Antidepressants May Help Improve Heart Health

When people think about the secondary effects of drugs, they naturally focus on adverse reactions like nausea or rashes. Sometimes, though, drugs can provide some extra benefits that may make them even more attractive as therapies.

In the case of the antidepressant paroxetine, sometimes sold under the brand name Paxil, new research suggests that it may help reverse heart failure.

These studies have been carried out only in animal models, but lead author Walter Koch, Ph.D., the William Wikoff Smith Endowed Chair in Cardiovascular Medicine at Temple University, believes the discovery heralds an intriguing new therapeutic path for a disease now considered irreversible.

“Heart failure is a pretty serious and terminal condition,” he noted in an interview with Psychiatric News. “And right now we don’t have a lot of treatment options; beta blockers have gotten some buzz, but they pose their own risks as they slow your heart rate down.”

“We still have a long way to go before we can have a therapy ready,” Koch continued. “But we have a molecule to serve as a template, and we have a target, and that’s a great start.”

Paroxetine’s heart benefits stem from its action on an enzyme called GRK2, so it’s separate from the drug’s antidepressant properties. GRK2 levels are elevated following a heart attack, and the enzyme tries to repair the damage caused. Unfortunately, the efforts result in heart tissue that is larger, thicker, and less efficient at pumping blood; over time, these problems progress until the heart eventually fails.

In their study, published in Science Translation Medicine, Koch and his team tested paroxetine against both another antidepressant (fluoxetine) and the beta blocker metroprolol in mice that had developed heart failure following a heart attack.

After four weeks of paroxetine therapy, the mice’s hearts returned to a more normal size and showed better pumping ability. Fluoxetine, which is a similar class of drug but has a different chemical structure, had no effect, confirming that the results were not related to actions against the serotonin receptor.

In another promising sign, paroxetine also proved more adept at restoring heart function than did metroprolol.

These mice were given doses that were about five to 10 times higher than a person would take for depression, so it may be difficult to extrapolate what sort of benefits someone with heart failure taking paroxetine for comorbid depression would experience.

Koch, though, thinks it is something clinicians should consider. “I’ve received numerous emails from patients with depression and heart problems asking whether they should tell their doctor they want to switch to Paxil. I personally think, why not at least give it a try?”

Given the large numbers of people with both illnesses, supporting data may already be out there, and Koch is gathering information from antidepressant clinical studies to see if there might be ways to analyze how different drug classes might affect heart health.

Some evidence in humans was scheduled to be presented at the American College of Cardiology Scientific Sessions in San Diego in March. Researchers from the Intermountain Medical Center Heart Institute in Utah found that in patients with moderate to severe depression, antidepressant therapy was more effective at reducing the risk of heart disease than statins were.

This analysis, which looked at the records of more than 26,000 patients, found that antidepressant medications reduced the risk of heart disease, stroke, or death by about 53 percent compared with patients taking no medications; this reduction was not as strong in patients taking statins or—somewhat surprisingly—statins and antidepressants.

“We thought we’d see an additive effect,” noted lead author Heidi May, Ph.D. “But we found that in the more depressed people, the antidepressant really was what made the biggest difference.”

May thinks that improvements in mood contributed a lot to the improved heart health, but she did not rule out that there might be biological effects from these medications, and more work into the relationship between depression and cardiovascular health is worthwhile.

Koch’s work was supported by grants from the National Heart, Lung, and Blood Institute and a Brody Family Medical Trust Fund Fellowship. ■