Figure 5. Relationship between major depressive and other current general medical disorders

Note: In some clinical situations, treatment of the depression (e.g., if severe, incapacitating, or life-threatening) cannot be delayed until treatment for the general medical disorder has been optimized.

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.)

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).

Dementia

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 dementing 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 dementing 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 "dementing" 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 dementing 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 dementing 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).

Diabetes

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 B12 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 followup 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.

Coronary Artery Disease

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