Influence of Comorbid Depression and Antidepressant Treatment on Mortality for Medicare Beneficiaries with Chronic Obstructive Pulmonary Disease by SSDI-eligibility J. Qian, PhD 1, L. Simoni-Wastila, PhD 2, G. B. Rattinger, PharmD, PhD 2, I. H. Zuckerman, PharmD, PhD 2, S. Lehmann, MD 3, P. Langenberg, PhD 4, M. Terrin, MD, MPH 4 1 Pharmacy Care Systems, Auburn University Harrison School of Pharmacy; 2 Pharmaceutical Health Services Research, University of Maryland School of Pharmacy; 3 Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine; 4 Epidemiology and Public Health, University of Maryland School of Medicine Chronic obstructive pulmonary disease (COPD) is a condition with high mortality and morbidity. Comorbid depression can place COPD patients at increased risk for COPD exacerbations and mortality. Although both COPD and depression are associated with significant disabling morbidity, to date few studies addressing COPD-related outcomes have included and compared individuals who receive Social Security Disability Insurance (SSDI). Background To examine the influence of comorbid depression and antidepressant treatment on mortality among a nationally- representative sample of Medicare beneficiaries suffering from COPD, and to determine if SSDI-eligibility status modifies these relationships. Objectives This study provides evidence of the benefit of antidepressant treatment on all-cause mortality in routine practice with a nationally-representative sample of COPD and depression. Depression is an independent risk factor for mortality in non- SSDI-eligible Medicare beneficiaries with COPD. Antidepressant treatment reduced risk of death for both SSDI- eligible and non-SSDI-eligible beneficiaries, with greater benefit seen in SSDI-eligible beneficiaries. In practice, clinicians should consider timely antidepressant treatment to improve outcomes for Medicare beneficiaries with both COPD and depression. Conclusions Data source and study sample: A 5% random sample of Chronic Condition Warehouse data was used, including a total of 75,699 Medicare beneficiaries aged 65 years and older with a diagnosis of COPD (ICD-9 codes 491.x, 492.x, and 496.x) who lived through 2006 and continuously enrolled in Medicare Parts A, B, and D. Measures: The dependent measures were defined over the two- year follow-up period ( ) while the independent measures are defined at baseline year 2006 (depression diagnosis) and the three-year study period (antidepressant treatment measured as time-varying). SSDI-eligibility was assessed using the original reason for entitlement in Medicare. All covariates (sociodemographics, insurance, comorbidities, and disease severity) were defined at baseline. Statistical analysis: Survival analyses using Cox proportional hazards models were conducted to compare the risk of death by depression, by evidence of antidepressant treatment, and by SSDI-eligibility status. Log-rank homogeneity test was used for model selection. The significance of interaction terms of depression diagnosis and antidepressant treatment with SSDI-eligibility status tested whether SSDI-eligibility modifies the influence of baseline depression and time-varying antidepressant treatment on mortality risk. Methods This study was from the dissertation work of Dr. Qian at University of Maryland School of Pharmacy. The authors thank Pharmaceutical Research Computing (PRC) for data management. Acknowledgement Results The mean age of the sample was 77 years. Nearly one-sixth (16.3%) were SSDI-eligible. Nearly two-thirds (65.3%) were female. One-fifth (21.1%) of the sample had severe baseline COPD. More than one-fifth (21.6%) of beneficiaries with COPD had a depression diagnosis at baseline; of those, 82.1% received antidepressants. Beneficiaries with depression (and among them, with antidepressant treatment) were more likely to be SSDI-eligible, female, and low-income subsidy eligible (all p<0.0001). They also had more counts of comorbidities but had no difference in COPD severity at baseline. Depressed beneficiaries were more likely to die, however, those with antidepressant treatment were less likely to die than those without treatment (Figures 1 & 2). Baseline depression heightened risk of death (HR=1.13, 95% CI=1.09, 1.18) in non-SSDI-eligible but not in SSDI-eligible beneficiaries (Table 1). Among depressed beneficiaries, the benefit of antidepressant treatment on mortality was greater in SSDI-eligible (HR=0.43, 95% CI=0.36, 0.51) than non-SSDI-eligible beneficiaries (HR=0.63, 95% CI=0.58, 0.68) (Figure 3). Figure 1: Characteristics, Severity, and Death by Baseline Depression Diagnosis (unadjusted, n=75,699) Figure 2: Among depressed beneficiaries, Characteristics, Severity, and Death by Evidence of Antidepressant Treatment (unadjusted, n=16,387) ModelAmong SSDI-eligibles HR 1 (95% CI) Among Non-SSDI-eligibles HR 1 (95% CI) Depression Diagnosis (0.96, 1.11)1.13 (1.09, 1.18) Table 1: Influence of Baseline Depression Diagnosis on All-cause Mortality* *Cox Proportional hazards model, controlling for sociodemographics (age, gender, race, and region), insurance (low-income subsidy eligibility, Medicare-Medicaid dual eligibility, and end stage renal disease), comorbidities (asthma, diabetes, ischemic heart disease, congestive heart failure, hypertension, other cardiovascular diseases [e.g. heart surgery)], Alzheimer's disease and related disorders or senile dementia, anxiety, bipolar, schizophrenia, neuropathic pain, smoking cessation, respiratory cancer, other respiratory diseases), COPD severity (baseline supplemental oxygen use), and depression severity (baseline severe depression diagnosis, evidence of depression hospitalization and non-pharmacological psychiatric health services). Interaction term of depression diagnosis and SSDI- eligibility was statistically significant at P= Hazard ratio and 95% confidence intervals. Analyses were conducted using SAS version 9.2 (SAS Institute, Inc., Cary, NC). 2 Depression diagnosis was defined by ICD-9-CM codes , , 300.4, and 311.x in claims data. Figure 3: Influence of Antidepressant Treatment on All-cause Mortality* *Extended Cox Proportional hazards model, controlling for sociodemographics, insurance, and COPD and depression severity. Limited to beneficiaries with a baseline depression diagnosis (n=16,387). Interaction term of antidepressant treatment and SSDI-eligibility was statistically significant at P< HR: Hazard ratio. Analyses were conducted using SAS version 9.2 (SAS Institute, Inc., Cary, NC). **Time: 1=baseline; 2-9 represented the follow-up period by quarter from 01/01/2007 to 12/31/2008.