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J Am Coll Cardiol, 2006; 48:2218-2222, doi:10.1016/j.jacc.2006.07.063
(Published online 10 November 2006). © 2006 by the American College of Cardiology Foundation |
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,¶,*
* Department of Psychiatry, Mount Sinai School of Medicine, New York, New York
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York
Division of General Internal Medicine, Mount Sinai School of Medicine, New York, New York
Department of Psychiatry, Centre Hospitalier de l’Université de Montréal, Montréal, Quebec, Canada
|| Department of Psychology, St. Johns University, Queens, New York
¶ Cardiovascular Institute, Mount Sinai School of Medicine, New York, New York.
Manuscript received May 9, 2006; revised manuscript received July 17, 2006, accepted July 23, 2006.
* Reprint requests and correspondence: Dr. Karina W. Davidson, Department of Medicine, Columbia University College of Physicians and Surgeons, 622 West 168th Street, PH9 Center, Room 948, New York, New York 10032. (Email: kd2124{at}columbia.edu).
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Abstract |
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BACKGROUND: Depression is associated with medication nonadherence in patients with ACS, but it is unclear whether changes in depression impact on adherence.
METHODS: Electronic medication monitoring was used to measure adherence to aspirin during a 3-month period in a consecutive cohort of 172 patients (25 to 85 years) recruited within 1 week of hospitalization for ACS. Depressive symptom severity was assessed using the Beck Depression Inventory (BDI) during hospitalization and at 1 and 3 months after hospitalization. Adherence was defined as the percentage of days aspirin was taken as prescribed.
RESULTS: Depression severity in hospital was associated with nonadherence in a gradient fashion: 15% of non-depressed patients (BDI score 0 to 4), 29% of mildly depressed patients (BDI score 10 to 16), and 37% of patients with moderately-to-severely depressive symptoms (BDI score >16) took aspirin less than 80% of the time (p = 0.03). A cross-lagged path analytic model revealed that improvements in depressive symptoms in the first month after the ACS were associated with improvements in adherence rates in the subsequent 2 months (standardized direct effect –0.32, p = 0.016).
CONCLUSIONS: Diagnosis and treatment of depressive symptoms may improve medication adherence in patients after ACS.
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Depression (with an estimated lifetime prevalence of 15% to 20%) has been shown to be associated with poor adherence across many patient samples, including those with coronary artery disease (7–9). Depression is common in patients who experience an ACS; approximately 1 in 3 patients experiences depressive symptoms during hospitalization (10). Moreover, depressive symptoms during hospitalization are independently associated with an adverse medical prognosis (11). Poor medication adherence has been proposed as a mechanism to explain why depressed patients as compared with non-depressed patients are at increased risk for mortality and other adverse outcomes after ACS (12,13). Previous data linking depression and adherence, however, is derived from cross-sectional or prospective studies that cannot address questions of temporal sequence and do not take into account that in many patients, depressive symptoms improve over the course of time (whether treated or untreated), whereas in others, symptoms worsen (8,9). Although it is a plausible assumption, no study has yet demonstrated that improvements in depressive symptoms lead to improvements in treatment adherence.
We used a cross-lagged panel design that included correlations of 3 consecutive assessments of depressive symptoms and medication adherence to address this question. This design can answer which of 2 variables temporally precedes the other. We tested whether changes in depressive symptoms from time 1 to time 2 precede changes in adherence from time 2 to time 3, or whether changes in adherence precede changes in depressive symptoms.
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METHODS |
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Depression assessment.
Patients were eligible for the study if they had a baseline score on the Beck Depression Inventory (BDI) (14) that was consistent with at least mild-to-moderate depression (BDI score 
10), which has been associated with increased mortality risk after an ACS event (15,16). Patients were also eligible if they reported no depression (BDI score 0 to 4). The BDI was readministered at 1 and 3 months after the baseline score.
Three BDI groups were used to examine difference between non-depressed (BDI 0 to 4), mildly depressed (BDI 10 to 16), and moderately-to-severely depressed (BDI >16) patients at baseline. The BDI was used as a continuous variable in the cross-lagged panel model.
Adherence assessment. Upon hospital discharge, patients were provided with a 90-day supply of aspirin in a Medication Event Monitoring System (APREX Corp, Fremont, California) bottle. This device records the date and time on each occasion the bottle cap is opened. The data from this system were collected continuously during the 3-month follow-up period. Adherence was defined as the percentage of days the bottle was opened the correct number of times (once a day). In addition to the continuous adherence score used in the cross-lagged panel model, a categorical adherence variable was computed. Nonadherence was defined as <80% days the correct number of pills was taken. Patients were informed that aspirin adherence was being monitored but did not receive any additional counseling about adherence.
Statistical analyses. Differences in characteristics between non-depressed, mildly, and moderately depressed patient groups were compared using analysis of variance for continuous variables and a chi-square test for dichotomous variables. Logistic regression was used to examine the association between depressive symptom groups at baseline and medication adherence across the 3 months, controlling for sociodemographic characteristics and the Charlson comorbidity index (17).
Cross-sectional and prospective relationships between depression and adherence were tested in a cross-lagged panel design using structural equation modeling (conducted using AMOS for windows 4.0 (18). Cross-lagged panel models examine the predictive association of 2 variables over time, each controlling for the effects at earlier time points. For example, depression at time 2 is residualized by depression at time 1 and thus represents change in depression from time 1 to time 2.
A model was tested that included: 1) correlations among the 3 continuous depression measures and the 3 adherence measures over time (stability of each variable); 2) cross-sectional correlations between depression and adherence; and 3) cross-(time-) lagged correlations between depression and adherence (and changes in these variables). Maximum likelihood estimation was used to estimate overall model fit using the chi-square goodness-of-fit statistic.
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Results |
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Discussion |
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We found a gradient relation between the severity of in-hospital depressive symptoms and rates of nonadherence, similar to findings from the Heart and Soul Study (9). However, in our sample rates of nonadherence were approximately 3 times greater. One major difference between the 2 studies is that we used an electronic assessment of medication adherence, whereas the Heart and Soul Study assessed nonadherence by self-report, suggesting that patients may overestimate their level of adherence.
We monitored adherence to only 1 medication—aspirin—whereas the self-report questions in the Heart and Soul Study asked about all medications. We have no information regarding adherence to medication other than aspirin, nor did we take into account the total number of medications patients were prescribed. However, this is unlikely to explain higher nonadherence rates in our study. Patients had a simple regimen (1 tablet per day), and the monitored drug (aspirin) has few side effects, both of which should predict better, not worse, adherence.
Our study might underestimate nonadherence rates in post-ACS patients because patients who refused participation were significantly more depressed. Patients with BDI scores of 5 to 9 at baseline were excluded from the study, which might have yielded inflated coefficients in our analysis. Adherence rates in our sample might not generalize to patients who use weekly pill boxes because we excluded those patients.
In this observational study, we showed that improvements in depressive symptoms were associated with subsequent improvements in adherence rates in a relatively short period of time. This has potential implications for future adherence interventions. Although medication adherence has been the target of a large number of interventions, these have, for the most part, not been very effective or were very complex (19,20). It is not known why these interventions tend to have small effects on improving adherence and clinical outcomes; perhaps treating depression first will show promise in future interventions designed to increase medication adherence.
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