Certain Antihypertensives Linked to Mood Disorders

October 26, 2016

A new study has suggested that different antihypertensive drug classes may have different effects on mood.

The observational study in 144,000 patients is published in the November issue of Hypertension.

"This is the first study to look at the issue of antihypertensive medication and depression in such a large group," senior author, Sandosh Padmanabhan, MD, Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom, commented to Medscape Medical News.

"Mental health is under-recognized in hypertension clinical practice, and the possible impact of antihypertensive drugs on mental health is an area that physicians should be aware of and consider if the treatment of high blood pressure is having a negative impact on their patient's mental health.

"While we can't really make any definite recommendations on this observational data and doctors need to follow guidelines on the prescription of antihypertensives," he added, "they perhaps could consider these results if mood deteriorates and think about switching to an ACE [angiotensin-converting enzyme] inhibitor or ARB [angiotensin receptor blocker] rather than a β-blocker or calcium antagonist in those circumstances."

Dr Padmanabhan noted that a genome-wide association study published in The Lancet last year found that the calcium channel gene was associated with bipolar disorder. "Following this, there was a small US study suggesting calcium blockers may be linked to a small improvement in bipolar disorder."

To investigate more about possible effects on mood disorders of various antihypertensive agents, the authors conducted the current study using a large hospital database of 525,000 patients.

From these, they identified 144,000 patients who had hypertension and were receiving monotherapy with one of the four major antihypertensive classes or no therapy. They assessed follow-up rates of admission to any hospital in Scotland for major depressive disorder or bipolar disorders during a 5-year period.

"We found that patients taking β-blockers and calcium blockers had higher rate of hospitalization for major depression and those on ACE inhibitors or ARBs had lower rates," Dr Padmanabhan said. "Patients taking no antihypertensive medication — the control group — were in the middle, so ACE inhibitors and ARBs looked better than no treatment in terms of major depression and β-blockers and calcium blockers looked worse."

The median time to hospital admission with a mood disorder was 847 days for the 299 admissions.

Patients receiving ACE inhibitors or ARBs had the lowest risk for mood disorder admissions, and compared with this group, those receiving β-blockers (hazard ratio [HR], 2.11; P = .02) and calcium antagonists (HR, 2.28; P = .02) showed higher risk, and those receiving no antihypertensives (HR, 1.63; P = .08) and thiazide diuretics (HR, 1.56; P = .32) showed no significant difference.

Results were corrected for comorbidity scores based on previous hospital admissions and prescription data, but no information was available on socioeconomic status or clinical data. Patients with a previous psychiatric hospital admission were excluded.

"We know β-blockers can be associated with depression, so this validates our results somewhat. There is also anecdotal data suggesting that ACE inhibitors may protect against depression, but the calcium blocker result was surprising," Dr Padmanabhan commented.

"Hospitalization for depression is just the tip of the iceberg," he added. "It is a major event and of course the majority of people with depression are not hospitalized, but this endpoint is a certain diagnosis, whereas trying to measure minor depression is much more difficult."

The next step will be to assess whether the various medications lead to changes in mood and quality of life, he concluded.

"We would like to do more analyses of randomized trial data where depression may have been an endpoint to look at this further in a systematic review."

The Medical Research Council, British Heart Foundation, a Lister Institute Prize Fellowship, and the Scottish Ecosystem for Precision Medicine supported the study. The authors have disclosed no relevant financial relationships.

Hypertension. Published online October 10, 2016. Full text

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