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A short list of antihypertensive medications were associated with decreased risk of depression in a population-based study.

Significantly lower risk of depression incidence was seen in Danish population-based registries for the following:

• The ACE inhibitors enalapril and ramipril
• Calcium channel blockers amlodipine, verapamil, and verapamil combinations
• The beta-blockers propranolol, atenolol, bisoprolol, and carvedilol

Diuretics had no link to depression risk, reported a group led by Lars Vedel Kessing, MD, DMSc, of the University of Copenhagen, in the .

People without any antihypertensive prescriptions (presumably those without high blood pressure [BP]) had the lowest depression risk of all, "reflecting that patients with hypertension and cardiovascular and cerebrovascular diseases are at increased risk of developing depression," the authors noted.

None of the 41 BP-lowering drugs investigated were associated with an increased risk of depression.

Kessing and colleagues recommended clinicians "use one of the identified individual nine drugs depending on the somatic indication, especially in patients at increased risk of developing depression, including patients with prior depression or anxiety and patients with a family history of depression."

Study results confirmed the hypothesis that angiotensin agents and calcium antagonists were associated with less depression. It was a surprise that this applied to beta-blockers as well, the group noted.

The nine antihypertensives identified by the investigators vary widely in their pharmacological characteristics, such as lipid solubility.

"It is possible that these nine drugs possess other off-target receptor or anti-inflammatory properties that they do not share with the remaining 32 antihypertensives, but we are not aware of studies specifically investigating potential anti-inflammatory effects of these nine drugs," according to the authors.

Their study sought out cases of incident depression from 2005 to 2015 among 5.4 million individuals in Denmark, nearly 3.75 million of whom were exposed to antihypertensives during that period.

Incident depression was defined either as a diagnosis of depressive disorder at a psychiatric hospital (inpatient or outpatient) or the broader outcome of depression diagnosis or use of antidepressants.

Diagnoses from primary care were not included in the registries used, and it was unclear if patients actually took the medications they were prescribed, Kessing's team cautioned.

Residual confounding was also possible despite multivariable adjustment.

"The findings should be replicated in well-designed larger randomized controlled trials and in other population-based registers using similar designs and statistical analyses to address selection and confounding factors," the investigators said.

They added that future research may address whether depression can be linked to polypharmacy or any specific sequencing of antihypertensive medications.

Patients with depression have been shown to have .

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