- Top of page
OBJECTIVE: Addressing the epidemic of poor compliance with antihypertensive medications will require identifying factors associated with poor adherence, including modifiable psychosocial and behavioral characteristics of patients.
DESIGN: Cross-sectional study, comparing measured utilization of antihypertensive prescriptions with patients' responses to a structured interview.
STUDY POPULATION: Four hundred ninety-six treated hypertensive patients drawn from a large HMO and a VA medical center.
DATA COLLECTION: We developed a survey instrument to assess patients' psychosocial and behavioral characteristics, including health beliefs, knowledge, and social support regarding blood pressure medications, , satisfaction with health care, depression symptom severity, alcohol consumption, tobacco use, and internal versus external locus of control. Other information collected included demographic and clinical characteristics and features of antihypertensive medication regimens. All prescriptions filled for antihypertensive medications were used to calculate actual adherence to prescribed regimens in a 365-day study period.
MAIN OUTCOME OF INTEREST: Adjusted odds ratios (ORs) of antihypertensive compliance, based on ordinal logistic regression models.
RESULTS: After adjusting for the potential confounding effects of demographic, clinical, and other psychosocial variables, we found that depression was significantly associated with noncompliance (adjusted OR per each point increase on a 14-point scale, 0.93; 95% confidence interval [95% CI], 0.87 to 0.99); in unadjusted analyses, the relationship did not reach statistical significance. There was also a trend toward improved compliance for patients perceiving that their health is controlled by external factors (adjusted OR per point increase, 1.14; 95% CI, 0.99 to 1.33). There was no association between compliance and knowledge of hypertension, health beliefs and behaviors, social supports, or satisfaction with care.
CONCLUSIONS: Depressive symptoms may be an underrecognized but modifiable risk factor for poor compliance with antihypertensive medications. Surprisingly, patient knowledge of hypertension, health beliefs, satisfaction with care, and other psychosocial variables did not appear to consistently affect adherence to prescribed regimens.
Despite the availability of effective therapy, hypertension remains poorly controlled in the United States and other industrialized countries. In the Third National Health and Nutrition Examination Survey, nearly half of hypertensive patients in the community-based sample were found to be taking no prescription medication, and only one quarter of those who were being treated had their blood pressure adequately controlled.1 Patient noncompliance with prescribed treatments is a central reason for the failure to control hypertension in those receiving therapy.2 Numerous investigations have found that half of hypertensive patients do not comply adequately with treatment, and that half of those with “refractory” hypertension are in fact nonadherent.3–7 Such high levels of noncompliance are of tremendous concern, given the serious consequences of uncontrolled hypertension on cardiovascular, cerebrovascular, and renal morbidity as well as mortality.8
Clearly, interventions to improve adherence with antihypertensive medications are needed. However, if such interventions are to be successfully designed, targeted, and cost-effective, it is critical to understand the complex reasons for nonadherence, and to identify those that are modifiable.9 Investigators have identified some sociodemographic and clinical features associated with compliance (e.g., age, gender, race, education, employment, socioeconomic status, or the presence of specific comorbid conditions such as cardiovascular disease), although the findings are inconsistent. 2,3,10–16
Despite the likelihood that psychosocial and behavioral characteristics may be important determinants of compliance, few rigorous studies have defined the impact of these features on adherence; those that have been conducted have produced inconsistent results. The variable receiving the most attention has been patients' health beliefs, including their perceptions of the threat posed by the condition, the effectiveness of treatments, and the importance of complying with therapy.17–19 Other psychosocial variables thought to influence antihypertensive medication adherence include: knowledge of hypertension and its treatment14,20; social support21,22; satisfaction with health care10,23,24; and the locus of control (i.e., the degree to which a patient feels that control over their circumstances is internal or external).25 Behaviors that have been examined and related to compliance with blood pressure medication have included use of alcohol or substances2,26 and smoking.14 The effect of psychopathology on compliance with medications for other cardiovascular conditions has been considered, but rigorous study of such relationships has been limited.27
Unfortunately, few studies of the relationships between psychosocial factors and compliance with antihypertensives have been adequately powered, simultaneously adjusted for other determinants of compliance, or conducted in typical clinical populations; and few have used precise assessments of compliance. Therefore, in the current study, we employed typical outpatient populations and an objective measure of compliance to test the hypothesis that believing in the importance of treating hypertension, possessing greater knowledge, having more social support, being more satisfied, having a more external locus of control, responding in a more socially desirable manner, having fewer depressive symptoms, and consuming less alcohol or tobacco would all be associated with greater compliance with antihypertensive medications. Although our hypothesis was limited to the independent effects on compliance of these understudied psychosocial and behavioral variables, we also considered it essential to adjust for more established determinants including demographic, clinical, and health care utilization variables.
- Top of page
The characteristics of the study population, stratified by study site, are presented in Table 1. A total of 496 patients treated for hypertension completed the telephone interview, 248 from the HMO and 248 from the VA setting. Most patients were ≥65, male, white, had a high school education or less, were retired, married, and not living alone. Approximately one third of patients had been hospitalized, and one in ten had a diagnosis of depression recorded in their medical charts. There was a narrower distribution of ages among VA than HMO patients. VA patients were also significantly more likely than HMO patients to be male, more highly educated, retired, and hospitalized. Over one third of patients did not have enough antihypertensive medication to cover 50% of the study year; another third had enough medication to cover only 79% to 50% of the study year; fewer than one third were covered for ≥80% of the study year. No significant crude difference in the percentage of days covered by antihypertensive medications was observed between the VA and HMO sites.
Table 1. Characteristics of the Study Population (N= 496) by Site
|Characteristic||VAMC Patients, % (n = 248)||HMO Patients, % (n = 248)||P Value|
|Age|| || ||.046|
| <55||15.3||21.0|| |
| 55–64||23.0||20.5|| |
| 65–74||45.2||35.5|| |
| 75+||16.5||23.0|| |
|Gender|| || ||.001|
| Female||4.0||61.3|| |
| Male||96.0||38.7|| |
|Race|| || ||.094|
| White||93.5||96.8|| |
| Non-white||6.5||3.2|| |
|Education|| || ||.001|
| <High school||10.1||15.3|| |
| High school||41.9||54.0|| |
| >High school||48.0||30.7|| |
|Retired|| || ||.001|
| Yes||20.6||33.5|| |
| No||79.4||66.5|| |
|Married|| || ||.851|
| Yes||64.5||65.3|| |
| No||35.5||34.7|| |
|Living alone|| || ||.605|
| Yes||24.2||26.2|| |
| No||75.8||73.8|| |
|Number of hospitalizations|| || ||.001|
| 0||59.7||75.0|| |
| 1+||40.3||25.0|| |
|Depression diagnosis in chart|| || ||.233|
| Yes||11.7||8.5|| |
| No||88.3||91.5|| |
|Antihypertensive compliance|| || ||.101|
| ≥80% of days covered||28.6||29.4|| |
| 79%–50% of days covered||31.1||38.7|| |
| <50% of days covered||40.3||31.9|| |
Table 2 presents the crude relationships between psychosocial variables and compliance, derived from univariate ordinal logistic regression models. In these unadjusted analyses, there were no statistically significant relationships with compliance for any of the psychosocial or behavioral variables studied.
Table 2. Crude Odds Ratios Between Psychosocial/Behavioral Characteristics and Compliance with Blood Pressure Medications (N = 496)
|Characteristic*||Crude OR*||95% CI|
|Depressive symptom severity (per 1-point increase)||0.97||0.91 to 1.03|
|External locus of control (per 1-point increase)||1.02||0.90 to 1.17|
|Satisfaction with medical care (per 1-point increase)||1.04||0.95 to 1.14|
|Knowledge regarding hypertension and its treatment (per 1-point increase)||1.03||0.94 to 1.12|
|Belief in the importance of hypertension treatment (per 1-point increase)||1.02||0.84 to 1.24|
|Social support regarding hypertension treatment (per 1-point increase)||0.93||0.71 to 1.21|
|Socially desirable responding (per 1-point increase)||1.02||0.94 to 1.11|
|Number of drinks per day (per 1-drink/day increase)||0.98||0.80 to 1.20|
|Smoker (compared to non-smokers)||0.90||0.56 to 1.45|
|Depression diagnosis in medical records||0.77||0.44 to 1.34|
However, after we controlled for the potential confounding effects of demographic variables (age, gender, race, education, employment status, treatment site), use of thiazide diuretics, the presence of comorbid conditions (coronary artery disease, cerebrovascular disease, and renal failure), and locus of control, we found that an increase in depression symptom severity was significantly associated with a lower odds of compliance (adjusted OR of good compliance per point increase in the 14-point depression score, 0.93; 95% confidence interval [95% CI], 0.87 to 0.99; see Table 3). The magnitude and significance of this effect was not attributable to the addition of any single confounder to the model, but rather to the combination of all other included study variables.
Table 3. Independent Psychosocial Predictors of Compliance (N = 496)
|Characteristic||Adjusted OR*||95% CI||P Value|
|Depression symptom severity (per 1-point increase)||0.93||0.87 to 0.99||.027|
|External locus of control (per 1-point increase)||1.15||0.99 to 1.33||.068|
When higher-order terms of depression severity score (i.e., squared, or squared as well as cubed) were forced into the final model, these terms were found to be statistically nonsignificant. When potential mediating psychosocial and behavioral variables were singly added to or subtracted from the final model, no change had an appreciable effect on the odds ratio for depression severity. For example, subtraction of the external locus of control score caused the odds ratio for depression severity to increase by only 1.6%; addition of satisfaction, social desirability, smoking status, social support, health beliefs, knowledge, or number of drinks had even less impact on the odds ratio for depression severity (0.5%, 0.1%, 0.1%, 0.1%, −0.1%, 0.1%, and 0.0% change, respectively). No significant interaction was found between depression severity and other demographic, clinical, or health care utilization variables.
In our adjusted analyses, we also observed a trend toward improved compliance with each point increase in the measure of external locus of control (adjusted OR per point increase, 1.14; 95% CI, 0.99 to 1.33; see Table 3). That is, patients who believed that events were determined by forces outside of themselves were more likely to take their antihypertensive medications as directed. The assumption of proportional odds was evaluated for the final ordinal logistic regression model and was found to be met (score test χ2, with 11 df, 8.84; P = .90).
Because some earlier investigations have suggested a possible link between use of β-blockers38 and depression, we examined whether depression symptom severity differed by antihypertensive drug class (i.e., ACE inhibitors, β-blockers, calcium channel blockers, thiazides, or other agents), and found no significant differences. Finally, in our analysis of the criterion validity of our adapted depression severity score, we found a statistically significant relationship between possessing a higher tertile of depression severity score and having a diagnosis of depression recorded in one's medical record (χ2 test for trend, 2 df, 34.7; P≤ .001).
- Top of page
To our knowledge, this is the first report of an association between depressive symptoms and poor compliance with antihypertensive medications. Strengths of this study include the fact that we used actual drug utilization data rather than patient recall of adherence. Objective measures of compliance are especially important in investigations of depression because “pessimism bias” can cause under-reporting of drug use among the more severely depressed.39 In addition, we adjusted for a wide range of other determinants of compliance, including sociodemographic, clinical, and health care utilization variables. As demonstrated in this study, unadjusted confounding can obscure the true effects of psychosocial variables such as depression by weakening both the strength and statistical significance of their apparent associations with noncompliance.
Depression has also been reported to have an effect on adherence to other primary and secondary prevention treatments. In one study of compliance with aspirin among elderly patients with coronary artery disease, depressed patients adhered to their regimen on a significantly lower proportion of days (45%) than those without depression (69%).27 Studies of compliance in a variety of other conditions, including AIDS,40 renal transplantation,41 and asthma,42 have also identified depression as a risk factor for nonadherence.
The precise mechanism by which depressive symptoms can affect compliance is not clear and may be quite complex. Several features of depression could have detrimental effects on adherence with preventive medications, including poor motivation, pessimism over the effectiveness of treatments, decrements in attention, memory, and cognition, decreased self-care, and even intentional self harm. 22,43–45 In addition, depression has been associated with greater sensitivity to unpleasant side effects from medications.46 We did not find evidence that other psychosocial and behavioral variables play a mediating role.
Among the other psychosocial and behavioral factors studied, we observed a trend toward increased compliance with external rather than internal locus of control. The effect of this variable on compliance in prior investigations has been mixed.25,47 One mechanism that could explain our observation is that patients who believe that their fate is determined by forces outside themselves may be more likely to take medications on the instructions of their physician.48
Some of the most interesting findings in relation to clinical practice are the psychosocial variables, which appeared to have no association with patient compliance. We did not observe significant independent effects on compliance for health beliefs or knowledge regarding hypertension and its treatment. Prior studies of the effects of these psychosocial variables have produced mixed results, and some investigators have suggested that their predictive value may be best for compliance with short-term (e.g., several weeks) rather than long-term treatments.17 We also found no independent effects for social supports or patient satisfaction with health care. Previous studies have also failed to identify effects for these variables on adherence to antihypertensive medications.21,30,49 The two health-related behaviors studied, alcohol consumption and tobacco use, also were not found to be related to compliance with antihypertensive medications; similar findings have been reported elsewhere.26 These negative findings, too, have interesting clinical implications. They underscore the fact that clinicians cannot assume that any set of psychosocial characteristics are predictive of good or bad compliance. With the possible exception of those who are depressed, each patient must be considered to be equally at risk of being noncompliant, and evaluated with this possibility in mind.
Results of this study should be interpreted in light of some potential limitations. First, by using a measure of compliance based on filled prescriptions, we may have misclassified some compliant patients as noncompliant, such as those who obtained free samples from their doctors, were hospitalized for extended periods, or achieved blood pressure control through diet changes or exercise and were taken off antihypertensive medications. On the other hand, by using filled prescriptions to identify participants, we may have missed the most noncompliant patients, who did not fill any antihypertensive prescription in the study year. In addition, although our definition of noncompliance based on filled prescriptions measured medication underuse, it did not capture other types of noncompliance, such as overuse or inappropriate timing of dosages.
Second, we did not formally evaluate the reliability and validity of many of our adapted psychosocial and behavioral scales. However, in a post hoc analysis of the criterion validity of our adapted depression severity scale, we did find that depression symptom severity scores were significantly related to having a diagnosis of depression recorded in one's medical record. Third, potential limitations may have been introduced by the high nonresponse rate in our study. For example, if nonrespondents had worse compliance than respondents, our observed levels of compliance would have been inflated and the generalizability of our findings would have been limited. Finally, we cannot exclude the possibility that the variables found to be associated with compliance were not a result of multiple comparisons made using a number of candidate variables.
If confirmed in future studies, these findings regarding the relationship between depressive symptoms and antihypertensive medication compliance may have important implications for both researchers and clinicians. First, they may help to explain the higher cardiovascular morbidity and mortality that have been repeatedly observed in depressed patients.50–54 Second, these data suggest that patients with depressive symptoms should have their adherence to antihypertensive medications monitored particularly closely and may require special encouragement from health care providers in this regard. Finally, these data provide additional impetus for improving the detection and treatment of mental health problems. Although the majority of patients with depression present in primary care, there is substantial evidence that depression is underdetected and inadequately treated in such settings.55–57 Increased efforts to detect and treat depression may be associated with additional health benefits due to better blood pressure control. In the future, intervention trials might be conducted to clarify whether treatment of depression in noncompliant patients results in improvement in their adherence to prescribed regimens. Several initial studies in this area have yielded some promising findings.58–60