Treating hypertension without the fear of increasing risk of depression

29 Oct 2020

Commonly observed in patients with hypertension, cardiovascular and cerebrovascular diseases, major depression and depressive symptoms are associated with increased mortality, morbidity, poorer quality of life, higher health service utilization, and health care cost.1 While various antihypertensive and cardiovascular drugs were implicated as potential risk factors for depression, it is unclear to what extent a previous history of depression and possible psychological side effects could contribute to these implications.2 This article summarizes recent studies that have investigated the relationship between mono and multi antihypertensive drug use and the symptoms of depression.

Hypertension is a major cardiovascular risk factor for the development of myocardial infarction and stroke that affects up to 30-40% of the general population.1,3 Among these patients, the prevalence of depression is approximately 30% which is higher than the general population.1 As the overlap of cardiovascular disease and depression is common and is often associated with worse outcomes when compared to single condition, the use of antihypertensive and cardiovascular drugs, which were implicated as potential risk factors for depression in numerous studies over the past decades, has become a concern in the clinical setting.2 However, as the relationship between multi antihypertensive drug use and the symptoms of depression remains unclear, further studies would be required to better guide the clinical treatment decisions in patients at risk of hypertension, cardiovascular and cerebrovascular diseases.

In the R-WAS study conducted among the Danish population, 5.4 million Danes from the Danish population-based registers from January 2005 to December 2015 were recruited.1 The 41 most used individual antihypertensive drugs were compared against diuretics for the association with incidents of depression.1 Interestingly, the continuous use of angiotensin agents, calcium antagonists and β-blockers was associated with a decrease in depression incidence (p<0.001), whereas the use of diuretics was not associated with such change.1 In particular, a decreased risk of depression was significantly associated with angiotensin agents of enalapril and ramipril, calcium antagonists of amlodipine, verapamil and verapamil combinations, β-blockers of propranolol, atenolol, bisoprolol, and carvedilol.1 As no antihypertensive drugs have been found to increase the risk of depression, antihypertensive drugs, especially the aforementioned 9 drugs, should be prescribed to patients who are at increased risk of developing depression to protect them from potential hypertension, cardiovascular and cerebrovascular diseases.1

A similar result was observed in the HUNT 2 study which was conducted across the Norwegian population where 55,472 Norwegians from 1995 to 1997 were analyzed.2 From the study, the differences in anxiety and depression symptom levels between the untreated and treated hypertensive patients versus the normotensive reference population can be explained by differences in age and gender.2 In fact, neither antihypertensive monotherapy nor any single antihypertensive drug class were associated with symptoms of depression, anxiety, or mixed anxiety and depression.2 However, the receipt of 2 or more antihypertensive drugs was associated with depressive symptoms alone (OR=1.40, 95% CI: 1.03-1.90), suggesting that there may be a positive association between multi-antihypertensive drug use and the symptoms of depression which can be contributed to poor antihypertensive treatment adherence or unfavorable health behaviors in patients with depression which have led to polypharmacy.2

To confirm whether depression is associated with the persistent use of antihypertensive drugs, a retrospective German study analyzed 24,627 adult patients with hypertension and depression who initially received antihypertensive drugs between January 2013 and December 2015.3 After 12 months of follow-up, the rate of persistence with antihypertensive therapy was 64.5% in patients with depression versus 66.9% in those without (p=0.232).3 Furthermore, depression was found to have no significant impact on the discontinuation of treatment in the overall population (HR=1.01, 95% CI: 0.00-1.03) or among different subgroups (HR ranging from 0.93 to 1.03).3 While depression is generally considered a risk factor for insufficient hypertension control, this study showed that there was no significant association between depression and persistence with antihypertensive drugs.3

Where some studies had previously suggested that there may a positive relationship between antihypertensive drugs and depression, the results from 3 large scale studies across Europe have demonstrated that there is no significant association between the use of hypertensive drugs and the risk of depression. In fact, one study suggests that the use of an appropriate antihypertensive drug may even lower the risk of depression.1 As hypertension, cardiovascular and cerebrovascular diseases are associated with an increased risk of depression, and that depression is associated with a plethora of detrimental effects, clinicians should consider the timely use of antihypertensive drugs in patients with increased risk of developing depression without the fear of adverse psychological side effects.

  1. Kessing L et al. Antihypertensive Drugs and Risk of Depression. Hypertension. August 24, 2020;76(4):1263-1279.
  2. Johansen A et al. Anxiety and depression symptoms in arterial hypertension: the influence of antihypertensive treatment. The HUNT study, Norway. European Journal of Epidemiology. January 1, 2020;7(1):63-72.
  3. Louise J, Karel K. Persistence with antihypertensive drugs in patients with depression in Germany. International Journal of Clinical Pharmacology and Therapeutics. April 2018;56(4):162-168.