Review of: Agustini B et al, J Hum Hypertens 2020;34(11):787–794

Study Type: Cross-sectional

Antihypertensives are among the world’s most widely prescribed drugs, but many of them impact pathways associated with depression. Beta blockers have long been believed to cause depression, but most of the studies suggesting this were carried out decades ago and their findings have been inconsistent. Other classes, like angiotensin-receptor blockers, are associated with lower rates of depression, albeit with weaker evidence.

In this multinational study, researchers examined mood outcomes in 14,195 hypertensive adults over age 65 who did not have heart disease. Depressive symptoms were measured with the self-reported Centre for Epidemiological Studies-Depression (CESD-10) scale. Each class of antihypertensive drugs was tested against the other classes and against a group of unmedicated hypertensive patients to see whether any class was associated with an increased risk of clinically significant depressive symptoms.

Patients who took beta blockers were more likely to meet or exceed the clinical cutoff score of 8 on the CESD-10 scale, a sign of clinically significant depressive symptoms, than those who took other antihypertensive drugs. Numerically, 13.4% of patients who used beta blockers showed clinical elevations in depression, whereas between 10.2% and 10.5% of patients who used other antihypertensives showed this elevation. Logistic regression analysis showed that this difference was indeed significant, even when controlling for numerous factors that included gender, age, and smoking history. Other classes of antihypertensives, including angiotensin-receptor blockers, angiotensin-converting enzyme inhibitors, and calcium-channel blockers, were not associated with depression.

The researchers also compared the beta blockers based on their selectivity for the β-receptor and their lipophilic properties. Lipophilic medications are more likely to cross the blood-brain barrier, and the more lipophilic beta blockers like propranolol and metoprolol were associated with a higher risk of depression than hydrophilic ones like atenolol. Meanwhile, the more selective beta blockers were less depressogenic, which weakens the argument that blockade at this receptor plays a causative role in depression.

TCPR’s Take
The fact that beta blockers were associated with depression while other antihypertensives were not gives us pause, but the risk here is very small (3%). If beta blockers must be used in depressed patients with hypertension, stick with atenolol. Whether this risk translates to the psychiatric use of propranolol—which generally involves lower doses and normotensive patients—remains unanswered.