Practice Guideline for the Treatment of Patients With Bipolar Disorder

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Practice Guideline for the Treatment of Patients With Bipolar Disorder (Revision)

page 9

PART B:
Background Information and Review of Available Evidence

IV. DISEASE DEFINITION, NATURAL HISTORY AND COURSE, AND EPIDEMIOLOGY

A. Definition of Bipolar Disorder

According to DSM-IV-TR (1), patients with bipolar I disorder have had at least one episode of mania (criteria for a manic episode are presented in). Some patients have had previous depressive episodes (Table 3), and most patients will have subsequent episodes that can be either manic or depressive. Hypomanic and mixed episodes (and, respectively) can occur, as well as significant subthreshold mood lability between episodes. Patients meeting criteria for bipolar II disorder have a history of major depressive episodes and hypomanic episodes only. Patients may also exhibit significant evidence of mood lability, hypomania, and depressive symptoms but fail to meet duration criteria for bipolar II disorder, thereby leading to a diagnosis of bipolar disorder not otherwise specified. Finally, cyclothymic disorder may be diagnosed in those patients who have never experienced a manic, mixed, or major depressive episode but who experience numerous periods of depressive symptoms and numerous periods of hypomanic symptoms for at least 2 years (1 year in children), with no symptom-free period greater than 2 months. The subtypes of bipolar disorder, as well as selected other affective illnesses, are summarized and compared in Table 6.

In addition to providing definitions of bipolar disorder, DSM-IV-TR also includes specifiers describing the course of recurrent episodes, such as seasonal pattern, longitudinal course (with or without full interepisode recovery), and rapid cycling.

Some investigators have advocated moving from a categorical to a more dimensional perspective in characterizing bipolar disorder. In particular, this perspective includes the concept of a bipolar spectrum that would encompass a range of presentations not currently considered bipolar (149). For example, a patient with antidepressant-induced hypomanic symptoms would be considered to have a form of bipolar disorder under the spectrum conceptualization.

B. Natural History and Course

Bipolar disorder is generally an episodic, lifelong illness with a variable course. The first episode of bipolar disorder may be manic, hypomanic, mixed, and depressive. Men are more likely than women to be initially manic, but both are more likely to have a first episode of depression. Patients with untreated bipolar disorder may have more than 10 total episodes of mania and depression during their lifetime, with the duration of episodes and interepisode periods stabilizing after the fouth or fifth episode (150). Often, 4 years or more may elapse between the first and second episodes, but the intervals between subsequent episodes usually narrow. However, it must be emphasized that variability is the hallmark of this illness. Thus, when taking a history, a number of longitudinal issues must be considered, including the number of prior episodes, the average length and severity of episodes, average interepisode duration, and the interval since the last episode of mania or depression.

Frequently, a patient will experience several episodes of depression before a manic episode occurs (34,151). Consequently, bipolar disorder should always be considered in the differential diagnosis of depression. Patients very often do not report prior episodes of mania and hypomania and instead seek treatment for complaints of depression, delaying correct diagnosis (5,152-157). For a patient who is not educated about bipolar disorder, symptoms of dysphoric hypomania may not be recognized or reported. Therefore, the psychiatrist needs to ask explicity about prior manic or hypomanic episodes, since knowledge of their presence can influence treatment decisions. The psychiatrist should also ask about a family history of mood disorders, including mania and hypomania. Consultation with family members and significant others may be extremely useful in establishing family history and identifying prior affective episodes.

In addition to substance abuse and risk-taking behavior, other cross-sectional features that can have an impact on diagnosis and treatment planning include the presence of psychotic symptoms or cognitive impairment and the risk of suicide or violence to persons or property (41).

Suicide rates are high among bipolar disorder patients. Completed suicide occurs in an estimated 10% - 15% of individuals with bipolar I disorder. Suicide is more likely to occur during a depressive or a mixed episode (8-13). Pharmacotherapy may substantially reduce the risk of suicide (56,60,153). For example, in an 11-year follow-up study of 103 patients with bipolar disorder who were receiving lithium, death rates were well below those expected for this group on the basis of age and sex (154).

Bipolar disorder causes substantial psychosocial morbidity, frequently affecting patients' relationships with spouses or partners, children, and other family members as well as their occupation and other aspects of their lives. Even during periods of euthymia, patients may experience impairments in psychosocial functioning or residual symptoms of depression or mania/hypomania. It is estimated that as many as 60% of people diagnosed with bipolar I disorder experience chronic interpersonal or occupational difficulties and subclinical symptoms between acute episodes (13,33,34,158-164). Divorce rates are substantially higher in patients with bipolar disorder, approaching two to three times the rate of comparison subjects (152). The occupational status of patients with bipolar is twice as likely to deteriorate as that of comparison subjects (152). The occupational status of patients with bipolar disorder is twice as likely to deteriorate as that of comparison subjects. Patients' ability to care or themselves, degree of disability or distress, childbearing status or plans, availability of supports such as family or friends, and resources such as housing and finances also bear on treatment plans.

Table 2. Diagnostic Criteria for a Manic Episode^a

A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least 1 week (or any duration if hospitalization is necessary).
B. During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree:

1) Inflated self-esteem or grandiosity

2) Decreased need for sleep (e.g., feels rested after only 3 hours of sleep)

3) More talkative than usual or pressure to keep talking

4) Flight of ideas or subjective experience that thoughts are racing

5) Distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli)

6) Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor

agitation

7) Excessive involvement in pleasurable activities that have a high potential for painful consequences

(e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)
C. The symptoms do not meet criteria for a mixed episode.
D. The mood disturbance

1) is sufficiently severe to cause marked impairment in occupational functioning, usual social activities,

or relationships with others,

2) necessitates hospitalization to prevent harm to self or others, or

3) has psychotic features.
E. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a

medication, or othertreatment) or a general medical condition (e.g., hyperthyroidism).

^aAdapted from DSM-IV-TR; manic-like episodes that are clearly caused by somatic antidepressant treatment (e.g., medication, ECT, light therapy) should not count toward a diagnosis of bipolar I disorder.

Table 3. Diagnostic Criteria for a Major Depressive Episode^a

A. Five (or more) of the following symptoms have been present nearly every day during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either depressed mood or loss of interest or pleasure:

1) Depressed moodb most of the day as indicated by either subjective report (e.g., feels sad or empty)

or observation made by others (e.g., appears tearful)

2) Markedly diminished interest or pleasure in all, or almost all, activities most of the day (as indicated

by either subjective account or observation made by others)

3) Significant weight loss when not dietingc, weight gain (e.g., a change of more than 5% of body

weight in a month), or a decrease or increase in appetite

4) Insomnia or hypersomnia

5) Psychomotor agitation or retardation (observable by others, not merely subjective feelings of

restlessness or being slowed down)

6) Fatigue or loss of energy

7) Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional)^d

8) Diminished ability to think or concentrate or indecisiveness (either by subjective account or as

observed by others)

9) Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific

plan, or previous suicide attempt or a specific plan for committing suicide
B.     The symptoms do not meet criteria for a mixed episode.
C.     The symptoms cause clinically significant distress or impairment in social, occupational, or other important         areas of functioning.
D.     The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a         medication) or a general medical condition (e.g., hypothyroidism).
E.     The symptoms are not better accounted for by bereavement (i.e., after the loss of a loved one) and have         persisted for longer than 2 months or are characterized by marked functional impairment, morbid preoccupation         with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation.

^aAdapted from DSM-IV-TR; mood-incongruent delusions, hallucinations, and symptoms that are clearly due to a general medical condition should not count toward a diagnosis of major depressive disorder.
^bIn children and adolescents, mood can also be irritable.
^cIn children, can also include failure to make expected weight gains.
^dSymptoms extend beyond mere self-reproach or guilt about being sick.

Table 4. Diagnostic Criteria for a Hypomanic Episode^a

A. A distinct period of persistently elevated, expansive, or irritable mood, lasting at least 4 days, that is clearly different from the usual nondepressed mood.
B. During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree:

1) Inflated self-esteem or grandiosity

2) Decreased need for sleep (e.g., feels rested after only 3 hours of sleep)

3) More talkative than usual or pressure to keep talking

4) Flight of ideas or subjective experience that thoughts are racing

5) Distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli)

6) Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation

7) Excessive involvement in pleasurable activities that have a high potential for painful consequences                  (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)
C.     The episode is associated with an unequivocal change in functioning that is uncharacteristic of the person         when not symptomatic.
D.     The disturbance in mood and the change in functioning are observable by others.
E.     The episode 1) is not severe enough to cause marked impairment in social or occupational functioning, 2) does         not necessitate hospitalization, and 3) does not have psychotic features.
F.     The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a
        medication, or other treatment) or a general medical condition (e.g., hyperthyroidism).

^aAdapted from DSM-IV-TR; hypomanic-like episodes that are clearly caused by somatic antidepressant treatment (e.g., medication, ECT, light therapy) should not count toward a diagnosis of bipolar II disorder.

C. Epidemiology

Bipolar I disorder affects approximately 0.8% of the adult population, with estimates from community samples ranging between 0.4% and 1.6%. These rates are consistent across diverse cultures and ethnic groups (165). Bipolar II disorder affects approximately 0.5% of the population (156). While bipolar II disorder is apparently more common in women (81), bipolar I disorder affects men and women fairly equally. These estimates of prevalence are considered conservative. Reasons for this underestimate may include differences in diagnostic definitions and inclusion of persons who fall within the bipolar spectrum but who do not meet DSM-IV-TR criteria for bipolar I or bipolar II disorder (166).

The Epidemiologic Catchment Area study reported a mean age at onset of 21 years for bipolar disorder (6). When studies examining age at onset are stratified into 5-year intervals, the peak age at onset of first symptoms falls between ages 15 and 19, followed closely by ages 20-24. There is often a 5- to 10-year interval, however, between age at onset of illness and age at first treatment of first hospitalization (34,151). Onset of mania before age 15 has been less well studied (167). Bipolar disorder may be difficult to diagnose in this age group because of its atypical presentation with ADHD (13, 157-163). Thus, the true age at onset of bipolar disorder is still unclear and may be younger than reported for the full syndrome, since there is uncertainty about the symptom presentation in children. Research that follows cohorts of offspring of patients with bipolar disorder may help to clarify early signs in children.

Onset of mania after age 60 is less likely to be associated with a family history of bipolar disorder and is more likely to be associated with identifiable general medical factors, including stroke or other central nervous system lesion (34,155,168).

Evidence from epidemiological and twin studies strongly suggests that bipolar disorder is a heritable illness (164,169). First-degree relatives of patients with bipolar disorder have significantly higher rates of mood disorder than do relatives of nonpsychiatrically ill comparison groups. However, the mode of inheritance remains unknown. In clinical practice, a family history of mood disorder, especially of bipolar disorder, provides strong corroborative evidence of the potential for a primary mood disorder in a patient with otherwise predominantly psychotic features.

Likewise, the magnitude of the role played by environmental stressors, particularly early in the course of the illness, remains uncertain. However, there is growing evidence that environmental and lifestyle features can have an impact on severity and course of illness (170-172). Stressful life events, changes in sleep-wake schedule, and current alcohol or substance abuse may affect the course of illness and lengthen the time to recovery (26,71,73,173-175).

Table 5. Diagnostic Criteria for a Mixed Episode^a

A. The criteria are met both for a manic episode and for a major depressive episode (except for duration) nearly every day during at least a 1-week period.
B. The mood disturbance

1) is sufficiently severe to cause marked impairment in occupational functioning, usual social activities,

or relationships with others,

2) necessitates hospitalization to prevent harm to self or others, or

3) has psychotic features.
C. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a

medication, or other treatment) or a general medical condition (e.g., hyperthyroidism).

^aAdapted from DSM-IV-TR; mixed-like episodes that are clearly caused by somatic antidepressant treatment (e.g., medication, ECT, light therapy) should not count toward a diagnosis of bipolar I disorder.

Table 6. Summary of Manic and Depressive Symptom Criteria in DSM-IV-TR Mood Disorders

Disorder Manic Symptom Depressive Symptom
Criteria Criteria

Major depressive disorder	No history of mania or hypomania	History of major depressive episodes (single or recurrent)
Dysthymic disorder	No history of mania or hypomania	Depressed mood, more days than not, for at least 2 years (but not meeting criteria for a major depressive episode)
Bipolar I disorder	History of manic or mixed episodes	Major depressive episodes typical but not required for diagnosis
Bipolar II disorder	One or more episodes of hypomania; no manic or mixed episodes	History of major depressive episodes
Cyclothymic disorder	For at least 2 years, the presence of numerous periods with hypomanic symptoms	Numerous periods with depressive symptoms that do not meet criteria for a major depressive episode
Bipolar disorder not otherwise specified	Manic symptoms present, but criteria not met for bipolar I, bipolar II, or cyclothymic disorder	Not required for diagnosis

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