Beta blockers, depression: breaking the link.

Beta blockers, a class of drugs frequently prescribed for high blood pressure, have been linked with depression in the past. But a new epidemiologic study may force doctors to reexamine the evidence linking beta blockers with the blues.

In general, physicians hail these drugs as a crucial weapon in the fight against hypertension, migraine headaches, certain forms of violent behavior and even stage fright. Yet during the 1980s, several scientific reports suggested beta blockers might cause clinical depression, a very serious disorder characterized by hopelessness and suicidal tendencies.

Now, Roselie A. Bright of the Food and Drug Administration in Rockville, Md., and Daniel E. Everitt of the Presbyterian Medical Center in Philadelphia offer evidence that may clear the shadow of depression from the beta blocker story.

Using Medicaid reimbursement claims filed in New Jersey from July 1980 to December 1983, the team identified 4,302 people who had at least one sign of serious depression, such as the use of antidepressant drugs or electroconvulsive shock therapy. The researchers then matched these individuals with 8,604 controls whose claim forms showed no signs of depression.

When the team went back and studied the claim forms for prescription drugs, they discovered an association between beta blockers and depression. Depressed individuals were 1.45 times more likely than controls to have taken beta blockers for at least a year before their mood disorder surfaced.

That seemed to lend credence to the earlier reports. But when the researchers added so-called confounding factors to their statistical analysis, the link between depression and beta blockers dissolved. The crucial factors were frequent use of prescription drugs, frequent trips to the doctor's office and repeated use of anti-anxiety drugs called benzodiazepines, the team reports in the April 1 JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION.

These data suggest that a statistical fluke might explain the seeming connection between beta blockers and depression. Everitt notes that a 1986 study he coauthored indicated an increased risk of depression among people taking beta blockers, but he now says that study didn't look hard enough at the confounding factors that can skew a statistical analysis.

Beta blockers don't appear to cause depression, at least in most people, he concludes. Rather, people who take beta blockers also appear more likely to get prescriptions filled for a variety of mood-altering drugs, including sedatives like the benzodiazepines, Everitt notes.

It is still possible that beta blockers cause depression in some cases, cautions psychiatrist Stuart C. Yudofsky of Baylor College of Medicine in Houston. Beta blockers are known to affect serotonin, a brain chemical that may be associated with depression, he says.

Everitt agrees. In the recent study, he and Bright looked for a link between long-term beta blocker use and depression. (The patients had taken beta blockers repeatedly during the year prior to their depressive episode.) However, he says, the study did not address the concern that some people may suffer depression right after taking a beta blocker drug. Until future research clears the question about short-term usage, Everitt advises physicians to consider switching patients to a different drug if they experience a first-time depressive episode shortly after starting treatment with beta blockers.

Yudofsky, who wrote an editorial accompanying the report, adds that most cases of depression among beta blocker users can be handled with traditional approaches such as antidepressants and psychotherapy.