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control. A meta-analysis of 24 studies found that depression was significantly associated with poor glycemic control in individuals with type 1 and type 2 diabetes.⁹⁰ Richardson and colleagues went a step further and assessed the longitudinal effects of depression on glycaemic control.⁹⁰ They found that over 4 years of follow-up there was a significant longitudinal relationship between depression and glycemic control and that depression was associated with persistently higher HbA1c levels over the time period.

Wagner et al. also found higher HbA1c and more diabetes complications in African Americans with higher depressive symptoms after controlling for confounders.⁹¹ In the study, diabetes self-care did not fully account for the relationship between depression and HbA1c levels.⁹¹

B) DEPRESSION ON MEDICATION ADHERENCE: Poor adherence to treatment remains a major impediment to improving care, particularly among patients with comorbid diabetes and depression. In comparing diabetes patients who are not depressed with depressed patients, the depressed are more likely to be non-adherent to medication regimens and exhibit worsening diabetes management.^92-93

Clinical management guidelines emphasize the importance of medication adherence, physical activity, diet and self-monitoring of blood glucose.⁹³ Gonzalez et al. proposed that the presence of depressive symptoms are good predictors of poor adherence to self-care particularly in adherence to medications and diet and exercise regimens.⁹⁴ Therefore, interventions should simultaneously address depression and self-care skills to achieve optimal diabetes outcomes. A systematic review of treatment adherence among individuals with diabetes and depression indicated that there was a significant relationship between depression and treatment non-adherence.⁹⁵ Effects sizes in the study were largest for medical appointments and composite measures of self-care (r= 0.31, 0.29).⁹⁵ Similarly, a systematic review of studies of medication adherence found that many patients did not adhere properly to diabetic medications.⁹⁶ A second review of self-management behaviours also concluded that comorbid depression in individuals with diabetes is associated with not only decreased adherence to medications but also decreased adherence to dietary recommendations.⁹³ Comorbid depression among individuals

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with diabetes generally has a negative impact on patient initiated activities such as less physical activity, unhealthy diet, and lower adherence to oral medications (hypoglycemic, antihypertensive, and lipid lowering). ⁹⁴ Gonzalez et al. found that after controlling for relevant covariates, patients with major depression reported significantly fewer days of adherence to diet, exercise and glucose self-monitoring self-management strategies and a 2.3-fold greater odds of missing medication doses compared with other respondents.⁹⁷ It is possible that patient attitudes play a critical role in self-care behaviours and depression impairs good care practices by influencing good care practices and perceived self-control.⁹⁷ The management of comorbid depression and diabetes should be integrated and tailored for preference, tolerance, and simplicity to enhance adherence to prescribed medical regimens.

Measurement of adherence.

Accurate assessment of adherence is necessary for effective and efficient treatment planning, and for ensuring that changes in health outcomes can be attributed to the recommended regimens. One of the most important problems is the lack of entirely satisfactory methods to measure adherence. This has made research into adherence difficult. Most methods are indirect and fault-prone. Indisputably, a commonly accepted gold standard does not exist. Adherence can be evaluated in several ways, these include;

a) Patients' self-reports: When this is used, patients are asked non-judgmentally how often they missed their doses. It is a structured, mostly close ended Questionnaire. It is a useful tool to assess adherence to drugs. It is usually pre-tested to assess its conformability to the population it is to be used on.⁹⁸

b) Morisky Medication Adherence Scale (MMAS): Is a 4-item questionnaire with high reliability and validity, which has been particularly useful in chronic conditions such as diabetes.⁹⁹ It measures both intentional and unintentional adherence based on forgetfulness, carelessness, stopping medication when feeling better, and stopping medication when feeling worse. The scale is scored 0, 1, 2, 3, and 4 for response of ‘Never, Rarely, Sometimes, Often and Always’ respectively. The total score ranges from 0 (adherent) to 16 (non-adherent). A total scores of 0-4 = good or high adherence, 5-8 = fair or medium

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adherence and 9-16 = poor or low adherence.¹⁰⁰ It can be used with patients’ self-report to increase the strength and consistency of the gotten result.⁹⁹

c) Pharmacy Records and Prescription claims (Pharmacy Refill Data or prescription database): This can serve as an adherence measure by providing the data on which medications were dispensed. They provide information on drug supply but give no information on the pattern of drug ingestion on a daily basis.¹⁰¹ The use of prescription database to measure adherence is based on assumption that patients are unlikely to continue collecting prescriptions if they have stopped taking their medicines. However, its disadvantage is found in some cases, like in health insurance schemes, where patients may collect their prescriptions and hoard their medicines or give them out to another person, but prescription database has no evidence to suggest this. Prescription databases provide information on what prescriptions were collected but not what was actually prescribed by the doctor or consumed by the patient, so that for the assessment of adherence the assumption is made that the medicine type and quantity received are exactly what were prescribed.¹⁰¹

When attempting to quantify adherence by pharmacy database, it is most appropriate to ascertain discontinuations and changes of therapy. To do this, it is necessary that all prescriptions collected by the patient during the time of observation are included in the database and this is typically estimated over a year.¹⁰¹ This may be difficult, and incomplete or inconclusive data may be gotten. Other pitfall of this, is that an estimate of the adherence of a patient who fails to collect a prescription in the third, fifth, and ninth months will be the same as for one who collects prescriptions continuously for 9 months and then stops.¹⁰¹

d) Pill counts adherence: This is usually calculated by counting the remaining doses of medication and assuming that the remaining pills in excess of which is expected represent missed doses.¹⁰² Counting the number of pills remaining in a patient's supply and calculating the number of pills that the patient has taken since filling the prescription is the easiest method for calculating patient medication adherence.

Adherence rates can be calculated as ‘pills taken over a specific period of time, divided by pills prescribed for that specific period of time. Some data indicate that this technique may underestimate

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adherence in older population. Patterns of non-adherence are often difficult to discern with a simple count of pills on a certain date weeks to months after the prescription was filled. Because pill counts are often based upon the date a prescription is filled, patients who get prescriptions refilled prior to their first one running out and then combining pills into a single (and possibly non-original) bottle presents complications. Even though, the pill counts adherence assumes patient get prescription from one source, yet loss of data is common among many studies.¹⁰³

e) Follow up review of case note: Reviewing the case note of the patients will enable one to know when the prescribed medication in the last visit is expected to finish and the date patient is due for his check-up. This could be done at every consultation with patients and when this is combined with pill counting, it increases the reliability and validity of this method.^101,102

f) Electronic Monitoring (Medication Event Monitoring System): This utilizes a computer chip embedded in a specially designed pill-bottle cap to record the time and duration of each bottle opening.¹⁰² This may be considered as the best existing system for measurement of compliance. The availability and cost of this system could limit the feasibility of its use.¹⁰³ Also the bottle may be opened and the drug is not used.

g) Biological Assays: Biological assays measure the concentration of a drug, its metabolites, or tracer compounds in the blood or urine of a patient. These measures are intrusive and often costly to administer.¹⁰¹ Patients who know that they will be tested may consciously take medication that they had been skipping so the tests will not detect individuals who have been non-adherent. Drug or food interactions, physiological differences, dosing schedules, and the half-life of the drugs may influence the results. Biological tracers that have known half-lives and do not interfere with the medication may be used, but there are ethical concerns.¹⁰¹ All of these methods have high costs for the assays that limit

the feasibility of these techniques especially in a developing country like Nigeria.