience one manic episode requiring
hospitalization will have a second episode. Patients hospitalized for mania are
more likely to have a mania relapse than a depressive relapse. Even with lifetime
maintenance therapy, patients may experience only partial remission of symptoms.TOH
Due to the recurrent nature of bipolar disorder—and high probability of relapse—
lifetime maintenance regimens of medication are recommended following the
successful treatment of an acute episode. Although few studies involving patients with
bipolar II disorder have been conducted, consideration of maintenance treatment for
this form of the illness is also strongly warranted. One long-term follow-up study
showed that patients with bipolar II disorder have chronic depressive symptoms more
than half of the time.JUD1, JUD2
Whatever medication or medication regimens
achieved remission of an acute episode
should be continued without reduction of
dosage as tolerated.
The medications with the best
empirical evidence (see medication details
on pages 13 – 16) to support their
use in maintenance treatment include
the following:KUP1,2; LEC1,2; LEX; POS; STA1,2; STO1,2
• Lithium, valproate, olanzapine, and
aripiprazole (better at preventing
manic relapse)
• Quetiapine when used in combination with
lithium and valproate
• Ziprasidone when used in combination with
fluoxetine
• Lamotrigine (better at preventing
depressive relapse)
©2007–2016 INTERMOUNTAIN HEALTHCARE. ALL RIGHTS RESERVED. 21
MANAGEMENT OF BIPOL AR DISORDER MARCH 2016
BE CONSISTENT
Outcomes assessment tools
Measure treatment
outcomes in a consistent,
comprehensive, and efficient
way, using the tools described
on these two pages.
Traditionally, symptomatic outcome measures — such as the Young Mania Rating
Scale or the Hamilton Depression Rating Scale — have been used in bipolar disorder.
These measures focus specifically on the core disease symptoms and are useful in
research. However, bipolar disorder is a highly comorbid condition; over half of patients
also suffer anxiety disorder and substance abuse disorders throughout their lifetime.
Medication side effects can also add a significant burden. For these and other reasons,
basic symptom measures do not adequately track these issues and often miss significant
functional impairment important to both patients and clinicians.
To address shortcomings in traditional outcomes measurement, this CPM recommends
two essential types of clinical measures:
• The clinician-rated Clinical Global Impressions (CGI) Scale for treatment
responseGUY
• The patient-rated Intermountain Disability Scale for functional response
In addition to these clinical measures, having selected patients use a daily mood chart
(see page 23) to track function impairment is also useful.
ASSESS SEVERITY
ROUTINELY
Rate and record the severity
score at the initial visit and at
all subsequent visits.
The Clinical Global Impressions (CGI) ScaleGUY
Requiring only 5 minutes or less to complete, the Clinical Global Impressions (CGI) Scale
is a simple, valid measure of treatment response. In its simplest form, the clinician rates
a patient’s severity of illness and response to treatment. This scale tracks well with
symptom scales, and clinicians often closely agree with each other when scoring the same
patient.
To use the CGI Scale, rate the severity of illness at the initial visit and all subsequent
visits. Based on your experience with this disorder, use the 1 – 7 scale below. Severely ill
patients routinely suffer comorbid illness; incorporate this factor into the rating.
Severity scale 1 – 7:
1
2
3
normal, not ill borderline ill mildly ill 4
5
moderately markedly ill ill 6
7
severely
ill extremely
ill
The Intermountain Disability Scale
Intermountain’s functional disability rating scale (on the next page) can be
downloaded at: https://intermountainhealthcare.org/ext/Dcmnt?ncid=526842760
Instruct the patient to rate their level of disability by asking, “In the past 2 weeks,
how much have your mental health symptoms interfered in the following areas of
life?”
Patients should rate each of the three domains (family life and home
responsibilities, work or school, and social or leisure activities), providing a total
functional disability score from 0 – 30.
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MARCH 2016
MANAGEMENT OF BIPOL AR DISORDER
Intermountain Disability Scale
Access the Intermountain Disability Scale at:
https://intermountainhealthcare.org/
ext/Dcmnt?ncid=526842760
Daily mood charting
RATE IMPAIRMENT DAILY
Daily mood charting provides a way for patients to rate impairment caused by
depressive or manic systems in relation to daily medications, interpersonal stress,
sleep, and other variables. Use of a mood chart is widely recommended for patients
with rapid cycling, particularly those who have mood cycling within a single month.
Recording a mood along with any medications taken, medication changes, or other
events can provide evidence for which interventions are helpful or destabilizing.
Instruct the patient to use this
chart every day to rate impairment
caused by symptoms, medications,
stress, sleep, and other variables.
Daily Mood Tracking Chart
Directions: At the end of each day, use this calendar to record your medications, overall mood, hours of sleep, and other symptoms and/or life events. This will help you
and your healthcare provider monitor and improve your treatment.
Month:
Patient name:
Year:
DATES
1. CHART YOUR MEDS (record number of pills each day)
Name of medication
Pill strength
1
2. CHART YOUR MOOD ( your mood each day and how it
Mania
has affected your ability to function at work, home, or school)
Depression
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31
# pills/day
4
Severe: Completely unable to function or hospitalized
3
Moderate to High: Great difficulty functioning
2
Moderate: Some difficulty functioning
1
Mild: Usual routine not affected much; may be more active than usual
0
Stable mood: no mania or depression
1
Mild: Usual routine not affected much; depressed mood
2
Moderate: Some difficulty functioning
3
Moderate to high: Great difficulty functioning
4
Severe: Completely unable to function or hospitalized
3. RECORD OTHER HABITS AND EVENTS
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31
Access this mood tracking
chart under the “bipolar
disorder” topic at:
intermountainphysician.org/
clinicalprograms
# hours slept last night
Used alcohol or drugs (
if yes – or enter number of drinks)
Other symptoms or life events ( if yes; date and describe on back)
Example symptoms: pain, taking risks, feeling paranoid or irritable
Example life events: argument, promotion, family conflict
© 2008–2015 Intermountain Healthcare. All rights reserved. Patient and Provider Publications MH200 -12/15
*50179*
Trc 50179
©2016 INTERMOUNTAIN HEALTHCARE. ALL RIGHTS RESERVED.
23
MANAGEMENT OF BIPOL AR DISORDER
TOOLS USED FOR SCREENING
AND DIAGNOSIS
Although there is disagreement within
the specialty of child psychiatry regarding
bipolar diagnoses, there are reasonable
guidelines and tools for diagnosing
childhood and adolescent bipolar disorder.
However, it is critical that the care provider
use the symptom expression information
at right and not rely solely on screening
instruments. Validated tools include:
• The MDQ-A (Mood Disorder
Questionnaire-Adolescent).
This screening instrument has been
validated in adolescents, with the parent
report version having the greatest
sensitivity and specificity.WAG
• The Young Mania Rating Scale.
This scale was developed to rate acute
mania severity but also functions as a
screening instrument when rated by a
parent. The P-YMRS is the parent-rated
version of this scale.GRA
• FIND guidelines. Childhood bipolar
disorder may present with symptoms
that are frequent, brief, and intense with
outbursts and behavioral dysregulation
fundamentally different from the adult
presentation of the illness. The FIND
guidelines below include duration and
intensity criteria, and are recommended by
many researchers to ascertain the presence
or absence of manic symptoms.KOW
F I N D GUIDELINES FOR
MARCH 2016
BIPOLAR DISORDER IN CHILDREN AND
ADOLESCENTS
Many emotional and behavioral illnesses of childhood have symptoms that converge
and confuse the identification and appropriate treatment of bipolar disorder in
children and adolescents. Presentation of symptoms often differs from that in adults,
and children tend to have higher rates of chronicity, mixed states, and rapid cycling.
A reliable diagnosis of bipolar disorder in the pediatric population depends
on symptoms:
• Occurring in concert rather than sequentially
• Being considered in the context of age and comorbidity
The diagnosis of cyclothymic disorder in children and adolescents is one year of
both hypomanic and depressive episodes without ever meeting criteria for mania,
depression, or hypomania, while the requirement for adults is 2 years.
Symptom expression
Symptom expression of bipolar disorder in children and adolescents differs from that
of adults and is influenced by developmental changes, temperament, and reaction
to environmental stress. Distinct periods of depression and mania are less likely
in younger populations, and these patients may present with chronic symptoms of
irritability, along with difficulties regulating moods, emotions, and behavior. Younger
children may also have periods of agitation, irritability, and oppositionality as generic
symptoms of any severe mental illness.
Mania in adolescents presents many diagnostic challenges based on historical
reporting. Both adolescents and their parents may either minimize symptoms of
mania (to downplay the seriousness of the situation) or exaggerate these symptoms
(hoping that a bipolar disorder diagnosis will explain the difficulties the patient is
experiencing). Symptoms that typically present include:
PEDIATRIC PATIENTSKOW
• Grandiosity: Determine the child’s ability to distinguish between pretending and
These guidelines can help clinicians
ascertain the presence or absence of manic
symptoms:
• Euphoria/Irritability: Review these moods in the context of special events, the
F
I
N
D
24 Frequency. Symptoms occur
most days of the week.
Intensity. Symptoms are
severe enough to cause extreme
disturbance in 1 domain or
moderate disturbance in 2 or
more domains (school, home,
friends, etc.)
Number. Symptoms occur 3 or
4 times per day.
Duration. Symptoms occur
4 or more hours a day total (not
necessarily contiguous hours)
reality to establish if grandiose symptoms are due to bipolar disorder.
behavior of other children, and exposure to steroids or substance abuse. Irritability
that results in major “meltdowns” lasting hours for trivial reasons should be
separated from less severe irritable moods.
• Decreased need for sleep: A child with bipolar disorder may need 2 hours less
sleep per night (adjusted for age without daytime fatigue). Children with limited
sleep due to mania are often active during the night whereas depressed children
may lie in bed and brood.
• Pressured speech: Speech is louder, faster, and more difficult to interrupt than a
child with ADHD who talks a lot.
• Mood lability: For adolescents, mood lability may be the way mania presents.
In fact, it is not unusual for patients to experience mixed manic and depressive
features of a mood disorder, a more common symptom picture than the persistent
euphoria found in adults.
©2016 INTERMOUNTAIN HEALTHCARE. ALL RIGHTS RESERVED.
MARCH 2016
MANAGEMENT OF BIPOL AR DISORDER
• Racing thoughts: These thoughts should be severe enough to interfere with daily
activities. Parents can help distinguish what behaviors are different than baseline.
• Distractibility: Compare distractibility to baseline symptoms when mood is
euthymic. Symptoms in children with comorbid ADHD should have distractibility
worse than baseline distractibility.
• Increase in goal-directed activity/agitation: Mania may be associated with
periods of copious drawing, writing, or play activities. This should be above and
beyond normal and associated with other diagnostic symptoms.
• Excessive Involvement in Pleasurable or Risky Activities: Hypersexual
behaviors may be present in children with or without a history of childhood
abuse. This behavior may be exhibited in an anxious and compulsive manner.
Hypersexuality in children due to mania can appear as erotic and pleasure-seeking
behaviors that might be appropriate between consenting adults in private but
grossly inappropriate in a child. Sexual and/or seductive advances towards a parent
would not be unusual.
• Psychosis: It is important to differentiate hallucinations or delusions from
common childhood perceptual disturbances such as hearing one’s name called or
other distortions when falling asleep. Symptoms of psychosis frequently occur in
adolescents experience bipolar disorder.
Differential diagnosis and comorbidity
One of the biggest challenges is differentiating children and adolescents with mania
from those with attention deficit hyperactivity disorder (ADHD). These patients
should also be screened for other problems such as learning problems, substance use,
and conduct disorders — and those problems should be treated concurrently.
There are high rates of comorbid disruptive, impulse-control, and conduct disorders
that accompany the bipolar diagnosis. Additionally, in disruptive mood dysregulation
disorder (a depressive disorder), children present with irritability as the chief
complaint. Temper outbursts occur on average more than 3 times per week, but
the moods in between the outbursts are “persistently irritable” unlike with bipolar
disorder where there is often some cycling nature.
Treatment guidelinesKOW
Treatment of bipolar disorder in young patients generally reflects that of adult
patients — and should include patient/family education, psychotherapy, and
pharmacotherapy. Young patients experiencing bipolar symptoms can benefit from
psychosocial interventions (see pages 19 – 20). In addition, patients may require
specialized educational programming, day treatment, and vocational training.
THE IMPORTANCE OF
REFERRAL
Bipolar disorder is relatively rare in
children and complicated to diagnose.
In terms of mania, “Bipolar ‘mood
episodes’ include unusual mood
changes along with unusual sleep
habits, activity levels, thoughts, or
behavior. In a child, these mood and
activity changes must be very different
from their usual behavior and from the
behavior of other children.”NIH Highly
irritable children are more likely to
have ADHD or an anxiety or depressive
disorder.
Red flag symptoms for diagnosing mania
in this patient population include:SHA
• Rage outbursts or verbal or
physical aggression — The patient
may be easily frustrated or provoked.
• Episodes of requiring little sleep
— The patient gets less sleep frequently
without suffering any loss of energy.
• Spontaneous mood shifts — The
patient may be giddy, then depressed,
then angry without any apparent trigger
for the mood shifts.
• Grandiosity – The patient may exhibit
a grossly inflated belief in himself
beyond typical boastfulness.
• Agitation or mania when taking
an antidepressant — The patient
may have had symptoms of being
unusually edgy, happy when taking an
antidepressant.
Given the uncertainty and potential
complications in diagnosing and treating
bipolar disorder in this population,
consultation with or referral to a
child mental health specialist is
recommended before initiating
treatment.
The literature on the use of ECT (see page 20) in pediatric bipolar patients is
extremely limited, and the treatment should only be considered for adolescent
patients suffering from bipolar I disorder with severe symptoms of mania or
depression that are unresponsive to multiple medication therapies.
©2016 INTERMOUNTAIN HEALTHCARE. ALL RIGHTS RESERVED.
25
MANAGEMENT OF BIPOL AR DISORDER
MARCH 2016
FDA-APPROVED MEDICATIONS
Medications
The following medications are approved
for treating bipolar disorder in children
and adolescents as indicated:
The choice of the medications used to treat pediatric bipolar disorder should be based
on evidence of efficacy, the phase of illness (manic versus depressive symptoms), the
drug’s side-effect profile, the patient’s history of medication response, and patient and
family preferences.
• lithium carbonate (Eskalith, Eskalith CR,
Lithobid) — Approved for ages >12 years
as monotherapy for acute mania and
maintenance
• aripiprazole (Abilify) — Approved for
ages >10 years (as monotherapy or in
combination with lithium or valproate (or
divalproex) for acute mania
• asenipine (Saphris) — Approved for ages
>10 years as monotherapy for acute mania/
mixed episodes
• olanzapine (Zyprexa, Zydis) — Approved
for ages >13 years as monotherapy for
acute mania/mixed mania and maintenance
• olanzapine (Zyprexa, Zydis) in
combination with fluoxetine
(Prozac) — Approved for ages 10–17
for treatment of bipolar depression
• quetiapine (Seroquel) — Approved
for ages >10 years as adjunct and
monotherapy for acute mania
• risperidone (Risperidol) — approved for
ages >10 years (as monotherapy for acute
mania/mixed episodes
Prescribing guidelines emphasis a stepwise nature of medication management as well as
rationale for combining medications. At each step in pharmacotherapy, the physician is
balancing the benefits and risks of either staying with a current regimen (if the patient
appears to be stable or improving) or changing medications or doses to optimize
treatment. This process should be very patient-specific, with the following key issues
guiding decision making at each step:SHAI
• Making only one medication change at a time
• Addressing the most problematic symptom or cluster of symptoms first
• Reducing the number of medications that will eventually be needed
• Making management of adverse effects a priority when warranted
• Targeting symptoms that appear to trigger other symptoms
• Preferring medications that work quickly
Both the range of symptoms present with bipolar disorder and the symptoms that
occur as a result of comorbidities often make medication management particularly
challenging for children and adolescents. Combining medications is often
appropriate when:SHAI
• Using an augmentation agent to address only partial response when symptoms either
improve but not to a degree that lessens significant distress or when symptoms fail to
improve at all
• Targeting a specific symptom that causes significant distress such as insomnia
• Cross-tapering medication that is not working as expected with another medication
• Treating symptoms of comorbid disorders such as those with ADHD or
anxiety disorder
CARE MANAGEMENT
The follow-up and maintenance care
of children and adolescents as well as
outcomes assessment tools used follow
the same processes as detailed for adults
on pages xx through xx. Note that, for a
younger child, a parent or other caregiver
would be completing the forms.
26 Use the dosage guidelines in the medication table (page 27) for treating children and
adolescents. For each medication, refer to the adult medication tables on pages 13
through 15 for tier/cost and side effect information that pertain to all populations.
Dosages must be modified for age, and response to treatment must be carefully
monitored. Side effects — particularly weight gain — may be exaggerated in children,
and children are more prone to medication toxicity.
Maintenance and medication monitoring
Patients are likely to require maintenance therapy to prevent symptom relapse with
a recommended trial of 12 to 24 months after an acute manic episode. Decisions to
continue treatment must be weighed along with risks of medication side effects.
Recommended medication monitoring for children and adolescents is the same as for
adults (see Tables 6A and 6B on page 16).
©2016 INTERMOUNTAIN HEALTHCARE. ALL RIGHTS RESERVED.
MARCH 2016
MANAGEMENT OF BIPOL AR DISORDER
TABLE 9. Medications
for treating children and adolescentsELB, LEC2, LEX, STA1, STA2
Strength of
Evidence1
Dosage guidelines2 /Notes (see pages 13 – 16 for specific medication side effects
and monitoring guidelines)
divalproex
sodium
(Depakote,
Depakote ER)
Not FDA
approved for
this population
Mania, bipolar
depression, and
maintenance (C)
Children:
•• Initiate at 125 mg 2 – 3 times daily
•• Increase gradually until side effects limit dose or
therapeutic plasma levels are reached
•• Range: 1000 – 1250 mg/day
lithium
carbonate
(Eskalith,
Eskalith CR,
Lithobid)
Mania, bipolar
depression (C)
maintenance (B)
Ages 6 – 12 years:
•• Initiate at 15 mg/kg/day in 3 – 4 divided doses
•• Adjust dose weekly based on serum concentrations
•• Range: 15 – 60 mg/kg/day (do not exceed adult dosage)
aripiprazole
(Abilify)
Mania,
maintenance (B),
bipolar
depression (C)
Ages ≥ 10 years:
•• Initiate at 2 mg once daily x 2 days
•• Increase to 5 mg PO once daily x 2 days, then may increase in 5 mg increments
•• Range: 10 – 30 mg/day
asenapine
Mania,
maintenance (B),
bipolar
depression (C)
Ages ≥ 10 years (Note: Sublingual administration only; no eating/drinking for 10 minutes after placing under
tongue):
•• Initiate at 2.5 mg twice daily
•• Increase to 5 mg twice daily after 3 days, then to 10 mg twice daily in another 3 days based on tolerability
olanzapine3
(Zyprexa, Zydis)
Mania,
maintenance (B)
bipolar
depression (B)4
Ages 6 – 12 years:
•• Initiate at 2.5 mg at bedtime
•• Increase in 2.5 – 5 mg increments
•• Range: 10 – 20 mg/day
Ages ≥ 12 years:
•• Initiate at 2.5 – 5 mg at bedtime Increase in
2.5 – 5 mg increments weekly
•• Range: 10 – 20 mg/day
combined
with
Bipolar depression:
ages 10 – 17 (C),
ages 6 – 10 (D)
Ages 6 – 10 years:
•• Initiate at 5 mg
•• Increase as clinically indicated
Ages 10 – 17 years:
•• Initiate at 10 mg
•• Increase as clinically indicated
quetiapine
(Seroquel)
Mania,
maintenance (B)
bipolar
depression (C)
Ages ≥ 10 years (Note: May be given once nightly if tolerated):
•• Initiate at 25 mg twice daily
•• Increase to 50 mg twice daily on day 2, then 100 mg twice daily on day 3, 150 mg twice daily on day 4, and
200 mg twice daily on day 5.
•• Range: 400 – 600 mg/day in divided doses
risperidone
(Risperidal)
Mania,
maintenance (B)
bipolar
depression (C)
Ages ≥ 10 years:
•• Initiate at 0.5 mg at bedtime
•• Titrate by 0.5 – 1 mg increments at daily intervals, as tolerated
•• Range: 0.5 – 2.5 mg at bedtime (may be split twice daily)
ziprasidone
(Geodon)
Not FDAapproved for this
population5
Mania (B)
bipolar depression,
maintenance (C)
Ages ≥ 10 years:
•• Initiate at 20 mg once daily with food
•• Titrate as tolerated
•• Range: 60 – 80 mg/day divided twice daily
(weight ≤ 45 kg) or 120 – 160 mg/day divided twice daily (weight > 45 kg)
Metallic salt,
antimanic
Anticonvulsants
Class Medication
(common
brands)
Atypical Antipsychotics
(Saphris)
fluoxetine
(Prozac,
Symbyax)
Adolescents:
•• Initiate at 250 mg 2 – 3 times daily
•• Increase gradually until side effects limit dose
or therapeutic plasma levels are reached
•• Range: 1000 – 2500 mg/day
•• Target: Serum level 50 – 125 mcg/mL (mid to upper range generally required)
Ages ≥ 12 years:
•• Initiate at 300 mg twice daily
•• Increase by ≤ 300 mg per day every 3 – 4 days
•• Range: 600 – 1800 mg/day
•• Target: Serum level 0.8 – 1.2 mEq/L
Strength of evidence key: (A) = Based on data from large controlled trials; (B) = Based on data from smaller controlled trials; (C) = Based on expert opinion, open-label data, or usual-care
experience; (D) = No acute efficacy. NOTE: See FDA-approved medication information for this population in the sidebar on page 26.
1
Some dosage guidelines are based on usual care experience and may differ from manufacturer’s package data.
2
Zyprexa is ONLY FDA-approved for treatment of acute bipolar depression for ages 10 – 17 in combination with fluoxetine and for treatment of acute manic or mixed episodes for
ages 13 – 17.
3
4
Strength of evidence is based on use as an adjunct to lithium or divalproex.
5
While an FDA advisory panel has advised that ziprasidone is effective in patients 10 – 17 years of age for the treatment of mixed and manic episodes of bipolar disorder, they were unable to
conclude that it was safe due to the large number of subjects lost to follow-up and ambiguity within QTc prolongation data
©2016 INTERMOUNTAIN HEALTHCARE. ALL RIGHTS RESERVED.
27
MANAGEMENT OF BIPOL AR DISORDER
USING TEACH-BACK STRATEGIES
What is Teach-back? — Teach-back is a
MARCH 2016
PATIENT/FAMILY EDUCATION
Patient and family education can lead to better compliance and treatment outcomes.
Review the available patient education materials (see page 29) and resources for using
teach-back strategies (see the information at left and the Teach-back Flashcard).
way to confirm that patients understand what
we tell them using open-ended questions that
invite the patient and family to “teach-back”
the information to us. It’s not a test of the
patient’s knowledge — it’s a test of how well
we explained something.
In addition to basic information about the symptoms, neurobiologic basis, and treatment
of the disease, patient education should include the following topics:
Why is it important? — Not
• Warning symptoms and prodromal symptoms. Symptoms may arise weeks or
understanding medical information is a
common reason for readmissions. Teachback is a proven tool for improving patient
understanding.
Who can use it? — Everyone who
explains anything to a patient or family.
When can I use it? — Use early in the
months prior to a full-blown episode. Often, these symptoms are the same before
each episode for an individual patient and are likely to include changes in sleep,
activity level, and impulsivity.FAV, SMI Help patients recognize these symptoms
and act to prevent relapse. Patients who develop strategies to handle prodromal
symptoms are less likely to relapse.LAM Educate family members about prodromal
symptoms; they often notice these changes before the patient is aware of them.
care process and at each decision point
or transition, especially when families or
caregivers are present. Make sure caregivers
participate in the Teach-back process to
ensure they understand key information.
• The effects of substance use and abuse. Alcohol and illegal drug use can
What are the Steps?
• The importance of treatment adherence. Treatment adherence is improved by
1.Explain or demonstrate a concept, using
simple lay language.
Tips: Avoid covering too much at one
time — explain no more than 2 or 3
concepts at a time. Slow down and take
pauses. If you’re giving the patient printed
information, mark or highlight key areas of
the handout or booklet as you explain.
2.Ask the patient/caregiver to repeat
the information in their own words or
demonstrate the process.
Tips: Own the responsibility (“I want to
see whether I explained this well”). Ask
the patient to tell you how he or she would
explain the information to a spouse or
family member. Avoid yes/no questions.
3.Identify and correct misunderstandings.
Tips: Show empathy and caring as you
correct. Avoid making the patient feel
they’ve failed a “test.” Don’t repeat the
entire explanation or demonstration again
unless it’s necessary — just focus on areas
that need clarification.
4.Ask the patient/caregiver to explain or
demonstrate again, to show improved
understanding.
Tips: Own the process again. “Let’s see if
I cleared that up.” Avoid yes/no questions
(such as “do you understand now?”).
lead to more frequent relapse, poor response to lithium, and a more severe course
of illness. Even limited use of alcohol or marijuana can destabilize this illness.
Educate patients who use or abuse substances on how and where to get help.
a better understanding of this illness, its course, and likelihood of relapse. During
times of normal mood or hypomania, patients may not perceive themselves as
being sick or needing treatment. Encourage patients to stick to the medication
schedule even when they are feeling well. Medication side effects may also lead to
poor treatment adherence. Teach patients to recognize and report side effects so
medications can be adjusted.
• The role of stress. Patients who understand the link between stress and symptom
recurrence and then learn strategies for coping with stressful events may be able
to reduce the impact stress has on the onset of mania and depression. Research
indicates that many patients with bipolar disorder suffer from recurring symptoms
after stressful life events that affect one’s ability to attain goals.JOH Additionally,
there is an association between recurrent episode onset and patients who have
experienced childhood physical, sexual, or emotional abuse.GIL
• The connection between sleep and episode severity. It is important to help
patients understand that the amount of sleep they get and the regularity of their
sleep patterns translates to less severe symptoms of both mania and depression.
Results from a study of concurrent and prospective associations from the National
Institute of Mental Health Systematic Treatment Enhancement Program for
Bipolar Disorder (STEP-BD) trial indicated an association between shorter total
sleep time and increased mania severity as well as an association between greater
sleep variability and increased mania and depression severity over 12 months.GRU
5.Continue this loop until you’re convinced
the patient/caregiver understands
the concept.
Tips: Be patient — this process is worth
the time it takes. Continue to be gracious
in the process — patients can worry about
judgment or wasting your time.
28 ©2016 INTERMOUNTAIN HEALTHCARE. ALL RIGHTS RESERVED.
MARCH 2016
MANAGEMENT OF BIPOL AR DISORDER
RESOURCES AND REFERENCES
Intermountain patient resources
Clinicians can order Intermountain patient education booklets and fact sheets for distribution to their patients from Intermountain’s Online Library and
Print Store, iprintstore.org. Call 801-442-3186 for ordering information.
Choose from an array of booklets, trackers, and forms to
help, including:
Mental Health Integration
Mood Disorder Questionnaire (MDQ)
Today’s Date:
Adult
(page 1 of 1)
Patient’s Name:
Date of Birth:
YES
NO
… you felt so good or so hyper that other people thought you were not your normal self,
or you were so hyper that you got into trouble?
…
…
… you were so irritable that you shouted at people or started fights or arguments?
…
…
… you felt much more self-confident than usual?
…
…
1 Has there ever been a period of time when you were not your usual self and…
• PHQ-9
Today’sslow
Date:
… thoughts raced through your head or you couldn’t
your mind down?
Patient’s Name:
Areyou
youthat
currently:
on medication
for depression?
… you were so easily distracted by things around
you had 
trouble
concentrating
or staying on track?
…
…
…
…
Over the last 2 weeks, how often have you been bothered by any of the
following problems?
…
 not sure?
Not at all
Several
days
More than
half the days
Nearly every
day
…
…
0
1
2
3
…
…
0
1
2
3
…
…
0
1
2
3
…
…
0
1
2
3
…
0
1
2
3
…
0
1
2
3
watching
television
3 During the period of time indicated above, do you thinkorany
of these
symptoms were brought on
0
1
2
3
thebeing
opposite
— to
being
so having
fidgety family,
or restless
that or
youlegal
havetroubles;
been or
4 How much of a problem did any of these cause you —orlike
unable
work;
money,
0
1
2
3
0
1
2
3
getting into arguments or fights?
… no problem
…
…
7. Trouble concentrating on things, such as reading the newspaper
by prescription or other drugs?
… minor problem
…
…
8. Moving or speaking so slowly that other people could have noticed,
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31
has affected your ability to function at work, home, or school)
4
Severe: Completely unable to function or hospitalized
3
Moderate to High: Great difficulty functioning
2
Moderate: Some difficulty functioning
1
Mild: Usual routine not affected much; may be more active than usual
0
Stable mood: no mania or depression
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31
1
Mild: Usual routine not affected much; depressed mood
2
Moderate: Some difficulty functioning
3
Moderate to high: Great difficulty functioning
4
Severe: Completely unable to function or hospitalized
3. RECORD OTHER HABITS AND EVENTS
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31
# hours slept last night
moving around a lot more than usual
9. Thoughts that you would be better off dead or of hurting yourself
…inmoderate
… serious problem
some wayproblem
DATES
1
# pills/day
2. CHART YOUR MOOD ( your mood each day and how it
2 If you checked YES to more than one of the above, haveyourself
severalorofyour
these
everdown
happened during
family
the same period of time?
Pill strength
 in counseling?
3. Trouble falling/staying asleep, sleeping too much
… you were much more interested in sex than usual?
6. Feeling bad about yourself — or that you’re a failure or have let
Mood Tracking Chart
Year:
1. CHART YOUR MEDS (record number of pills each day)
Name of medication
… you did things that were unusual for you or that other people might have thought were
4. Feeling tired or having little energy
excessive, foolish, or risky?
…
Month:
Date of Birth:
 not on medication for depression?
…
Adult
(page 1 of 1)
… you were much more social or outgoing than usual;
for example,
you telephoned
friends
2. Feeling
down, depressed,
or hopeless
in the middle of the night?
5. Poor appetite or overeating
… spending money got you or your family into trouble?
• Daily
…
Little
interest
or pleasure in doing things
… you were much more active or did many more1.things
than
usual?
… you had much more energy than usual?
• MDQ
Daily Mood Tracking Chart
Patient Health Questionnaire (PHQ-9)
Total each column
For Office Use Only:
Used alcohol or drugs (
if yes – or enter number of drinks)
Other symptoms or life events ( if yes; date and describe on back)
Example symptoms: pain, paranoia, risky behaviors
Example life events: argument, promotion, family conflict
© 2007 Intermountain Healthcare. All rights reserved. Clinical Education Services 801.442.2963 IHCEDMH200 - 3/08
13 care of things at home, or get along with other people?
How difficult have these problems made it for you to do your work,/take
Reprinted with permission from the American Journal of Psychiatry, (Copyright 2000).
American Psychiatric Association.
A.  Not
©2004–2014 Intermountain Healthcare. All rights reserved.
Patient and Provider Publications 801-442-2963 MHI019 - 10/14
*50402*
difficult at all
 Somewhat difficult
 Very difficult
*50179*
Patient Name:
… you were much more talkative or spoke much faster than usual?
Directions: At the end of each day, use this calendar to record your medications, overall mood, hours of sleep, and other symptoms and/or life events.
This will help you and your healthcare provider monitor and improve your treatment.
Mental Health
Integration
…
…
… you got much less sleep than usual and found you didn’t really miss it?
Mania
Disorder Information for Patients and families
Depression
• Bipolar
Trc 50179
 Extremely difficult
MHI Pack 50402
B. In the past 2 years, have you felt depressed or sad most days, even if you felt okay sometimes?
 YES
 NO
Comments:
For Office Use Only:
Symptom score (total # of answers in shaded areas):
Severity score (total all points from all questions):
*50408*
PHQ 50408
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MANAGEMENT OF BIPOL AR DISORDER
References
ADA American Diabetes Association, American Psychiatric Association, American
Association of Clinical Endocrinologists, and the North American Association
for the Study of Obesity. Consensus development conference on antipsychotic
drugs and obesity and diabetes. Diabetes Care. 2004;27(2):596-601.
AKI Akiskal HS, Maser JD, Zeller PJ, et al. Switching from ‘unipolar’ to bipolar II.
An 11-year prospective study of clinical and temperamental predictors in 559
patients. Arch Gen Psychiatry. 1995;52(2):114-123.
ANG Angst F, Stassen H, Clayton PJ, Angst J. Mortality of patients with mood
disorder: follow-up over 34-38 years. J Affect Disord. 2002;68(2-3):167-181.
APA1 American Psychiatric Association. Diagnostic and Statistical Manual of
Mental Disorders, Fifth Edition. Washington, DC: American Psychiatric
Association; 2013.
MARCH 2016
GHA Ghaemi SN, El-Mallakh RS, Baldassano CF. A randomized clinical trial of
efficacy and safety of long-term antidepressant use in bipolar disorder.
Bipolar Disorder. 2005;7(suppl 2):59.
GIL
Gilman SE, Ni MY, Dunn EC, et al. Contributions of the social environment to
first-onset and recurrent mania. Molecular Psychiatry. 2015;20(3):329–336;
doi:10.1038/mp.2014.36.
GIT
Gitlin MJ, Swensen J, Heller TL, Hammen C. Relapse and impairment in
bipolar disorder. Am J Psychiatry. 1995;152(11):1635-1640.
GOL1 Goldberg JF, Garno JL, Portera L, Leon AC, Kocsis JH, Whiteside JE. Correlates
of suicidal ideation in dysphoric mania. J Affect Disord. 1999;56(1):75-81.
GOL2 Goldberg JF, Garno JL, Leon AC, Kocsis JH, Portera L. A history of substance
abuse complicates remission from acute mania in bipolar disorder. J Clin
Psychiatry. 1999;60(11):733-740.
APA2 APA guidelines for the treatment of patients with bipolar disorder. Am J
Psychiatry. 2002;59(suppl):4.
GOLD Goldstein BI, Velyvis VP, Parikh SV. The association between moderate
alcohol use and illness severity in bipolar disorder: Aapreliminary report.
J Clin Psychiatry. 2006;67(1):102-106.
APA3 American Psychiatric Association. Practice guideline for the treatment of
patients with bipolar disorder (2nd edition). 2010 Washington, DC: American
Psychiatric Association: 51-54.
GOO Goodwin FK, Jamison KR. Manic Depressive Illness. New York, NY: Oxford
University Press; 1990.
APA4 American Psychiatric Association, Task Force on Electroconvulsive Therapy.
The practice of electroconvulsive therapy: Recommendations for treatment,
training, and privileging. Washington, DC: American Psychiatric Association,
2001.
BEN Benazzi F. Unipolar depression with racing thoughts: A bipolar
spectrum disorder? Psychiatry Clin Neurosci. 2005;59(5):570-575.
BIR
Birnbaum HG, Shi L, Dial E, Oster EF, Greenberg PE, Mallett DA. Economic
consequences of not recognizing bipolar disorder patients: a cross-sectional
descriptive analysis. J Clin Psychiatry. 2003;64(10):1201-1209.
BOD Bodnar A, Krzywotulski M, Lewandowska A, et al. Electroconvulsive therapy
and cognitive functions in treatment-resistant depression. World J Biol
Psychiatry. 2016;17(2):159-164.
CAS Cassidy F, Ahearn E, Carroll BJ. Elevated frequency of diabetes mellitus in
hospitalized manic-depressive patients. Am J Psychiatry. 1999;156(9):
1417-1420.
CIP
Cipriani A, Hawton K, Stockton S, Geddes JR. Lithium in the prevention of
suicide in mood disorders: updated systematic review and meta-analysis.
BMJ. 2013;346:f3646. doi: 10.1136/bmj.f3646.
GOT Gothefors D, Adolfsson R, Attvall S, et al; Swedish Psychiatric Association.
Swedish clinical guidelines – prevention and management of metabolic risk
in patients with severe psychiatric disorders. Nord J Psychiatry. 2010;64(5):
294-302.
GRA Gracious BL, Youngstrom EA, Findling RL, Calabrese JR. Discriminative
validity of a parent version of the Young Mania Rating Scale. J Am Acad Child
Adolesc Psychiatry. 2002;41(11):1350-1359.
GRU Gruber J, Miklowitz DJ, Harvey AG, et al. Sleep matters: sleep functioning
and course of illness in bipolar disorder. J Affect Disord. 2011;134(1): 416420. doi:10.1016/j. jad.2011.05.016.
GUY Guy W. ECDEU Assessment Manual for Psychophamacology. Rockville, MD:
U.S. Dept of Health, Education, and Welfare, Public Health Services, Alcohol,
Drug Abuse, and Mental Health Administration, National Institute of Mental
Health, Psychopharmacology Research Branch, Division of Extramural
Research Programs; 1976.
GYU Gyulai L, Bowden CL, McElroy SL, et al. Maintenance efficacy of divalproex
in the prevention of bipolar depression. Neuropsychopharmacology.
2003;28(7):1374-1382.
CRA Craddock N, Sklar P. Genetics of bipolar disorder. Lancet. 2013;381(9878):
1654-1662. doi: 10.1016/S0140-6736(13)60855-7.
HEN1 Hendrick V. Bipolar disorder in pregnant women: treatment of major
depression. In: UpToDate, Keck P (Ed), UpToDate, Waltham, MA. Updated
January 11, 2016. Accessed on April 13, 2016.
EIMA Ei-Mallakh RS, Karippot A. Antidepressant-associated chronic irritable
dysphoria (acid) in bipolar disorder: a case series. J Affect Disord. 2005;84(23):267-272.
HEN2 Hendrick V. Bipolar disorder in pregnant women: treatment of mania and
hypomania. In: UpToDate, Keck P, Wilkins-Haug L (Eds), UpToDate, Waltham,
MA. Updated January 11, 2016. Accessed on April 13, 2016.
ELB
Elbe D, Bezchlibnyk-Butler KZ, Virani AS, Procyshyn RM, eds. Clinical
Handbook of Psychotropic Drugs for Children and Adolescents (3rd ed.).
Boston, MA: Hogrefe; 2015.
ELM Elmslie JL, Silverstone JT, Mann JI, Williams SM, Romans SE. Prevalence of
overweight and obesity in bipolar patients. J Clin Psychiatry. 2000;61(3):
179-184.
FAV
Fava GA, Kellner, R. Prodromal symptoms in affective disorders. Am J
Psychiatry. 1991;148(7):823-830.
FRA Frank E, Soreca I, Swartz HA, et al. The role of interpersonal and social
rhythm therapy in improving occupational functioning in patients with
bipolar I disorder. Am J Psychiatry. 2008;165(12):1559-1565. doi:10.1176/
appi.ajp.2008.07121953.
FRY1 Frye MA, Calabrese JR, Reed ML, et al. Use of health care services
among persons who screen positive for bipolar disorder. Psychiatr Serv.
2005;56(12):1529-1533.
FRY2 Frye MA, Altshuler LL, McElroy SL, et al. Gender differences in prevalence,
risk, and clinical correlates of alcoholism comorbidity in bipolar disorder. Am
J Psychiatry. 2003;160(5):883-889.
30 HEN3 Hendrick V. Bipolar disorder in women: preconception and prenatal
maintenance pharmacotherapy. In: UpToDate, Keck P (Ed), UpToDate,
Waltham, MA. Updated January 12, 2016. Accessed on April 13, 2016.
HEN4 Hendrick V. Teratogenic, pregnancy complications, and postnatal risks of
antipsychotics, benzodiazepines, lithium, and electroconvulsive therapy. In:
UpToDate, Keck P (Ed), UpToDate, Waltham, MA. Updated January 14, 2016.
Accessed on April 13, 2016.
HIR1 Hirschfeld RM, Lewis L, Vornik LA. Perceptions and impact of bipolar
disorder: how far have we really come? Results of the National Depressive
and Manic-depressive Association 2000 survey of individuals with bipolar
disorder. J Clin Psychiatry. 2003;64(2):161-174.
HIR2 Hirschfeld RM, Calabrese JR, Weissman MM, et al. Screening for
bipolar disorder in the community. J Clin Psychiatry. 2003;64(1):53-59.
HIR3 Hirschfeld RM, Williams JB, Spitzer RL, et al. Development and
validation of a screening instrument for bipolar spectrum disorder: the Mood
Disorder Questionnaire. Am J Psychiatry. 2000;157(11):1873-1875.
HSIN Hsin H, Suppes T. Psychopharmacology of bipolar II depression and bipolar
depression with mixed features. Focus. 2014;12(2):137-143. http://dx.doi.
org/10.1176/appi.focus.12.2.136.
©2016 INTERMOUNTAIN HEALTHCARE. ALL RIGHTS RESERVED.
MARCH 2016
MANAGEMENT OF BIPOL AR DISORDER
HUS Husain MM, Rush AJ, Fink M, et al. Speed of response and remission in
major depressive disorder with acute electroconvulsive therapy (ECT):
a Consortium for Research in ECT (CORE) report. J Clin Psychiatry.
2004;65(4):485-491.
JOH
Johnson SL. Life events in bipolar disorder: towards more specific models.
Clin Psychol Rev. 2005;25(8):1008-1027.
JUD1 Judd LL, Akiskal HS, Schettler PJ, et al. The long-term natural history of
the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry.
2002;59(6):530-537.
JUD2 Judd LL, Akiskal HS, Schettler PJ, et al. A prospective investigation of the
natural history of the long-term weekly symptomatic status of bipolar II
disorder. Arch Gen Psychiatry. 2003;60(3):261-269.
KEC
Keck PE; Annenberg Center for the Health Sciences; Expert Knowledge
Systems, LLC. Treatment of Bipolar Disorder 2004. Minneapolis, MN:
McGraw-Hill; 2004.
LEC2 Leckband, SG. Bipolar disorder. In: College of Psychiatric & Neurologic
Pharmacists: 2014-2015 Psychiatric Pharmacotherapy Review Course.
Lincoln, Nebraska: College of Psychiatric & Neurologic Pharmacists; 2014.
LEX
Lexicomp Online. Wolters Kluwer Web site. http://www.wolterskluwercdi.
com/lexicomp-online/ Accessed September 13, 2015.
LIC
Lichtenstein P, Yip BH, Björk C, et al. Common genetic determinants of
schizophrenia and bipolar disorder in Swedish families: a population-based
study. Lancet. 2009;373(9659):234-239.
LIE
Lieberman JA, Stroup TS, McEvoy JP, et al; Clinical Antipsychotic Trials
of Intervention Effectiveness (CATIE) investigators. Effectiveness of
antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med.
2005;353(12):1209-1223.
LIN
Lingam R, Scott J. Treatment non-adherence in affective disorders. Acta
Psychiatr Scand. 2002;105(3):164-172.
KEL1 Kellner CH, Knapp R, Husain MM, et al. Bifrontal, bitemporal and right
unilateral electrode placement in ECT: randomised trial. Br J Psychiatry.
2010;196(3):226-234. doi: 10.1192/bjp.bp.109.066183.
LOO Loo C, Katalinic N, Mitchell PB, Greenberg B. Physical treatments for bipolar
disorder: a review of electroconvulsive therapy, stereotactic surgery and
other brain stimulation techniques. J Affect Disord. 2011;132(1-2):1-13. doi:
10.1016/j.jad.2010.08.017.
KEL2 Kellner CH, Greenberg RM, Murrough JW, Bryson EO, Briggs MC,
Pasculli RM. ECT in treatment-resistent depression. Am J Psychiatry.
2012;169(12):1238-1244. doi: 10.1176/appi.ajp.2012.12050648.
MAH Mahmood T, Romans S, Silverstone T. Prevalence of migraine in bipolar
disorder. J Affect Disord. 1999;52(1-3):239-241.
KES1 Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE. Prevalence,
severity, and comorbidity of 12-month DSM-IV disorders in the National
Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):617-627.
KES2 Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE.
Lifetime prevalence and age-of-onset distributions of DSM-IV disorders
in the National Comorbidity Survey Replication. Arch Gen Psychiatry.
2005;62(6):593-602.
KES3 Kessler RC, Akiskal HS, Ames M, et al. Prevalence and effects of mood
disorders on work performance in a nationally representative sample of U.S.
workers. Am J Psychiatry. 2006;163(9):1561-1568.
KES4 Kessler RC, Rubinow DR, Holmes C, Abelson JM, Zhao S. The epidemiology
of DSM-III-R bipolar I disorder in a general population survey. Psychol Med.
1997;27(5):1079-1089.
KESS Kessler U, Schoeyen HK, Adnreassen OA, et al. The effect of
electroconvulsive therapy on neurocognitive function in treatment-resistant
bipolar disorder depression. J Clin Psychiatry. 2014;75(11):e1306-e1313. doi:
10.4088/JCP.13m08960.
KIE
Kieseppa T, Partonen T, Haukka J, Kaprio J, Lonnqvist J. High
concordance of bipolar I disorder in a nationwide sample of twins. Am J
Psychiatry. 2004;161(10):1814-1821.
KUP1 Kupka R. Rapid cycling bipolar disorder in adults: treatment of mania and
hypomania. In: UpToDate, Keck P (Ed), UpToDate, Waltham, MA. Updated
June 4, 2015. Accessed on September 13, 2015.
KUP2 Kupka R. Rapid cycling bipolar disorder in adults: treatment of major
depression. In: UpToDate, Keck P (Ed), UpToDate, Waltham, MA. Updated
August 30, 2015. Accessed on September 13, 2015.
KOW Kowatch RA, Fristad M, Birmaher B, et al. Treatment guidelines for children
and adolescents with bipolar disorder: child psychiatric workgroup on
bipolar disorder. J Am Acad Child Adolesc Psychiatry. 2005;44(3):213-235.
LAK Lakshmi NY, Kennedy SH, Parikh SV, et al. Canadian Network for Mood
and Anxiety Treatments (CANMAT) and International Society for Bipolar
Disorders (ISBD) collaborative update of CANMAT guidelines for the
management of patients with bipolar disorder: update 2013. Bipolar
Disorders. 2013;15(1):1-44. doi: 10.1111/bdi.12025.
MANS Mansur RB, McIntyre RS. Metabolic comorbidity and physical health
implications for bipolar disorder: an update. Focus. 2015;13(1):12-18.
doi: 10.1176/appi.focus.130105.
MAR Marder S, Stroup TS. Pharmacotherapy for schizophrenia: side effect
management. In: UpToDate, Stein MB (Ed), UpToDate, Waltham, MA.
Updated March 28, 2016. Accessed April 13, 2016.
MCG McGuffin P, Rijsdijk F, Andrew M, Sham P, Katz R, Cardno A. The heritability
of bipolar affective disorder and the genetic relationship to unipolar
depression. Arch Gen Psychiatry. 2003;60(5):497-502.
MIK
Miklowitz DJ, Gitlin MJ. Psychosocial approaches to the treatment of bipolar
disorder. Focus. 2015;13(1):37-46. doi: 10.1176/appi.focus.130106.
MOL Moller HJ, Nasrallah HA. Treatment of bipolar disorder. J Clin Psychiatry.
2003;64(suppl 6):9-17.
NIH
National Institute of Mental Health. Bipolar disorder in children and teens.
NIH Publication Number QF 15-6380. Revised 2015. http://www.nimh.nih.
gov/health/publications/bipolar-disorder-in-children-and-teens-qf-15-6380/
index.shtml. Accessed April 27, 2016.
NOR Nordenson B, Gruber SA, Yurgelun-Todd DA. Neurocognition in bipolar
disorder: a review of the current research. Current Psychosis Ther Rep.
2004;2(4):147-152. doi: 10.1007/BF02629416.
NUR Nurnberger JI Jr, Koller DL, Jung J, et al. Identification of pathways for bipolar
disorder: a meta-analysis. JAMA Psychiatry. 2014;71(6):657-664.doi:10.1001/
jamapsychiatry.2014.176.
PAL
Palmer BA, Pankratz VS, Bostwick J. The lifetime risk of suicide in
schizophrenia: a reexamination. Arch Gen Psychiatry. 2005;62(3):247-253.
PAR Parikh SV, Zaretsky A, Beaulieu S, et al. A randomized controlled trial of
psychoeducation or cognitive-behavioral therapy in bipolar disorder: a
Canadian Network for Mood and Anxiety Treatments (CANMAT) study. J Clin
Psychiatry. 2012;73(6):803-810. doi: 10.4088/JCP.11m07343.
PEE
Peele PB, Xu Y, Kupfer DJ. Insurance expenditures on bipolar disorder: clinical
and parity implications. Am J Psychiatry. 2003;160(7):1286-1290.
PER
Perlis RH, Brown E, Baker RW, Nierenberg AA. Clinical features of bipolar
depression versus major depressive disorder in large multicenter trials. Am J
Psychiatry. 2006;163(2):225-231.
LAM Lam D, Wong G, Sham P. Prodromes, coping strategies and course of illness
in bipolar affective disorder—a naturalistic study. Psychol Med. 2001;31(8):
1397-1402.
POST Post RM. Bipolar disorder in adults: choosing maintenance treatment. In:
UpToDate, Keck P (Ed), UpToDate, Waltham, MA. Updated January 7, 2016.
Accessed on April 13, 2016.
LEC1 Leckband SG, Kelsoe JR, Dunnenberger HM, et al; Clinical Pharmacogenetics
Implementation Consortium. Clinical Pharmacogenetics Implementation
Consortium guidelines for HLA-B genotype and carbamazepine dosing. Clin
Pharmacol Ther. 2013;94(3):324-328.
PRI
©2016 INTERMOUNTAIN HEALTHCARE. ALL RIGHTS RESERVED.
Prien RF, Himmelhoch JM, Kupfer DJ. Treatment of mixed mania. J Affect
Disord. 1988;15(1):9-15.
SAC Sachs GS, Nierenberg AA, Calabrese JR, et al. Effectiveness of adjunctive
antidepressant treatment for bipolar depression. N Engl J Med. 2007;356(17):
1711-1722.
31
MANAGEMENT OF BIPOL AR DISORDER
MARCH 2016
SAR Sareen J, Cox B, Afifi T, et al. Anxiety disorders and risk for suicidal ideation
and suicide attempts: a population-based longitudinal study of adults. Arch
Gen Psychiatry. 2005;62(11):1249-1257.
SCHI Schiffer RB, Wineman NM, Weitkamp LR. Association between bipolar
affective disorder and multiple sclerosis. Am J Psychiatry. 1986;143(1):94-95.
SCHN Schneck CD, Miklowitz DJ, Calabrese JR, et al. Phenomenology of rapidcycling bipolar disorder: data from the first 500 participants in the Systematic
Treatment Enhancement Program. Am J Psychiatry. 2004;161(10):1902-1908.
SHA Shah NN, Averill PM, Shack A. Mixed versus manic bipolar disorder: a
comparison of demographic, symptomatic, and treatment differences.
Psychiatr Q. 2004;75(2):183-196.
SHAI Shain BN; Committee on Adolescence. Clinical report: Collaborative role
of the pediatrician in the diagnosis and management of bipolar disorder in
adolescents. Pediatrics. 2012;130(6):e1723-e1742.
SMI
Smith JA, Tarrier N. Prodromal symptoms in manic depressive
psychosis. Soc Psychiatry Psychiatr Epidemiol. 1992;27(5):245-248.
STA1 Stahl SM. Prescriber’s Guide: Stahl’s Essential Psychopharmacology (5th ed).
New York, NY: Cambridge University Press; 2014.
STA2 Stahl SM. Stahl’s Essential Psychopharmacology: Neuroscientific Basis and
Practical Applications (4th ed). New York, NY: Cambridge University Press;
2013.
STO1 Stovall J. Bipolar disorder in adults: pharmacotherapy for acute mania and
hypomania. In: UpToDate, Keck P (Ed), UpToDate, Waltham, MA. Updated
March 14, 2016. Accessed on April 13, 2016.
STO2 Stovall J. Bipolar disorder in adults: pharmacotherapy for acute depression.
In: UpToDate, Keck P (Ed), UpToDate, Waltham, MA. Updated December 22,
2015. Accessed on April 13, 2016.
SUP1 Suppes T, Leverich GS, Keck PE, et al. The Stanley Foundation
Bipolar Treatment Outcome Network II: demographics and illness
characteristics of the first 261 patients. J Affect Disord. 2001;67(1-3):45-59.
SUP2 Suppes T, Mintz J, McElroy SL, et al. Mixed hypomania in 908 patients with
bipolar disorder evaluated prospectively in the Stanley Foundation Bipolar
Treatment Network: a sex-specific phenomenon. Arch Gen Psychiatry.
2005;62(10):1089-1096.
TOH Tohen M, Zarate CA Jr, Hennen J, et al. The McLean-Harvard First-Episode
Mania Study: prediction of recovery and first recurrence. Am J Psychiatry.
2003;160(12):2099-2107.
TOR Torrent C, Bonnin Cdel M, Martinez-Arán A, et al. Efficacy of functional
remediation in bipolar disorder: a multicenter randomized controlled study.
Am J Psychiatry. 2013;170(8):852-859.
VA
Department of Defense, Department of Veterans Affairs. VA/DoD
Clinical Practice Guideline for Management of Bipolar Disorder in Adults.
Washington, DC: Department of Defense, 2010. 43-58.
VER
Versiani M, Cheniaux E, Landeira-Fernandez J. Efficacy and safety of
electroconvulsive therapy in the treatment of bipolar disorder: a systematic
review. J ECT. 2011;27(2):153-164. doi: 10.1097/YCT.0b013e3181e6332e.
WAG Wagner KD, Hirschfeld RM, Emslie GJ, Findling RL, Gracious BL, Reed ML.
Validation of the Mood Disorder Questionnaire for bipolar disorders in
adolescents. J Clin Psychiatry. 2006;67(5):827-830.
WEE Weeke A, Juel K, Vaeth M. Cardiovascular death and manic-depressive
psychosis. J Affect Disord. 1987;13(3):287-292.
WEI
Weissman MM, Johnson J. Drug use and abuse in five US communities.
N Y State J Med. 1991;91(11 Supp):19S-23S.
WHE Wher TA, Deal S. Rapid cycling affective disorder: contributing factors and
treatment responses in 51 patients. Am J Psychiatry. 1988;145(2):179-184.
doi: 10.1176/ajp.145.2.179.
WHO Global burden of disease (GBD). World Health Organization web site. http://
www.who.int/healthinfo/global_burden_disease/gbd/en/. Accessed March
15, 2016.
YON Yonkers KA, Vigod S, Ross LE. Diagnosis, pathophysiology, and management
of mood disorders in pregnant and postpartum women.
Obstet Gynecol. 2011;117(4):961-977. doi: 10.1097/AOG.0b013e31821187a7.
CPM DEVELOPMENT TEAM
Mark Foote, MD
Christopher Rich, MD
Richard Arbogast, MD
Carolyn Tometich, APRN
Nathan Parent, PharmD
Richard Martini, MD
Shannon Saldana, MD
George Nikopoulos, MD
Sam Weber, MD
This CPM presents a model of best care based on the best available scientific evidence at the time of publication. It is not a prescription for every physician or
every patient, nor does it replace clinical judgment. All statements, protocols, and recommendations herein are viewed as transitory and iterative. Although
physicians are encouraged to follow the CPM to help focus on and measure quality, deviations are a means for discovering improvements in patient care and
expanding the knowledge base. Send feedback to Mark Foote, MD, Intermountain Healthcare, Medical Director Behavioral Health ([email protected])
or Carolyn Tometich, APRN, Intermountain Healthcare, Behavioral Health Operations Director ([email protected]).
32
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