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Chronic obstructive pulmonary disease (COPD) is a chronic condition associated with significant morbidity and mortality. It has become the third leading cause of death among US adults (Centers for Disease Control and Prevention, 2008). Approximately one in eight community-dwelling Medicare beneficiaries is diagnosed with COPD (Stuart et al., 2007). Preventing exacerbations is an important goal of COPD management. A cornerstone of COPD management is pharmacotherapy, which aims to reduce symptoms, decrease the frequency and severity of exacerbations, and improve health status and exercise tolerance (American Thoracic Society, 2004, Global Initiative for Chronic Obstructive Pulmonary Disease, 2008). However, COPD maintenance medication use among COPD patients remains low: only 40% of Medicare beneficiaries with COPD fill one or more COPD maintenance medications annually (Stuart et al., 2010).
Among individuals who take at least one COPD maintenance medication, many fail to adhere to prescribed therapy. In the literature, adherence to COPD medications ranges from 40% to 60% (Rand, 2005, Restrepo et al., 2008, Charles et al., 2010). One observational study, using national Veteran's Affairs data, found only half of COPD patients used any maintenance medication. Among users, the overall medication adherence, measured by mean Medication possession ratio (MPR [standard deviation]), was 0.44 [0.32] during the last year of life (Jung et al., 2009). Another observational study estimated adherence to inhalation medications through refill rates among stable COPD patients in Belgium. This study found almost half (48%) of COPD patients were under-adherent annually (Mehuys et al., 2010).
There is empirical evidence demonstrating the beneficial influence of good adherence on clinical outcomes among COPD patients (Vestbo et al., 2009, Toy et al., 2011). One study, using administrative claims data from US employees and retirees and measuring proportion of days covered (PDC) to assess COPD medication adherence, concluded that good adherence was associated with a lower annual rate of inpatient and emergency room visits (Toy et al., 2011). Another clinical study found association between good medication adherence and improved mortality and reduction in hospital admission among moderate and severe COPD patients (Vestbo et al., 2009). Despite the importance of adherence to maintenance medications in preventing COPD exacerbations, adherence to these medications remains a problematic area where improvements could result in significant benefits.
Depression remains an important and overlooked risk factor for medication non-adherence. In other chronic conditions, including diabetes and heart failure, comorbid depression has been found to be associated with lower medication use and adherence (Ciechanowski et al., 2000, DiMatteo et al., 2000, Lin et al., 2004, Morgan et al., 2006, Hansen et al., 2009). Depression occurs commonly in COPD patients. Prevalence estimates of comorbid depression range between 10% and 42% in stable COPD patients (Yohannes et al., 2000, Lacasse et al., 2001, van Manen et al., 2002, Kunik et al., 2005, Maurer et al., 2008, Yohannes et al., 2010). The wide range of estimates is due to differences in study populations, depression assessment measures, and illness severity. Increased evidence has shown depression places COPD patients at higher risks for hospitalizations, readmissions, and increased hospital days (Almagro et al., 2002, Ng et al., 2007, Xu et al., 2008, Stuart et al., 2010). However, despite the high prevalence of comorbid depression in COPD patients, little is known about the role of depression on COPD maintenance medication use or adherence.
The objective of this study is to estimate the association between comorbid depression diagnosis and COPD maintenance medication adherence among a nationally representative sample of Medicare beneficiaries with COPD. This study is among the first to date to explore the relationships among diagnosed depression and COPD maintenance medication use and adherence in Medicare beneficiaries with COPD.
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Among the COPD cohort (n = 74,863), 33.6% had diagnosed depression. The mean age within the cohort was 72 years and almost two thirds (63.2%) were women (Table 1). Over 85% of the sample was identified as White and over three fifths (61.0%) were LIS eligible for Part D benefits. Relative to non-depressed COPD beneficiaries, depressed beneficiaries were younger, more likely to be women and White, and more likely to be LIS eligible (all p < 0.0001). A higher proportion of those with depression had other conditions, including asthma, diabetes, ischemic heart disease, congestive heart failure, hypertension, Alzheimer's disease and related dementias, and anxiety (all p < 0.0001). Compared with non-depressed COPD beneficiaries, those with diagnosed depression had a higher proportion of baseline all-cause hospitalization and rescue medication use (all p < 0.0001) but similar supplemental oxygen use (p = 0.4492).
Table 1. Characteristics of beneficiaries with COPD enrolled in Medicare Part D plans, stratified by depression status (n = 74,863)
|Characteristics||All COPD beneficiaries||Depressiona|
|Age† (years)|| || || || || || |
|≥65 years were SSDIb eligible||10,286||13.7||3,686||14.7||6,600||13.3|
|Sex†|| || || || || || |
|Race†|| || || || || || |
|Region†|| || || || || || |
|Low-income subsidy status†|| || || || || || |
|Comorbid medical conditions†|| || || || || || |
|Ischemic heart disease||41,481||55.4||14,686||58.4||26,795||53.9|
|Congestive heart failure||32,772||43.8||12,146||48.3||20,626||41.5|
|All other cardiovascular disease||51,708||69.1||17,124||68.1||34,584||69.5|
|Alzheimer's disease and related dementias||14,662||19.6||7,519||29.9||7,143||14.4|
|COPD severity indicators|| || || || || || |
|Had supplemental oxygen claims||14,699||19.6||4,973||19.8||9,726||19.6|
|Had any COPD rescue medication†||23,138||30.9||8,736||34.8||14,402||29.0|
|Hospitalization at baseline†|| || || || || || |
|Had any hospitalization||34,905||46.6||14,683||58.4||20,222||40.7|
|# of hospitalization (mean, SD)||2.2||1.8||2.5||2.1||1.9||1.4|
Overall, more than three fifths (61.8%) of the cohort received at least one COPD maintenance medication prescription during the 2-year study period (Table 2). The proportion of COPD maintenance medication use was higher in depressed than in non-depressed beneficiaries (64.1% vs. 60.6%). Among COPD maintenance medication users with at least two Part D prescription claims (n = 35,985), depressed patients were more likely to discontinue (23.9% vs. 20.6%) and were less likely to exhibit PDC ≥ 0.80 (31.4% vs. 38.5%) than non-depressed patients (all p < 0.0001).
Table 2. Two-year COPD maintenance medication use and adherence in Medicare Part D beneficiaries with COPD, stratified by depression status
|Drug use and hospitalization measures||All COPD||Depressiona|
|Any COPD maintenance medication|| || || || || || |
|Sample sizec||35,985|| ||12,574|| ||23,411|| |
|Proportion of days covered ≥ 0.80c†||12,956||36.0||3,953||31.4||9,003||38.5|
In multivariable models, depression was associated with a higher likelihood of COPD maintenance medication use (adjusted PR = 1.02; 95% CI = 1.01, 1.03) (Table 3). However, among users with two or more Part D claims, depressed patients were 9% more likely to discontinue medication (PR = 1.09; 95% CI = 1.04, 1.14) and 11% less likely to exhibit PDC ≥ 0.80 (PR = 0.89; 95% CI = 0.86, 0.92) than non-depressed patients, controlling for all covariates.
Table 3. Association between depression diagnosis and 2-year COPD maintenance medication use and adherence in Medicare Part D beneficiaries with COPD
|Predictors||Medication use and adherence|
|Any usea||Discontinuationb||PDC (≥ 0.8) b|
|PR||Lower 95% CI||Upper 95% CI||PR||Lower 95% CI||Upper 95% CI||PR||Lower 95% CI||Upper 95% CI|
|Age (years)|| || || || || || || || || |
|≥65 years were SSDIc eligible||0.99||0.97||1.00||1.06||1.00||1.13||1.01||0.97||1.05|
|Race|| || || || || || || || || |
|Region|| || || || || || || || || |
|Low-income subsidy status|| || || || || || || || || |
|Comorbid medical conditions|| || || || || || || || || |
|Ischemic heart disease||0.97||0.96||0.99||1.13||1.08||1.18||0.92||0.89||0.95|
|Congestive heart failure||1.03||1.02||1.04||1.04||0.99||1.09||0.98||0.95||1.01|
|All other cardiovascular disease||1.00||0.98||1.01||1.07||1.02||1.12||0.97||0.94||1.00|
|Alzheimer's disease and related dementias||0.92||0.91||0.94||1.10||1.04||1.16||0.84||0.81||0.88|
|Had any baseline hospitalization||0.94||0.93||0.95||1.20||1.15||1.25||0.86||0.83||0.89|
|COPD severity indicators|| || || || || || || || || |
|Had supplemental oxygen claims||1.39||1.38||1.41||0.76||0.73||0.80||1.33||1.30||1.37|
|Had any COPD rescue medication||1.44||1.43||1.46||0.93||0.89||0.97||1.10||1.07||1.13|
In addition, differences in COPD maintenance medication use and adherence also were found by covariates (Table 3). For example, compared with beneficiaries less than 65 years old, those 65 years and older (except for the subgroup of 85 years and older) were more likely to fill a COPD maintenance medication and less likely to discontinue their treatment. Women were less likely to exhibit PDC ≥ 0.80 (PR = 0.93; 95% CI = 0.90, 0.96) than men. Compared with Whites, Blacks were less likely to fill a COPD maintenance medication (PR = 0.90; 95% CI = 0.88, 0.91), more likely to discontinue their treatment (PR = 1.19; 95% CI = 1.12, 1.28), and less likely to exhibit PDC ≥ 0.80 (PR = 0.79; 95% CI = 0.75, 0.84). Geographically, beneficiaries residing in north central, south, and west regions were less likely to fill a COPD maintenance medication and adhere to treatment than those in the northeast region. Beneficiaries who were eligible for LIS were more likely to fill a COPD maintenance medication and less likely to discontinue treatment than non-LIS beneficiaries. Further, beneficiaries with worse health status (having any all-cause hospitalization at baseline) and selected comorbidities (including diabetes, ischemic heart disease, and Alzheimer's disease) were less likely to fill a COPD maintenance medication and adhere to treatment. However, beneficiaries with severe COPD were more likely to use COPD maintenance medication and adhere to treatment.
Sensitivity analyses confirmed the robustness of study results (Table 4). First, after restricting the sample to beneficiaries without comorbid asthma (excluding 28.7% of study sample with both COPD and asthma), depression diagnosis was still associated with a 7% higher likelihood of discontinuation (PR = 1.07; 95% CI = 1.01, 1.14) and 9% lower likelihood of PDC ≥ 0.80 (PR = 0.91; 95% CI = 0.87, 0.95). Second, after excluding beneficiaries with comorbid bipolar and/or schizophrenia (n = 2919), depressed beneficiaries still were 8% more likely to discontinue medication (PR = 1.08; 95% CI = 1.03, 1.13) and 10% less likely to exhibit PDC ≥ 0.80 (PR = 0.90; 95% CI = 0.87, 0.93). Third, using different PDC cut points (e.g., 0.90 and 0.70) to define “good” adherence did not affect the findings—those with depression were less likely to exhibit good adherence. Finally, after excluding beneficiaries who died in 2007 (n = 9287) to avoid bias on medication adherence measures before death, depression was still independently associated with 10% higher likelihood of discontinuation (PR = 1.10; 95% CI = 1.05, 1.16) and 13% lower likelihood of PDC ≥ 0.80 (PR = 0.87; 95% CI = 0.84, 0.91).
Table 4. Influence of depression on 2-year COPD maintenance medication use and adherence in Medicare Part D beneficiaries with COPD sensitivity analysisa
| ||Discontinuation||PDC (≥ 0.8)|
| ||PR||Lower 95% CI||Upper 95% CI||PR||Lower 95% CI||Upper 95% CI|
|I: Excluding asthma||1.07||1.01||1.14||0.91||0.87||0.95|
|II: Excluding bipolar and/or other psychotic disorders||1.08||1.03||1.13||0.90||0.87||0.93|
|IIIa: Using PDC cut point 0.90|| || || ||0.83||0.79||0.87|
|IIIb: Using PDC cut point 0.70|| || || ||0.92||0.89||0.94|
|IV: Excluding beneficiaries who died in 2006||1.10||1.05||1.16||0.87||0.84||0.91|
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Findings from this study demonstrate COPD maintenance medication use is low in Medicare beneficiaries with COPD, regardless of the presence of depression. However, among those COPD patients who filled COPD maintenance medications, depression diagnosis is associated with lower COPD maintenance medication adherence. This study is among the first to date to explore the relationships among diagnosed depression and COPD maintenance medication use and adherence in Medicare beneficiaries with COPD. Findings indicate that interventions to improve medication adherence for COPD patients may consider management of comorbidities such as depression.
Indeed, the finding that 40% of Medicare beneficiaries diagnosed with COPD failed to use any COPD maintenance medication in 2 years indicates the challenges clinicians face in managing the care of their COPD patients. Our finding is consistent with previous studies demonstrating that less than half of COPD patients were prescribed maintenance medication (Jung et al., 2009, Stuart et al., 2010). Sub-analyses from the Understanding Potential Long-term Impacts on Function with Tiotropium trial indicated that initiating maintenance treatment at early stages of COPD can alter progression of the disease and maximize patient benefit at later stages of the disease (Troosters et al., 2010). Therefore, clinicians might focus on improving maintenance medication use to reduce symptoms.
Consistent with studies demonstrating depression as an independent risk factor for reduced adherence to treatments for other chronic conditions (Ciechanowski et al., 2000, DiMatteo et al., 2000, Lin et al., 2004), this study found that depression is associated with lower COPD maintenance medication adherence. Depression may cause patients to neglect medical care and their prescribed regimens so that, in turn, being non-adherent may increase respiratory symptoms (Restrepo et al., 2008). In addition, COPD patients who report poor quality of life are more likely to be depressed, feel unsupported by clinic staff, and be poorly adherent to treatment (Bosley et al., 1996). One study investigating psychosocial factors on medication adherence among COPD patients in outpatient clinics also found that the presence of depressed mood was associated with medication non-adherence (Khdour et al., 2012). Future research is warranted to investigate causal inferences and explore mechanisms to explain this relationship.
Limited evidence has demonstrated that patients who are most severely ill with chronic conditions may be at greatest risk for treatment non-adherence (DiMatteo et al., 2007). However, in this study, COPD severity indicators (supplemental oxygen use and COPD rescue medication use) were associated with better adherence to COPD maintenance medications. In sensitivity analyses estimating adherence among beneficiaries requiring supplemental oxygen (considered the most severe stage of COPD), the association between depression diagnosis and lower medication adherence still presented (data not shown but available from the authors).
The independent association between comorbid depression and COPD maintenance medication adherence has implications for both research and practice. It suggests that interventions to improve COPD medication use and adherence are needed for this particular population. Growing evidence suggests antidepressant medications may be effective in treating depression and depressive symptoms in COPD patients (Borson et al., 1992, Smoller et al., 1998, Yohannes et al., 2001, Lacasse et al., 2004). Thus, interventions to better manage depression in COPD population are needed.
This study has several limitations. First, as in all analyses conducted using administrative claims data, measurements and disease ascertainment are limited to information available in such data. Thus, it was unable to ascertain the severity of COPD or depression afforded from laboratory data and other clinical measures (e.g., forced expiratory volume in 1 s measures and clinical depression scales). Although we controlled COPD severity in multivariable analysis and conducted a series of sensitivity analyses to examine potential disease misclassification (e.g., COPD and asthma, or depression and schizophrenia/bipolar disorders), the unobservable variation in depression severity and potential duration may affect study outcomes. In addition, depression diagnosis regardless of treatment effects on depression was assessed. Beneficiaries with evidence of treatment for depression might exhibit improved COPD maintenance medication adherence. Future investigations on the relationships between treatment effects for depression on COPD medication adherence and clinical outcomes are needed.
Second, measures were determined by refill patterns available in prescription drug event claims data and do not reflect actual patient consumption. However, adherence measured by prescription refill patterns in administrative claims data is widely accepted and shown to be valid in observational studies (Choudhry et al., 2009, Toy et al., 2011). Different from two other studies examining COPD medication adherence in one year (Jung et al., 2009, Toy et al., 2011), this study assessed COPD maintenance medication adherence over 2 years, which achieves more stable adherence measurements. Furthermore, because COPD patients can be on multiple inhalation medications concurrently, PDC was used instead of MPR to avoid overestimation of adherence behaviors (Choudhry et al., 2009). Sensitivity analyses using varying PDC levels other than 0.80 obtained similar results on the associations among depression diagnosis and COPD maintenance medication adherence. However, reasons for medication discontinuation such as intolerance or inadequate response to the regimens were not taken into account in the multivariate analysis because of the lack of information used to identify reasons of discontinuation in claims data.
Third, because both depression diagnosis and COPD maintenance medication adherence were measured during the same 2-year study period, findings are associational rather than causal. At the time of this analysis, only 2006–2007 CCW data were available. Future research incorporating additional years of data will allow construction of longitudinal analytic files and time-to-event analyses to confirm the associations reported in this study. Additionally, study results might not be generalizable to newly approved COPD maintenance medications after 2007.
Finally, even though a wide range of potential confounders were controlled, unobservable factors were not. Findings therefore may not be generalizable to Medicare Advantage plans and/or Health Maintenance Organization enrollees and those with characteristics excluded from the study sample and other non-Medicare population.