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Bipolar Affective Disorder

Synonyms: bipolar disorder, manic-depressive disorder

Background: Manic-depressive illness (MDI) is one of the most common, severe,

and persistent mental illnesses. It is characterized by periods of deep, prolonged, and
profound depression that alternate with periods of excessively elevated and/or
irritable mood known as mania. The symptoms of mania include a decreased need
for sleep, pressured speech, increased libido, reckless behavior without regard for
consequences, grandiosity, and severe thought disturbances, which may or may not
include psychosis. Between these highs and lows, patients usually experience
periods of higher functionality and can lead a productive life. MDI is a serious lifelong
struggle and challenge (Bowden, 2003). MDI has been recognized for a long time.
Hippocrates described patients as "amic" and "melancholic." In 1899, Emil Kraepelin
defined MDI. He noted that persons with this problem did not suffer the deterioration
and dementia associated with schizophrenia.

MDI constitutes one pole of a spectrum of mood disorders including bipolar I (BPI),
bipolar II (BPII), cyclothymia (oscillating high and low moods), and major depression.
BPI also is referred to as classic manic-depression, characterized by distinct
episodes of major depression contrasting vividly with episodes of mania, which lead
to severe impairment of function. In comparison, BPII is a milder disorder consisting
of depression alternating with periods of hypomania. Hypomania may be thought of
as a less severe form of mania that does not include psychotic symptoms or lead to
major impairment of social or occupational function.

Pathophysiology: The etiology and pathophysiology of bipolar disorder have not

been determined, and no objective biological markers exist that correspond
definitively with the disease state. However, twin, family, and adoption studies all
indicate strongly that bipolar disorder has a genetic component. In fact, first-degree
relatives of a person with bipolar disorder are approximately 7 times more likely to
develop bipolar disorder than the rest of the population. Genetic studies of patients
with bipolar disorder are ongoing and are expected to be facilitated by recent
advances in information and technology developed, in part, by the Human Genome
Project.
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Other molecular genetic approaches also are being used to gain insight into the
pathophysiology of bipolar disorder. For instance, investigators have demonstrated
recently that 2 chemically unrelated drugs used to treat bipolar disorder, lithium and
valproate, both up-regulate the expression of the cytoprotective protein in the frontal
cortex and the hippocampus of rat brains. Neuroimaging studies of individuals with
bipolar disorder or other mood disorders also suggest evidence of cell loss in these
same brain regions. Thus, a suggested cause of bipolar disorder is abnormal
programmed cell death, or apoptosis, in critical brain circuitry that regulates emotion.
According to this hypothesis, mood stabilizers and antidepressants are thought to
alter mood by stimulating cell survival pathways and increasing levels of neurotrophic
factors to improve cellular resiliency.

• In the US: Lifelong prevalence rate of bipolar disorder in the United States is
1-1.6%. The 2 types of disorders differ in adult populations, with approximately
0.8% having BPI and 0.5% having BPII.
• Internationally: Lifelong prevalence rate is 0.3-1.5%.

Mortality/Morbidity: MDI has a very significant morbidity and mortality rate. In terms
of lost work, the cost of lost productivity resulting from this illness in the United States
during the early part of the 1990s was estimated at approximately $15.5 billion
annually. Approximately 25-50% of individuals with MDI attempt suicide, and 11%
actually commit suicide.

Race: No racial predilection exists. However, a point of historical interest is that

clinicians often tend to consider populations of African Americans and Hispanics as
more likely to be diagnosed with schizophrenia than with affective disorders and MDI.

Sex: BPI occurs equally in both sexes; however, rapid-cycling bipolar disorder (4 or
more episodes a year) is more common in women than in men. Incidence of BPII is
higher in females than in males.

Age: The age of onset of MDI varies greatly. The age range for both types of bipolar
disorders is from childhood to 50 years, with a mean age of approximately 21 years.
Most cases commence when individuals are aged 15-19 years. The second most
frequent age of onset is 20-24 years. Some patients diagnosed as having recurrent
major depression may indeed have bipolar disorder and go on to develop their first
manic episode after age 50 years. They may have a family history of bipolar disorder.
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However, for most patients, the onset of mania after age 50 years should lead to an
investigation for medical or neurological disorders such as cerebrovascular disease.

CLINICAL

The diagnosis of BPI disorder requires the presence of a manic episode of at least 1
week's duration that leads to hospitalization or other significant impairment in
occupational or social functioning. The episode of mania cannot be caused by
another medical illness or by substance abuse. These criteria are based on the
specifications of the Diagnostic and Statistical Manual of Mental Disorders, Fourth
Edition, Text Revision (DSM-IV-TR).

• Manic episodes are characterized by the following symptoms:

o At least 1 week of profound mood disturbance is present, characterized

by elation, irritability, or expansiveness

o Three or more of the following symptoms are present:

 Grandiosity
 Diminished need for sleep
 Excessive talking or pressured speech
 Racing thoughts or flight of ideas
 Clear evidence of distractibility
 Increased level of goal-focused activity at home, at work, or
sexually
 Excessive pleasurable activities, often with painful consequences

o The mood disturbance is sufficient to cause impairment at work or

danger to the patient or others.
o The mood is not the result of substance abuse or a medical condition.
o In many ways, the behavior of a patient in the manic phase reflects
behavior opposite of a person in the depressed phase. Patients experiencing the
manic phase are hyperactive and might be hypervigilant. They are restless,
energized, and active. They talk and act fast. Their attire reflects the mania.
Their clothes might have been put on in haste and are disorganized. Alternately,
their garments often are too bright, colorful, or garish. They stand out in a crowd
because their dress frequently attracts attention.
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o The mood is inappropriately joyous, elated, and jubilant. They are
euphoric. They also may demonstrate annoyance and irritability, especially if the
mania has been present for a significant length of time.
o During the manic phase, patients have very expansive and optimistic
thinking. They may be excessively self-confident and/or grandiose. They often
have a very rapid production of ideas and thoughts. They perceive their minds
as being very active and see themselves as being highly engaging and creative.
They are highly distractible and quickly shift from one subject to another.
o Approximately three fourths of patients in the manic phase have
delusions. As in major depression, the delusional content is either consistent or
inconsistent with the mania. Manic delusions reflect perceptions of power,
prestige, position, self-worth, and glory.
o Persons in mania can be openly combative and aggressive. They have
no patience or tolerance for others. They can be highly demanding, violently
assertive, and highly irritable. The homicidal element particularly emerges if
these individuals have a delusional content to their mania. They are acting out of
the grandiose belief that others must obey their commands, wishes, and
directives. If their delusions become persecutory in nature, they may defend
themselves against others in a homicidal fashion.
o The hallmark of this phase is seriously impaired judgment. They make
terrible decisions in terms of their work and family. They may invest the family
fortune in very questionable programs. They may become professionally over-
involved in work activities or with coworkers. They start a series of dramatic very
unsound fiscal or professional ventures. They do not listen to any feedback,
suggestions, or advice from friends, family, or colleagues. They have no insight
into the extreme nature of their demands, plans, and behavior. Often,
commitment proves the only way to contain them.

• Hypomanic episodes are characterized by the following:

o The patient has an elevated, expansive, or irritable mood of at least 4 days'

duration.

o Three or more of the following symptoms are present:

 Grandiosity or inflated self-esteem
 Diminished need for sleep
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 Pressured speech
 Racing thoughts or flight of ideas
 Clear evidence of distractibility
 Psychomotor agitation at home, at work, or sexually
 Engaging in activities with a high potential for painful
consequences

o The mood disturbance is observable to others.

o The mood is not the result of substance abuse or a medical condition.
o These patients are busy, active, and involved. They have energy and are always
on the go. They are always planning and doing things. Others notice their
energy levels and mood changes. Their mood is up, expansive, and often
irritable.
o Patients in this state are optimistic, forward thinking, and have a positive
attitude.
o Patients in this state do not experience perceptual disturbances.
o Patients who are hypomanic frequently show evidence of irritability and
aggressiveness. They can be pushy and impatient with others.
o Generally, these people have good but expansive judgment. They may take on
too many tasks or become over-involved. Often, their distractibility impairs their
judgment, and they have little insight into their driven qualities. They see
themselves as productive and conscientious, not as hypomanic.

• Major depressive episodes are characterized by the following:

o For the same 2 weeks, the person experiences 5 or more of the following
symptoms, with at least 1 of them being either a depressed mood or
characterized by a loss of pleasure or interest:
 Depressed mood
 Markedly diminished pleasure or interest in nearly all activities
 Significant weight loss or gain or significant loss or increase in appetite
 Hypersomnia or insomnia
 Psychomotor retardation or agitation
 Loss of energy or fatigue
 Decreased concentration ability or marked indecisiveness
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 Preoccupation with death or suicide; patient has either a plan or has
attempted suicide

o The symptoms cause significant impairment and distress.

o The mood is not the result of substance abuse or a medical condition.
o Persons experiencing a depressed episode demonstrate poor to no eye contact.
Their clothes are unkempt, unclean, holed, unironed, and ill fitting. If significant
weight loss has occurred, the garments may fit loosely. The personal hygiene of
individuals experiencing a depressed episode reflects their low mood, as
evidenced by poor grooming, lack of shaving, and lack of washing. In women,
fingernails may show different layers of polish or one layer partially removed.
They may not have paid attention to their hair. Men may exhibit dirty fingernails
and hands. When these individuals move, their depressed affect is
demonstrated. They move slowly and very little. They show psychomotor
retardation. They may talk in low tones or in a depressed or monotone voice.
o Sadness dominates the affect of individuals experiencing a depressed episode.
They feel sad, depressed, lost, vacant, and isolated. The “2 Hs” command their
mood, hopeless and helpless. When in the presence of such patients, one
comes away feeling sad and down.
o Patients experiencing a depression have thoughts that reflect their sadness.
They are preoccupied with negative ideas and nihilistic concerns, and they
metaphorically see “the glass as half empty." They likely are to focus on death
and morbid subjects. Many think about suicide.
o Two forms of a major depression are described. One has psychotic features and
the other does not. With psychosis, the patient experiences delusions and
hallucinations that are either consistent or inconsistent with the mood. In the
former, the patient's delusions of having sinned are accompanied by guilt and
remorse or the patient feels he or she is utterly worthless and should live in total
deprivation and degradation. Hence, the delusional content remains consistent
with the depressed affect. In contrast, some patients experience delusions that
are inconsistent with the depression. For example, the individual feels that he is
the Messiah in the presence of his very depressed affect.
o Depressed patients have a very high rate of suicide. They are the individuals
who attempt and succeed at killing themselves. Query patients to determine if
they have any thoughts of hurting themselves (suicidal ideation) and any plans
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to do so. The more specific the plan, the higher the danger. As patients emerge
from a period of depression, their suicide risk may increase. This may be
because, as the illness remits, executive functions are improved such that the
person is again capable of making and carrying out a plan.
o Generally, suicide remains the paramount issue. However, certain persons in
the depths of a depression not only see the world as hopeless and helpless for
themselves but also for others. Frequently, that perspective can create and lead
to a homicide followed by a suicide. One example of this occurred when a 42-
year-old mother of 2 was experiencing a significant depression as part of her
bipolar disorder. She believed the earth was doomed and was a terrible place to
dwell. Furthermore, she thought that if she died, her children would be left in a
wretched place. Because of this view, she planned to kill her 2 children and then
herself. Fortunately, her family recognized the state of affairs, which led to an
emergency intervention and her hospitalization.
o Depression clouds and dims these individuals' judgment and colors their
insights. They fail to make important actions because they are so down and
preoccupied with their own plight. They see no tomorrow; therefore, planning for
it is very difficult. Frequently, persons in the middle of a depression have done
things such as forgetting to pay their income taxes. At that time, they have little
insight into their behavior. Often, others have to persuade them to seek therapy
because of their lack of insight.

• Mixed episodes are characterized by the following:

o Persons must meet both the criteria for mania and major depression;
the depressive event is required to be present for 1 week only.
o The mood disturbance results in marked disruption in social or vocation
function.
o The mood is not the result of substance abuse or a medical condition.
The patient exhibits both depression and mania within a brief period of time (1 wk
or less).
o Patients in this state can oscillate dramatically between depression and
euphoria, and often they demonstrate marked irritability.
o Patients might exhibit delusions and hallucinations consistent with
either depression or mania or congruent to both.
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Causes: Bipolar disorder has a number of contributing factors, including genetic,
biochemical, psychodynamic, and environmental elements.

Bipolar disorder, especially BPI, has a major genetic component. The evidence
indicating a genetic role in bipolar disorder takes several forms. Twin studies
demonstrate a concordance of 33-90% for BPI in identical twins. Children whose
biologic parents have either BPI disorder or a major depressive disorder remain at
increased risk of developing an affective disorder, even if they are reared in a home
with adopted parents who are not affected. Because of the nature of their work,
certain individuals have periods of high demands followed by periods of few
requirements. For example, one person was a landscaper and gardener. In the
spring, summer, and fall, he was very busy. During the winter, he was relatively
inactive except for plowing snow. Thus, he appeared manic for a good part of the
year, and then he would crash and hibernate for the cold months.

A number of reasons exist to obtain the following laboratory studies. First, the
practitioner needs to perform the tests to determine the diagnosis. Because bipolar
disorder encompasses both depression and mania and because a significant number
of medical causes for each state exists, an extensive range of tests is indicated. The
basic principle remains, "do not miss a treatable medical cause for the mental status."
Second, the physician employs a number of medications that require certain body
systems to be working properly; for example, lithium requires an intact genitourinary
(GU) system and can affect certain other systems, and certain anticonvulsants can
suppress bone marrow. Third, because bipolar illness is a lifelong disorder,
performing certain baseline studies is important to establish any long-term effects of
the medications.

Medical Care: The treatment of bipolar disorder is directly related to the phase of the
episode, eg, depression or mania, and the severity of that phase. For example, a
person who is extremely depressed and exhibits suicidal behavior requires inpatient
treatment. In contrast, an individual with a moderate depression who still can work
would be treated as an outpatient.

Inpatient hospital treatment: The indications for hospitalization in a person with

bipolar disorder include the following:
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◊ Danger to self: A patient, especially one in a depressive episode, may
present with a significant risk for suicide. Serious suicide attempts and
specific ideation with plans constitute clear evidence of the need for constant
observation and preventive protection; however, in other situations, the
danger to the person may come from other aspects of the disease. For
example, a person who is depressed enough to not eat might be at risk of
death. Alternately, a person in extreme mania, who foregoes rest, sleep, or
food, may be in a state of serious exhaustion.
◊ Danger to others: Patients with bipolar disorder can become a threat to
others. For example, a patient experiencing a severe depression believed
the world was so bleak that she planned to kill her children to spare them
from the world's misery. In the other extreme, a delusional patient having a
manic episode believed everyone was against him; he searched for a rifle in
order to defend himself and to get them before they got him.
◊ Total inability to function: Occasionally, depression is so profound that the
person cannot function at all. Leaving such a person alone would be
dangerous and not therapeutic.
◊ Totally out of control: This is true especially during a manic episode. In this
situation, a person's behavior is so beyond limits, they are destroying their
career and can be harmful to those around them.
◊ Medical conditions that warrant medication monitoring: For example, patients
with certain cardiac conditions should be in a medical environment where the
effects of the psychotropic medications can be monitored and observed
closely.

Partial hospitalization or a day-treatment program

◊ In general, these patients have severe symptoms but have a level of control
and a stable living environment.
◊ For example, a patient with severe depression who has thoughts of suicide
but no plans to act upon them and who has a high degree of motivation can
get well when given a great deal of interpersonal support, especially during
the day, and with the help of a very involved and supportive family. The
family needs to be home every night and should be very concerned with the
patient's care. Partial hospitalization also offers a bridge to return to work.
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Returning directly to work often is difficult for patients with severe symptoms,
and partial hospitalization provides support and interpersonal relationships.

Outpatient treatment

◊ Outpatient treatment has 4 major goals.

◊ First, look at areas of stress and find ways to handle them. The stresses can
stem from family or work, but if they accumulate, they propel the person into
mania or depression. This is a form of psychotherapy.
◊ Second, monitor and support the medication. Medications make an
incredible difference. The key is to get the benefits and avoid adverse
effects. Patients are ambivalent about their medications. They recognize that
the drugs help and prevent hospitalizations, yet they also resent that they
need them. The job is to address their feelings and allow them to continue
with the medications.
◊ Third, develop and maintain the therapeutic alliance. This is one of the many
reasons for the practitioner to deal with the patient's ambivalence about the
medications. Over time, the strength of the alliance helps keep the patient's
symptoms at a minimum and helps the patient remain in the community.
◊ The fourth aspect involves education. The clinician must help educate both
the patient and the family about bipolar illness. They need to be aware of the
dangers of substance abuse, the situations that would lead to relapse, and
the essential role of medications. Support groups for patients and families
are of tremendous importance.

Activity: Patients in the depressed phase are encouraged to exercise. Propose a

regular exercise schedule for all patients, especially those with bipolar disorder. Both
the exercise and the regular schedule are keys to surviving this illness. However,
increases in exercise level, with increased perspiration, can lead to increased serum
lithium levels and lithium toxicity.

Appropriate medication depends on the stage of the bipolar disorder the patient is
experiencing. Thus, a number of drugs are indicated for an acute manic episode,
primarily the antipsychotics and benzodiazepines (eg, lorazepam, clonazepam). The
choice of agent depends on the presence of symptoms such as psychotic symptoms,
agitation, aggression, and sleep disturbance. Atypical antipsychotics are being used
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increasingly for treatment of both acute mania and mood stabilization. The broad
range of antidepressants and ECT are used for an acute depressive episode (ie,
major depression). Finally, another set of medications is chosen for the maintenance
and preventive phases of treatment.

Clinical experiences have shown that, if treated with mood-stabilizing drugs, patients
with bipolar disorder have fewer episodes of mania and depression. These
medications serve to stabilize the patient's mood, as the name implies. They also can
dampen extremes of mania or depression.

Lithium is the drug commonly used for prophylaxis and treatment of manic episodes.
Lithium, traditionally the first-line treatment for bipolar disorder, has been found
effective as an acute treatment for mania and depression and as a prophylactic
agent. A recent study suggests that lithium may also have a neuroprotective role.
During acute mania, approximately 80% of patient respond to lithium, although such
response may take 1-2 weeks. Also can be used to treat acute mania, although
cannot be titrated up to an effective level as quickly as valproic acid. Evidence
suggests that lithium, unlike any other mood stabilizer, may have a specific
antisuicide effect. Monitoring blood levels is critical with this medication.

Anticonvulsants have been effective in preventing mood swings associated with

bipolar disorder, especially in patients known as rapid cyclers. For the depressed
phase, mood stabilizers, such as lithium and lamotrigine, are preferred because
antidepressants may propel a patient into a manic episode or exacerbate irritability in
mixed-symptom mania. Gabapentin, although not a mood stabilizer, also may have
antidepressant and anxiolytic properties. The most widely used anticonvulsants have
been carbamazepine, divalproex sodium, and lamotrigine. More recently, topiramate
and tiagabine also are being tried.

Antipsychotic drugs are often coadministered during initial period to control behavior
and psychosis. Antipsychotic drugs are commonly used during the acute phases of
mania or psychotic depression because they provide symptomatic relief while mood
stabilizers are taking effect. The older agents are not usually used as a maintenance
treatment because of the risk of tardive dyskinesia, unless mood stabilizers alone
have been unsuccessful or poorly tolerated. The newer, atypical antipsychotics (e.g.
clozapine, risperidone, olanzapine) are being used adjunctively in bipolar disorder but
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may also have a role as monotherapy for psychotic and nonpsychotic mania and in
treatment-resistant depression. Benzodiazepines, particularly clonazepam, may be
used to treat mania. Sedation and a full night*s sleep can markedly improve
symptoms in some patients.

All patients with bipolar disorder need outpatient monitoring for both medications and
psychotherapy. In addition, they need education. The schedule must be regular, with
great flexibility if they need extra sessions. Fortunately, most patients recover from
the first manic episode, but their course beyond that is variable.

Prevention is the key to the long-term treatment of bipolar disorders. It takes several
forms, as follows:

◊ First, medications such as lithium serve as mood stabilizers.

◊ Second, psychoeducation is instituted for the patient and the patient's family.
Both the patient and the patient's family must understand and recognize the
importance of medication compliance and the early signs of mania and
depression. This is critical.
◊ Patients with BPI fare worse than patients with a major depression. Within
the first 2 years after the initial episode, 40-50% of patients experience
another manic attack. Only 50-60% of patients with BPI who are on lithium
gain control of their symptoms. In 7% of these patients, symptoms do not
recur. Forty-five percent of patients experience more episodes and 40% go
on to have a persistent disorder. Often, the cycling between depression and
mania accelerates with age.

Factors suggesting a worse prognosis include the following:

◊ Poor job history

◊ Alcohol abuse
◊ Psychotic features
◊ Depressive features between periods of mania and depression
◊ Evidence of depression
◊ Male sex

Indicators of a better prognosis include the following:

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◊ Manic phases (short in duration)
◊ Late age of onset
◊ Few thoughts of suicide
◊ Few psychotic symptoms
◊ Few medical problems

Patient Education:

Treatment of patients with bipolar disorder involves initial and ongoing patient
education. The educational efforts must be directed not only toward the patient but
also toward their family and support system. Furthermore, evidence continues to
mount that these educational efforts not only increase patient compliance and their
knowledge of the disease, but also their quality of life.

◊ First, an explanation of the biology of the disease must be provided. This

lessens the guilt and promotes medication compliance.
◊ Second, include information about how to monitor the illness in terms of an
appreciation of the early warning signs, reemergence, and symptoms.
Recognition of changes can serve as a powerful preventive step.
◊ A strong therapeutic alliance remains an essential part of treatment and
education.
◊ Education also must encompass the dangers of stressors. Helping the
individual identify and work with stressors provides a critical aspect of patient
and family awareness.
◊ Finally, inform the patient about relapses within the total context of the
disorder.
◊ Individual stories help patients and families. The National Institute of Mental
Health (NIMH) has a story of a person with MDI that can help the patient see
the struggle and challenge from another perspective (NIMH, 2003). Others
have written about their family struggles and challenges (Webb, 2003).

Medical/Legal Pitfalls:

1. Involuntary hospitalization for depression: In the clearest case of the

bipolar/depressed phase, the patient is suicidal and homicidal in a few
situations (this can result in homicide followed by suicide). In these
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scenarios, commitment is in order and indicated. In other situations, the
depression has led to an inability to work, eat, and function;
hospitalization also is indicated in these cases.
2. Involuntary hospitalization for mania: In the situation of a patient in
bipolar/manic phase, often, less clear and dramatic evidence of
homicide or suicide is present, but a pattern of very poor judgment and
impairment emerges. Because of the behavior during the manic phase,
the person often does major damage to their finances, career, and
position in the community. This type of self-destructive mania calls for
containment with good documentation and family support.