Scientists claim that a side effect of the drug, paroxetine, is thought to be responsible for overcoming symptoms of heart failure, which occurs when the organ is too weak to pump sufficient blood around the body.
"This may open the way for a new class of therapies for a disease for which we lack effective interventions," said US lead researcher Dr Walter Koch, from Temple University Health System in Philadelphia.
Previous research shows that heart failure in animals can be reversed by using genetic engineering to lower levels of the enzyme GRK2 (G protein-coupled receptor kinase-2).
In a new study, mice were given induced heart attacks which caused their hearts to fail over a period of two weeks.
When the heart failure was well developed, they were treated with paroxetine, fluoxetine (Prozac) - another widely used antidepressant - or an inactive dummy drug.
Only paroxetine restored heart function to near-normal levels, proving that its effect was unrelated to antidepressant properties shared with fluoxetine.
Paroxetine was also tested against the beta-blocker drug metoprolol, a standard treatment for heart failure.
"The beneficial effects of paroxetine were far greater than beta-blocker therapy," Dr Koch said.
GRK2 appears to be important for the unhealthy "remodeling" of a heart responding to damage caused by a heart attack. The maladaptive adjustments cause the heart to grow larger, weaker and less efficient.
One measure of heart efficiency, ejection fraction, shows how much oxygenated blood is pumped out by the heart's left ventricle chamber with each beat.
In the mice, ejection fraction fell from a pre-heart attack level of 70% to 35%.
After paroxetine treatment, it rose back up by roughly 30%.
The drug also caused pressure in the heart before each beat to return to normal and reduced heart weight and length, both of which increase in heart failure.
Dilation of the heart caused by patches of scar tissue was also greatly reduced when GRK2 activity was suppressed.
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Dr Koch said: "We believe this validates that GRK2 is a viable therapeutic target for heart failure and paroxetine is the starting point for a novel small molecule.
"We're looking at a totally new class of drugs for heart failure."
The therapeutic effect of paroxetine seemed to be long lasting, which was demonstrated when one one group of mice was treated for four weeks and then left untreated for two.
Co-author Dr Sarah Schumacher, from the Temple Centre for Translational Medicine, said: "The improvement was maintained. We think we reset the system. We stopped the vicious cycle of heart failure and restored basic function."
The research was reported in the journal Science Translational Medicine.
At present, symptoms of heart failure can be treated with drugs such as beta-blockers and angiotensin-converting enzyme inhibitors, but only a heart transplant can reverse the condition.
About half of people diagnosed with heart failure die within five years.
The concentrations of paroxetine used in the study were equivalent to those found in the blood of people treated with the drug for depression.
Dr Koch cautioned there could be no guarantee the effects in mice would also be seen in humans, but suggested that "at a minimum" physicians could consider prescribing paroxetine to heart failure patients who also suffered from depression.
"If you have to give these patients antidepressants, why not give them this one, which may improve heart function?" he said.
The scientists are now working on producing a derivative of paroxetine that can shut off GRK2 at lower doses without the antidepressant effect.
Dr Shannon Amoils, senior research adviser at the British Heart Foundation, said: "This interesting study shows that a drug, currently used as an antidepressant, can improve heart function in mice with heart failure apart from its antidepressant activity.
"The researchers found that paroxetene blocks an enzyme, called GRK2, which is known to be overactive in heart failure, and which contributes to the damaging changes in heart structure that occur in heart failure.
"However, the results need to be confirmed in humans. As paroxetine is already used in people, the next step is to see if it can be repurposed as a safe and effective treatment for heart failure in clinical studies."