Depressive Symptoms and 3-Year Mortality in Older Hospitalized Medical Patients

Hospitalization is associated with a long-term increased risk for death, especially in older persons (1-4). Although the mediators for this increased risk have not been fully elucidated, depression may play an important role. Because depression is common in hospitalized older patients, an association between depression and mortality in this population would be of significant clinical importance (5-13). The hypothesis that depression may be a mediator of death in hospitalized patients is supported by studies demonstrating that depressive symptoms are associated with increased mortality in community-dwelling patients and in highly selected groups of hospitalized older patients, such as those with acute myocardial infarction (14-18). These studies have often been limited by inadequate accounting for the complex interrelations between depressive symptoms and other predictors of death, such as acute physiologic impairment, chronic comorbid illness, functional impairment, and cognitive impairment. Because depressive symptoms are clearly correlated with and may partly be the result of these other factors (5, 19-20), improving our understanding of the relation between depression and death requires use of standardized methods to measure and adjust for confounders. We tested the hypothesis that depressive symptoms are associated with long-term mortality in hospitalized older patients. We demonstrated previously that depressive symptoms are strongly associated with adverse health status outcomes in hospitalized medical patients through 90 days after admission (21). However, our initial study found no association between depressive symptoms and mortality during the first 90 days after admission (21). In this report, we extend mortality follow-up to 3 years by merging our data with a national mortality database. Furthermore, we adjusted for standard measures of physiologic impairment, comorbid illness, and functional impairment at hospital admission to control for the possibility that higher levels of these confounders in patients with more depressive symptoms affect the association between depressive symptoms and death. Methods Patients Patients were drawn from serial, prospective longitudinal studies of functional change in older hospitalized patients on the general medical service of University Hospitals of Cleveland. The inclusion and exclusion criteria for these studies are described elsewhere (3, 21, 22). The first study enrolled 206 patients 75 years of age or older who were admitted between March 1990 and July 1990. The second study, a controlled trial of an intervention to improve functional outcomes, enrolled 651 patients 70 years of age or older who were admitted between November 1990 and March 1992. The first study, which was a pilot study for the second study, enrolled consecutive patients. The second study randomly assigned patients to an intervention designed to improve functional outcomes in older persons or to usual care (22). In each study, patients admitted to the intensive care unit, telemetry service, or oncology service were excluded. Data collection procedures in both studies were almost identical. Other than a slightly higher mean patient age in the first study cohort, the demographic, clinical, and functional characteristics of patients in the first study, the control group of the second study, and the intervention group of the second study were similar. Additional analyses that adjusted for whether patients were in the first study cohort or the control group compared with the intervention group of the second study cohort yielded results that were almost identical to the results reported here. Of 857 older patients enrolled in the two studies, 284 were excluded from the current study because they were too ill or confused to be interviewed about depressive symptoms at the time of admission (n=164), were admitted from nursing homes (n=38), were not available for interview (n=37), declined interview (n=27), or died before being approached (n=18). We excluded patients admitted from nursing homes because interview data were less consistently obtained from these patients. Thus, the analytic sample for this study comprised 573 patients. Assessment of Depressive Symptoms Within 48 hours of admission, patients were interviewed by using the 15-item Geriatric Depression Scale to assess depressive symptoms over the past week (23, 24). The Geriatric Depression Scale is well suited for use in acutely ill older persons because it focuses on symptoms of depression that are less likely to be directly influenced by somatic illness. Examples of items on this scale include feeling bored, dropping activities and interests, feeling helpless, feeling worthless, feeling that life is empty, feeling that others are better off, preferring to stay at home instead of doing new things, and feeling hopeless. We divided patients into those reporting five or fewer symptoms and those reporting six or more symptoms; these are commonly recommended cutoffs on the 15-item Geriatric Depression Scale (24-26). Measurement of Mortality We determined mortality and date of death during the 3 years after hospitalization by merging our files with the National Death Index, a database of all deaths in the United States generated from state death certificates. Its sensitivity and specificity have been reported to be 98% and 100%, respectively (27). Measurement of Potential Confounders Shortly after admission, we surveyed each patient's primary nurse about the patient's independence in six activities of daily living (dressing, bathing, grooming, toileting, transferring, and eating) based on the scale of Katz (28). Within 48 hours of admission, we administered to patients the first 21 items of the 30-item Folstein Mini-Mental State Examination (29). To minimize respondent burden, we used only the first 21 items. Scores on the 21-item instrument have previously been shown to correlate highly (r=0.9) with scores on the 30-item instrument and to have construct validity on the basis of their strong association with functional outcomes (30). Data gathered from medical records included the reason for admission, the components of the Acute Physiology and Chronic Health Evaluation (APACHE) II score (31), and the components of the weighted Charlson comorbidity index of illness (32). The APACHE II score is a commonly used measure of physiologic severity, and the Charlson score is often used as a measure of the burden of comorbid illness. Statistical Analysis For our primary set of analyses, we compared patients who had six or more depressive symptoms (depressed patients) with patients who had five or fewer symptoms (nondepressed patients). We used the chi-square test or t-test to compare the characteristics of patients in each category at hospital admission. Survival curves describing mortality in the 3 years after hospitalization in each group were prepared by using the method of Kaplan and Meier. We used Cox regression to determine whether depressive symptoms were independently associated with mortality over 3 years. In the first model, we measured the unadjusted association between depressive symptoms and mortality. In the next four models, we determined the association between depressive symptoms and mortality after controlling for APACHE II scores, Charlson comorbidity index scores, dependence in activities of daily living, or cognitive function. In the sixth model, we controlled for all of these potential confounders as well as age, sex, ethnicity, and whether the patient lived alone. We did two secondary analyses. First, we modeled depression scores as the number of depressive symptoms on admission. We also determined the hazard ratio associated with multiple cut-points on the Geriatric Depression Scale. Results The mean age of the 573 patients was 79.9 years; 67.8% of patients were women and 39.4% were African-American. About half were independent in all activities of daily living at hospital admission. Table 1 lists the 10 most common reasons for hospital admission, classified by using the method of Charlson (33). The mean number of depressive symptoms at hospital admission was 4.5, and 34% of patients reported six or more symptoms. At admission, patients with six or more depressive symptoms had higher comorbidity scores, were more likely to have congestive heart failure or chronic obstructive pulmonary disease, had lower cognitive function scores, and were dependent in more activities of daily living (Table 2). Three years after admission (Figure), the mortality rate was higher among patients with six or more depressive symptoms than among patients with five or fewer depressive symptoms (56% compared with 40%; P<0.001). Of the 376 patients with five or fewer depressive symptoms at admission, 78 (21%) died during the first year of follow-up, 121 (32%) died during the first 2 years, and 151 (40%) died during the 3 years. Of the 197 patients with six or more depressive symptoms on admission, 58 (29%) died in the first year, 88 (45%) died during the first 2 years, and 110 (56%) died during the 3 years. The unadjusted hazard ratio over 3 years of follow-up for patients with six or more depressive symptoms was 1.56 (95% CI, 1.22 to 2.00). Patients with six or more depressive symptoms were also slightly more likely than patients with five or fewer symptoms to be discharged to a nursing home (8.3% compared with 4.9%; P=0.11). Table 1. Most Common Reasons for Hospital Admission (n=573) Table 2. Characteristics of Patients at Hospital Admission Figure. Mortality over 3 years (1095 days) in patients who had six or more depressive symptoms compared with patients who had five or fewer symptoms. Although adjustment for physiologic severity, comorbid illness, dependence in activities of daily living, and cognitive function each reduced the strength of the association between depressive symptoms and mortality, in each case this association remained statistically