Acomplia (Rimonabant / Zimulti) produced disappointing results in slowing progression of coronary artery disease in patients and it significantly raised the risk of anxiety and depression, according to a report in the April 2 issue of the Journal of the American Medical Association.

The results of the trial called STRADIVARIUS, released a day early to coincide with a presentation at the annual conference of the American College of Cardiology, seem certain to increase questions as to whether this once promising diet drug will ever be approved in the U.S. because of side effects.

More than 40 percent of patients who took acomplia in the STRADIVARIUS trial developed psychiatric problems and one committed suicide, the researchers reported.

While Acomplia is sold in European Union countries and some other nations, Sanofi Aventis pulled back its U.S. application last year after an FDA advisory panel recommended against approval of acomplia because of concerns over psychiatric risks.

The STRADIVARIUS study, which involved 839 abdominally obese patients with coronary disease and metabolic risk factors at 112 centers, sought to determine whether acomplia rimonabant might help slow progression of atherosclerotic disease, often commonly known as “hardening” of the arteries.

The researchers reported that the study failed to meet its main goal of reducing the Percent Atheroma Volume (PAV), a measure of plaque in a cross-section of the arteries, although it did reduce the Total Atheroma Volume (TAV), a measurement of total plaque in the coronary artery.

“Because the current study failed to achieve a statistically significant effect for the primary efficacy measure, additional studies will be required to further define the role of acomplia in the treatment of abdominally obese patients with coronary disease and metabolic risk factors,” the researchers concluded.

But more attention seems certain to be focused on this latest effort to assess the extent to which Acomplia carries with it an increased risk of psychiatric side effects.

The researchers in the STRADIVARIUS study included patients with a history of such problems, and reported that 43.4 percent of patients who got Acomplia suffered psychiatric side effects such as depression and anxiety compared to 28.4 percent of patients who were in the control group.

Dr. John Rumsfeld of the Denver Veterans Affairs Medical Center and Dr. Brahmajee Nallamothu of the University of Michigan, in a commentary in the medical journal, observed that while the promise of Acomplia remains, “it certainly has faded.

“The potential benefits are offset by the very real risks of depression and anxiety,” they added.