Table 1. DSM-III-R criteria for major depressive disorder

At least five of the following symptoms are present during the same period. At least (1) depressed mood or (2) loss of interest or pleasure must be present. Symptoms are present most of the day, nearly daily for at least 2 weeks.

(1) Depressed mood (sometimes irritability in children and adolescents) most of the day, nearly every day.

(2) Markedly diminished interest or pleasure in almost all activities most of the day, nearly every day (as indicated either by subjective account or observation by others of apathy most of the time).

(3) Significant weight loss/gain.

(4) Insomnia/hypersomnia.

(5) Psychomotor agitation/retardation.

(6) Fatigue (loss of energy).

(7) Feelings of worthlessness (guilt).

(8) Impaired concentration (indecisiveness). (9) Recurrent thoughts of death or suicide.

Source: American Psychiatric Association, 1987.

use of selected prescription medications. Finally, a grief reaction (bereavement) may initially (within the first 2 months) meet the criteria for a major depressive episode. (Strength of Evidence = A.)

Whether general medical conditions or medications simply precipitate mood episodes in vulnerable individuals or whether they cause episodes de novo is unclear (Figure 2).

Unipolar forms of primary mood disorders are divided into three

groups:

■ Major depressive disorder consists of one or more episodes of major depression with or without full recovery between these episodes.

■ Dysthymic disorder features a low-grade, more persistent (less episodic) depressed mood and associated symptoms for at least 2 years, during which a major depressive episode has not occurred. Many patients with dysthymic disorder subsequently suffer superimposed episodes of major depression over the course of their illness. In such cases, both dysthymic and major depressive disorders are diagnosed according to DSM-III-R. ■ Depression not otherwise specified is a residual category reserved for patients with symptoms and signs of depression that do not meet the formal diagnostic criteria for either dysthymic or major depressive disorders. If patients have previously met the criteria for major depressive disorder, which then goes into partial remission, major depressive disorder in partial remission (not DNOS) is diagnosed.

Figure 2. Conditions associated with mood symptoms or major depressive episodes

'Depending on the clinical situation and the patient's history, both the mood disorder and the associated condition may be primary treatment objectives.

Guideline: Bipolar disorders are recurrent, episodic conditions characterized by a history of at least one manic or hypomanic episode. Ninety-five percent of persons with bipolar disorder also have recurrent episodes of major depression. (Strength of Evidence = A.) Bipolar disorders have been grouped into three types:

■ Bipolar I disorder requires at least one manic episode, along with (nearly always) major depressive episodes. A manic episode consists of a distinct period of elevated or irritable mood, along with several symptoms such as grandiosity, decreased need for sleep, pressured speech, and poor judgment.

■ Bipolar disorder not otherwise specified is a residual category that includes bipolar II disorder, a condition characterized by recurrent episodes of major depression along with hypomanic (but not full-blown manic) episodes, as well as other forms that do not meet formal criteria for bipolar I or cyclothymic disorder.

■ Cyclothymic disorder is characterized by numerous hypomanic episodes and numerous periods of mild depressive symptoms insufficient in duration or severity to meet the criteria for major depressive episodes. Cyclothymic disorder is typically chronic, lasting at least 2 years by definition.

Figure 3 summarizes the differential diagnosis of primary mood disorders. The clinically depressed patient must suffer either a sustained sad mood or a significant loss of interest/pleasure, plus associated criterion

symptoms. If at least five total symptoms are present for at least 2 weeks, the patient has either a grief reaction or a major depressive episode. The typical bereaved person and nearly all patients with adjustment reactions suffer only two or three associated symptoms. Such patients are rarely suicidal and do not have any significant functional impairment. By definition, these reactions are time-limited (classically lasting less than 6 months) and are not associated with hallucinations or delusions. Some bereaved persons evidence sufficient symptoms to meet the criteria for a major depressive episode within the first month or two following the loss. If these symptoms persist beyond 2 months, the diagnosis should be changed to major depression.

Nearly all patients with major depressive disorder report significant life stresses. The simple presence of a life stress is not a basis for diagnosing either a grief or a situational adjustment reaction, nor is it a basis for excluding the diagnosis of major depressive disorder. Rather, if the patient has only two to three associated symptoms that are mild and present for a short time and if there is no history of major depressive, manic, or hypomanic episodes, an adjustment disorder with depressed mood may be diagnosed. Treatment for this condition and for a classic grief reaction is usually support and reassurance. For some cases of adjustment disorder with depressed mood, a change in lifestyle or relationship patterns may be needed.

If someone has only two or three (but not five or more) symptoms associated with a major depressive episode, it is essential that the practitioner ask about prior major depressive episodes to see if the patient has only partially recovered from a prior major depressive episode. If so, treatment proceeds as for major depressive disorder.

If prior or current major depressive episodes are diagnosed, a history of manic (or hypomanic) episodes should be sought to evaluate the possibility of the presence of a bipolar disorder. If no such episodes have occurred, a history of prior episodes of major depression is sought to determine whether the major depressive disorder is single episode or recurrent. The number of episodes, including the present one, determines whether maintenance treatment should be a consideration.

Even if the patient has only two or three symptoms of major depression and no prior major depressive episodes, it is still important to elicit a history of manic episodes. The patient may have a full bipolar disorder without yet having sustained a full major depressive episode.

Major Depressive Disorder

Clinical Features and Course

Major depressive disorder may begin at any age, although it usually begins in the mid-20s and 30s. Symptoms develop over days to weeks. Some people have only a single episode, with a full return to premorbid functioning. However, more than 50 percent of those who initially suffer a single major depressive episode eventually develop another. In these cases, the diagnosis is revised to recurrent major depressive disorder. Individuals with recurrent major depressive disorder are at greater risk of developing bipolar disorder than are those with single episodes, and they are more likely to have first-degree biologic relatives with major depressive disorder. Some patients who meet the criteria for major depressive disorder, especially of the recurrent type, have a genotype that groups them more clearly with patients with bipolar disorder, as evidenced by a family history of bipolar disorder, early onset of their major depressive disorder, a higher frequency of depressive episodes, and a greater tendency to show psychomotor retardation and hypersomnia during the episode of major depression (Akiskal, 1983). These patients may have a greater tendency to develop hypomania with standard tricyclic antidepressants (TCAs), and their recurrent depressive episodes may be more responsive to lithium alone (Akiskal, 1983).

The course of recurrent major depressive disorder is variable. In some patients, the episodes are separated by many symptom-free years of normal functioning. For others, the episodes become increasingly frequent with greater age. Major depressive episodes nearly always reduce social, occupational, and interpersonal functioning to some degree, but functioning usually returns to the premorbid level between episodes if the episodes remit completely.

Studies of patients with major depressive disorder have found that most untreated episodes last 6 to 24 months. (For a review of these studies, see Goodwin and Jamison, 1990, and Rush, Cain, Raese, et al., 1991.) For two-thirds of cases, symptoms remit completely and functioning

returns to the premorbid level. In the remaining cases, the full episode may persist for more than 2 years (about 5 to 10 percent), or recovery between episodes may be partial (about 20 to 25 percent). Approximately onefourth of patients develop major depression superimposed on a low-grade chronic depression (dysthymic disorder), which accounts for the majority of those with poor interepisode recovery.

Major depressive episodes may end completely or only partially. If the latter occurs, clinical experience and some research data suggest that: ■ The likelihood of a subsequent episode is higher.

■The need for longer term treatment is increased.

The prognosis is for continuing poor or partial interepisode recovery following subsequent episodes.

The need for treatment with both medication and psychotherapy may be greater.

According to data from community samples, women are more likely to remain depressed at 1-year followup than are men (Weissman and Myers, 1978). For women, older age, less than a high school education, and an unstable marital history are risk factors. In addition, women with major depressive disorder whose disease was more severe, more recurrent, or associated with greater prior or current co-morbidity for panic or somatization disorder (but not drug or alcohol abuse) at initial evaluation are more likely to have major depressive disorder 1 year later. Men, but not women, with both dysthymic and major depressive disorders initially are more likely to have major depressive disorder 1 year later. For men, age, education, and marital history are unrelated to outcome. For both sexes, longer lasting episodes of major depressive disorder at initial evaluation are related to the presence of major depressive disorder 1 year later.

The panel commissioned a reanalysis of the data from the large, multisite Epidemiologic Catchment Area (ECA) Study, which involved more than 18,000 interviews in several communities (Eaton, Holzer, von Korff, et al., 1984; Eaton, Regier, Locke, et al., 1981; Regier, Boyd, Burke, et al., 1988; Regier, Myers, Kramer, et al., 1984; Weissman and Klerman, 1978; Weissman, Leaf, Tischler, et al., 1988; Weissman and Myers, 1978) and revealed that at 1-year followup 40.3 percent of those with major depressive disorder still had the same diagnosis, 2.6 percent had developed dysthymic disorder, 16.7 percent had improved somewhat but had not completely recovered, and 40.5 percent had no mood disorder (Johnson and Weissman, unpublished manuscript). Studies also indicate that treatment for major depressive disorder is more effective earlier in the episode, before it becomes chronic (Bielski and Friedel, 1976; Kupfer, Frank, and Perel, 1989; Rush, Hollon, Beck, et al., 1978). Taken together, these findings suggest that early treatment is essential to reduce subsequent morbidity and mortality.