Abstract: Few studies were conducted on risk factor in medication nonadherence in developing rural area in China. The goal of this study was to perform a survey to address the prevalence of medication nonadherence and the reasons for nonadherence. Outpatients with chronic diseases (chronic obstructive pulmonary disease, diabetes, hyperlipidemia, hypertension, etc) in a rural hospital far away from Shanghai downtown, from Jan 1 to June 30, 2014 were invited to participate in this survey. Patients were answered a combination questionnaire including self-reported medication adherence and depression/anxiety symptoms. A total of 325 patients with chronic diseases were treated with regular medication without any anti-anxiety drugs or antidepressants. The 255 (78.5%) patients were regarded as medication nonadherence. Age, gender, educational level, brand preference and health literacy were not associated with medication adherence, while the number of chronic diseases, anxiety and depression were negatively impact medication adherence. Depression and anxiety symptoms are possible risk factors causing the nonadherence.
INTRODUCTION
Medication adherence usually refers to whether patients take their medications as prescribed (e.g., twice daily), as well as whether they continue to take a prescribed medication. Medication nonadherence is a growing concern to clinicians, healthcare systems and other stakeholders (e.g., payers). Its prevalence was associated with adverse outcomes and higher costs of care and has been recognized as a barrier to achieve better outcomes for patients (Osterberg and Blaschke, 2005). In general, medication nonadherence rates range from around 30-70% among patients with chronic diseases (Briesacher et al., 2008; Jackevicius et al., 2002; Lee et al., 2006).
Evidences documented that many factors including complex medication regimen, multi-drugs treatment, old-age, unawareness of health status, doubt about medication benefit and so forth are associated with medication nonadherence (Lacro et al., 2002; Cao et al., 2011; Shrank et al., 2006). Currently, brand preference and health literacy are interesting topics in clinical practice (Xiao and Xu, 2014). Brand preference means patients prefer to choose patent/brand-name drug, rather than the generic counterpart. Quite a number of patients prefer brand name drugs to generic drugs especially in developing countries (Wang et al., 2010). Health literacy refers to capacity of individuals to make appropriate health decisions based on health information (Manganello, 2008). A few studies suggested that poor health literacy has a negative impact on medication adherence (Kripalani et al., 2010; Noureldin et al., 2012). Furthermore, mood disorder is also reported to impact medication adherence. Depression and anxiety are common in patients with chronic diseases. A meta-analysis found that the relationship between depression and non-adherence was substantial and significant while the associations between anxiety and non-adherence were variable (DiMatteo et al., 2000). A longitudinal study demonstrated that severe anxiety was a predictor of non-adherence to antiretroviral therapy in AIDS patients (Campos et al., 2010).
To date, few studies were reported on risk factor in medication nonadherence in the rural areas. People in rural areas are less-educated and poor in economic condition in a large proportion. Medical expense cost a lot and many rural people cannot afford to see a doctor. In spite of seeing a doctor, many cannot afford to get their whole prescription filled. Their medication adherence has been ignored for quite a long time. For this reason, this survey was conducted to explore the risk factors associated with medication nonadherence in the rural area of China.
MATERIALS AND METHODS
Outpatients with chronic diseases (chronic obstructive pulmonary disease, diabetes, hyperlipidemia, hypertension, etc) in this hospital, from Jan 1 to June 30, 2014 were invited to participate in this survey. All patients were briefed the aim and significance of this survey before the interview by pharmacist and gave verbal informed consent in this study. They were informed of their right to decline, discontinue the survey at anytime and without any reason. Then every patient was interviewed with a senior pharmacist individually in Out-patient Drug Information Consulting room. Patient was asked to answer a group of questionnaire including Chinese Medication Adherence Scale, PHQ 9, GAD7 and other self-designed instruments. The demographic information such as patient’s age, gender, education and the number of chronic diseases were obtained. The survey was approved by this hospital’s Clinical Research Ethics Committee.
Chinese Medication Adherence Scale (CMAS) was measured for each patient (Cao et al., 2011). Using a cutpoint of <6, the sensitivity of the measure to identify patients with poor adherence was estimated to be 93% and the specificity was 53%. Patients with a score of less than 6 were regarded as medication nonadherence.
Brand preference (Cao et al., 2011; Wang et al., 2010) was measured by three questions as follows: (1) Do you think the quality of brand-name drugs is better than that of its generic counterpart? (2) Do you think the efficacy of brand-name drugs is better than that of its generic counterpart? (3) Do you prefer to choose brand-name drug in spite of high price? Each question is answered on a 4-point scale, with 4 being "Strongly agree" and 1 being "Strongly disagree". An integrated score was created by the addition of responses to each item (range from 3-12). Score of 12, 9-11 and 3-8 were defined as high brand preference, moderate brand preference and no preference, respectively.
Different from the general definition, health literacy inhere was defined as people’s awareness to manage their health status in this study. It was measured by four questions as follows: (1) Do you think medication adherence is beneficial for disease control? (2) Do you know well about the medication you take? (3) Do you drink? (4) Do you smoke? The first two questions were on a 4-point scale, with 4 being "Strongly agree/quite understand" and 1 being "Strongly disagree/don’t understand". The third question was on a 3-point scale, with 3 being "Never" and 1 being "often". The last question was on a 2-point scale, with 2 being "No" and 1 being "Yes". An integrated score was generated by the addition of responses to each item (rang from 4 to 13). Score of 10-13 and 4-9 were defined as adequate and inadequate health literacy, respectively.
Depression and anxiety symptom was evaluated by Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder 7(GAD-7), respectively (Al-Ghafri et al., 2014; Kroenke et al., 2010; Beard and Bjorgvinsson, 2014). The two questionnaires were on a 10-point scale, with ≥15 being "Severe depression or severe anxiety" and 10 being "No depression or no anxiety". Score between 10~15 was defined as moderate depression or moderate anxiety.
Statistical analysis: Data was analyzed with SPSS 13.0. All variables were analyzed by Chi-square tests for significant associations with medication adherence. The p<0.05 were regarded as statistically significant.
RESULTS
The survey was carried on in Pharmacy Information Consult Room. This hospital is located in Fengxian, an agricultural less-developed rural area far away (55 km) from Shanghai downtown. It is the only biggest hospital within a radius of 30 km in the rural area. The surrounding residents usually come to this hospital to see a doctor.
A total of 325 patients with chronic diseases were recruited in this study, with 51.7% males, age ranging from 53-78 (the mean age 60±9 years). All patients were treated with regular medication without any anti-anxiety drugs or antidepressants. The mean score of the CMCQ was 4.0±1.7 (ranging from 0 to 8). About 80% of patients with a score of less than 6 were regarded as medication nonadherence, while about 20% of patients were regarded as medication adherence.
First of all, there is no significant difference between gender and age groups among the patient population regarding medication adherence. Although the low education patients accounted for a high proportion in the whole sample, each section showed similar medication adherence regardless of different education background (from illiteracy to higher education recipient) (Table 1).
More than 50% of patients had only one number of chronic disease and about 20% of patients suffered from 3 or more chronic diseases at the same time. Medication adherence decreased as the number of chronic diseases increased. The difference was statistically significant (p<0.05) (Table 1).
Although the ratio of patients with moderate to high brand preference was greater (87.1%) than that of patients with no brand preference (12.9%) in the whole sample, each section showed same medication adherence of more than 20%. Meanwhile, the capacity to obtain, process and integrate health information and service do not necessarily improve practical medication adherence (Table 1).
In this survey, depression/anxiety symptoms significantly impacted medication adherence (p<0.01).
| Table 1: | Three hundred and twenty five patients’ characteristics and proportion of adherence patients |
| *Proportion = n0/325, **Proportion = n1/n0 | |
Patient with severe depression or severe anxiety symptoms showed 10% medication adherence compared to 40~80% medication adherence in patients with no anxiety or no depression (Table 1).
DISCUSSION
Medication adherence is the degree to which patients take medications as directed by physician or pharmacist. There is no standard definition of "Adequate" adherence. No matter how it is defined, medication nonadherence is common. Many patients do not take a prescribed medication. Patients with chronic diseases typically take only 50% of prescribed doses (Bubalo et al., 2010). In addition, about half of patients discontinue statins after only six months of treatment (Lemstra et al., 2012). And up to 50% of patients discontinue antihypertensive therapy within the first year of treatment (Evans et al., 2012). Nonadherence can lead to more morbidity, mortality and medical expense (Manning, 2011).
In this study medication adherence situation was investigated in an agricultural, less-developed area was investigated. The respondents are mainly elderly people, with no to elementary education. The primary finding of this study was that medication adherence is associated with the number of chronic diseases, anxiety and depression. The overall rate of adherence was 21.5%, which was much less than previous study among patients with hypertension in Hong Kong (65.1%) and community-dwelling older adults in US (59%) (Cao et al., 2011; Sirey et al., 2013). No significant difference between gender, age and education for medication adherence in this study. A study conducted in Nigeria also found that age, gender and education level did not impact medication adherence but the employment was a significant variable (Okuboyejo, 2014). Meanwhile a few studies have concluded that age and education level were significantly related to medication adherence in elderly patients with chronic disease and female patients were at increased risk for nonadherence to statins therapy (Lee et al., 2013; Lewey et al., 2013).
In this study, patients with more than 3 chronic diseases were more non-adherent than patients with one chronic disease. This may be due to the reason that the former had more multiple drugs therapy. Dosing frequency is a determinant of medication adherence. Patients appear to be more adherent with once-daily medication regimen compared with multiple or complex regimens (Coleman et al., 2012). In order to improve medication adherence, physicians should simplify the medication regimens for patients at the most extent.
It is a global problem for patients to choose brand-name drugs instead of generics especially in developing countries such as China (Xiao and Xu, 2014). A few studies compared medication adherence of patients treated with brand-name drugs to generic counterparts. A study reported that generic drugs were associated with more medication adherence than brand-name drugs in patients with hypercholesterolemia or diabetes (Briesacher et al., 2009). Generic medications could improve medication adherence (Shrank et al., 2006). However, on the contrary, a study found that switching from brand-drug to generic counter-part led to decrease medication use (Tseng et al., 2006). The result of this study showed that there was no significant association between brand preference and medication adherence. Although most respondents showed strong brand preference, they had to take prescribed medications. In this an agricultural, less-developed area, many respondents are not covered by health insurance and most respondents are not rich.
Health literacy seems not to be associated with medication adherence in this study. It suggested that the capacity to obtain, process and integrate health information and service do not necessarily improve practical medication adherence. A recent study also fails to find a significant relationship between health literacy and medication adherence (Ostini and Kairuz, 2014). It is worth noting that patients without health literacy were more likely to hold negative beliefs about generics (Iosifescu et al., 2008). Furthermore, patients with health literacy had better adherence than those without health literacy (Ngoh, 2009).
In this study, patients with depression/anxiety were likely to be noncompliant. Depression has been recognized as one of the predictor of medication nonadherence. The latest research indicated that depression was independently associated with nonadherence among patients with advanced non-small cell lung cancer (Arrieta et al., 2013). Depression and anxiety may be potential target for pharmacists and physicians in the effort to improve medication adherence of patients with chronic diseases.
The sample size was the primary limitation of this survey. The instrument used to measure the health literacy in this work was too simple and subjective and needed to be validated in future. Further well-designed, large sample of investigation is warranted to confirm our preliminary conclusion.
CONCLUSION
Medication nonadherence is common among patients with chronic diseases in the rural area in China. Depression/anxiety and the numbers of chronic diseases are risk factors for nonadherence.