The lifetime prevalence of major depression in the United States is 17 percent.[1] In primary care, its prevalence rate is 4.8 to 8.6 percent.[2] Of all adult medical inpatients, 14.6 percent meet the diagnostic criteria for major depression.[3] Significant percentages of patients with uncomplicated depression are treated by family physicians. Untreated major depression results in significant impairment of social function and occupational activities, and may end in suicide.[4-6] Untreated depression also leads to the increased utilization of medical and substance-abuse services and causes academic difficulties in student populations.[6] The overall national economic burden of mood disorders is approximately $44 billion.[7]

Fortunately, two thirds to three fourths of patients improve with antidepressant pharmacotherapy, a rate comparable to outcomes in other medical disorders.[8] The greater penetration of health maintenance organizations has led to a greater emphasis on treating depression in the primary care setting by using antidepressant medications.[9] The effective treatment of major depression reduces mortality, and human pain and suffering, and yields significant social and economic benefits with improved quality of life.[10,11]

Diagnosis

The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV)[6] includes nine symptoms in the diagnosis of major depression. For simplicity and ease of remembrance, two schematics are suggested. First, these nine symptoms can be divided into two clusters: (1) physical or neurovegetative symptoms and (2) psychologic or psychosocial symptoms (Table 1).[6] Second, the acronym "SIGECAPS," in association with depressed mood, may be used to diagnose patients with major depression. In this format, the nine symptoms are: depressed mood plus sleep disturbance; interest/pleasure reduction; guilt feelings or thoughts of worthlessness; energy changes/fatigue; concentration/attention impairment; appetite/weight changes; psychomotor disturbances, and suicidal thoughts.

To meet the criteria for the diagnosis of major depression, five of nine symptoms must be present for two weeks with at least one of the five symptoms being depressed mood or loss of interest/pleasure. In addition, the symptoms are not solely caused by general medical illness, medication, alcohol or drugs of abuse. Depression must also cause significant impairment in social, occupational or role functions.[6] Beck's Depression Inventory,[12] a self-rating depression scale with 21 items, may easily be used in the primary care setting as a screening instrument to quantify severity of depression and to measure progress once therapy is begun.

Work-up of Patients Before

Antidepressant Therapy

Before antidepressant therapy is initiated, the patient should have a directed history and physical examination. Consideration should be given to including routine laboratory tests such as complete blood cell count and chemistry panel, as well as tests to rule out thyroid dysfunction, diabetes and menopause. If the history and physical examination warrant it, further testing for connective tissue diseases (e.g., arteritis, systemic lupus erythematosus) or infectious diseases (e.g., acquired immunodeficiency syndrome, hepatitis, syphilis) may be indicated. An electrocardiogram is recommended in patients being considered for therapy with tricyclic antidepressants, maprotiline (Ludiomil) or amoxapine (Asendin), or if the patient is more than 40 years of age.

Treatment Considerations

Once the diagnosis of depression is established, assessments of the following 10 areas should guide a primary care physician to appropriate and safe selection of treatment options.

SUICIDE

Suicide risk is higher in depressed patients who are divorced or widowed, elderly, white, male or living alone, and those with associated chronic medical illness or psychotic symptoms. A past history of suicide attempt(s), a family history of completed suicide, and associated substance abuse also increase a depressed patient's risk of suicide attempt. Psychiatric consultation and treatment in a safe inpatient setting is recommended in these cases.

SECONDARY DEPRESSION

Medical conditions such as cancer[2] or endocrinopathy, medications (e.g., propranolol [Inderal]), and alcohol or drug abuse (e.g., cocaine withdrawal) can cause depression. The underlying cause should be treated, but if improvement in depressive symptoms fails to occur after four weeks of such treatment, depression should be independently diagnosed and treated.

BIPOLAR DEPRESSION

Bipolar depression is diagnosed by a past history of at least a single episode of mania (bipolar type I) or hypomania (bipolar type II). If no past history of mania or hypomania is elicited, a discrete episode of depression with hypersomnia without hyperphagia raises the index of suspicion for bipolar depression. Presence of bipolar depression would warrant treatment with a mood stabilizer such as lithium, valproic acid (Depakene, Depakote) or carbamazepine (Tegretol), with the possible addition of an antidepressant.

PSYCHOTIC DEPRESSION

This condition would be diagnosed by the presence of major depression with hallucination(s) or delusion(s). Psychotic depression generally requires combination pharmacotherapy with an antidepressant and an antipsychotic medication. Alternatively, monotherapy with amoxapine, which has mixed antidepressant and neuroleptic properties, may be used.[13]

MASKED DEPRESSION

Depression may present with a variety of "masks," such as a somatic mask (especially with gastrointestinal or hypochondriacal manifestations).[14] A cognitive mask or so-called pseudodementia may mimic dementia. An anxiety-disorder mask manifests as agitation or attentional difficulties. Normal physical, neurologic and laboratory findings in patients who are overusers of medical services should raise the index of suspicion for the diagnosis of depression.

SEASONAL DEPRESSION

This disorder presents as discrete episodes of depression during the fall and winter months (October through February). The patient gives a history of similar episodes in the previous fall and winter seasons. Light therapy with approximately 2,500 to 10,000 lux of full-spectrum light (10 to 20 times brighter than ordinary indoor light) for 30 to 60 minutes a day is recommended. The patient is advised to glance periodically at the light during each light exposure session.[15]

ATYPICAL DEPRESSION

Atypical depression is characterized by hypersomnia, hyperphagia with carbohydrate craving and weight gain, a longstanding pattern of interpersonal rejection sensitivity, leaden paralysis (i.e., heavy, leaden feelings in arms and legs) and reactivity of mood.[6] Monoamine oxidase inhibitors (Ma01s), such as phenelzine (Nardil), given at 45 to 90 mg per day in divided doses, are more effective for treatment of atypical depression than tricyclic antidepressants.[16] Recent data suggest that selective serotonin reuptake inhibitors (SSRIs) may also be beneficial.

MAJOR DEPRESSION SUPERIMPOSED

ON DYSTHYMIA

Dysthymia is characterized by a low-grade depression lasting for two years or longer with periods of improvement lasting for two months or less. Major depression is treated with an antidepressant and/or cognitive-behavioral or interpersonal psychotherapy,[2,17] whereas dysthymia is treated primarily with psychotherapeutic techniques.

TREATMENT-REFRACTORY DEPRESSION

This condition is characterized by a history of therapeutic failure of two antidepressants used sequentially at an adequate dosage level for an adequate length of time. Referral to a psychiatrist for antidepressant augmentation therapy may be necessary. Stimulants, liothyronine (Cytomel) or simultaneous use of two or more antidepressants with or without a mood stabilizer (e.g., lithium), or electroconvulsive therapy may be prescribed.

ADJUSTMENT DISORDER

WITH DEPRESSED MOOD

This type of depression persists at least eight weeks past an identifiable loss. The treatment of choice for this condition is usually Psychotherapy, which emphasizes coping skills. If physical symptoms (Table 1) are present, an antidepressant medication may be warranted.

TABLE 1

Diagnostic Criteria for Major Depression

Cluster 1: physical or neurovegetative symptoms Sleep disturbance Appetite/weight changes Attention/concentration problem Energy-level change/fatigue Psychomotor disturbance

Cluster 2: psychologic or psychosocial symptoms Depressed mood and/or Interest/pleasure reduction Guilt feelings Suicidal thoughts