No Link Between Blood Pressure Medications and Increased Depression Risk

Lars Vedel Kessing, MD

An analysis of data from more than 3.7 million patients is providing clinicians an answer to one of the most common questions associated with antihypertensive therapies: do medications for hypertension increase the risk of depression?

An assessment of patients taking any of the 41 most common high blood pressure medications, including 37 approved by the US Food and Drug Administration, found no link between individual medications and increased risk of depression but revealed 9 medications were linked to a decrease in risk.

"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," said Lars Vedel Kessing, MD, DMSc, the study’s lead investigator and professor of psychiatry at the Psychiatric Center Copenhagen and the University of Copenhagen, in a statement from the American Heart Association.

While associations between cardiovascular disease and risk of depression have been well-documented, little consensus exists over whether antihypertensive therapies increased or decreased that risk. To further investigate these potential associations, Kessing and a team from New Zealand and Australia designed the current study to examine the topic using Danish population-based registers and prescription data.

Using a time period ranging from January 2005-December 2015, investigators identified a cohort of 5.4 million patients for inclusion in their analysis. Investigators included a diagnosis of a depressive disorder identified in the Danish Psychiatric Central Register and a combined end point of either a diagnosis of depressive disorder or use of antidepressants as outcomes of interest for the analysis. For the purpose of analysis, investigates divided antihypertensive mediations into angiotensin agents, calcium channel blockers, β-blockers, and diuretics for each drug included in the analysis.

Of note, patients were excluded if they purchased antidepressants between 1995 and the start of the study period if they had a diagnosis of depression anytime between 1970-1995. Additionally, ICD codes DF32-DF33.31 were used to identify diagnoses of depressive disorders in follow-up analyses.

Of the 5.4 million patients included in the Danish registers, 3,747,190 patients had a documented exposure to an antihypertensive drug during the study period. Of the 3.7 million with exposure to an antihypertensive agent, 1,000,683 received angiotensin agents, 833,281 received calcium antagonists, 777,038 received β-blockers, and 1,136,188 received diuretics.

Upon analysis, none of the 41 medications included in the study were associated with an increased risk of depression. Additionally, 9 of the medications included in the analysis was associated with a decrease in the risk of depression. These 9 medications included enalapril, ramipril, amlodipine, verapamil, verapamil combinations, propranolol, atenolol, bisoprolol, and carvedilol—all of which are approved in the US.

Of note, investigators found there was no effect on the risk of depressive disorders based on use of diuretic therapy.

"It is possible that the mechanism involved in decreasing the risk of depression is the anti-inflammatory effect among these nine medications," added Kessing, in the aforementioned statement. "In the future, it will be important to compare the inflammatory properties of these nine hypertensives that lowered depression risk."

Investigators pointed out several limitations within their study. These limitations included relying on a clinical diagnosis of depression, not being a controlled clinical trial, and the risk of depression was assessed for each medication individually, and reliance on registry-based data.

This study, “Antihypertensive Drugs and Risk of Depression: A Nationwide Population-Based Study,” was published in Hypertension.