Copenhagen, Denmark—Depression is common among patients with hypertension, heart disease, and stroke, raising questions about whether certain medications could exacerbate the condition.

A new Danish study in the journal Hypertension demonstrates, however, that none of the 41 most common high blood pressure medications increased the risk of depression.

In fact, according to University of Copenhagen–led researchers, nine of the medications actually appear to decrease depression risk.

The study is thought to be the first to systematically investigate whether individual blood pressure medications might influence the risk of developing depression.

“It was highly surprising that none of the 41 most-used anti-hypertensives was associated with increased risk of developing depression and that some within each of the three classes of anti-hypertensives showed protective effects against depression,” explained lead author Lars Vedel Kessing, MD, MSc, professor of psychiatry at the Psychiatric Center Copenhagen and the University of Copenhagen, Faculty of Health and Medical Sciences in Denmark.

“Hypertension, cardiovascular diseases, and cerebrovascular diseases are associated with an increased risk of depression, but it remains unclear whether treatment with antihypertensive agents decreases or increases this risk. The effects of individual drugs are also unknown,” the authors write.

The study team used Danish population-based registers to systematically investigate whether the 41 most-used individual antihypertensive drugs affected risk of incident depression. For comparison, diuretic use also was analyzed.

The study began in January 2005 with more than 3.7 million adults who took any of the 41 most-commonly prescribed high blood pressure medications, and who were followed until December 2015. Researchers focused on two different outcome measures: (1) a diagnosis of depressive disorder at a psychiatric hospital as an inpatient or outpatient and (2) a combined measure of a diagnosis of depression or use of antidepressants.

Results indicate that continued use of classes of angiotensin agents, calcium antagonists, and beta-blockers was associated with significantly decreased rates of depression, but diuretic use was not.

Researchers report that Individual drugs associated with decreased depression included:
• Two of 16 angiotensin agents: enalapril and ramipril
• Three of 10 calcium antagonists: amlodipine, verapamil, and verapamil combinations 
• Four of 15 β-blockers: propranolol, atenolol, bisoprolol, and carvedilol 

The study determined that no drug was associated with an increased risk of depression 

“In conclusion, real-life population-based data suggest a positive effect of continued use of 9 individual antihypertensive agents,” the authors wrote. “This evidence should be used in guiding prescriptions for patients at risk of developing depression including those with prior depression or anxiety and patients with a family history of depression.”
Most blood pressure medications—37 of the 41—are approved for use in the United States by the FDA. 

“It is possible that the mechanism involved in decreasing the risk of depression is the anti-inflammatory effect among these nine medications,” Dr. Kessing suggested. “In the future, it will be important to compare the inflammatory properties of these nine hypertensives that lowered depression risk.” (Low-grade inflammation is common in high blood pressure and heart disease, as well as in depression.)

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