Larry Culpepper, MD, MPH

Unplanned hospital readmission within 30 days is an important marker of the quality of care provided in the hospital and in the immediate posthospital setting.[1] In the United States, 1 in 5 Medicare patients is readmitted within 30 days, and related Medicare costs are estimated to be $17 billion annually.[2] Public policy is attempting to drive down healthcare costs in the United States via the Affordable Care Act by reducing payments to hospitals that have high 30‐day readmission rates.[3]

The prevalence of depression is 6.7% of adults,[4] and depressive symptomatology has been linked to hospital readmission.[5, 6] Depressive symptoms are associated with poor health outcomes and increased utilization. Patients with cardiac disease and depressive symptoms have worse outcomes.[7] Mild symptoms are associated with increased primary care and mental health care visits.[8] Both mild and moderate‐to‐severe depressive symptomatology are associated with symptom burden, physical limitation, quality of life, and overall health.[9] Importantly, many hospitalized patients, who do not have a diagnosis of depression, display depressive symptomatology.[10] A gap in knowledge exists as to the utility of stratifying depressive symptomatology between mild and moderate to severe in determining risk for hospital readmission.

Although the causal pathway to worse outcomes in patients with a diagnosis of depression has been studied,[11] the reasons for poor outcomes of patients with depressive symptomatology have not been well described, particularly in hospitalized general medical patients. Nonadherence to physician recommendations, decreased cognitive function, and poor adherence to self‐care recommendations[12, 13, 14] may explain increased healthcare utilization. Physiological models hypothesize heightened levels of proinflammatory markers[15, 16] and vascular depression[17] may play a role. There remains a gap in knowledge as to the postdischarge utilization of hospitalized patients with depressive symptomatology.

We studied the rate of hospital readmission among hospitalized adult patients with mild and moderate‐to‐severe depressive symptoms as defined by the 9‐Item Patient Health Questionnaire (PHQ‐9) depression screening tool.[18]

METHODS

RESULTS

Of the total study population, 15.9% (225/1418) demonstrated mild depressive symptoms, and 23.7% (336/1418) demonstrated moderate‐to‐severe symptoms. Of those in our study, 38.9% (551/1418) self‐reported being told by a healthcare professional that they had depression. Of those self‐reporting depression, 27.9% (273/540) were currently taking antidepressant medication at the time of the index hospitalization. Table 1 shows baseline characteristics by dichotomized utilization outcome. Mean age, marital status, health insurance, employment status, mean length of stay, admissions in the previous 6 months, mean Charlson score, and substance abuse were significantly associated with hospital readmission. Of these characteristics, all but mean length of stay and previous history of substance abuse were significantly associated with ED utilization.

Table 2 shows the unadjusted 30 day hospital readmission, ED utilization, and PCP follow‐up rates. Participants with mild symptoms had higher readmission rates than those without symptoms (0.20 vs 0.13). In other words, 20 readmissions occurred per 100 subjects with mild symptoms, compared with 13 readmissions per 100 subjects without symptoms (P<0.001). The readmission rate was 0.21 for subjects with moderate‐to‐severe depression. The rate of ED utilization for subjects with mild symptoms was 0.18. This was significantly different from ED utilization rates of those with no depression and those with moderate‐to‐severe symptoms, which were 0.16 and 0.28, respectively (P<0.001). The postdischarge follow‐up rates were different for those without depression compared to those with mild and moderate‐to‐severe symptoms (58.7, 49.5, and 51.1, respectively), but this did not reach statistical significance (P=0.06).

Poisson analyses were conducted to control for potential confounding in the relationship between symptom severity and readmission or ED utilization (Table 3). Compared to subjects with no depression, the association between mild symptoms and readmission remained significant (adjusted IRR: 1.49; 95% confidence interval [CI]: 1.11‐2.00) after controlling for relevant confounders. For those with moderate‐to‐severe symptoms, the adjusted IRR was 1.96 (95% CI: 1.51‐2.49). When compared to those without depression, the adjusted IRR for ED reutilization was not found to be significant for those with mild symptoms (1.30; 95% CI: 0.96‐1.76) and significant for those participants with moderate‐to‐severe symptoms (1.48; 95% CI: 1.16‐1.89).

Figure 1 depicts the hazard curve generated for the time to first hospital readmission, stratified by depressive symptom severity. A readmission within 30 days following an index discharge date occurred in 10% of participants without depression, 14% of those with mild symptoms, and 19% of those with moderate‐to‐severe symptoms (P=0.03).

Figure 1

DISCUSSION

Our study shows hospitalized medical patients at an urban academic hospital with a positive screen for depressive symptoms are significantly more likely to be readmitted within 30 days of discharge as compared to those who do not screen positive. The significant association of depressive symptoms and readmission remains even after stratifying by severity and controlling for relevant confounders. Further, there appears to be a dose‐response relationship between depressive symptom severity and readmission. This graded effect makes the distinction between mild and moderate‐to‐severe depressive symptoms a better instrument at predicting rehospitalization than a diagnostic code for depression. Few studies have analyzed the readmission of general medical patients stratified by depressive symptomatology, and even fewer have addressed the presence of mild depressive symptomatology as it relates to readmission. A diagnosis of mild depression is associated with similar though less severe outcomes as compared to major depression, including negative effects on quality of life, functional disability, health status, and mortality.[29] Patients with heart failure and mild depressive symptoms have higher rates of readmission at 3 months and 1 year as compared with those without depressive symptoms, but these findings were not found to be significant.[30] Mild depressive symptoms may contribute to readmission, accrued medical cost, and burden of disease.

We extend previous research[5, 31, 32] by showing that, compared to those without and those with mild symptoms, the readmission risk is even greater for those who screen positive for moderate‐to‐severe symptoms. The mechanism linking depressive symptoms and readmission is not well understood. Behavioral mechanisms such as physical symptom amplification or anxiety about symptoms link depressive symptoms to healthcare utilization after discharge.[33] Depressive symptoms among patients with diabetes, asthma, hypertension, or human immunodeficiency virus (HIV) impairs medication adherence and self‐care behavior.[14, 34, 35, 36] Depressed patients might have reduced social support leading to increased stress, worsened symptoms, and prolonged recovery.[37] These mechanisms may prompt patients to present to hospitals for reevaluation. The direct physiologic consequences of depressive symptoms may be similar to that of the diagnosis of depression. Patients with cardiovascular disease and depression have poor outcomes, which may be related to decreased heart rate variability, hypercoagulability, high burden of inflammatory markers, and severity of left ventricular dysfunction.[38, 39] Among patients with HIV/acquired immunodeficiency syndrome and coronary artery disease, depression is linked to increased proinflammatory marker levels and less favorable outcomes, which may signal a more severe form of the disease or an impaired response to treatment.[15, 16]

Our data have several implications. Though disease burden may play a role in the presence of depressive symptomatology in hospitalized patients, screen‐positive patients still experienced more readmission events as compared to those without depressive symptoms after controlling for relevant confounders. Further, there appears to be a dose‐dependent relationship between depressive symptom severity and rate of readmission. Use of a categorical ICD‐9 code often implies that the diagnosis of depression has been confirmed. Rather than using administrative ICD‐9 codes to account for readmission risk, hospitals may consider screening patients for depressive symptoms during hospitalizations to both identify and risk‐stratify patients at high risk for readmission. Procedures should be implemented to address barriers to safe transitions in care in the screen‐positive population. The relationship between symptom severity and readmission rate may aid in the decision to devote resources to those at highest risk of readmission. Lastly, though research on the treatment of depressive symptoms in medical inpatients has been inconclusive in determining whether this approach is better than usual care or structured pharmacotherapies,[40] further study is needed to determine whether treatment of mild and moderate‐to‐severe depressive symptoms during an acute medical hospitalization will decrease readmission.

Strengths of the current study include the large dataset, the broad range of covariates available for analyses, and the inclusive nature of the sample, which was not restricted to factors such as age or medical condition.

Several limitations should be noted. We did not conduct a psychiatric evaluation to evaluate screen‐positive patients who met diagnostic criteria for minor or major depressive disorder, nor did we reconfirm the presence of symptoms at the time of or following hospital discharge. Our data, then, may not reflect patients' depressive symptomatology prior to the index hospitalization or at the time of discharge. Although such data might further refine the use of depressive symptomatology in identifying patients at high risk for readmission, our findings demonstrate that simply screening positive for depressive symptomatology at time of admission is associated with increased risk of readmission. We do not know the direction of the reported associations. If depressive symptoms are the consequence of higher disease burden, treatment of the underlying disease may be the most important intervention. Although this is possible, our model does include variables (eg, length of stay, Charlson Comorbidity Index), which are likely to adjust for disease severity, pointing to the likelihood that depressive symptoms truly predict hospital readmission independent of disease severity. Data on utilization outside Boston Medical Center (about 9% of outcomes) were determined by patient self‐report and not confirmed by document review. Our results may not be generalizable to populations other than those served by an urban safety‐net hospital or other populations excluded from analysis (eg, nonEnglish‐speaking patients, patients from nursing homes). Finally, social factors such as social support may residually confound the relationship between depressive symptom severity and readmission.

Our finding linking both mild and moderate‐to‐severe depressive symptoms to increased readmission when compared to those without depressive symptoms is significant for future policy. If future studies demonstrate that the initiation of treatment of patients who screen positive for depressive symptoms during an acute hospitalization leads to reduced readmission, policymakers should increase support for mental health screening and programming as an integral portion of general medical patient management.

In conclusion, screening positive for mild or moderate‐to‐severe depressive symptoms is associated with an increased rate of early hospital readmission as compared to those without depressive symptoms, even after controlling for relevant confounders. The rate and hazard of hospital readmission increase with symptom severity. This finding has important implications for future research for hospital screening programming and interventions for patients who screen positive for depressive symptoms.

Disclosures: This research was funded in part by grants from the Agency for Healthcare Research and Quality (NCT00252057) and the National Heart, Lung, and Blood Institute (NCT00217867). Dr. Cancino has been paid for consulting work for PracticeUpdate, a subsidiary of Elsevier. Dr. Culpepper has been paid for participation in advisory boards by AstraZeneca, Eli Lilly and Co., Boehringer Ingelheim Pharmaceuticals Inc., Forest Labs, Janssen Pharmaceuticals, Inc., Jazz Pharmaceuticals plc, H. Lundbeck A/S, Merck & Co., Pfizer Inc., Reckitt Benckiser Pharmaceuticals Inc., Sunovion Pharmaceuticals Inc., and Takeda Pharmaceuticals Inc. He has received payment for educational presentations regarding hospital readmission without mention of any pharmaceutical or other products from Merck. Dr. Mitchell has received honoraria from Merck for lectures on health behavior counseling. Trial registration: NCT00252057, NCT00217867.

Unplanned hospital readmission within 30 days is an important marker of the quality of care provided in the hospital and in the immediate posthospital setting.[1] In the United States, 1 in 5 Medicare patients is readmitted within 30 days, and related Medicare costs are estimated to be $17 billion annually.[2] Public policy is attempting to drive down healthcare costs in the United States via the Affordable Care Act by reducing payments to hospitals that have high 30‐day readmission rates.[3]

The prevalence of depression is 6.7% of adults,[4] and depressive symptomatology has been linked to hospital readmission.[5, 6] Depressive symptoms are associated with poor health outcomes and increased utilization. Patients with cardiac disease and depressive symptoms have worse outcomes.[7] Mild symptoms are associated with increased primary care and mental health care visits.[8] Both mild and moderate‐to‐severe depressive symptomatology are associated with symptom burden, physical limitation, quality of life, and overall health.[9] Importantly, many hospitalized patients, who do not have a diagnosis of depression, display depressive symptomatology.[10] A gap in knowledge exists as to the utility of stratifying depressive symptomatology between mild and moderate to severe in determining risk for hospital readmission.

Although the causal pathway to worse outcomes in patients with a diagnosis of depression has been studied,[11] the reasons for poor outcomes of patients with depressive symptomatology have not been well described, particularly in hospitalized general medical patients. Nonadherence to physician recommendations, decreased cognitive function, and poor adherence to self‐care recommendations[12, 13, 14] may explain increased healthcare utilization. Physiological models hypothesize heightened levels of proinflammatory markers[15, 16] and vascular depression[17] may play a role. There remains a gap in knowledge as to the postdischarge utilization of hospitalized patients with depressive symptomatology.

We studied the rate of hospital readmission among hospitalized adult patients with mild and moderate‐to‐severe depressive symptoms as defined by the 9‐Item Patient Health Questionnaire (PHQ‐9) depression screening tool.[18]

METHODS

RESULTS

Of the total study population, 15.9% (225/1418) demonstrated mild depressive symptoms, and 23.7% (336/1418) demonstrated moderate‐to‐severe symptoms. Of those in our study, 38.9% (551/1418) self‐reported being told by a healthcare professional that they had depression. Of those self‐reporting depression, 27.9% (273/540) were currently taking antidepressant medication at the time of the index hospitalization. Table 1 shows baseline characteristics by dichotomized utilization outcome. Mean age, marital status, health insurance, employment status, mean length of stay, admissions in the previous 6 months, mean Charlson score, and substance abuse were significantly associated with hospital readmission. Of these characteristics, all but mean length of stay and previous history of substance abuse were significantly associated with ED utilization.

Table 2 shows the unadjusted 30 day hospital readmission, ED utilization, and PCP follow‐up rates. Participants with mild symptoms had higher readmission rates than those without symptoms (0.20 vs 0.13). In other words, 20 readmissions occurred per 100 subjects with mild symptoms, compared with 13 readmissions per 100 subjects without symptoms (P<0.001). The readmission rate was 0.21 for subjects with moderate‐to‐severe depression. The rate of ED utilization for subjects with mild symptoms was 0.18. This was significantly different from ED utilization rates of those with no depression and those with moderate‐to‐severe symptoms, which were 0.16 and 0.28, respectively (P<0.001). The postdischarge follow‐up rates were different for those without depression compared to those with mild and moderate‐to‐severe symptoms (58.7, 49.5, and 51.1, respectively), but this did not reach statistical significance (P=0.06).

Poisson analyses were conducted to control for potential confounding in the relationship between symptom severity and readmission or ED utilization (Table 3). Compared to subjects with no depression, the association between mild symptoms and readmission remained significant (adjusted IRR: 1.49; 95% confidence interval [CI]: 1.11‐2.00) after controlling for relevant confounders. For those with moderate‐to‐severe symptoms, the adjusted IRR was 1.96 (95% CI: 1.51‐2.49). When compared to those without depression, the adjusted IRR for ED reutilization was not found to be significant for those with mild symptoms (1.30; 95% CI: 0.96‐1.76) and significant for those participants with moderate‐to‐severe symptoms (1.48; 95% CI: 1.16‐1.89).

Figure 1 depicts the hazard curve generated for the time to first hospital readmission, stratified by depressive symptom severity. A readmission within 30 days following an index discharge date occurred in 10% of participants without depression, 14% of those with mild symptoms, and 19% of those with moderate‐to‐severe symptoms (P=0.03).

Figure 1

DISCUSSION

Our study shows hospitalized medical patients at an urban academic hospital with a positive screen for depressive symptoms are significantly more likely to be readmitted within 30 days of discharge as compared to those who do not screen positive. The significant association of depressive symptoms and readmission remains even after stratifying by severity and controlling for relevant confounders. Further, there appears to be a dose‐response relationship between depressive symptom severity and readmission. This graded effect makes the distinction between mild and moderate‐to‐severe depressive symptoms a better instrument at predicting rehospitalization than a diagnostic code for depression. Few studies have analyzed the readmission of general medical patients stratified by depressive symptomatology, and even fewer have addressed the presence of mild depressive symptomatology as it relates to readmission. A diagnosis of mild depression is associated with similar though less severe outcomes as compared to major depression, including negative effects on quality of life, functional disability, health status, and mortality.[29] Patients with heart failure and mild depressive symptoms have higher rates of readmission at 3 months and 1 year as compared with those without depressive symptoms, but these findings were not found to be significant.[30] Mild depressive symptoms may contribute to readmission, accrued medical cost, and burden of disease.

We extend previous research[5, 31, 32] by showing that, compared to those without and those with mild symptoms, the readmission risk is even greater for those who screen positive for moderate‐to‐severe symptoms. The mechanism linking depressive symptoms and readmission is not well understood. Behavioral mechanisms such as physical symptom amplification or anxiety about symptoms link depressive symptoms to healthcare utilization after discharge.[33] Depressive symptoms among patients with diabetes, asthma, hypertension, or human immunodeficiency virus (HIV) impairs medication adherence and self‐care behavior.[14, 34, 35, 36] Depressed patients might have reduced social support leading to increased stress, worsened symptoms, and prolonged recovery.[37] These mechanisms may prompt patients to present to hospitals for reevaluation. The direct physiologic consequences of depressive symptoms may be similar to that of the diagnosis of depression. Patients with cardiovascular disease and depression have poor outcomes, which may be related to decreased heart rate variability, hypercoagulability, high burden of inflammatory markers, and severity of left ventricular dysfunction.[38, 39] Among patients with HIV/acquired immunodeficiency syndrome and coronary artery disease, depression is linked to increased proinflammatory marker levels and less favorable outcomes, which may signal a more severe form of the disease or an impaired response to treatment.[15, 16]

Our data have several implications. Though disease burden may play a role in the presence of depressive symptomatology in hospitalized patients, screen‐positive patients still experienced more readmission events as compared to those without depressive symptoms after controlling for relevant confounders. Further, there appears to be a dose‐dependent relationship between depressive symptom severity and rate of readmission. Use of a categorical ICD‐9 code often implies that the diagnosis of depression has been confirmed. Rather than using administrative ICD‐9 codes to account for readmission risk, hospitals may consider screening patients for depressive symptoms during hospitalizations to both identify and risk‐stratify patients at high risk for readmission. Procedures should be implemented to address barriers to safe transitions in care in the screen‐positive population. The relationship between symptom severity and readmission rate may aid in the decision to devote resources to those at highest risk of readmission. Lastly, though research on the treatment of depressive symptoms in medical inpatients has been inconclusive in determining whether this approach is better than usual care or structured pharmacotherapies,[40] further study is needed to determine whether treatment of mild and moderate‐to‐severe depressive symptoms during an acute medical hospitalization will decrease readmission.

Strengths of the current study include the large dataset, the broad range of covariates available for analyses, and the inclusive nature of the sample, which was not restricted to factors such as age or medical condition.

Several limitations should be noted. We did not conduct a psychiatric evaluation to evaluate screen‐positive patients who met diagnostic criteria for minor or major depressive disorder, nor did we reconfirm the presence of symptoms at the time of or following hospital discharge. Our data, then, may not reflect patients' depressive symptomatology prior to the index hospitalization or at the time of discharge. Although such data might further refine the use of depressive symptomatology in identifying patients at high risk for readmission, our findings demonstrate that simply screening positive for depressive symptomatology at time of admission is associated with increased risk of readmission. We do not know the direction of the reported associations. If depressive symptoms are the consequence of higher disease burden, treatment of the underlying disease may be the most important intervention. Although this is possible, our model does include variables (eg, length of stay, Charlson Comorbidity Index), which are likely to adjust for disease severity, pointing to the likelihood that depressive symptoms truly predict hospital readmission independent of disease severity. Data on utilization outside Boston Medical Center (about 9% of outcomes) were determined by patient self‐report and not confirmed by document review. Our results may not be generalizable to populations other than those served by an urban safety‐net hospital or other populations excluded from analysis (eg, nonEnglish‐speaking patients, patients from nursing homes). Finally, social factors such as social support may residually confound the relationship between depressive symptom severity and readmission.

Our finding linking both mild and moderate‐to‐severe depressive symptoms to increased readmission when compared to those without depressive symptoms is significant for future policy. If future studies demonstrate that the initiation of treatment of patients who screen positive for depressive symptoms during an acute hospitalization leads to reduced readmission, policymakers should increase support for mental health screening and programming as an integral portion of general medical patient management.

In conclusion, screening positive for mild or moderate‐to‐severe depressive symptoms is associated with an increased rate of early hospital readmission as compared to those without depressive symptoms, even after controlling for relevant confounders. The rate and hazard of hospital readmission increase with symptom severity. This finding has important implications for future research for hospital screening programming and interventions for patients who screen positive for depressive symptoms.

Disclosures: This research was funded in part by grants from the Agency for Healthcare Research and Quality (NCT00252057) and the National Heart, Lung, and Blood Institute (NCT00217867). Dr. Cancino has been paid for consulting work for PracticeUpdate, a subsidiary of Elsevier. Dr. Culpepper has been paid for participation in advisory boards by AstraZeneca, Eli Lilly and Co., Boehringer Ingelheim Pharmaceuticals Inc., Forest Labs, Janssen Pharmaceuticals, Inc., Jazz Pharmaceuticals plc, H. Lundbeck A/S, Merck & Co., Pfizer Inc., Reckitt Benckiser Pharmaceuticals Inc., Sunovion Pharmaceuticals Inc., and Takeda Pharmaceuticals Inc. He has received payment for educational presentations regarding hospital readmission without mention of any pharmaceutical or other products from Merck. Dr. Mitchell has received honoraria from Merck for lectures on health behavior counseling. Trial registration: NCT00252057, NCT00217867.

Unplanned hospital readmission within 30 days is an important marker of the quality of care provided in the hospital and in the immediate posthospital setting.[1] In the United States, 1 in 5 Medicare patients is readmitted within 30 days, and related Medicare costs are estimated to be $17 billion annually.[2] Public policy is attempting to drive down healthcare costs in the United States via the Affordable Care Act by reducing payments to hospitals that have high 30‐day readmission rates.[3]

The prevalence of depression is 6.7% of adults,[4] and depressive symptomatology has been linked to hospital readmission.[5, 6] Depressive symptoms are associated with poor health outcomes and increased utilization. Patients with cardiac disease and depressive symptoms have worse outcomes.[7] Mild symptoms are associated with increased primary care and mental health care visits.[8] Both mild and moderate‐to‐severe depressive symptomatology are associated with symptom burden, physical limitation, quality of life, and overall health.[9] Importantly, many hospitalized patients, who do not have a diagnosis of depression, display depressive symptomatology.[10] A gap in knowledge exists as to the utility of stratifying depressive symptomatology between mild and moderate to severe in determining risk for hospital readmission.

Although the causal pathway to worse outcomes in patients with a diagnosis of depression has been studied,[11] the reasons for poor outcomes of patients with depressive symptomatology have not been well described, particularly in hospitalized general medical patients. Nonadherence to physician recommendations, decreased cognitive function, and poor adherence to self‐care recommendations[12, 13, 14] may explain increased healthcare utilization. Physiological models hypothesize heightened levels of proinflammatory markers[15, 16] and vascular depression[17] may play a role. There remains a gap in knowledge as to the postdischarge utilization of hospitalized patients with depressive symptomatology.

We studied the rate of hospital readmission among hospitalized adult patients with mild and moderate‐to‐severe depressive symptoms as defined by the 9‐Item Patient Health Questionnaire (PHQ‐9) depression screening tool.[18]

METHODS

RESULTS

Of the total study population, 15.9% (225/1418) demonstrated mild depressive symptoms, and 23.7% (336/1418) demonstrated moderate‐to‐severe symptoms. Of those in our study, 38.9% (551/1418) self‐reported being told by a healthcare professional that they had depression. Of those self‐reporting depression, 27.9% (273/540) were currently taking antidepressant medication at the time of the index hospitalization. Table 1 shows baseline characteristics by dichotomized utilization outcome. Mean age, marital status, health insurance, employment status, mean length of stay, admissions in the previous 6 months, mean Charlson score, and substance abuse were significantly associated with hospital readmission. Of these characteristics, all but mean length of stay and previous history of substance abuse were significantly associated with ED utilization.

Table 2 shows the unadjusted 30 day hospital readmission, ED utilization, and PCP follow‐up rates. Participants with mild symptoms had higher readmission rates than those without symptoms (0.20 vs 0.13). In other words, 20 readmissions occurred per 100 subjects with mild symptoms, compared with 13 readmissions per 100 subjects without symptoms (P<0.001). The readmission rate was 0.21 for subjects with moderate‐to‐severe depression. The rate of ED utilization for subjects with mild symptoms was 0.18. This was significantly different from ED utilization rates of those with no depression and those with moderate‐to‐severe symptoms, which were 0.16 and 0.28, respectively (P<0.001). The postdischarge follow‐up rates were different for those without depression compared to those with mild and moderate‐to‐severe symptoms (58.7, 49.5, and 51.1, respectively), but this did not reach statistical significance (P=0.06).

Poisson analyses were conducted to control for potential confounding in the relationship between symptom severity and readmission or ED utilization (Table 3). Compared to subjects with no depression, the association between mild symptoms and readmission remained significant (adjusted IRR: 1.49; 95% confidence interval [CI]: 1.11‐2.00) after controlling for relevant confounders. For those with moderate‐to‐severe symptoms, the adjusted IRR was 1.96 (95% CI: 1.51‐2.49). When compared to those without depression, the adjusted IRR for ED reutilization was not found to be significant for those with mild symptoms (1.30; 95% CI: 0.96‐1.76) and significant for those participants with moderate‐to‐severe symptoms (1.48; 95% CI: 1.16‐1.89).

Figure 1 depicts the hazard curve generated for the time to first hospital readmission, stratified by depressive symptom severity. A readmission within 30 days following an index discharge date occurred in 10% of participants without depression, 14% of those with mild symptoms, and 19% of those with moderate‐to‐severe symptoms (P=0.03).

Figure 1

DISCUSSION

Our study shows hospitalized medical patients at an urban academic hospital with a positive screen for depressive symptoms are significantly more likely to be readmitted within 30 days of discharge as compared to those who do not screen positive. The significant association of depressive symptoms and readmission remains even after stratifying by severity and controlling for relevant confounders. Further, there appears to be a dose‐response relationship between depressive symptom severity and readmission. This graded effect makes the distinction between mild and moderate‐to‐severe depressive symptoms a better instrument at predicting rehospitalization than a diagnostic code for depression. Few studies have analyzed the readmission of general medical patients stratified by depressive symptomatology, and even fewer have addressed the presence of mild depressive symptomatology as it relates to readmission. A diagnosis of mild depression is associated with similar though less severe outcomes as compared to major depression, including negative effects on quality of life, functional disability, health status, and mortality.[29] Patients with heart failure and mild depressive symptoms have higher rates of readmission at 3 months and 1 year as compared with those without depressive symptoms, but these findings were not found to be significant.[30] Mild depressive symptoms may contribute to readmission, accrued medical cost, and burden of disease.

We extend previous research[5, 31, 32] by showing that, compared to those without and those with mild symptoms, the readmission risk is even greater for those who screen positive for moderate‐to‐severe symptoms. The mechanism linking depressive symptoms and readmission is not well understood. Behavioral mechanisms such as physical symptom amplification or anxiety about symptoms link depressive symptoms to healthcare utilization after discharge.[33] Depressive symptoms among patients with diabetes, asthma, hypertension, or human immunodeficiency virus (HIV) impairs medication adherence and self‐care behavior.[14, 34, 35, 36] Depressed patients might have reduced social support leading to increased stress, worsened symptoms, and prolonged recovery.[37] These mechanisms may prompt patients to present to hospitals for reevaluation. The direct physiologic consequences of depressive symptoms may be similar to that of the diagnosis of depression. Patients with cardiovascular disease and depression have poor outcomes, which may be related to decreased heart rate variability, hypercoagulability, high burden of inflammatory markers, and severity of left ventricular dysfunction.[38, 39] Among patients with HIV/acquired immunodeficiency syndrome and coronary artery disease, depression is linked to increased proinflammatory marker levels and less favorable outcomes, which may signal a more severe form of the disease or an impaired response to treatment.[15, 16]

Our data have several implications. Though disease burden may play a role in the presence of depressive symptomatology in hospitalized patients, screen‐positive patients still experienced more readmission events as compared to those without depressive symptoms after controlling for relevant confounders. Further, there appears to be a dose‐dependent relationship between depressive symptom severity and rate of readmission. Use of a categorical ICD‐9 code often implies that the diagnosis of depression has been confirmed. Rather than using administrative ICD‐9 codes to account for readmission risk, hospitals may consider screening patients for depressive symptoms during hospitalizations to both identify and risk‐stratify patients at high risk for readmission. Procedures should be implemented to address barriers to safe transitions in care in the screen‐positive population. The relationship between symptom severity and readmission rate may aid in the decision to devote resources to those at highest risk of readmission. Lastly, though research on the treatment of depressive symptoms in medical inpatients has been inconclusive in determining whether this approach is better than usual care or structured pharmacotherapies,[40] further study is needed to determine whether treatment of mild and moderate‐to‐severe depressive symptoms during an acute medical hospitalization will decrease readmission.

Strengths of the current study include the large dataset, the broad range of covariates available for analyses, and the inclusive nature of the sample, which was not restricted to factors such as age or medical condition.

Several limitations should be noted. We did not conduct a psychiatric evaluation to evaluate screen‐positive patients who met diagnostic criteria for minor or major depressive disorder, nor did we reconfirm the presence of symptoms at the time of or following hospital discharge. Our data, then, may not reflect patients' depressive symptomatology prior to the index hospitalization or at the time of discharge. Although such data might further refine the use of depressive symptomatology in identifying patients at high risk for readmission, our findings demonstrate that simply screening positive for depressive symptomatology at time of admission is associated with increased risk of readmission. We do not know the direction of the reported associations. If depressive symptoms are the consequence of higher disease burden, treatment of the underlying disease may be the most important intervention. Although this is possible, our model does include variables (eg, length of stay, Charlson Comorbidity Index), which are likely to adjust for disease severity, pointing to the likelihood that depressive symptoms truly predict hospital readmission independent of disease severity. Data on utilization outside Boston Medical Center (about 9% of outcomes) were determined by patient self‐report and not confirmed by document review. Our results may not be generalizable to populations other than those served by an urban safety‐net hospital or other populations excluded from analysis (eg, nonEnglish‐speaking patients, patients from nursing homes). Finally, social factors such as social support may residually confound the relationship between depressive symptom severity and readmission.

Our finding linking both mild and moderate‐to‐severe depressive symptoms to increased readmission when compared to those without depressive symptoms is significant for future policy. If future studies demonstrate that the initiation of treatment of patients who screen positive for depressive symptoms during an acute hospitalization leads to reduced readmission, policymakers should increase support for mental health screening and programming as an integral portion of general medical patient management.

In conclusion, screening positive for mild or moderate‐to‐severe depressive symptoms is associated with an increased rate of early hospital readmission as compared to those without depressive symptoms, even after controlling for relevant confounders. The rate and hazard of hospital readmission increase with symptom severity. This finding has important implications for future research for hospital screening programming and interventions for patients who screen positive for depressive symptoms.

Disclosures: This research was funded in part by grants from the Agency for Healthcare Research and Quality (NCT00252057) and the National Heart, Lung, and Blood Institute (NCT00217867). Dr. Cancino has been paid for consulting work for PracticeUpdate, a subsidiary of Elsevier. Dr. Culpepper has been paid for participation in advisory boards by AstraZeneca, Eli Lilly and Co., Boehringer Ingelheim Pharmaceuticals Inc., Forest Labs, Janssen Pharmaceuticals, Inc., Jazz Pharmaceuticals plc, H. Lundbeck A/S, Merck & Co., Pfizer Inc., Reckitt Benckiser Pharmaceuticals Inc., Sunovion Pharmaceuticals Inc., and Takeda Pharmaceuticals Inc. He has received payment for educational presentations regarding hospital readmission without mention of any pharmaceutical or other products from Merck. Dr. Mitchell has received honoraria from Merck for lectures on health behavior counseling. Trial registration: NCT00252057, NCT00217867.

Fully 19% of Medicare patients are readmitted to the hospital within 30 days of discharge.1 This represents a large amount of potentially avoidable morbidity and cost. Indeed, projects to improve the discharge process and post‐hospital care have shown that as much as one‐third of hospital utilization in the month after discharge can be avoided.2 Consequently, the rate of early, unplanned hospital utilization after discharge has emerged as an important indicator of hospital quality and the Centers for Medicare and Medicaid Services (CMS) has proposed a policy to decrease payments to hospitals with high rates of early unplanned hospital utilization. Thus, there is great interest in identifying modifiable risk factors for rehospitalization that could be used to refine intervention models and lead to improvements in quality of care, patient outcomes, and cost savings.

To date, known predictors of readmission include: lower socioeconomic status,3 history of prior hospitalization4 and advanced age,5 length of stay greater than 7 days,6 a high burden of comorbid illnesses (based on Charlson score),7 poor social support,8 and specific diagnoses (eg, congestive heart failure, chronic obstructive pulmonary disease [COPD] and myocardial infarction).5, 9, 10 In addition, unplanned readmissions and emergency department (ED) visits have been linked to polypharmacy and adverse drug events related to treatment with medications such as warfarin, digoxin and narcotics.11, 12 Another characteristic that has also been linked to readmission is depression;13 however5 reports supporting this association are from studies of elderly patients or with patients who have specific diagnoses (eg, congestive heart failure [CHF], COPD, myocardial infarction).1416

Depression is common, affecting 13% to 16% of people in the US, and is recognized as an important risk factor for poor outcomes among patients with various chronic illnesses.1719 The mechanisms by which depression can be linked to health outcomes and health service utilization have been studied in age‐specific or disease‐specific cohorts such as cardiac patients or frail elders and include both physiologic factors such as hypercoagulability and hyperinflammatory conditions, as well as behavioral factors such as poor self‐care behaviors and heightened sensitivity to somatic symptoms. How these mechanisms link depression to health outcomes and hospital utilization in a general medical population is not clearly understood. Kartha et al.13 reported findings indicating that depression is a risk factor for rehospitalization in general medical inpatients, but the study sample was relatively small and the study design methodology significantly limited its generalizability.12 It would be useful to provide supporting evidence showing depression as an important risk factor for readmission in the general medical in‐patient population using more rigorous study methods and a larger cohort.

We hypothesized that depressive symptoms would be an independent risk factor for early unplanned hospital utilization after discharge for all medical patients. Therefore, we conducted a secondary analysis of the Project RED clinical trial dataset to assess the association between a positive depression screen during inpatient hospitalization and the rate of subsequent hospital utilization.

Methods

Data from the Project RED clinical trial were reviewed for inclusion in a secondary analysis. Complete data were available for 738 of the 749 subjects recruited for Project RED.

Results

A total of 28% of subjects were categorized as having a positive depression screen. More women (36%) had positive depression screens than men (28%). Among patients with a positive depression screen, 58% had a history of depression and 53% were currently taking medications at the time of enrollment, compared with 25% and 22% respectively for subjects with a negative depression screen. Table 1 presents the means or percentages for baseline characteristics by depression status in the analytic cohort. Subjects with Medicaid for insurance had a higher rate of depression (61%) than subjects with Medicare (13%), private insurance (9%), or those who qualified for the Free Care pool (17%) which is the Massachusetts state funding for healthcare to uninsured persons. Subjects who were unemployed, unmarried, or who reported earnings less than $10,000 per year were also more likely to screen positive for depression. In addition, depressed subjects had a higher severity of co‐morbid disease and longer length of stay for the index hospitalization. Patients categorized as frequent utilizers (2 or more prior admissions) for the 6 months prior to the index hospitalization were also more likely to be depressed. Of further note, is the relatively younger average age among both depressive patients (49.6 years) and non‐depressive patients (49.9) of these study subjects.

The unadjusted hospital utilization rate at 30, 60, and 90 days post‐discharge by depression status is shown in Table 2. At 30 days post‐discharge, those with depressive symptoms had a higher rate of hospital utilization than those without depressive symptoms (0.563 vs. 0.296). In other words, 56 utilization events occurred per 100 patients with depressive symptoms, compared with 30 utilization events per 100 patients without depressive symptoms. The unadjusted 30‐day post‐discharge hospital utilization rate among those with depressive symptoms was higher compared with those without symptoms (IRR, 1.90, 95% confidence interval [CI], 1.242.71). A similar trend was found among subjects at 60 and 90 days post‐discharge.

Poisson regression analyses were conducted to control for potential confounding in the relationship between depressive symptoms and hospital utilization rate within 30 days after discharge (Table 3). After controlling for relevant confounders, including age, gender, employment status, frequent prior hospitalization status, marital status, Charlson score, Project RED study group assignment and the interaction variable for RED study group assignment and depression, the association between symptoms of depression, and hospital utilization rate remained significant (IRR, 1.73; 95% CI, 1.272.36).

Figure 1 depicts the Kaplan‐Meier hazard curve generated for time to first hospital utilization, stratified by depression status. While 21% of participants without symptoms of depression had a hospital utilization within 30 days, fully 29% of participants with symptoms of depression had a hospital utilization within 30 days (P = 0.011).

Figure 1

Discussion

Our study shows hospitalized patients who screen positive for depressive symptoms are significantly more likely to have a hospital visit (emergency room or rehospitalization) within 30 days of discharge than those who do not screen positive for depressive symptoms among medical patients admitted to an urban, academic, safety‐net hospital. These findings are consistent with, and extend, prior reports regarding depression and rehospitalization in specific populations (ie, geriatrics) and specific diagnoses (ie, cardiovascular disease [CVD] and COPD).1012 We observed a 73% higher incidence rate for hospital utilization within 30 days of discharge for those with symptoms of depression. This puts symptoms of depression on par with frequent prior rehospitalization, advanced age and low social support, as known risk factors for rehospitalization.4, 5, 23

Also of significance is the relatively young age of this study population (49.9 years non‐depressive patients and 49.6 years for depressive patients) compared with the study cohorts used for research in the majority of the existing literature. The chief reason for the young age of our cohort is that potential subjects were excluded if they came from a skilled nursing facility or other hospital. This may limit the generalizability of our findings; however, it seems likely that interventions relating to depression and transitions of care will need to be quite different for patients that reside in long‐term care facilities vs. patients that live in the community. For example, patients living in the community may have significant barriers to access post‐discharge services due to insurance status and are more likely to be sensitive to variations in social support.

Early rehospitalization is associated with significant morbidity, mortality, and expense. It is also a potential marker for poor quality of care.24 Concerns for patient safety, escalating healthcare costs, and possible change in hospital reimbursement mechanisms are fueling the search for modifiable risk factors associated with early rehospitalization. Our data provide evidence that symptoms of depression may be an important focus of attention. We do not know, however whether treating hospitalized patients who screen positive for depression will decrease early rehospitalization and emergency room utilization rates.

Various physiologic and behavioral mechanisms may link symptoms of depression to hospital utilization after discharge. For example, depressed patients with features of somatization may be more likely to experience worrisome physical symptoms after discharge and present prematurely for reevaluation. Patients who are sicker in some fashion not captured by our measured confounders may have symptoms of depression related to chronic, debilitating disease warranting early return to the hospital. Depression may also yield nonadherence to aspects of the discharge treatment plan leading to rehospitalization as a result of poor post‐discharge disease management. For example, research shows that patients with depression following coronary artery bypass surgery are less likely to adhere with cardiac rehabilitation programs.25 Likewise, depression among chronically ill patients such as diabetics, asthmatics, or human immunodeficiency virus (HIV)‐positive patients impairs medication adherence and self‐care behavior which may lead to disease relapse or recurrence.2628 One study examining depression effects on hypertensive medicine adherence in African Americans identified self‐efficacy as a mediating factor between depression and nonadherence.29 This implies that interventions such as self‐management education, a program through which chronically‐ill patients learn to better manage their illnesses through enhanced self‐confidence and problem‐solving strategies (including mood disorder challenges) may reduce early rehospitalization among depressed patients.30

There is also evidence that depression may have direct physiologic consequences. In patients with CVD, depression is associated with poor outcomes possibly related to decreased heart rate variability, hypercoagulability, high burdens of inflammatory markers, and severity of left ventricular dysfunction.3134 Similarly, depression among HIV/acquired immune deficiency syndrome (AIDS), diabetics and multiple sclerosis (MS) patients is linked to heightened levels of proinflammatory markers and less favorable outcomes that may signal a more severe form of the disease or an impaired response to treatment.3538 Indeed, MS investigators now hypothesize that the proinflammatory environment associated with the neurologic manifestations of MS are also causing depression symptoms among MS patients.34 This theory contrasts the common belief that depression in the chronically ill manifests independent of the chronic illness or in response to living with chronic disease.

A major strength of the current study is the large dataset and the broad range of covariates available for analyses. However, several limitations should be noted. First, data on hospital utilization outside Boston Medical Center were determined by patient self‐report and were not confirmed by document review. Second, we do not know the direction of the associations we report. If symptoms of depression are merely the consequence of having a higher disease burden, treatment of the underlying disease may be the most important response. While this is possible, our model does include several variables (eg, Charlson score and length of stay) that are likely to adjust for disease severity, pointing to the likelihood that symptoms of depression truly predict hospital utilization in a fashion that is independent of disease severity. Third, our results may not be generalizable to populations other than those served by urban safety‐net hospitals or other populations excluded from the Project RED trial (eg, non‐English speaking patients and patients from nursing homes). Finally, social factors such as substance use and social support system variables may residually confound the relationship between depression and hospital reutilization demonstrated in this study. While this dataset does not include a measure of social support other than marital status and housing status, data is available on substance use. Analyses conducted by our colleagues using Project RED data found that in this study population depression was significantly more prevalent among substance users (29% vs. 14%) compared with non‐users and that substance use is an independent risk factor for hospital reutilization (unpublished data).

Our findings linking depression to increased hospital utilization also warrant further consideration from healthcare policymakers. Central to the Obama Administration's February 2009 healthcare reform proposal is the pursuit of cost savings through reductions in unplanned hospital readmissions.39 Thus, identifying potentially modifiable risk factors for readmission, such as depression, is of great concern to healthcare providers and policymakers across the nation. If, through testing of interventions, depression proves to be a modifiable risk for readmission, policymakers, while negotiating healthcare reform measures, must provide for the services required to address this comorbidity at the time of discharge. For example, if a patient screens positive for depressive symptoms during a hospitalization for COPD exacerbation, will the proposed payment reforms allow for mental health services during the immediate post‐discharge period in order to reduce the likelihood of hospital readmission? Will those mental health services be readily available? Payment reforms that account for all necessary transitional care services will indeed help reduce readmission costs with less risk for untoward consequences.

In conclusion, our results indicate that a positive depression screen is a significant risk factor for early post‐discharge hospital utilization among hospitalized adults on a general medical service, even after controlling for relevant confounders. Screening for depression during acute hospitalizations may be an important step in identifying patients at increased risk for readmission. Future research should focus on further characterizing and stratifying populations at highest risk for depression. Efforts should also include developing and evaluating targeted interventions for patients with symptoms of depression among hospitalized patients as part of discharge planning. Timely depression therapy during the hospitalization or following hospital discharge might reduce costly readmissions and enhance patient safety.

Fully 19% of Medicare patients are readmitted to the hospital within 30 days of discharge.1 This represents a large amount of potentially avoidable morbidity and cost. Indeed, projects to improve the discharge process and post‐hospital care have shown that as much as one‐third of hospital utilization in the month after discharge can be avoided.2 Consequently, the rate of early, unplanned hospital utilization after discharge has emerged as an important indicator of hospital quality and the Centers for Medicare and Medicaid Services (CMS) has proposed a policy to decrease payments to hospitals with high rates of early unplanned hospital utilization. Thus, there is great interest in identifying modifiable risk factors for rehospitalization that could be used to refine intervention models and lead to improvements in quality of care, patient outcomes, and cost savings.

To date, known predictors of readmission include: lower socioeconomic status,3 history of prior hospitalization4 and advanced age,5 length of stay greater than 7 days,6 a high burden of comorbid illnesses (based on Charlson score),7 poor social support,8 and specific diagnoses (eg, congestive heart failure, chronic obstructive pulmonary disease [COPD] and myocardial infarction).5, 9, 10 In addition, unplanned readmissions and emergency department (ED) visits have been linked to polypharmacy and adverse drug events related to treatment with medications such as warfarin, digoxin and narcotics.11, 12 Another characteristic that has also been linked to readmission is depression;13 however5 reports supporting this association are from studies of elderly patients or with patients who have specific diagnoses (eg, congestive heart failure [CHF], COPD, myocardial infarction).1416

Depression is common, affecting 13% to 16% of people in the US, and is recognized as an important risk factor for poor outcomes among patients with various chronic illnesses.1719 The mechanisms by which depression can be linked to health outcomes and health service utilization have been studied in age‐specific or disease‐specific cohorts such as cardiac patients or frail elders and include both physiologic factors such as hypercoagulability and hyperinflammatory conditions, as well as behavioral factors such as poor self‐care behaviors and heightened sensitivity to somatic symptoms. How these mechanisms link depression to health outcomes and hospital utilization in a general medical population is not clearly understood. Kartha et al.13 reported findings indicating that depression is a risk factor for rehospitalization in general medical inpatients, but the study sample was relatively small and the study design methodology significantly limited its generalizability.12 It would be useful to provide supporting evidence showing depression as an important risk factor for readmission in the general medical in‐patient population using more rigorous study methods and a larger cohort.

We hypothesized that depressive symptoms would be an independent risk factor for early unplanned hospital utilization after discharge for all medical patients. Therefore, we conducted a secondary analysis of the Project RED clinical trial dataset to assess the association between a positive depression screen during inpatient hospitalization and the rate of subsequent hospital utilization.

Methods

Data from the Project RED clinical trial were reviewed for inclusion in a secondary analysis. Complete data were available for 738 of the 749 subjects recruited for Project RED.

Results

A total of 28% of subjects were categorized as having a positive depression screen. More women (36%) had positive depression screens than men (28%). Among patients with a positive depression screen, 58% had a history of depression and 53% were currently taking medications at the time of enrollment, compared with 25% and 22% respectively for subjects with a negative depression screen. Table 1 presents the means or percentages for baseline characteristics by depression status in the analytic cohort. Subjects with Medicaid for insurance had a higher rate of depression (61%) than subjects with Medicare (13%), private insurance (9%), or those who qualified for the Free Care pool (17%) which is the Massachusetts state funding for healthcare to uninsured persons. Subjects who were unemployed, unmarried, or who reported earnings less than $10,000 per year were also more likely to screen positive for depression. In addition, depressed subjects had a higher severity of co‐morbid disease and longer length of stay for the index hospitalization. Patients categorized as frequent utilizers (2 or more prior admissions) for the 6 months prior to the index hospitalization were also more likely to be depressed. Of further note, is the relatively younger average age among both depressive patients (49.6 years) and non‐depressive patients (49.9) of these study subjects.

The unadjusted hospital utilization rate at 30, 60, and 90 days post‐discharge by depression status is shown in Table 2. At 30 days post‐discharge, those with depressive symptoms had a higher rate of hospital utilization than those without depressive symptoms (0.563 vs. 0.296). In other words, 56 utilization events occurred per 100 patients with depressive symptoms, compared with 30 utilization events per 100 patients without depressive symptoms. The unadjusted 30‐day post‐discharge hospital utilization rate among those with depressive symptoms was higher compared with those without symptoms (IRR, 1.90, 95% confidence interval [CI], 1.242.71). A similar trend was found among subjects at 60 and 90 days post‐discharge.

Poisson regression analyses were conducted to control for potential confounding in the relationship between depressive symptoms and hospital utilization rate within 30 days after discharge (Table 3). After controlling for relevant confounders, including age, gender, employment status, frequent prior hospitalization status, marital status, Charlson score, Project RED study group assignment and the interaction variable for RED study group assignment and depression, the association between symptoms of depression, and hospital utilization rate remained significant (IRR, 1.73; 95% CI, 1.272.36).

Figure 1 depicts the Kaplan‐Meier hazard curve generated for time to first hospital utilization, stratified by depression status. While 21% of participants without symptoms of depression had a hospital utilization within 30 days, fully 29% of participants with symptoms of depression had a hospital utilization within 30 days (P = 0.011).

Figure 1

Discussion

Our study shows hospitalized patients who screen positive for depressive symptoms are significantly more likely to have a hospital visit (emergency room or rehospitalization) within 30 days of discharge than those who do not screen positive for depressive symptoms among medical patients admitted to an urban, academic, safety‐net hospital. These findings are consistent with, and extend, prior reports regarding depression and rehospitalization in specific populations (ie, geriatrics) and specific diagnoses (ie, cardiovascular disease [CVD] and COPD).1012 We observed a 73% higher incidence rate for hospital utilization within 30 days of discharge for those with symptoms of depression. This puts symptoms of depression on par with frequent prior rehospitalization, advanced age and low social support, as known risk factors for rehospitalization.4, 5, 23

Also of significance is the relatively young age of this study population (49.9 years non‐depressive patients and 49.6 years for depressive patients) compared with the study cohorts used for research in the majority of the existing literature. The chief reason for the young age of our cohort is that potential subjects were excluded if they came from a skilled nursing facility or other hospital. This may limit the generalizability of our findings; however, it seems likely that interventions relating to depression and transitions of care will need to be quite different for patients that reside in long‐term care facilities vs. patients that live in the community. For example, patients living in the community may have significant barriers to access post‐discharge services due to insurance status and are more likely to be sensitive to variations in social support.

Early rehospitalization is associated with significant morbidity, mortality, and expense. It is also a potential marker for poor quality of care.24 Concerns for patient safety, escalating healthcare costs, and possible change in hospital reimbursement mechanisms are fueling the search for modifiable risk factors associated with early rehospitalization. Our data provide evidence that symptoms of depression may be an important focus of attention. We do not know, however whether treating hospitalized patients who screen positive for depression will decrease early rehospitalization and emergency room utilization rates.

Various physiologic and behavioral mechanisms may link symptoms of depression to hospital utilization after discharge. For example, depressed patients with features of somatization may be more likely to experience worrisome physical symptoms after discharge and present prematurely for reevaluation. Patients who are sicker in some fashion not captured by our measured confounders may have symptoms of depression related to chronic, debilitating disease warranting early return to the hospital. Depression may also yield nonadherence to aspects of the discharge treatment plan leading to rehospitalization as a result of poor post‐discharge disease management. For example, research shows that patients with depression following coronary artery bypass surgery are less likely to adhere with cardiac rehabilitation programs.25 Likewise, depression among chronically ill patients such as diabetics, asthmatics, or human immunodeficiency virus (HIV)‐positive patients impairs medication adherence and self‐care behavior which may lead to disease relapse or recurrence.2628 One study examining depression effects on hypertensive medicine adherence in African Americans identified self‐efficacy as a mediating factor between depression and nonadherence.29 This implies that interventions such as self‐management education, a program through which chronically‐ill patients learn to better manage their illnesses through enhanced self‐confidence and problem‐solving strategies (including mood disorder challenges) may reduce early rehospitalization among depressed patients.30

There is also evidence that depression may have direct physiologic consequences. In patients with CVD, depression is associated with poor outcomes possibly related to decreased heart rate variability, hypercoagulability, high burdens of inflammatory markers, and severity of left ventricular dysfunction.3134 Similarly, depression among HIV/acquired immune deficiency syndrome (AIDS), diabetics and multiple sclerosis (MS) patients is linked to heightened levels of proinflammatory markers and less favorable outcomes that may signal a more severe form of the disease or an impaired response to treatment.3538 Indeed, MS investigators now hypothesize that the proinflammatory environment associated with the neurologic manifestations of MS are also causing depression symptoms among MS patients.34 This theory contrasts the common belief that depression in the chronically ill manifests independent of the chronic illness or in response to living with chronic disease.

A major strength of the current study is the large dataset and the broad range of covariates available for analyses. However, several limitations should be noted. First, data on hospital utilization outside Boston Medical Center were determined by patient self‐report and were not confirmed by document review. Second, we do not know the direction of the associations we report. If symptoms of depression are merely the consequence of having a higher disease burden, treatment of the underlying disease may be the most important response. While this is possible, our model does include several variables (eg, Charlson score and length of stay) that are likely to adjust for disease severity, pointing to the likelihood that symptoms of depression truly predict hospital utilization in a fashion that is independent of disease severity. Third, our results may not be generalizable to populations other than those served by urban safety‐net hospitals or other populations excluded from the Project RED trial (eg, non‐English speaking patients and patients from nursing homes). Finally, social factors such as substance use and social support system variables may residually confound the relationship between depression and hospital reutilization demonstrated in this study. While this dataset does not include a measure of social support other than marital status and housing status, data is available on substance use. Analyses conducted by our colleagues using Project RED data found that in this study population depression was significantly more prevalent among substance users (29% vs. 14%) compared with non‐users and that substance use is an independent risk factor for hospital reutilization (unpublished data).

Our findings linking depression to increased hospital utilization also warrant further consideration from healthcare policymakers. Central to the Obama Administration's February 2009 healthcare reform proposal is the pursuit of cost savings through reductions in unplanned hospital readmissions.39 Thus, identifying potentially modifiable risk factors for readmission, such as depression, is of great concern to healthcare providers and policymakers across the nation. If, through testing of interventions, depression proves to be a modifiable risk for readmission, policymakers, while negotiating healthcare reform measures, must provide for the services required to address this comorbidity at the time of discharge. For example, if a patient screens positive for depressive symptoms during a hospitalization for COPD exacerbation, will the proposed payment reforms allow for mental health services during the immediate post‐discharge period in order to reduce the likelihood of hospital readmission? Will those mental health services be readily available? Payment reforms that account for all necessary transitional care services will indeed help reduce readmission costs with less risk for untoward consequences.

In conclusion, our results indicate that a positive depression screen is a significant risk factor for early post‐discharge hospital utilization among hospitalized adults on a general medical service, even after controlling for relevant confounders. Screening for depression during acute hospitalizations may be an important step in identifying patients at increased risk for readmission. Future research should focus on further characterizing and stratifying populations at highest risk for depression. Efforts should also include developing and evaluating targeted interventions for patients with symptoms of depression among hospitalized patients as part of discharge planning. Timely depression therapy during the hospitalization or following hospital discharge might reduce costly readmissions and enhance patient safety.

Fully 19% of Medicare patients are readmitted to the hospital within 30 days of discharge.1 This represents a large amount of potentially avoidable morbidity and cost. Indeed, projects to improve the discharge process and post‐hospital care have shown that as much as one‐third of hospital utilization in the month after discharge can be avoided.2 Consequently, the rate of early, unplanned hospital utilization after discharge has emerged as an important indicator of hospital quality and the Centers for Medicare and Medicaid Services (CMS) has proposed a policy to decrease payments to hospitals with high rates of early unplanned hospital utilization. Thus, there is great interest in identifying modifiable risk factors for rehospitalization that could be used to refine intervention models and lead to improvements in quality of care, patient outcomes, and cost savings.

To date, known predictors of readmission include: lower socioeconomic status,3 history of prior hospitalization4 and advanced age,5 length of stay greater than 7 days,6 a high burden of comorbid illnesses (based on Charlson score),7 poor social support,8 and specific diagnoses (eg, congestive heart failure, chronic obstructive pulmonary disease [COPD] and myocardial infarction).5, 9, 10 In addition, unplanned readmissions and emergency department (ED) visits have been linked to polypharmacy and adverse drug events related to treatment with medications such as warfarin, digoxin and narcotics.11, 12 Another characteristic that has also been linked to readmission is depression;13 however5 reports supporting this association are from studies of elderly patients or with patients who have specific diagnoses (eg, congestive heart failure [CHF], COPD, myocardial infarction).1416

Depression is common, affecting 13% to 16% of people in the US, and is recognized as an important risk factor for poor outcomes among patients with various chronic illnesses.1719 The mechanisms by which depression can be linked to health outcomes and health service utilization have been studied in age‐specific or disease‐specific cohorts such as cardiac patients or frail elders and include both physiologic factors such as hypercoagulability and hyperinflammatory conditions, as well as behavioral factors such as poor self‐care behaviors and heightened sensitivity to somatic symptoms. How these mechanisms link depression to health outcomes and hospital utilization in a general medical population is not clearly understood. Kartha et al.13 reported findings indicating that depression is a risk factor for rehospitalization in general medical inpatients, but the study sample was relatively small and the study design methodology significantly limited its generalizability.12 It would be useful to provide supporting evidence showing depression as an important risk factor for readmission in the general medical in‐patient population using more rigorous study methods and a larger cohort.

We hypothesized that depressive symptoms would be an independent risk factor for early unplanned hospital utilization after discharge for all medical patients. Therefore, we conducted a secondary analysis of the Project RED clinical trial dataset to assess the association between a positive depression screen during inpatient hospitalization and the rate of subsequent hospital utilization.

Methods

Data from the Project RED clinical trial were reviewed for inclusion in a secondary analysis. Complete data were available for 738 of the 749 subjects recruited for Project RED.

Results

A total of 28% of subjects were categorized as having a positive depression screen. More women (36%) had positive depression screens than men (28%). Among patients with a positive depression screen, 58% had a history of depression and 53% were currently taking medications at the time of enrollment, compared with 25% and 22% respectively for subjects with a negative depression screen. Table 1 presents the means or percentages for baseline characteristics by depression status in the analytic cohort. Subjects with Medicaid for insurance had a higher rate of depression (61%) than subjects with Medicare (13%), private insurance (9%), or those who qualified for the Free Care pool (17%) which is the Massachusetts state funding for healthcare to uninsured persons. Subjects who were unemployed, unmarried, or who reported earnings less than $10,000 per year were also more likely to screen positive for depression. In addition, depressed subjects had a higher severity of co‐morbid disease and longer length of stay for the index hospitalization. Patients categorized as frequent utilizers (2 or more prior admissions) for the 6 months prior to the index hospitalization were also more likely to be depressed. Of further note, is the relatively younger average age among both depressive patients (49.6 years) and non‐depressive patients (49.9) of these study subjects.

The unadjusted hospital utilization rate at 30, 60, and 90 days post‐discharge by depression status is shown in Table 2. At 30 days post‐discharge, those with depressive symptoms had a higher rate of hospital utilization than those without depressive symptoms (0.563 vs. 0.296). In other words, 56 utilization events occurred per 100 patients with depressive symptoms, compared with 30 utilization events per 100 patients without depressive symptoms. The unadjusted 30‐day post‐discharge hospital utilization rate among those with depressive symptoms was higher compared with those without symptoms (IRR, 1.90, 95% confidence interval [CI], 1.242.71). A similar trend was found among subjects at 60 and 90 days post‐discharge.

Poisson regression analyses were conducted to control for potential confounding in the relationship between depressive symptoms and hospital utilization rate within 30 days after discharge (Table 3). After controlling for relevant confounders, including age, gender, employment status, frequent prior hospitalization status, marital status, Charlson score, Project RED study group assignment and the interaction variable for RED study group assignment and depression, the association between symptoms of depression, and hospital utilization rate remained significant (IRR, 1.73; 95% CI, 1.272.36).

Figure 1 depicts the Kaplan‐Meier hazard curve generated for time to first hospital utilization, stratified by depression status. While 21% of participants without symptoms of depression had a hospital utilization within 30 days, fully 29% of participants with symptoms of depression had a hospital utilization within 30 days (P = 0.011).

Figure 1

Discussion

Our study shows hospitalized patients who screen positive for depressive symptoms are significantly more likely to have a hospital visit (emergency room or rehospitalization) within 30 days of discharge than those who do not screen positive for depressive symptoms among medical patients admitted to an urban, academic, safety‐net hospital. These findings are consistent with, and extend, prior reports regarding depression and rehospitalization in specific populations (ie, geriatrics) and specific diagnoses (ie, cardiovascular disease [CVD] and COPD).1012 We observed a 73% higher incidence rate for hospital utilization within 30 days of discharge for those with symptoms of depression. This puts symptoms of depression on par with frequent prior rehospitalization, advanced age and low social support, as known risk factors for rehospitalization.4, 5, 23

Also of significance is the relatively young age of this study population (49.9 years non‐depressive patients and 49.6 years for depressive patients) compared with the study cohorts used for research in the majority of the existing literature. The chief reason for the young age of our cohort is that potential subjects were excluded if they came from a skilled nursing facility or other hospital. This may limit the generalizability of our findings; however, it seems likely that interventions relating to depression and transitions of care will need to be quite different for patients that reside in long‐term care facilities vs. patients that live in the community. For example, patients living in the community may have significant barriers to access post‐discharge services due to insurance status and are more likely to be sensitive to variations in social support.

Early rehospitalization is associated with significant morbidity, mortality, and expense. It is also a potential marker for poor quality of care.24 Concerns for patient safety, escalating healthcare costs, and possible change in hospital reimbursement mechanisms are fueling the search for modifiable risk factors associated with early rehospitalization. Our data provide evidence that symptoms of depression may be an important focus of attention. We do not know, however whether treating hospitalized patients who screen positive for depression will decrease early rehospitalization and emergency room utilization rates.

Various physiologic and behavioral mechanisms may link symptoms of depression to hospital utilization after discharge. For example, depressed patients with features of somatization may be more likely to experience worrisome physical symptoms after discharge and present prematurely for reevaluation. Patients who are sicker in some fashion not captured by our measured confounders may have symptoms of depression related to chronic, debilitating disease warranting early return to the hospital. Depression may also yield nonadherence to aspects of the discharge treatment plan leading to rehospitalization as a result of poor post‐discharge disease management. For example, research shows that patients with depression following coronary artery bypass surgery are less likely to adhere with cardiac rehabilitation programs.25 Likewise, depression among chronically ill patients such as diabetics, asthmatics, or human immunodeficiency virus (HIV)‐positive patients impairs medication adherence and self‐care behavior which may lead to disease relapse or recurrence.2628 One study examining depression effects on hypertensive medicine adherence in African Americans identified self‐efficacy as a mediating factor between depression and nonadherence.29 This implies that interventions such as self‐management education, a program through which chronically‐ill patients learn to better manage their illnesses through enhanced self‐confidence and problem‐solving strategies (including mood disorder challenges) may reduce early rehospitalization among depressed patients.30

There is also evidence that depression may have direct physiologic consequences. In patients with CVD, depression is associated with poor outcomes possibly related to decreased heart rate variability, hypercoagulability, high burdens of inflammatory markers, and severity of left ventricular dysfunction.3134 Similarly, depression among HIV/acquired immune deficiency syndrome (AIDS), diabetics and multiple sclerosis (MS) patients is linked to heightened levels of proinflammatory markers and less favorable outcomes that may signal a more severe form of the disease or an impaired response to treatment.3538 Indeed, MS investigators now hypothesize that the proinflammatory environment associated with the neurologic manifestations of MS are also causing depression symptoms among MS patients.34 This theory contrasts the common belief that depression in the chronically ill manifests independent of the chronic illness or in response to living with chronic disease.

A major strength of the current study is the large dataset and the broad range of covariates available for analyses. However, several limitations should be noted. First, data on hospital utilization outside Boston Medical Center were determined by patient self‐report and were not confirmed by document review. Second, we do not know the direction of the associations we report. If symptoms of depression are merely the consequence of having a higher disease burden, treatment of the underlying disease may be the most important response. While this is possible, our model does include several variables (eg, Charlson score and length of stay) that are likely to adjust for disease severity, pointing to the likelihood that symptoms of depression truly predict hospital utilization in a fashion that is independent of disease severity. Third, our results may not be generalizable to populations other than those served by urban safety‐net hospitals or other populations excluded from the Project RED trial (eg, non‐English speaking patients and patients from nursing homes). Finally, social factors such as substance use and social support system variables may residually confound the relationship between depression and hospital reutilization demonstrated in this study. While this dataset does not include a measure of social support other than marital status and housing status, data is available on substance use. Analyses conducted by our colleagues using Project RED data found that in this study population depression was significantly more prevalent among substance users (29% vs. 14%) compared with non‐users and that substance use is an independent risk factor for hospital reutilization (unpublished data).

Our findings linking depression to increased hospital utilization also warrant further consideration from healthcare policymakers. Central to the Obama Administration's February 2009 healthcare reform proposal is the pursuit of cost savings through reductions in unplanned hospital readmissions.39 Thus, identifying potentially modifiable risk factors for readmission, such as depression, is of great concern to healthcare providers and policymakers across the nation. If, through testing of interventions, depression proves to be a modifiable risk for readmission, policymakers, while negotiating healthcare reform measures, must provide for the services required to address this comorbidity at the time of discharge. For example, if a patient screens positive for depressive symptoms during a hospitalization for COPD exacerbation, will the proposed payment reforms allow for mental health services during the immediate post‐discharge period in order to reduce the likelihood of hospital readmission? Will those mental health services be readily available? Payment reforms that account for all necessary transitional care services will indeed help reduce readmission costs with less risk for untoward consequences.

In conclusion, our results indicate that a positive depression screen is a significant risk factor for early post‐discharge hospital utilization among hospitalized adults on a general medical service, even after controlling for relevant confounders. Screening for depression during acute hospitalizations may be an important step in identifying patients at increased risk for readmission. Future research should focus on further characterizing and stratifying populations at highest risk for depression. Efforts should also include developing and evaluating targeted interventions for patients with symptoms of depression among hospitalized patients as part of discharge planning. Timely depression therapy during the hospitalization or following hospital discharge might reduce costly readmissions and enhance patient safety.