Some Antihypertensives May Be Linked to Mood Disorders

• Patients taking beta blockers and calcium channel antagonists had 2x the risk of being hospitalized with a mood disorder.
• Patients taking angiotensin converting enzymes for hypertension had a lower risk of developing a severe mood disorder.
• Patients taking a diuretic had a similar mood disorder risk as did control participants.

A variety of antihypertensive drugs were found to influence rates of hospitalization for mood disorders, according to a large review study published recently in Hypertension, a journal of the American Heart Association. Patients taking beta blockers and calcium channel blockers had significantly higher rates of hospitalization for disorders such as depression and anxiety. Patients taking angiotensin converting enzyme (ACE) antihypertensives appeared to be a lower risk of hospitalization for a major mood disorder. Diuretics were not linked with any change is hospitalization risk vs. controls.

Given the study structure, there is no evidence of a causal relationship between the antihypertensives and hospitalization risk but the relationship is clinically relevant and should both be borne in mind by clinicians and is a basis for further research.

“Overall, our exploratory findings suggest possible differential effects of antihypertensive medications on mood that merits further study: calcium antagonists and beta blockers may be associated with increased risk, whereas angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be associated with a decreased risk of mood disorders,” the authors noted.

The Data

The researchers endeavored to determine whether antihypertensive drugs have an impact on mood disorders. They analyzed the records of 525,046 patients who were receiving antihypertensive monotherapy with one of four different classes of antihypertensive agents. The researchers identified 144,066 eligible patients who fulfilled the inclusion criteria. Those criteria were age 40 to 80 years old at time of antihypertensive prescription and medication exposure >90 days.

“The burden of comorbidity assessed by Charlson and Elixhauser scores showed an independent linear association with mood disorder diagnosis. The median time to hospital admission with mood disorder was 847 days for the 299 admissions (641,685 person-years of follow-up),” the authors noted in the abstract.

Patients taking ACE inhibitors or angiotensin receptor blockers had the lowest risk of being admitted to the hospital for a mood disorder versus patients taking a beta blocker (hazard ratio=2.11; [95% confidence interval, 1.12–3.98]; P=0.02) or a calcium channel blocker. (2.28 [95% confidence interval, 1.13–4.58]; P=0.02) who showed higher risk. Patients not taking an antihypertensives (1.63 [95% confidence interval, 0.94–2.82]; P=0.08) and those taking a thiazide diuretic (1.56 [95% confidence interval, 0.65–3.73]; P=0.32) showed no significant difference versus the control group.

Patients taking antihypertensive were compared with more than 111,000 controls who were not receiving any form of treatment for either hypertension or depression, over a 5-year period. The numbers admitted to a hospital for severe mood disorders, such as depression of bipolar disorder, were monitored.

Previous Investigation

A systematic review published in the Journal of Clinical Psychiatry in 2013 found that the calcium channel blocker lamotrigine was associated with a significant reduction in symptoms related to bipolar disorder.

In this study, data were selected from 29 randomized controlled trials, 6 open label trials, 10 retrospective case studies, and 4 case series. The authors extracted data from trials of both monotherapy and medication augmentation when lamotrigine was used in the treatment of bipolar disorder.

“Lamotrigine is recommended in bipolar maintenance when depression is prominent. It also has a role in treating acute bipolar depression and unipolar depression, though the latter warrants more research. Data are too limited in other psychiatric disorders to recommend its use at this time,” the authors concluded.

This trial and others like it served as the impetus for the trial published recently in Hypertension.