Ramon S. Cancino, MD

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.