Journal of Hypertension:
Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
Correspondence to Claudio Borghi, UOC di Medicina Interna, Ospedale S.Orsola-Malpighi-Via Albertoni 15, Bologna 40138, Italy. Tel: +300516362843; fax: +391051391320; e-mail: email@example.com
Adherence is ‘the extent to which a person's behaviour – taking medication, following a diet, and/or executing lifestyle changes – corresponds with agreed recommendations from a healthcare provider’.
Adherence to antihypertensive treatment is a major problem for the correct management of cardiovascular diseases in general and for arterial hypertension in particular. In detail, it has been estimated that the proportion of hypertensive patients who are persistent in their medications after 3 years from the first prescription is about one-third of the treated population [2,3]. This can fairly explain the results of the EURIKA survey in which, despite the availability of very effective antihypertensive medications, the proportion of hypertensive patients who achieve an adequate blood pressure control does not exceed the value of 40% . The negative consequences of this unsatisfactory situation are twofold ranging from a reduced preventive impact of drug strategies aimed at decreasing the burden of cardiovascular risk to a significant waste of economic resources because of the shortage of the expected benefit of the prescribed medications. On the contrary, a good adherence to prescribed antihypertensive medications has been associated with a significant reduction in the odds ratio of major cardiovascular events  supporting a primary role for adherence as a key factor for any successful strategy aimed at reducing the cardiovascular risk by improving blood pressure control.
Despite its very high prevalence, poor adherence to treatment in the hypertensive population is a modifiable condition. The probability of an adequate use of medications is increased by the preliminary identification of the possible causes of nonadherence. Several factors can be responsible for a poor adherence to antihypertensive therapy  and among them the most common are: the patient's perception of the efficacy of treatment, the nature of the disease to be treated (adherence is reduced when drugs are prescribed to treat largely asymptomatic chronic diseases such as hypertension), the presence and severity of symptoms, the number of pills prescribed and the tolerability of the medications with an inverse relationship between the individual adherence and the rate of side effects . The individual adherence to blood pressure-lowering treatments is higher in patients treated with a fixed-dose combination  of well tolerated and effective antihypertensive drugs. However, this approach does not seem to be enough. Despite a significant improvement in the use of drugs combining a favorable tolerability profile with a remarkable clinical efficacy, the control of elevated blood pressure values is still far from the expected target. This may be partially explained by the crucial attention that has been paid to the ‘drug-related’ factors of drug discontinuation without considering the possible role of other comorbidities affecting the individual propensity to individual compliance.
Among modifiable risk factors for poor adherence to antihypertensive treatment, depression has recently gained more attention [8,9]. Psychic disorders are largely represented in the population and their prevalence as well as their negative impact on public health is expected to remain very high in the future . Depression has been shown to considerably increase the risk of nonadherence to medical prescriptions in some studies [8,11] while this finding has not been confirmed by others  and the overall issue is still a matter of scientific controversy. In particular no information has been provided about the individual adherence to antihypertensive treatment in patients who develop depression after the initial prescription of antihypertensive medications. As a matter of fact, the onset of mood disturbances may negatively affect the individual adherence to prescribed treatments beyond the negative influence of traditional risk factors of poor compliance. In the present issue of the Journal, Sjösten et al. have prospectively demonstrated that the onset of depression can be associated with a significant increase of ‘days-not-treated’ in a cohort of hypertensive male patients. As expected the nonadherence after depression was more pronounced in older patients and in those with a longer duration of hypertension. The same difference in individual adherence was not observed in women and this opens a ‘sex issue’ based on a sex-related difference in the relative weight of depressive symptoms as a potential cause of poor adherence to antihypertensive treatment. The sex-related difference in the impact of depression on adherence to medications is hard to explain as the prevalence of depressive symptoms is usually higher and more disabling in the female population. Probably, the presence of a depressed mood in women does not affect the perception of the disease or the symptoms develop more gradually with a lesser decline in the self-esteem and cognitive reactivity. Regardless of the mechanisms involved, this sex difference can have important clinical implications for the prevention of cardiovascular disease, suggesting the greater preventive impact of managing depressive symptoms in hypertensive men. Unfortunately, the study does not provide any information about the overall rate of blood pressure control in patients who complain of different levels of adherence to medications, and this reduces the strength of the observation in terms of translation to clinical practice. The same study limitation does not allow us to understand if the difference in ‘days-not-treated’ between depressive patients and controls is the consequence of poor compliance or is due to a progressive improvement of blood pressure control because of the reduction of depressive symptoms. Indeed, according to inclusion criteria the study has involved only patients with a ‘certified’ diagnosis of depression (hospital admission or use of antidepressive strategies) in which the antidepressant intervention may significantly improve the mood disorders and spontaneous blood pressure control. Further studies implementing the information about depressive symptoms and the adherence to antihypertensive treatment with a measure of blood pressure control are warranted for the future. From the practical point of view one of the major strengths of the article is the fact that the extent of nonadherence was estimated by prescription data without any direct involvement of the patients. This allows for a more objective estimate of the actual attitude to regularly taking the prescribed drugs by patients with different levels of mood disturbances. Indeed, the presence of what Sjösten and co-workers define as ‘pessimism bias’ is very common in depressed patients and might irregularly affect the daily life thus jeopardizing the reliability of any self-report of individual adherence to treatment. The same methodological issue is also one of the major limitations of the study as it provides information only about the number of days covered by refills without any measurable evidence that the prescribed drugs are actually taken by the patients. The direct consequence of this optimistic approach is the risk of some degree of over-interpretation of data with the inclusion of ‘drug-accumulators’ among those patients with a satisfactory adherence to treatment. Again the problem can be solved by relying on a measurable estimate of drug effect that can be identified in the blood pressure decrease or in the proportion of patients reaching the recommended targets of treatment according to guidelines.
As adherence to antihypertensive medications is a crucial issue for the prevention and treatment of cardiovascular diseases, we must definitely encourage the early identification of any possible factor that might promote drug discontinuation. Depression and mood disturbances in general, may negatively affect the likelihood of a correct assumption of antihypertensive drugs and might be considered in addition to the other risk factors for poor adherence. The practical consequence of the identification of a depressive profile in hypertensive patients could be two-fold. First, to adopt educational measures aimed at reinforcing the patients’ commitment to reducing the rate of drug discontinuation (e.g. motivational approach). Second, to preferentially address the therapeutic choice toward better tolerated classes of antihypertensive drugs with a more extensive use of fixed-dose combinations. Whether or not a larger use of antidepressant drugs might further improve the adherence to antihypertensive treatment is still a matter of speculation and must be discounted against the actual risk that the apperarance of one more actor on the stage may, actually, break the delicate balance among willingness to be treated, perception of efficacy and risk of untoward adverse events.
Conflicts of interest
There are no conflicts of interest.
1. Banegas JR, López-García E, Dallongeville J, Guallar E, Halcox JP, Borghi C, et al. Achievement of treatment goals for primary prevention of cardiovascular disease in clinical practice across Europe: the EURIKA study. Eur Heart J
2. World Health OrganisationNoncomunicable dseases and mental health adherence to long-term therapies project. Geneva, Switzerland:World Health Organisation; 2003.
3. Corrao G, Zambon A, Parodi A, Poluzzi E, Baldi I, Merlino L, et al. Discontinuation of and changes in drug therapy for hypertension among newly-treated patients: a population-based study in Italy. J Hypertens
4. Mazzaglia G, Ambrosioni E, Alacqua M, Filippi A, Sessa E, Immordino V, et al. Adherence to antihypertensive medications and cardiovascular morbidity among newly diagnosed hypertensive patients. Circulation
5. Hill MN, Miller NH, Degeest S, Materson BJ, Black HR, Izzo JL Jr, et al. American Society of Hypertension Writing GroupAdherence and persistence with taking medication to control high blood pressure. J Am Soc Hypertens
6. Ambrosioni E, Leonetti G, Pessina AC, Rappelli A, Trimarco B, Zanchetti A. Patterns of hypertension management in Italy: results of a pharmacoepidemiological survey on antihypertensive therapy. Scientific Committee of the Italian Pharmacoepidemiological Survey on Antihypertensive Therapy. J Hypertens
7. Bangalore S, Kamalakkannan G, Parkar S, Messerli FH. Fixed-dose combinations improve medication compliance: a meta-analysis. Am J Med
8. Wang PS, Bohn RL, Knight E. Noncompliance with antihypertensive medications. The impact of depressive symptoms and psychosocial factors. J Gen Intern Med
9. DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med
10. Murray JL, Lopez AD. Alternative projection of mortality and disability by cause 1990–2020 Global Burden of Disease study. Lancet
11. Siegel D, Lopez J, Meier J. Antihypertensive medication adherence in the department of Veterans Affairs. Am J Med
12. Hashmi SK, Afridi MB, Abbas K, Sajwani RA, Saleheen D, Frossard PM, et al. Factors associated with adherence to antihypertensive treatment in Pakistan. PLoS One
13. Sjösten N, Nabi H, Westerlund H, Salo P, Oksanen T, Pentti J, et al. Effect of depression onset on adherence to medication among hypertensive patients: a longitudinal modelling study. J Hypertens