Can blood pressure-lowering drugs be repurposed as treatments for depression?

Antihypertensive drugs do not appear to be useful for treating major depressive disorder (MDD), although angiotensin antagonists (AAs) may be protective against bipolar disorder, as shown in a recent study.

The analysis involved two cohorts of patients treated with antihypertensives: one included patients with no previous history of mood disorder (n=538,730), while the other cohort did (n=262,278). These cohorts were matched to untreated comparators according to age, sex and area deprivation.

Patients on thiazide diuretics, beta blockers and other patterns of antihypertensive treatments were more frequently female, while those treated with AAs, calcium channel blockers (CCBs) and polytherapy were more commonly male.

In the group without a history of mood disorder, antihypertensives conferred an increased risk of new-onset MDD. Specifically, AA monotherapy conferred a 17-percent risk increase (hazard ratio [HR], 1.17, 95 percent confidence interval [CI], 1.04–1.31). The association with beta blockers was stronger at 2.68 (95 percent CI, 2.45–2.92), possibly indicating pre-existing anxiety.

Meanwhile, certain classes of antihypertensives exerted a protective effect on bipolar disorder, especially AAs (HR, 0.46, 95 percent CI, 0.30–0.70).

In the group with a history of mood disorders, all classes of antihypertensive drugs were associated with a heightened risk of future episodes of MDD.

According to the researchers, the finding that AAs may offer some protection against bipolar disorder may be attributed to selection biases and warrants further investigation.