depression based on chart notations by primary care physicians vary from 1.5 to 4.5 percent. Structured psychiatric interviews based on standard diagnostic systems (DSM-III-R or ICD-9) provide the best prevalence data because they identify all who have the conditions and differentiate them from those with depressive symptoms from other causes. (However, even many of the studies in which the investigators used structured interviews may not fully exclude patients whose depression was caused by concurrent nonpsychiatric medical disorders, medications, or substances of abuse.) Eleven studies have used structured psychiatric interviews and specific diagnostic criteria to determine the prevalence of major depressive disorder in primary care settings (Table 2). The point prevalence of major depressive disorder in primary care outpatient settings ranged from 4.8 to 8.6 percent; 14.6 percent of adult medical inpatients studied met ICD-9 criteria for major depressive disorder (Feldman, Mayou, Hawton, et al., 1987).

Costs of Untreated Major Depressive Disorder

Guideline: Patients with major depressive disorder have substantial amounts of physical and psychological disability, as well as occupational difficulties. (Strength of Evidence = A.)

Untreated major depressive disorder has a substantial effect on health and functioning. Patients in a major depressive episode report substantially poorer intimate relationships and less satisfying social interactions than do members of the general population who have previously suffered from depression or who currently have other psychiatric disorders (Fredman, Weissman, Leaf, et al., 1988).

Physical complaints are also common during a major depressive episode. Twenty-three percent of patients in one study reported some days in which their health kept them in bed all or most of the day in the previous 2 weeks, compared to 5 percent for the general population (Wells, Golding, and Burnam, 1988a). This finding is supported by reports of the health status of community respondents with major depressive disorder, 48 percent of whom described their health as either fair or poor, compared to only 19 percent of the general population (Wells, Golding, and Burnam, 1988a). Other general population data indicate that patients with major depressive disorder reported 11 disability days per 90-day interval versus 2.2 disability days for the general population (Broadhead, Blazer, George, et al., 1990). Data from community respondents indicate that 38 percent of patients with major depressive disorder have some chronic activity restriction, and 30 percent of those with depression reported decreased activity days in the previous 2 weeks (Wells, Golding, and Burnam, 1988a).

Clinical samples of patients with major depressive disorder also provide evidence of severe impairment in interpersonal and occupational

Table 2. Prevalence of major depressive and other mood disorders

=

Note: SCL = Symptom Checklist. SADS-RDC = Schedule for Affective Disorders and Schizophrenia-Research Diagnostic Criteria. GHQ = General Health Questionnaire. PSE = Present State Examination. DIS Diagnostic Interview Schedule. SADS-L Schedule for Affective Disorders and Schizophrenia--Lifetime Version. MDD = major depressive disorder. ECA = Epidemiologic Catchment Area. CES-D = Center for Epidemiological Studies Depression Scale.

functioning, including loss of work time (Wells, Stewart, Hays, et al., 1989). Patients with major depressive disorder have more physical illnesses than do other patients seen in primary care settings (Coulehan, Schulberg, Block, et al., 1990). Health care utilization is increased in persons in the community with major depressive disorder compared to other patients in the general medical setting (Regier, Hirschfeld, Goodwin, et al., 1988).

Major depressive disorder is associated with increased mortality, which is generally considered to be secondary to suicide and accidents (Wells, 1985). A recent report indicated that patients with major depressive disorder admitted to nursing homes had a 59 percent greater likelihood of death in the first year following admission compared to those without major depressive disorder (Rovner, German, Brant, et al., 1991). Patients with major depressive disorder in the ECA Study aged 55 and over had a mortality rate over the next 15 months that was four times higher than that of nondepressed age-matched controls. Up to 15 percent of patients with major depressive disorder severe enough to require hospitalization eventually die by suicide (Coryell, Noyes, and Clancy, 1982).

Subgroups of Major Depressive Disorder

Studies of major depressive disorder reveal heterogeneity with regard to the biology, family history, pharmacologic response, genetics, and course of illness. Several schemes have been proposed to subdivide major depressive conditions. The common subgroups and possible clinical relevance of each are shown in Table 3. These subtypes are not allinclusive. For example, a large number of patients who have major depressive disorder without melancholic, psychotic, or atypical features have episodes that are not seasonally related and do not have a postpartum

onset.

Three subgroups based on cross-sectional symptom features— psychotic, melancholic, and atypical-may have implications for treatment selection. Two based on course features-seasonal pattern and postpartum onset-have prognostic utility; the seasonal type may also suggest the specific therapeutic option of light therapy. However, these subgroups may not be etiologically distinct. Rather, they may represent varying clinical expressions of the same condition over time, in different age groups, or in the context of particular provoking stimuli.

Psychotic Features

Guideline: Psychotic features refer to the presence of delusions or hallucinations. They occur in 15 percent of patients with major depressive disorders. (Strength of Evidence = A.)

In psychotic depressions, psychotic features are never present without concurrent mood symptoms. Psychotic depressions must be distinguished from schizoaffective disorder. In the latter only, there are periods of at

Note: ECT = electroconvulsive therapy. TCA = tricyclic antidepressant. MAOIs = monoamine oxidase inhibitors. SSRIs = selective serotonin reuptake inhibitors.

least 2 weeks during which delusions or hallucinations are present without mood disturbances.

The content of the hallucinations or delusions in psychotic depressions is usually logically consistent with the predominant sad mood (moodcongruent). For example, there may be a delusion that the patient has

sinned in an unforgivable way. Less commonly, the hallucinations or delusions have no obvious relationship to sadness (mood-incongruent); for example, there may be persecutory delusions, for which the person has no explanation. Studies to date suggest that mood-incongruent symptoms are associated with a worse prognosis; evolve into schizophreniform or schizoaffective disorders; involve a less episodic, more chronic course; and require more assiduous, longer maintenance treatment(s). (See LaliveAubert and Rush, 1992; Lalive-Aubert and Rush, in press, for reviews.)

The psychotic features of psychotic major depressive disorder usually recur in subsequent episodes, should such episodes occur. Some studies suggest that psychotic depressive episodes are familial (Schatzberg and Rothschild, in press; Weissman and Johnson, 1990).

For psychotic depressions, TCAs plus a neuroleptic or electroconvulsive therapy (ECT) are each superior to TCAs alone in treating the illness (Depression Guideline Panel, forthcoming). Given the markedly disabling nature of psychotic depression, maintenance treatments are strongly indicated when the disorder is recurrent. However, the relative efficacy of maintenance treatment compared to placebo; the value of including both a neuroleptic and an antidepressant in maintenance treatment; and the acute and maintenance phase efficacy of non-TCA medications, lithium, or selected anticonvulsants have not been studied in randomized controlled trials (Schatzberg and Rothschild, 1992).

Melancholic Features

Guideline: The key melancholic features of major depressive disorder

are:

■ Psychomotor retardation or agitation.

■Loss of interest or pleasure.

■Lack of reactivity to usually pleasant stimuli.

■ Worse depression in the morning.

■ Early morning awakening.

(Strength of Evidence = A.)

Melancholic symptom features appear to repeat from episode to episode in individuals with recurrent, severe major depressive disorder. They are more commonly present in older depressed patients (see Rush and Weissenburger, in press, for a review). Melancholic features are not uniquely associated with a family history of depression. They are associated with reduced rapid eye movement latency and/or dexamethasone nonsuppression (Rush, Cain, Raese, et al., 1991).

Severely symptomatic patients whose depression has melancholic features are likely to respond to treatment with TCAS or to ECT.

Melancholic features do not predict which antidepressants will be effective, though their presence indicates that anxiolytics will not be effective (Depression Guideline Panel, forthcoming). The presence of melancholic