Impact of depression on drug intake in hypertensive patients

Waeber, Bernarda; Stiefel, Friedrichb

Journal of Hypertension:
doi: 10.1097/HJH.0b013e32833d1f26
Editorial commentaries
Author Information

aDivision of Clinical Pathophysiology, Switzerland

bService de psychiatrie de liasion, University Hospital, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland

Correspondence to Professor Bernard Waeber, MD, Division of Clinical Pathophysiology, University Hospital, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland

Article Outline

In this issue Eze-Nliam et al. [1] examined in a systematic review of the literature, the possible association between hypertension, depression or symptoms of depression, and adherence to antihypertensive medications. This is an important issue considering the fact that uncontrolled hypertension represents a leading risk factor for cardiovascular and renal complications. Furthermore, depressive disorders, which have a high prevalence in the population [2], are associated by increased cardiovascular morbidity and mortality, both in individuals with and without history of previous cardiovascular events [3–7].

A number of studies have prospectively attempted to assess whether psychological factors are linked with the development of hypertension. Some [8–10], albeit not all, support this view [11–14]. In a prospective, long-term follow-up population study, even an inverse relationship was described with the presence of depression predicting lower subsequent blood pressure (BP) [15]. Overall, however, a positive association seems to exist, as indicated by a review of prospective cohort studies [16]. The relative prevalence of depressive individuals in the normotensive population and the hypertensive population is another controversial issue. According to some investigators, depression and depressive symptoms occur more frequently in individuals with high BP than in those with normal BP [17,18]; again, such differences have not been found in all studies [14,19–21]. Within the depressed population, elderly depressive individuals might have lower BP than nondepressed, independent of potential confounders, including the use of antihypertensive or psychotropic medications [22]. A recent study has also evidenced lower BP levels in individuals with depressive disorders compared with healthy controls [23].

The fact that it remains difficult to draw firm conclusions regarding the relationship between depressive disorders and BP is not really surprising. The lack of consensus among studies may be explained to a large extent by differences in terms of study protocol, assessment of psychological variables, methods used to measure BP and, of course, the criteria defining the depressive and hypertensive conditions. It was therefore adequate that Eze-Nliam et al. chose a meta-analytical approach to explore the impact of depression in patients with high BP on adherence to antihypertensive treatment. Meta-analyses are widely used to increase the power of individual studies [24] and have also become very popular in the field of hypertension. For example as many as 1174 publications are identified, using the Medline database over the period of January 2000–December 2009, when selecting as key words ‘meta-analysis’ and ‘hypertension’. During the same period, 290 meta-analyses were published on patient adherence. According to a meta-analysis of 63 studies carried out in a broad array of medical conditions, it is now established that adherence with therapy influences health outcome, especially in chronic diseases like hypertension [25]. Relevantly in this context, the risk of noncompliance with therapy is increased in depressed patients, as demonstrated in a meta-analysis of 12 studies [26].

As discussed above, Eze-Nliam et al. had a clinically relevant question and, because of the limited number of published trials available, decided to conduct a pooled analysis. Such an analysis requires selection of appropriate trials meeting pre-established criteria. The search of pertinent trials was therefore based on a predefined strategy, using ‘a priori’ eligibility and exclusion criteria. In spite of these efforts, the authors faced a large heterogeneity of studies, which forced them to renounce a pooled analysis, which would have led to potentially misleading, not ubiquitously conclusions [24]. By reporting the results of each study individually, the authors avoided a classical pitfall of meta-analysis. The paper ends with a separate description of trials, which is still very informative because the studies were selected based on strict criteria.

A significant relationship between depression and poor adherence to antihypertensive medications was found in each study, which represents a strong argument for the existence of such a relationship. This has important implications considering the high prevalence of depressive disorders in hypertensive populations (30–40%), as reported in the studies selected by Eze-Nliam et al. Poor compliance with antihypertensive therapy is a major cause of unsatisfactory BP control [27] and there is sound evidence that depressive symptoms have a negative impact on adherence with antihypertensive therapy.

Despite this well known high prevalence of depression and the availability of efficient treatments, depression – as other psychiatric disorders – in the medically ill is still underdiagnosed and undertreated, mainly because of the difficulty of medicine to conceptualize and organize integrated care addressing both somatic and psychiatric comorbidities based on the biopsychosocial model of disease [28]. Interventions based on the concept of integrated care, on the contrary, have been demonstrated to have a positive impact on outcome, such as the patient's perception of physical symptoms, psychiatric disorders, quality of life and healthcare utilization [29]. However, detection and treatment of depression is not only necessary because of the benefice for medical treatment outcome, but because it is a severe disorder [30].

Finally, we would like to address a more general issue, which is illustrated by a sentence in the discussion of this meta-analysis: ‘… addressing depression may be a potential useful intervention in improving medication adherence in a variety of medical conditions’.

From a clinical perspective, ‘addressing depression’ is not a ‘potential useful’, but a necessary intervention. Depression is a frequent psychiatric disorder in the general population and even more prevalent in the medically ill [31]. Depression is not only associated with noncompliance and poor medical outcome, it is in itself a very distressing condition with a heavy burden of suffering for the concerned patient and his significant others and untreated it may have severe somatic and psychiatric consequences including death by suicide.

On the contrary, depression can be easily prevented by integrated care combining somatic and psychiatric treatment [31]. How therefore would practitioners, internists and cardiologists react if we stated: ‘… addressing hypertension in the depressed psychiatric patient may be a potential useful intervention in improving adherence to antidepressant medication’?

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1 Eze-Nliam CM, Throms BD, Lima BB, Smith CG, Ziegelstein RC. The association of depression with adherence to antihypertensive medications: a systemic review. J Hypertens 2010: 28:1785–1795.
2 Scott KM, Von Korff M, Alonso J, Angermeyer M, Bromet EJ, Bruffaerts R, et al. Age patterns in the prevalence of DSM-IV depressive/anxiety disorders with and without physical co-morbidity. Psychol Med 2008; 38:1659–1669.
3 Gump BB, Matthews KA, Eberly LE, Chang YF. Depressive symptoms and mortality in men: results from the Multiple Risk Factor Intervention Trial. Stroke 2005; 36:98–102.
4 Barefoot JC, Schroll M. Symptoms of depression, acute myocardial infarction, and total mortality in a community sample. Circulation 1996; 93:1976–1980.
5 Pulska T, Pahkala K, Laippala P, Kivela SL. Follow up study of longstanding depression as predictor of mortality in elderly people living in the community. BMJ 1999; 318:432–433.
6 Luukinen H, Laippala P, Huikuri HV. Depressive symptoms and the risk of sudden cardiac death among the elderly. Eur Heart J 2003; 24:2021–2026.
7 Mallik S, Spertus JA, Reid KJ, Krumholz HM, Rumsfeld JS, Weintraub WS, et al. Depressive symptoms after acute myocardial infarction: evidence for highest rates in younger women. Arch Intern Med 2006; 166:876–883.
8 Heine B. Psychogenesis of hypertension. Proc R Soc Med 1970; 63:1267–1270.
9 Jonas BS, Franks P, Ingram DD. Are symptoms of anxiety and depression risk factors for hypertension? Longitudinal evidence from the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study. Arch Fam Med 1997; 6:43–49.
10 Kahn HA, Medalie JH, Neufeld HN, Riss E, Goldbourt U. The incidence of hypertension and associated factors: the Israel ischemic heart disease study. Am Heart J 1972; 84:171–182.
11 Raikkonen K, Matthews KA, Kuller LH. Trajectory of psychological risk and incident hypertension in middle-aged women. Hypertension 2001; 38:798–802.
12 Paffenbarger RS Jr, Thorne MC, Wing AL. Chronic disease in former college students. VIII: characteristics in youth predisposing to hypertension in later years. Am J Epidemiol 1968; 88:25–32.
13 Vogt T, Pope C, Mullooly J, Hollis J. Mental health status as a predictor of morbidity and mortality: a 15-year follow-up of members of a health maintenance organization. Am J Public Health 1994; 84:227–231.
14 Goldberg EL, Comstock GW, Graves CG. Psychosocial factors and blood pressure. Psychol Med 1980; 10:243–255.
15 Hildrum B, Mykletun A, Holmen J, Dahl AA. Effect of anxiety and depression on blood pressure: 11-year longitudinal population study. Br J Psychiatry 2008; 193:108–113.
16 Rutledge T, Hogan BE. A quantitative review of prospective evidence linking psychological factors with hypertension development. Psychosom Med 2002; 64:758–766.
17 Rabkin JG, Charles E, Kass F. Hypertension DSM-III depression in psychiatric outpatients. Am J Psychiatry 1983; 140:1072–1074.
18 Wells KB, Golding JM, Burnam MA. Affective, substance use, and anxiety disorders in persons with arthritis, diabetes, heart disease, high blood pressure, or chronic lung conditions. Gen Hosp Psychiatry 1989; 11:320–327.
19 Wheatley D, Balter M, Levine J, Lipman R, Bauer ML, Bonato R. Psychiatric aspects of hypertension. Br J Psychiatry 1975; 127:327–336.
20 Friedman MJ, Bennet PL. Depression and hypertension. Psychosom Med 1977; 39:134–142.
21 Paterniti S, Alperovitch A, Ducimetiere P, Dealberto MJ, Lepine JP, Bisserbe JC. Anxiety but not depression is associated with elevated blood pressure in a community group of French elderly. Psychosom Med 1999; 61:77–83.
22 Lenoir H, Lacombe JM, Dufouil C, Ducimetiere P, Hanon O, Ritchie K, et al. Relationship between blood pressure and depression in the elderly: The Three-City Study. J Hypertens 2008; 26:1765–1772.
23 Licht CM, de Geus EJ, Seldenrijk A, van Hout HP, Zitman FG, van Dyck R, et al. Depression is associated with decreased blood pressure, but antidepressant use increases the risk for hypertension. Hypertension 2009; 53:631–638.
24 Swales JD. Meta-analysis as a guide to clinical practice. J Hypertens 1993; 11:S59–S63.
25 DiMatteo MR, Giordani PJ, Lepper HS, Croghan TW. Patient adherence and medical treatment outcomes: a meta-analysis. Med Care 2002; 40:794–811.
26 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 2000; 160:2101–2107.
27 Waeber B, Burnier M, Brunner HR. Compliance with antihypertensive therapy. Clin Exp Hypertens 1999; 21:973–985.
28 Mayou R, Hawton K. Psychiatric disorder in the general hospital. Br J Psychiatry 1986; 149:172–190.
29 Stiefel F, Zdrojewski C, Bel Hadj F, Boffa D, Dorogi Y, So A, et al. Effects of a multifaceted psychiatric intervention targeted for the complex medically ill: a randomized controlled trial. Psychother Psychosom 2008; 77:247–256.
30 Evans DL, Charney DS, Lewis L, Golden RN, Gorman JM, Krishnan KR, et al. Mood disorders in the medically ill: scientific review and recommendations. Biol Psychiatry 2005; 58:175–189.
31 de Jonge P, Hadj FB, Boffa D, Zdrojewski C, Dorogi Y, So A, et al. Prevention of major depression in complex medically ill patients: preliminary results from a randomized, controlled trial. Psychosomatics 2009; 50:227–233.
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