Beta-blockers appear to be more likely to trigger or aggravate depressive symptoms than calcium antagonists, according to an article in the May-June issue of Psychosomatic Medicine.

Because the prevalence of depression may be found in as many as one third of patients with heart disease and the mood disorder is a strong risk factor for cardiovascular disease, American researchers designed the Study of Antihypertensive Drugs and Depressive Symptoms (SADD-Sx) as a substudy of the International Verapamil SR-Trandolapril study, or INVEST trial.

For the substudy on mood over the one-year course of the antihypertension trial, researchers followed 2,317 of the more than 22,500 patients randomized to one of two regimens: a sustained-release form of verapamil or to atenolol and diuretics. Both groups could receive an angiotensin-converting enzyme inhibitor if needed.

Nearly half the patients in the substudy, known as the Study of Antihypertensive Drugs and Depressive Symptoms, or SADD-Sx, were women; most were older than 65 and were white. Researchers compared self-reported symptoms of depression after one year of treatment and also sought to determine factors that would predict depressive symptoms. Study participants completed a standardized questionnaire known as the Center for Epidemiologic Studies-Depression, or CES-D, scale.

On average, after one year of treatment the mood of patients on verapamil SR improved, but mood did not improve among patients on atenolol: 17 percent of patients taking verapamil SR reported being highly depressed compared with 22 percent of those taking atenolol.

After controlling for prior history of depression and for heart disease, a year later patients on atenolol still describe more depressive symptoms compared with patients on verapamil.

Past studies, which have had conflicting results, led some practitioners to recommend beta-blockers not be used to treat hypertension among older patients because of possible depression-related side effects. Other research has linked calcium antagonists to increased risk of suicide among patients prone to depression.

The advantage of the SADD-Sx study, the authors said, was the number of patients enrolled in the randomized, controlled trial - a larger number than any previous study - and its design, a head-to-head comparison of both treatment strategies. Researchers also accounted for biases that plagued past studies.

Still, future research should involve a more rigorous measure of depression, the authors concluded, writing “It may be that these patients say they feel poorer, which is important, but whether there end up being differences in the number of patients being diagnosed with a major depressive disorder, that’s a different issue. It’s a clinically important issue. It has public policy considerations. It has patient care-related issues associated with it. So people who make the decisions about prescribing have to weigh that.”