effective treatment, 23 percent of 4,341 patients with a manic episode admitted between 1912 and 1932 died in the hospital, 60 percent from "exhaustion" (Derby, 1933).

Patients with bipolar disorder experience considerable impairment in social and occupational functioning. While manic, they often need to be protected from the consequences of their poor judgment and overactivity, which often results in involuntary hospitalization. Over time, even with periods of remission, the chronicity and unpredictability of the disorder lead to secondary problems, such as joblessness, legal difficulties, divorce, and death by suicide, as well as medical morbidity.

Epidemiology

Bipolar I disorder affects men and women equally. It has a lifetime prevalence of 0.4 to 1.2 percent. The 1-month prevalence for bipolar disorder is 0.1 to 0.6 percent. Bipolar I disorder occurs at much higher rates in first-degree biologic relatives of persons with bipolar I disorder than in the general population. First-degree relatives of those with bipolar I disorder have a 12 percent chance of having the same disorder over their lifetimes. Another 12 percent have recurrent major depressive disorder, and roughly an additional 12 percent have dysthymic or other mood disorders (Goodwin and Jamison, 1990; Rush, Cain, Raese, et al., 1991).

Subtypes of Bipolar Disorder

Guideline: Psychoactive substances, such as cocaine and amphetamines; head trauma; certain neurologic diseases;

endocrinopathies; and some other disorders can produce secondary manic and hypomanic episodes similar to those seen in primary bipolar disorder. In addition, in some patients with a family history of bipolar disorder, antidepressant medications can precipitate a manic or hypomanic episode. (Strength of Evidence = A.)

Case reports suggest that secondary bipolar disorders may be more effectively treated with anticonvulsants than with lithium. (For a review, see Goodwin and Jamison, 1990.)

A seasonal pattern has been found in a subset of patients who have bipolar II disorder (and in some, but fewer, cases of bipolar I disorder). The requisite feature is the occurrence of major depressive episodes in a seasonal pattern (typically, fall onset, spring offset). Perhaps 10 percent of patients with bipolar II disorder experience such seasonal episodes. It is unclear whether lithium is differentially effective in these patients and, indeed, whether the disorder becomes nonseasonal over time.

Some patients with bipolar I or II disorder exhibit a “rapid cycling" pattern, experiencing four or more mood episodes each year. Mood episodes include manic (or mixed manic-depressive), hypomanic, and major depressive episodes. The mood episodes may follow one another

with or without intervening asymptomatic periods. According to nearly all studies, from 80 to 90 percent of those with a rapid cycling pattern are

women.

Bipolar disorder begins with a rapid cycling pattern in some patients, while rapid cycling develops during the course of the illness for others. Rapid cycling may occur spontaneously or, in some cases, may be caused or maintained by tricyclic and possibly other antidepressant medications. Concurrent thyroid axis disease may also cause rapid cycling.

For those with a rapid cycling pattern, the prognosis is poorer than is that for others with bipolar disorder, as is the response to lithium. Treatment with high-dose thyroid hormone may be effective, even if there is no thyroid disease (three studies). Carbamazepine or other anticonvulsants may be particularly effective for both acute and prophylactic treatment of bipolar disorders with a rapid cycling pattern, according to at least four studies. (For a review of these studies, see Bauer and Whybrow, in press.)

Under DSM-III-R, bipolar disorder not otherwise specified is a residual category for disorders with manic or hypomanic features that do not meet the criteria for bipolar I disorder. This category presently includes what some investigators have called bipolar II disorder. Bipolar II disorder usually consists of multiple episodes of major depression interspersed with episodes of hypomania. If a manic episode develops, the diagnosis is changed to bipolar I disorder.

Bipolar II disorder has an earlier age of onset than does major depressive disorder and displays a relatively stable lifetime course, although 5 to 17 percent of bipolar II patients develop mania and convert their diagnoses to bipolar I disorder over 5 to 40 years. Compared with patients with major depressive disorder, those with bipolar II disorder have more frequent episodes, increased frequency of suicide attempts, greater propensity to commit suicide following hospital discharge, and higher familial incidence of suicide.

In addition to bipolar II disorder, the category of bipolar disorder not otherwise specified includes various bipolar conditions that are insufficiently clear-cut in their clinical presentation to be definitively considered either bipolar I or bipolar II disorders. Examples include single or recurrent hypomanic episodes without interepisode subsyndromal depressive symptoms (which, if continuous, would be diagnosed as cyclothymic disorder) and without major depressive episodes (which, if present, would lead to a bipolar II diagnosis). As a category, bipolar disorder not otherwise specified has not been subjected to randomized controlled treatment trials.

Cyclothymic Disorder

Guideline: Cyclothymic disorder features numerous, alternating hypomanic and mild depressive periods, lasting days to weeks and

nearly continuous. There are few truly symptom-free periods. The symptoms fluctuate, but never reach the severity/duration criteria of major depressive or manic episodes. The course is chronic, often lasting years. (Strength of Evidence = A.)

A variety of clinical, family history, biologic, and treatment response characteristics suggest that this "subsyndromal" condition falls within the domain of mood disorders. A subgroup of those with symptoms of cyclothymic disorder do not have a significant family history of mood disorder or do not respond to lithium. However, various personality traits, temperaments, and disorders are associated with cyclothymic disorder. Socially problematic behaviors, such as marital discord, promiscuity, poor work performance, and substance abuse, are recognized as psychosocial complications of such subsyndromal mood disorders.

Accurate clinical assessment of these patients is difficult, especially when they manifest mood instability among their symptoms. For example, patients with borderline personality disorder frequently manifest a variety of mood symptoms, making it difficult to distinguish their illness from a mood disorder. On the other hand, many patients with borderline personality disorder may have unrecognized, and hence untreated, mood disorders. Given the likely clinical heterogeneity of cyclothymic disorder and its similarities to selected personality disorders, the clinician should carefully and comprehensively evaluate the conditions of patients with subtle, often more chronic, mood symptoms.

The onset of cyclothymic disorder is generally before age 30. During a 1- to 2-year followup of patients with cyclothymic disorder, 6 percent were reclassified as having bipolar I and 30 percent as having bipolar II disorder (Akiskal, Khani, and Scott-Strauss, 1979). However, this followup period is likely to be too short to assess the ultimate outcome of cyclothymic disorder. On the other hand, these findings indicate that a significant number of patients with cyclothymic disorder do go on to develop a formal bipolar condition.

The lifetime prevalence of cyclothymic disorder is 0.4 to 1.0 percent (Weissman and Myers, 1978). Cyclothymic disorder was diagnosed in 3 to 10 percent of a mental health clinic population (Akiskal, Khani, and ScottStrauss, 1979).

Mood Disorders in Special Age Populations

Guideline: The clinical features of major depressive episodes are more similar than different in children, adolescents, adults, and geriatric patients; in men and women; and in all ethnic groups. (Strength of Evidence = A.)

Children and Adolescents

For children, it is important to differentiate between behavioral problems in those who are primarily depressed and depression in those who have a primary behavioral disorder. In the former, behavioral problems are less severe and follow the onset of depression. In the latter, the behavioral problems are more severe and chronic, and they precede the onset of depression.

In prepubertal children, boys and girls seem equally affected with major depressive disorder. After puberty, girls are two to three times more likely to be affected than are boys. The prevalence of clinical depression is reported to be 0.8 percent in preschool children, 2.0 percent in school-aged prepubertal children, and 4.5 percent in adolescents. In clinical samples, the prevalence of depression in children and adolescents is estimated to be 58 percent in educational clinics, 28 percent in outpatient psychiatric clinics, and 40 to 60 percent in psychiatric hospitals, compared to 7 percent in hospitalized pediatric patients (Weller and Weller, 1990). The offspring of one or more parents with a history of major depression are at markedly higher risk for major depression, including prepubertal onset illness (Weissman, Gershon, Kidd, et al., 1984).

The course of major depressive disorder in prepubertal children and adolescents has not yet been fully studied. On the other hand, one study found that up to 30 percent of adolescents hospitalized with severe major depressive disorder may go on to develop bipolar disorder over 3 to 8 years (Strober and Carlson, 1982). Early onset of major depression (first episode prior to age 20) is associated with a greater likelihood of a more recurrent pattern in adulthood (Giles, Jarrett, Biggs, et al., 1989; Grof, Angst, and Haines, 1974). To date, evidence suggests a problematic course for at least some patients with onset of major depressive disorder prior to age 20 particularly those with a positive family history.

Geriatric Patients

Depression in the elderly is a significant matter for primary care practitioners because of its prevalence and the complexity of the

differential diagnosis. The clinical presentation of depression in the elderly is similar to that in other adults. However, it can be difficult to distinguish depression from dementia in those over age 65, as some symptoms of depression (e.g., disorientation, memory loss, and distractibility) may suggest dementia. Coexisting major depressive disorder and dementia are more common than is pseudodementia, and they tend to occur early in the course of Alzheimer's disease. The most representative prevalence estimate for elderly hospitalized patients with major depressive disorder is 6.0 to 11.5 percent.

The course of major depressive disorder or DNOS in the elderly is poorly studied. It is known from studies of adults that the co-occurrence of

medical disorders is a poor prognostic factor in the longer term course of illness. The practitioner must consider the confounding problems created by co-morbid medical conditions in older patients with mood symptoms, as well as the concurrent use of selected prescription medications and occult alcohol or substance abuse (Table 6).

Table 6. Confounds in the diagnosis and treatment of depression in the elderly

A. Concurrent nonpsychotropic medications may:

(1) Cause depression.

(2) Change antidepressant blood levels.

(3) Increase antidepressant side effects.

(4) Biochemically block antidepressant effects. (5) Call for modifying the oral dosage.

B. Concurrent medical illnesses may:

(1) Cause depression biologically.

(2) Reduce the efficacy of antidepressant medication or psychotherapy. (3) Change antidepressant drug metabolism.

(4) Impair ability to participate in psychotherapy.

(5) Create disability contributing to both chronicity and reduced treatment efficacy.

(6) Increase the need for simplified medication dosing schedules (e.g., once daily).

C. Concurrent nonmood psychiatric conditions may:

(1) Cause depression (e.g., early Alzheimer's).

(2) Call for different medications.

(3) Impair participation in psychotherapy.

(4) Reduce response to antidepressant medications (e.g., personality disorders).

(5) Worsen prognosis of the depression (e.g., alcoholism).

D. Other issues:

(1) Slower metabolism with age often requires lower dosages.

(2) Transportation difficulties may restrict access to care.

(3) Increased interview time needed.

(4) Fixed income may limit availability of therapy and nongeneric antidepressant medications due to cost.