Antihypertensive medications as repurposed treatments for mood disorders: analysis of linked healthcare data for 1.8 million patients

Background: Recent work suggests that antihypertensive medications may be useful as repurposed treatments for mood disorders. Using large-scale linked healthcare data we investigated whether certain classes of antihypertensive, such as angiotensin antagonists and calcium channel blockers, may have potential as repurposed treatments for Major Depressive Disorder (MDD) and bipolar disorder. Method: Two cohorts of patients treated with antihypertensives were identified from Scottish prescribing (2009-2016) and hospital admission (1981-2016) records. Eligibility for cohort membership was determined by receipt of a minimum of four prescriptions for antihypertensives within a 12-month window. One treatment cohort (n=538,730) included patients with no previous history of mood disorder, whereas the other (n=262,278) included those who did. Both cohorts were matched by age, sex and area deprivation to untreated comparators. Associations between antihypertensive treatment and new-onset MDD or bipolar episodes were investigated using Cox regression. Results: For patients without a history of mood disorder, antihypertensives were associated with increased risk of new-onset MDD. This was most marked for beta-blockers, with a hazard ratio (HR) of 2.68 (95%CI 2.45-2.92). For angiotensin antagonist monotherapy, the HR for new-onset MDD was 1.17 (95%CI 1.04-1.31). Some classes of antihypertensive were associated with protection against bipolar disorder, particularly angiotensin antagonists (HR 0.46; 95%CI 0.30-0.70). For patients with a past history of mood disorders, all classes of antihypertensives were associated with increased risk of future episodes of MDD. Conclusions: There was no evidence that antihypertensive medications prevented new episodes of MDD but angiotensin antagonists may represent a novel treatment avenue for bipolar disorder.