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Up to one in eight individuals may require treatment for depression during their lifetimes. The direct costs of treatment for major depressiv_ disorder combined with the indirect costs from lost productivity are significant, accounting for approximately $16 billion per year in 1980 dollars. Regrettably, only one-third to one-half of those with major depressive disorder are properly recognized by practitioners. Fewer than one-third of patients with bipolar disorder are in treatment.
Despite the high prevalence of depressive symptoms and major depressive episodes in patients of all ages, depression is underdiagnosed and undertreated by primary care and other nonpsychiatric practitioners, who are, paradoxically, the providers most likely to see these patients initially. Depression may occur concurrently with other nonpsychiatric general medical disorders or with other psychiatric disorders; it may also be brought on by the use of certain medications. Major risk factors for depression include a personal or family history of depressive disorder, prior suicide attempts, female gender, lack of social supports, stressful life events, and current substance abuse. The social stigma surrounding depression is substantial and often prevents the optimal use of current knowledge and treatments. The cost of the illness in pain, suffering, disability, and death is high.
Once identified, depression can almost always be treated successfully, either with medication, psychotherapy, or a combination of both. Not all patients respond to the same therapy, but a patient who fails to respond to the first treatment attempted is highly likely to respond to a different treatment.
This Clinical Practice Guideline focuses on the diagnosis of depressive disorders, particularly in outpatients. Depression is defined according to the current U.S. standard diagnostic system in the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R), published by the American Psychiatric Association.
A clinical depression or a mood disorder is a syndrome (i.e., a constellation of signs and symptoms) that is not a normal reaction to life’s difficulties. Depressive and other mood disorders involve disturbances in emotional, cognitive, behavioral, and somatic regulation. Depressive disorders should not be confused with the depressed or sad mood that is a normal response to specific life experiences—particularly losses or disappointments. These responses are transient and are not associated with significant functional impairment. A sad or depressed mood is only one of the many signs and symptoms of clinical depression. In fact, the mood disturbance may include apathy, anxiety, or irritability rather than or in addition to sadness; further, the patient’s interest or capacity for pleasure or enjoyment may be markedly reduced.
Primary mood disorders include both depressive (unipolar) and manicdepressive (bipolar) conditions. Major depressive disorder (sometimes called unipolar depression) is characterized by one or more episodes of mild, moderate, or severe clinical depression without episodes of mania or hypomania (i.e., low-level mania). By definition, major depressive episodes last at least 2 weeks (typically much longer) in both major depressive and bipolar disorders. A sad mood or a significant loss of interest is required, along with several associated signs and symptoms, to warrant a diagnosis of a major depressive episode. A major depressive episode can occur as part of a primary mood disorder (e.g., major depressive or bipolar disorder), as part of other nonmood psychiatric conditions (e.g., eating, panic, or obsessive-compulsive disorders), in association with drug or alcohol intoxication or withdrawal, as a biologic consequence of various general medical conditions (secondary mood disorders), or as a consequence of selected prescribed medications.
Unipolar forms of primary mood disorders are divided into three groups:
Bipolar disorders are recurrent, episodic conditions characterized by a history of at least one manic or hypomanic episode. Bipolar disorders have been grouped into three types:
Major depressive disorder may begin at any age, but it most commonly begins in the 20s to 30s. Symptoms develop over days to weeks. Some persons 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.
The course of recurrent major depressive disorder is variable. In some patients, the episodes are separated by many years of normal functioning without symptoms. 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 they remit completely. Major depressive episodes may end completely or only partially. If the latter occurs:
The point prevalence for major depressive disorder in the Western industrialized nations is 2.3 to 3.2 percent for men and 4.5 to 9.3 percent for women. The lifetime risk for major depressive disorder is 7 to 12 percent for men and 20 to 25 percent for women. Prevalence rates are unrelated to race, education, income, or civil status. Risk factors for major depressive disorder include female gender, a history of depressive illness in first-degree relatives, and prior episodes of major depression. The point prevalence of major depressive disorder seen in primary care outpatient settings ranges from 4.8 to 8.6 percent.
Three subgroups of major depressive disorder based on cross-sectional symptom features—psychotic (with delusions or hallucinations), melancholic, and atypical—may have implications for treatment selection. Two subgroups 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.
The essential feature of dysthymic disorder is a chronic mood disturbance (sadness in adults; sadness and, possibly, irritability in children and adolescents) present most of the time for at least 2 consecutive years (1 year for children and adolescents). The differentiation between dysthymic disorder and major depressive disorder can be difficult. Their symptoms are similar, differing only in duration and severity. Data from the large, multisite Epidemiologic Catchment Area (ECA) Study indicate a lifetime rate of dysthymic disorder of 4.1 percent for women and 2.2 percent for men.
Depression not otherwise specified identifies mood conditions with depressive symptoms that do not meet either the severity or the duration criteria for dysthymic, major depressive, or bipolar disorders. An analysis of the ECA Study data showed that 11.0 percent of subjects met the criteria for DNOS. The point prevalence of DNOS in primary care outpatients is 8.4 to 9.7 percent.
Bipolar disorders classically feature episodes of major depression interspersed with episodes of mania and/or hypomania. Manic episodes are distinct periods of persistently elevated, abnormally expansive, or irritable mood with other associated symptoms, such as inflated self-esteem and decreased need for sleep. Manic episodes markedly impair occupational, social, and interpersonal function and often require hospitalization to prevent harm to self or others. Hypomanic episodes are similar to, but milder than, manic episodes. Some patients with bipolar I (with mania) or bipolar II (with hypomania) disorder exhibit a “rapid cycling” pattern, in which they experience four or more mood episodes per year. The prognosis is poorer for these rapid cyclers.
The mean age at onset of the bipolar disorders is in the early 20s. The sexes do not differ in age at onset. The morbidity and mortality associated with bipolar I disorders are high. Ten to 15 percent of untreated patients commit suicide, which is 15 to 20 times the suicide rate in the general population. Bipolar I disorder affects men and women equally. It has a lifetime prevalence of 0.8 to 1.2 percent. Bipolar I disorder occurs at much higher rates in first-degree relatives of people with this condition than in the general population.
Psychoactive substances, such as cocaine and amphetamines; head trauma; multiple sclerosis and other necrologic diseases; endocrinopathies; and some other general medical disorders can produce secondary manic and hypomanic episodes similar to those in primary bipolar disorder. Antidepressant medications in persons with a genetic disposition to bipolar disorder can precipitate manic or hypomanic episodes as well.
Cyclothymic disorder features numerous, alternating hypomanic and mild depressive periods, which last days to weeks and are nearly continuous. There are few truly symptom-free periods. The symptoms fluctuate, but never reach the severity/duration criteria for the diagnosis of major depressive or manic episodes. The lifetime prevalence of cyclothymic disorder is 0.4 to 1.0 percent.
The signs and symptoms of major depressive disorder are more similar than different in children, adolescents, and geriatric patients; in men and women; and in all ethnic groups.
Patients with depressive symptoms or in a major depressive episode may also be suffering from another, nonmood psychiatric disorder. When the formal major depressive syndrome is associated with another psychiatric condition, the decision of which to treat first rests on the nature of the nonmood disorder. If the nonmood disorder is causing the mood symptoms, then it should usually be treated first. If it is an eating or obsessive-compulsive disorder, that is usually the initial treatment target. If the nonmood disorder is generalized anxiety or personality disorder, the major depressive disorder is the first treatment target, because patients with one of these two nonmood conditions are not typically excluded from randomized controlled treatment trials for major depressive disorder. If the associated nonmoodcondition is panic disorder, the practitioner must decide which is primary by considering the patient’s personal and family history, as well as by gauging which of the two conditions is causing the greater impairment.
Although alcoholics do become depressed over time, alcoholism is rarely a consequence of depression. Rather, alcoholism and major depressive disorder are distinct clinical entities. They are not different expressions of the same underlying condition. Overall, the prevalence of alcoholism in patients with primary depression is probably no higher than in the general population.
Somatization is defined as the presentation of somatic symptoms by patients with underlying psychiatric illness or psychosocial distress. These somatic symptoms are not accounted for by an underlying general medical disorder. Somatization may well be the main reason for the misdiagnosis of mental illness by primary care physicians. In primary care settings, many depressed and nondepressed patients complain of medically unexplained symptoms, particularly pain. The condition of most patients with such complaints does not meet the formal criteria for somatization disorder, which in DSM-III-R requires the presence of 13 or more medically unexplained symptoms. While many depressed patients have medically unexplained somatic complaints, their symptoms are rarely of sufficient intensity or frequency to meet the threshold for somatization disorder.
Clinically significant depressive symptoms are detectable in approximately 12 to 16 percent of patients with another nonpsychiatric, general medical condition. Rates in patients with specific medical disorders may be even higher. These figures far exceed the approximate 4 percent prevalence of diagnosable depression in large community samples. Thus, the presence of a general medical disorder is a risk factor for major depression. On the other hand, most patients with a nonpsychiatric medical condition do not have a mood disorder. Therefore, the mood disorder should be viewed as an independent condition to be specifically treated. The differential diagnosis is not always readily apparent. Some somatic symptoms are part of the syndrome of major depression, and many medical disorders cause some criterion symptoms of depression, such as weight loss, sleep disturbances, and low energy. These disorders include endocrine disorders, such as diabetes; pituitary, adrenal, or thyroid disorders; certain malignancies; some infections; some necrologic disorders; autoimmune disorders; cardiovascular disease; and vitamin/mineral deficiency and/or excess states.
Once the syndrome of major depression has been identified in patiems with co-morbid medical illness, the differential causes of depressive symptomatology must be reviewed to ensure that the appropriate treatment is administered. The risk factors associated with primary mood disorders should be reviewed to determine whether the patient’s condition fits a typical picture of primary mood disorder or whether alternative causes can explain the depressive syndrome or symptoms.
When depression and another general medical condition occur together, there are several logically plausible explanations for the co-morbidity:
It is important for the practitioner to differentiate among these options for patients with depressive and other general medical conditions. In the first two instances, treatment aims first at the general medical disorder. If depression persists, it is treated once the general medical disorder is stabilized. In the third case, the general medical disorder is treated while counseling, education, support, and medication are used to treat the depression. In the last instance, specific treatment is initiated for both problems.
Various medications have long been reported to cause or to be associated with mood symptoms or formal disorders as side effects. These agents include antihypertensives; various hormones, such as corticosteroids and anabolic steroids; histamine-2 receptor blockers; anticonvulsants; levodopa; antibiotics; and antiarrhythmics. Limited data are available to support an association among these, except for reserpine, corticosteroids, and anabolic steroids. However, it is essential to recognize that idiosyncratic reactions to medications do occur. Even without data to suggest a causal relationship between a medication and mood symptoms, good clinical judgment dictates that the medication should be stopped or changed if a patient develops depressive symptoms after beginning to use the medication. Such an event does not suggest that the particular medication should not be used in other patients who appropriately require it. That is, the reaction should be regarded as truly idiosyncratic and should not form the basis for a general conclusion applicable to the medication.
Both recognition and diagnosis of depression rest on an awareness of the risk factors for depression, as well as elicitation of the key signs, symptoms, and history of illness. The risk factors include:
The signs and symptoms of depression can be sought by direct interview, which may be supplemented with self-report ratings and/or a history from the patient’s spouse or a friend. A clinical interview is the most effective method for detecting depression. The interview elicits the nine criterion symptoms of major depressive disorder and the longitudinal course of illness. Because either a depressed, blue, or sad mood or a loss of interest or pleasure is required, these symptoms should be ascertained first. The clinician who suspects or diagnoses a depressive disorder should perform and record the results of a mental status examination, which includes whether the patient has suicidal ideation/intention; is oriented, alert, cooperative, and communicative; exhibits a normal level of motor activity; and is psychotic. If the symptoms of depression are present, the time course of these symptoms should be established. Symptom severity should be gauged by either a clinical interview or rating scales, as severity plays a role in treatment planning. Where historical, symptomatic, or physical findings point toward an underlying general medical disorder as the cause of the depression, laboratory tests to detect the specific disorder(s) should be used as appropriate in the differential diagnosis.
Differential diagnosis of depressive disorders rests largely on clinical phenomenological grounds and proceeds according to the following steps for the practitioner:
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