Depression and medication-adherence in patients with hypertension attending a tertiary health facility in South-West Nigeria

Introduction In Nigeria, approximately 4.33 million adults suffer from hypertension and about a third of them do not adhere to prescribed medications. Depression has been reported to significantly predict poor medication adherence. The relationship between medication non-adherence and co-morbid depressive disorder in patients with hypertension has not been adequately explored in this environment. The study aimed to determine the prevalence of depression in patients with hypertension. The association between socio-demographic characteristics and presence of co-morbidity on medication adherence was also determined. Methods A cross-sectional descriptive research design was adopted for the study. A socio-demographic questionnaire, the modified Morisky Medication Adherence Scale (MMAS), the Hamilton Rating Scale for Depression (HAM-D) and the Mini International Neuropsychiatric Interview (MINI), were administered to four hundred patients with hypertension attending medical out-patient clinic between August and September 2012. Results About 43% (168) were aged 61 to 64 years the majority being females, with a female to male ratio of 1.63:1. The prevalence of comorbid depression was 22.8%, made up of mild (21.8%) and moderate (1.0%) depressive episodes only. Depression was commoner among females than males in a ratio of 3:1. A majority of the participants (96.8%) had high medication adherence; 2.8% and 0.4% had moderate and low adherence respectively. Depression was more among patients with good medication adherence. Conclusion The occurrence of mild depressive disorder among hypertensives did not affect the level of medication adherence. Review of Antihypertensive drugs should also be done often to ensure patients are not likely to have depressive illness as a side effect of drugs used.


Introduction
Depression is a very common mental health problem worldwide. The World Health Organization (WHO) estimates that 121 million people currently suffer from depression and that depression will become the second most common cause of disability after heart disease by 2020 [1]. Depression often co-occurs with chronic physical illnesses such as hypertension, diabetes mellitus and epilepsy [2][3][4]. These chronic physical illnesses sometimes lead to a decrease in the patient's quality of life and thus increase the risk of developing depression. Compared with healthy people, cardiac patients appear to be at greater risk of developing depression many years after the initial medical diagnosis is made [5]. The physiological mechanisms underlying the relationship between depression and hypertension are complex, intricately interwoven and appear to be largely mediated by neurotransmitter effects involving the sympathetic nervous system [6]. For instance, some drugs used in the treatment of hypertension such as methyldopa and reserpine are known to precipitate depression, while some of the drugs used in the treatment of depression like bupropion, venlafaxine and phenelzine have been reported to cause hypertension [7,8].
Medication adherence refers to patient's use of medications in strict compliance with the prescription [9]. Poor medication adherence is a significant risk factor for poor treatment outcome in patients with hypertensive disease particularly with the associated high rate of preventable deaths. Uncontrolled blood pressure often from nonadherence to medication use, is associated with such untoward sequelae as sudden deaths, stroke and renal failure. In a Nigerian study involving patients attending a secondary health facility in Oyo State, only about a third (33.6%) of the cases were reported to have controlled blood pressure (CBP) and this was partly blamed on poor adherence to antihypertensive medications. Depression has been reported to significantly predict poor medication adherence [10][11][12].
About a third of persons with physical ailment in Nigeria, on the average, have a co-existing mental disorder [13]. This modifiable risk factor, when identified, can be well managed by physicians thereby improving adherence to medication and avoid the attendant dangerous health consequences of non-compliance. Despite the mounting evidence regarding the association between poor medication adherence, depression, and uncontrolled blood pressure, assessment of patients' adherence to prescribed medications, screening for depression and use of individualised interventions to improve adherence are rarely carried out in routine clinical practice [9]. The study aimed to determine the prevalence of depression in patients with hypertension. The association between sociodemographic characteristics and presence of comorbidity on medication adherence was also determined. It is hoped that the findings will serve as baseline data for working out appropriate intervention protocol for the clinic services, for future medical education and health campaign programs. Sample size calculation: in an earlier study conducted in Nigeria, the prevalence of medication non-adherence among hypertensive patients was found to be 34.2% [14]. Using appropriate statistical formulae, with 10% non-response rate and probability of making type 1 error of 5%.
Sampling method: systematic random sampling method was used to select 12 patients daily for a period of 7 weeks (35 clinic days).
The daily sampling frame was made up of 20-30 eligible patients. The sampling interval was 30/12, that is 2. From the first three patients seen daily one was randomly selected, then every third patient was selected until a total number of 12 patients were seen. Associations between categorical and continuous variables were tested using the chi-square and student t-test respectively. Sociodemographic and illness variables were entered into a logistic regression model to determine predictors of poor medicationadherence. Level of significance was 0.05. Table 1 shows the socio-demographic characteristics of the respondents. The mean age of respondents was 59.6 +/-8.0 years. (13.7%) of those who earned ≥ N20,000 per month. Even though respondents aged 60 years and above, those practicing other religion apart from Christianity, the unemployed, those with co-morbidity and those who earned ≤ N5000 per month were more likely to have depression, these were not statistically significant. Unmarried respondents compared to married, those with primary education and below compared to secondary and above and those who earned less < N20,000 compared to ≥ N20,000 had two times likelihood of having depression.

Discussion
A prevalence rate of 22.8% for co-morbid depression in patients with hypertensive disease in this study is similar to the reported rate of 22% among outpatients with stable coronary heart disease in the United States, but would seem much higher than the 6.2% recently reported in patients with similar condition attending a cardiology clinic in Lagos, Nigeria [19,20]. The Lagos study was noted to have excluded participants older than 60 years, an age group known to be vulnerable to developing depressive disorders for myriad psychosocial reasons; and the subgroup of patients who had developed complications from hypertension [20]. In this study, most of their identified cases had mild depressive disorder. The finding that depression was more prevalent among females compared to males with a female to male ratio of 3:1 is in keeping with the reports of earlier studies [21][22][23]. More prevalence of depression among females could be due to the fact that females use a high degree of ruminative coping and a low degree of distractive and problem-focused coping [23]. In addition, because females were nearly twice as likely to be included in the sample could have confounded the gender prevalence rate differentials observed. The non-married were found to be more amongst the cases with co-morbid depressive disorder than the married. Other researchers have found that participants with major depressive disorder have poor social support [21]. It is therefore understandable that married females tend to have good social support which could reduce their risk of developing depression.
Religion, employment status and presence of co-morbidity, were not significantly associated with a diagnosis of depression. However, a population-based study in the United States reported that unemployment predicted greater odds of major depressive episode (MDE) among African American men, while there was an inverse relationship between level of education and 12-month MDE [24].
Also in this study, participants with depression were older, although this difference was not statistically significant. This is similar to a previous study report that depression occurred more in old age, reaches its lowest level in the middle age at about 45 years, and has a tendency to fall in early adulthood and rise in late life reflecting lifecycle gains and losses in marriage, employment and economic wellbeing [25]. Duration of formal education was significantly associated with depression in that participants with lower formal education had more co-morbid depression than those with higher formal educational attainment. This is because individuals with lower formal education tend to be more susceptible to the deleterious effects of negative cognitive and affective states [22]. More participants with lower income or allowance per month had depression compared to those who earned higher income; this is in keeping with Akhtar-Danesh and Landeen study finding which reported an inverse relationship between the level of income and the prevalence of depression [26].
Paradoxically, a higher proportion of those with co-morbidity had good medication adherence. Sometimes patients with co-morbidity take other medicines in addition to their hypertensive medications daily and this could have helped to improve their compliance. Also the good social support that the patients had could have been responsible for good medication adherence. However, some studies have shown that the presence of co-morbidity did not affect medication adherence [14,27].
As shown in this study there was no significant relationship between age, marital status, educational status, monthly income, cost of treatment per month, and medication adherence. Previous studies had reported that old age and being married were independent predictors of medication adherence [28,29]. This could be because older people that are married tend to have good social support which is associated with good medication adherence among patients with hypertension. Other studies found that having a strong social support system was associated with high medication adherence among patients with hypertension [30,31]. The high cost of antihypertensive medications also contributes to non-adherence in developing countries where health care insurance facilities seldom exist. In a study conducted in Nigeria among patients with hypertension on treatment, 34.2% of them were non-adherent to their medication and lack of finance accounted for 23.8% of such cases [14]. In Ghana, 93% of hypertensive patients were non-adherent with medication regimens and 96% of such patients cited unaffordable drug prices as the main reason [32]. Even though in this study there was no significant relationship between age and medication adherence, a cross-sectional study of out-patients at a Veterans Health Administration site showed that concomitant use of more than one antihypertensive medication increases with patient's age and may have an impact on the patient's willingness or ability to comply with the overall regime [10]. The high medication adherence prevalence rate of 96.8% found in this study could be because more medication adherent patients attended the Centre, being the only tertiary health facility in the locality. Also, there is the possibility that the patients had recall bias about their compliance. This finding is similar to a prevalence rate of 91.44% that was reported in a study conducted among patients with hypertension in the United Kingdom with age range of 40 to 79 years, unlike the reported 43% in a Gambian study [14,27].
In this study, depression did not affect level of medication adherence. This is contrary to findings in previous studies [29,33]. Majority of the patients in this study with co-morbid depression had mild depressive episodes which was less likely to affect their level of medication adherence. Also, health talk given by the community health nursing officers before each clinic starts could have influenced the patients level of adherence positively. A study conducted among patients with hypertension in Nigeria reported that poor medication adherence was mainly due to ignorance on need for regular treatment [34]. Prior reports had demonstrated that the presence of depressive symptoms were associated with inadequate blood pressure control and complications of hypertension [6]. Some recent, investigations have reported association between depressive symptoms and low anti-hypertensive medication adherence [22].

Conclusion
The prevalence of co-morbid depression among patients with hypertension attending the Medical Out-patient Clinic at the Federal Medical Centre, Owo was 22.8%. Mild depressive episode was the commonest form (21.8%) and afflicts nearly three times as many females as the males and the unmarried more than the married.
Participants with low level of formal education were more likely to have co-morbid depression than those with higher level of formal education. Also, those with monthly income of < N20,000 were more likely to have depressive episode in comparison with those with monthly income of ≥ N20,000. It was an unexpected finding that the majority of the patients that reported high medication-adherence also had co-morbid depression. Physicians caring for patients with hypertension should routinely screen them for depression which can be easily missed in patients attending hypertensive disease clinic. The detection of co-morbid depression could be facilitated by use of brief questionnaires similar to that used in this study; they should be made available in all consulting rooms because they are easy to administer and score by clinicians. Review of antihypertensive drugs should also be done often to ensure patients are not likely to have depressive illness as a side effect of drugs used. To help patients better understand their health condition and co-operate with their management, regular health talk about co-morbidities and the adverse consequences if undetected, aided with educational video recordings while waiting to see their primary care physicians is strongly recommended. In this study, though unintended, more participants belonged to the age group of ≥ 60 years, reflecting the pattern of patients seen in the centre where this study was carried out. Generalizing the findings here to other centres where younger patients may be more, may not be appropriate. Also, because medication adherence was assessed by self-report, pill counting was not done and experience of side effect was not captured.

Ascertainment bias coupled with the problem of recall is noteworthy limitations.
What is known about this topic  Prevalence of hypertension in Nigeria;  Poor adherence to medication among hypertensives;  Depression has been reported to significantly predict poor medication adherence.
What this study adds  The relationship between medication non-adherence and comorbid depressive disorder in patients with hypertension;  Importance of routine screening of hypertensive patients for depression;  Review of antihypertensive drugs should also be done often to ensure patients are not likely to have depressive illness as a side effect of drugs used.

Competing interests
The authors declare no competing interests.

Authors' contributions
Hannah Iyabo Okunrinboye and Alexander Ndubusi Otakpor conceived the study and participated in its design and coordination.
Hannah Iyabo Okunrinboye and Olayinka Stephen Ilesanmi performed the statistical analysis. All authors contributed to drafting of the manuscript and they read and approved the final version. Table 1: socio-demographic characteristics of the study participants