| Contents | Previous | Next |
Guideline: Many general medical conditions are risk factors for major depression. Major depressive disorder, when present, should be viewed as an independent condition and specifically treated. Treatment may include (a) optimizing the treatment of the general medical disorder and/or (b) providing specific treatment for the depression. (Strength of Evidence = A.)
Clinically significant depressive symptoms are detectable in approximately 12 to 36 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. On the other hand, most patients with a general medical condition do not have a mood disorder. Therefore, the mood disorder, when present, should be viewed as an independent condition (perhaps precipitated by the biologic or psychological vulnerability of the individual) that should be specifically treated.
Since every co-occurrence of major depression and every general medical disorder cannot be covered in this guideline, the panel has chosen several specific examples to outline a general approach to the diagnosis of depression in patients with other medical disorders and to illustrate the primary treatment principles. Somatic symptoms are part of the syndrome of major depression, according to DSM-III-R. Many other medical disorders also cause some criterion symptoms of depression, such as weight loss, sleep disturbances, and low energy. These disorders include endocrinopathies, such as diabetes; pituitary, adrenal, or thyroid disorders; certain malignancies; some infections; some necrologic disorders; collagen disorders; cardiovascular disease; and vitamin/mineral deficiency and/or excess states. The clinician can substitute cognitive and emotional symptoms, such as fearful or depressed appearance, social withdrawal or decreased talkativeness, brooding, self-pity, or pessimism and unreactive mood for the standard DSM-III-R somatic symptoms when there is concern that the suspected concurrent medical disorder may be causing the criterion somatic symptoms of depression (Endicott, 1984; Kathol, Mutgi, Williams, et al., 1990).
Once the syndrome of depression has been identified in patients with a general medical illness, the differential causes of depressive symptomatology must be reviewed to make sure 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 medical condition occur together, there are several logically plausible explanations:
It is important for the practitioner to differentiate among these options for patients with depressive and other psychiatric or medical conditions. In the first two instances, treatment aims first at the general medical disorder. If the 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 disorders (Figure 5; see also Figure 2). While one uncontrolled study (Hall, Gardner, Stickney, et al., 1980) suggests that depressive symptoms resolve with treatment of the general medical illness alone in more than 60 percent of patients with depression associated with treatable general medical disorders, the prognosis for such patients remains ill-defined.
Once it has been established that the depressive symptoms are due to a primary mood disorder, treatment is aimed at the mood disorder. If, on the other hand, the depression is caused by the general medical condition, several additional steps are necessary. First, treatment of the general medical illness should be optimized. Thereafter, sufficient time should be allowed for this treatment to alter the course of the mood symptoms. If the patient’s mood disorder or symptoms do not respond to treatment for the general medical illness, or if the patient has an illness, such as cancer or diabetes, that is under optimal control but is not curable, the depression should be treated as a primary mood disorder.
Guideline: Depression following stroke is not fully explained as a psychological response to the associated impairment. There appear to be subgroups of depressed post-stroke patients whose depression is causally related to the injury, possibly including its strategic location in the brain (left dorsal lateral frontal cortex or left basal ganglia); a family history of depression; premorbid subcortical atrophy; and premorbid or ongoing social factors. When a patient with a recent stroke meets the criteria for a major depressive episode, organic (secondary) mood disorder is diagnosed. (Strength of Evidence = B.)
Figure 5. Relationship between major depressive and other current general medical disorders
The association between cerebral infarction and depression has long been recognized. However, systematic studies (Depression Guideline Panel, forthcoming) have found only a weak relationship between depression severity and physical/cognitive impairment following stroke. Case reports (Ross and Rush, 1981) indicate that post-stroke patients who are also depressed, especially those with major depressive disorder, are less compliant with treatment, are more irritable and demanding, and have an apparent personality change.
Six prospective evaluations of depressive symptoms/syndromes using various criteria revealed the prevalence of major depressive disorder to be between 10 and 27 percent in post-stroke patients, with an additional 15 to 40 percent showing less severe forms of illness within 2 months of the stroke (Eastwood, Rifat, Nobbs, et al., 1989; Ebrahim, Barer, and Nouri, 1987; House, Dennis, Magridge, et al., 1991; Morris, Robinson, and Raphael, 1990; Robinson, Starr, Kubos, et al., 1983; Wade, Leigh-Smith, and Heuer, 1987). In the four studies using DSM-III criteria (total n = 378), the same approximate prevalence rates for major depressive disorder and DNOS were found as in those studies not using such criteria (Eastwood, Rifat, Nobbs, et al., 1989; House, Dennis, Magridge, et al., 1991; Morris, Robinson, and Raphael, 1990; Robinson, Starr, Kubos, et al., 1983).
Two studies have prospectively examined the longitudinal course of depression following stroke (Morris, Robinson, and Raphael, 1990; Robinson, Bolduc, and Price, 1987). Both found the mean duration of major depressive disorder to be just under 1 year. The course of DNOS is more variable and may be either short (2 to 3 months) or prolonged (more than 2 years).
Guideline: In patients presenting with signs of both depression and dementia, if symptoms suggestive of dementia are significantly more prominent than depressive symptoms, the diagnosis is dementia with depressive symptoms. If symptoms suggesting a major depressive episode are at least as prominent as those consistent with dementia, the diagnosis is major depressive disorder. In selecting treatment, it is prudent to assume that symptoms suggesting dementia may be manifestations of the depressive disorder until proven otherwise. When the depressive episode ends, so should the symptoms suggestive of dementia. If they do not, the diagnosis of early dementia should be entertained. (Strength of Evidence = B.)
Distinguishing depressive disorders from early cementing disorders (from known or unknown causes) is a complex clinical problem. Apathy, impaired concentration, or memory loss may occur in primary major depressive episodes in the elderly, as well as early in the course of cementing disorders with or without depression. The term pseudodementia refers to the clinical presentation of cognitive impairment due to depression in the elderly. The co-occurrence of depression and dementia is by far the more frequent clinical problem. In some patients with symptoms of both depression and dementia, a personal or family history of depression suggests a depressive condition as the primary diagnosis.
If treatment for the depression succeeds and is associated with disappearance of the “cementing” symptoms, the appropriate diagnosis is major depressive disorder without dementia. If the symptoms of dementia persist, the appropriate diagnosis is dementia and major depressive disorder.
Guideline: Depressive symptoms are associated with both cortical and subcortical cementing disorders. (Strength of Evidence = A.)
Parkinson’s disease is associated with mild dementia in approximately 38 percent of patients, while 46 percent suffer severe dementia in the end stages of the disease. Approximately 50 percent of Parkinson’s patients with cementing symptoms have major depressive disorder sometime during the course of the illness. Unlike primary degenerative dementia, Parkinson’s dementia is considered a subcortical dementia; it is associated with physiologic changes in the subcortical regions (substantia nigra and globus pallidus). In those with subcortical dementia (e.g., patients with Parkinson’s or Huntington’s disease), cognitive symptoms appear to improve with improvement of mood, so assessment for and treatment of the depression may be particularly helpful to these patients (Blazer, 1993).
Guideline: Depression is often seen in patients with and/or antecedent to primary dementia. (Strength of Evidence = A.)
Approximately 30 to 40 percent of Alzheimer’s disease patients demonstrate formal depressive mood syndromes and/or psychotic symptoms sometime during their illness. The exact relationship between the two disorders is not clear. The earlier or concurrent presence of depression does not alter either the progression of dementia per se or its neuropsychological features. Some suggest that depression may occur during the early stages of dementia and that treatment of the depression may reduce some of the cognitive difficulties. However, long-term followup shows that many older patients presenting with both depression and cognitive difficulties go on to develop primary degenerative dementia without depressive features (Blazer, 1993).
Guideline: The symptomatic expression of depression in patients with diabetes is analogous to that in patients without diabetes. Given the impact of depression on the management of diabetes and the fact that most diabetic patients do not develop major depression, the practitioner is advised to screen, assess fully, and treat major depression when present in these patients. (Strength of Evidence = A.)
A variety of metabolic and endocrinologic diseases (e.g., vitamin Be deficiency; thyroid, parathyroid, and renal diseases) are associated with depressive symptoms/syndromes. The following discussion of diabetes illustrates one such condition.
Numerous recent studies that have estimated the prevalence of depression in treated samples of diabetic adults suggest that major depressive syndrome is approximately three times more common in patients with diabetes than in the general population (Biglan, Toobert, Farmer, et al., unpublished manuscript; Fris and Nanjundappa, 1986; Geringer, Perlmuter, Stern, et al., 1986; Lustman, Griffith, Clouse, et al., 1986; Montague, Eaton, Larson, et al., 1990; Popkin, Callies, Lentz, et al., 1988; Robinson, Fuller, and Edmeades, 1988; Slawson, Flynn, and Kollar, 1963; Wing, Marcus, Blair, et al., 1990). The prevalence of major depression in patients with insulin-dependent diabetes mellitus (IDDM) is similar to that in patients with non-insulin-dependent diabetes mellitus (NIDDM).
General population surveys (i.e., nontreated samples) indicate that the prevalence of depression is elevated in persons with diabetes, compared to those without a chronic medical condition. The sex- and age-adjusted prevalence of lifetime depression was significantly higher in patients with diabetes than in patients without a chronic illness (14.4 and 6.9 percent, respectively) (Wells, Golding, and Burnam, 1989). The excess prevalence of depression in diabetics suggests either an etiologic relationship or a higher detection rate secondary to increased contact with the health care system in patients with co-morbid diabetes and depression. The mean age of onset of depression was 22.1 years in patients with IDDM and 28.6 years in patients with NIDDM. In patients with NIDDM, the onset of depression occurred significantly earlier than did the onset of diabetes (Lustman, Griffith, and Clouse, 1988). A family history of depression was also significantly more common in diabetic patients with depression (35 percent) than in those without depression (3 percent). Depression in association with diabetes is a female-preponderant illness, as it is in general.
Depressions are recognized and treated in fewer than one-third of diabetic patients. Diabetes per se is not associated with sufficient depressive symptoms to impair clinical recognition of depression in diabetes. The symptom of weight loss in diabetes is not specific to depression and should not be used to diagnose the presence of depression in diabetic patients.
Only one systematic follownp study of depressed diabetic patients is available (Lustman, Griffith, and Clouse, 1988). Eighteen (64 percent) patients had been depressed within the previous 12 months, and 12 met the criteria for a current major depressive episode at the time of reevaluation. By contrast, only 10 percent of a comparison group of diabetic patients without a mood disorder at index evaluation had developed depression by the time of followup. This significant difference suggests that the risk of developing depression is restricted to a predisposed group and is less related to diabetes per se. These modest data suggest that the natural course of major depression in diabetes is chronic and severe, perhaps even more so than in those with major depressive disorder without other general medical illnesses. No randomized controlled studies of the efficacy of pharmacotherapy and/or psychotherapy have been performed in depressed diabetic patients.
Depression in diabetes is associated with poor glucose regulation, probably because of poor adherence. Since poor glucose regulation is associated with increased complications, attention to treatment of depressive symptoms is particularly relevant in management of patients with diabetes. Even without empirical studies, logic argues for treating the major depression in diabetics as a primary mood disorder, once the diabetes is optimally controlled by routine means.
Guideline: The relationship between depression and increased morbidity and mortality is well documented in both post-myocardial infarction patients and in coronary artery disease patients without myocardial infarction. Given the higher morbidity and the fact that most of these patients do not develop a major depression, the practitioner is advised to screen, assess fully, and treat major depression when present in these patient groups. (Strength of Evidence = A.)
The prevalence of various forms of depression in patients who have had a myocardial infarction is estimated at 40 to 65 percent. High prevalence rates have also been found in patients undergoing coronary artery or heart transplant surgery. The prevalence of minor and major depressive disorders combined has been reported to be as high as 40 percent in patients who have coronary heart disease and 45 percent in those who recently experienced a myocardial infarction (Schleifer, MacariHinson, Coyle, et al., 1989). The point prevalence of major depressive disorder is 18 to 25 percent for those with a recent myocardial infarction and 18 to 20 percent in those without a history of myocardial infarction, but with angiographically proven coronary artery disease. Most studies have found that depression in these patients is seldom diagnosed or treated.
The ECA survey ascertained that, over 15 months, patients aged 55 and older with mood disorders had a mortality rate four times higher than expected, and that 63 percent of these deaths were from coronary heart disease or stroke. Other studies have also shown higher myocardial infarction rates in depressed patients. Unfortunately, risk factors for coronary artery disease, such as smoking, were not controlled in these studies.
Carney, Rich, Freedland, and colleagues (1988) found that major depressive disorder leads to equal and additive disability in patients with coronary artery disease, perhaps resulting from the effects of depression on amplification of symptoms. Several studies have also linked depression with poor adherence to cardiac treatment regimens (Blumenthal, Williams, Wallace, et al., 1982; Guiry, Conroy, Hickey, et al., 1987). Kellet (1990) speculated that depression may be responsible for the poor compliance and, consequently, for the worse outcomes among noncompliant patients.
Some evidence indicates that major depressive disorder generally runs a chronic course during the first 12 months after an acute infarction. Patients who have never experienced a psychiatric disorder before their myocardial infarction have a shorter duration of symptoms. Major, but not minor, depressions follow a chronic course, suggesting that “minor” forms of depression (officially DNOS) may be better understood as transitory adjustment reactions to the medical illness (Schleifer, Macari-Hinson, Coyle, et al., 1989).
Patients with moderate to severe depression during the weeks following the myocardial infarction are more likely than are nondepressed controls to experience social problems over the first year of recovery. They are also slower to return to work and report more stress than do their nondepressed counterparts. Whether their ultimate life expectancy is shorter is not yet clear.
Guideline: It is essential to separate the symptoms of cancer or its treatment from those of a depressive disorder. A history and clinical interview are needed for a definitive diagnosis. The symptoms of persistent dysphoria, feelings of helplessness and worthlessness, loss of self-esteem, and wishes to die are the most reliable indicators of clinical depression in patients with cancer. Since major depression occurs in approximately 25 percent of patients with cancer, it should be independently diagnosed and treated. (Strength of Evidence = B.)
The diagnosis of cancer can be a catastrophic event to which many individuals initially react with shock and denial. This early reaction is often followed by emotional turmoil accompanied by anxiety, depressed mood, poor concentration, and cessation of daily activities. This response is normal. Dysphoria and sadness are parts of this normal reaction. These symptoms usually abate within a week or two with support from caregivers, family, and friends (Massie and Holland, 1990). Patients return to normal adaptation over the ensuing weeks to months.
Physicians must be able to differentiate between this normal reaction and a psychiatric disorder. Considerable evidence indicates that, for patients with cancer, a.depressive disorder leads to greater distress; decreased physical, social, and occupational functioning; and decreased ability to adhere to medical recommendations. Therefore, diagnosis and effective management of the depressive disorder in patients with cancer are potentially very important.
Several risk factors predispose cancer patients to develop depressive disorders:
The depressed patient with cancer must be assessed for suicidal risk.Suicidal risk factors include:
Many drugs used to treat cancer are associated with depressed mood as a side effect (Lesko, Massie, and Holland, 1987). The practitioner is also advised to consider other concurrent medical conditions, medications, and uncontrolled pain, all of which can contribute to depressed mood, especially in the elderly.
The prevalence of clinical depression in cancer patients ranges from 5 to 50 percent. The most systematic study of psychiatric disorders in ambulatory patients with cancer (200 patients) found that 53 percent were coping well and did not have a formal DSM-III diagnosis (American Psychiatric Association, 1980). Of the remaining 47 percent, 68 percent had an adjustment disorder; 13 percent had major depressive, dysthymic, or bipolar disorder; and 19 percent had organic mental, personality, or anxiety disorders. Adjustment disorders with depressed mood and major mood disorders were the most common psychiatric disorders identified in cancer patients.
The highest rates of clinical depression are in those with advanced cancer and with a greater level of disability and discomfort. One study found that 77 percent of bedridden patients met criteria for major depressive syndrome, compared to only 23 percent of functionally independent patients (Bukberg, Penman, and Holland, 1984).
Most studies suggest that 20 to 25 percent of cancer patients suffer major depression at some point during their illness. These percentages are remarkably similar to the rates of depression associated with other medical illnesses and a similar level of physical functioning. The finding that patients with cancer do not evidence a greater rate of major depression than do those with other medical disorders invalidates the common, but incorrect, assumption that persons with cancer should be depressed—an assumption that contributes to underdiagnosisand undertreatment of these depressions.
Guideline: Nearly all depressed patients complain of fatigue and low energy. This symptom is associated with a 46 to 75 percent lifetime rate of major depressive disorder. Complaints of chronic fatigue must be differentiated from the formal chronic fatigue syndrome. (Strength of Evidence = B.)
Only a small minority of patients with complaints of chronic fatigue meet the Centers for Disease Control (CDC) criteria for chronic fatigue syndrome. When the patient meets criteria for major depression, dysthymia, or other formal mood syndromes, the mood syndrome is diagnosed. The complaint of chronic fatigue per se is insufficient for the diagnosis of chronic fatigue syndrome. The symptom of chronic fatigue (not the syndrome) is the seventh most common complaint among adult patients in primary care settings and may be a significant problem in as many as 20 to 25 percent of these patients. Studies of patients with chronic fatigue symptoms reveal lifetime rates of psychiatric disorders in the 50 to 77 percent range, based on structured psychiatric interviews. In all studies, major depressive disorder was the most commonly reported illness (lifetime rates ranging from 46 to 75 percent). These studies also found that various anxiety disorders and somatization disorder occurred in 15 to 40 percent of patients with chronic fatigue symptoms (Hickie, Lloyd, Wakefield, et al., 1990; Kroenke, Wood, Mangelsdorff, et al., 1988; Kruesi, Dale, and Straus, 1989; Manu, Lane, and Matthews, 1988; Manu, Matthews, and Lane, 1988).
Most studies that examined the temporal sequence of chronic fatigue symptoms found a 50 to 90 percent onset rate of psychiatric illness (most commonly, major depressive disorder) prior to the onset of chronic fatigue symptoms (Kruesi, Dale, and Straus, 1989; Manu, Matthews, and Lane, 1988).
While the central feature of chronic fatigue syndrome is persistent, excessive fatiguability, it must be accompanied by various other somatic and psychological symptoms, including aching muscles and joints, headache, sore throat, painful lymph nodes, muscle weakness, sleep disturbance, mental fatigue, difficulty in concentrating, emotional lability, and sadness. In chronic fatigue syndrome, the somatic and fatigue complaints are out of proportion to physical and laboratory findings. According to the CDC criteria, the presence of a diagnosable formal psychiatric disorder, such as major depressive or dysthymic disorder, excludes the diagnosis of chronic fatigue syndrome. That is, patients who present with the formal symptomatic CDC criteria for chronic fatigue syndrome and who also meet the criteria for a formal mood disorder are treated for the mood disorder. Whether this mood disorder is etiologically connected to the chronic fatigue syndrome or whether it is an independent illness is unclear.
Guideline: As with other medical conditions, patients with fibromyalgia may or may not have clinical depression. If present, it should be diagnosed and treated as a separate entity. (Strength of Evidence = B.)
Fibromyalgia (f~brositis) is a syndrome of diffuse, aching, musculoskeletal pain associated with chronic insomnia, daytime tiredness, morning stiffness, dysesthesia in the hands, and symptoms of irritable bowel type. The American College of Rheumatology has published the currently accepted criteria for the diagnosis of fibromyalgia (Wolfe, Smythe, Yunus, et al., 1990).
Two studies have compared fibromyalgia and rheumatoid arthritis patients in structured psychiatric interviews. In one, patients with f~bromyalgia had significantly higher rates of lifetime major depressive disorder than did rheumatoid arthritis patients (71 versus 14 percent), and they had significantly more fret-degree relatives with mood and anxiety disorders (Hudson, Hudson, Pliner, et al., 1985). The second study also found higher rates of mood disorders in patients with fbromyalgia than in those with rheumatoid arthritis (20 versus 8.7 percent). Statistical significance was not attained, probably because of the small sample size (Alfici, Sigal, and Landau, 1989).
| Contents | Previous | Next |