Fait Acomplia? New Study Lends Weight to FDA Concerns

Nov. 15, 2007— -- Obese patients taking the weight-loss drug rimonabant — also known as Acomplia — have an increased risk of developing severe depression and anxiety, a new study reports.

The study confirms similar findings by the Food and Drug Administration on rimonabant earlier this year — findings that led an FDA advisory panel to recommend against marketing approval of the appetite suppressant in the United States in June.

In addition to a potential risk of depression and anxiety, the FDA also found an increased chance of irritability, insomnia, panic attacks, aggression and suicide in patients taking the diet pill. Several patients taking rimonabant were prescribed antidepressants or tranquillizers to keep their symptoms under control.

Before the decision, pharmaceutical giant Sanofi-Aventis had intended to sell rimonabant under the brand name Zimulti in the United States. Currently, rimonabant is available in several European countries under the Acomplia brand name.

The study was published Thursday in the medical journal Lancet. Researchers at the University of Copenhagen looked at data gathered from four previous studies.

The analysis showed that the drug was effective. Patients taking rimonabant, on average, lost 4.7 kilograms — 10.3 pounds — more weight after one year than did patients who, instead, took a placebo.

But the study also found that patients taking rimonabant were at risk for adverse psychiatric events — specifically, depressed mood disorders and anxiety.

Obese Already at Higher Depression Risk

The psychiatric side effects of the diet pill were apparent in some patients, even though all these studies excluded those who had existing psychiatric problems.

What this means is that the potential side effects of rimonabant could be especially dangerous to those in the general population who already have underlying psychological illnesses.

"The increased risk of depression and anxiety is certainly concerning, especially since the authors excluded patients with pre-existing depression," said David Kroll, pharmacologist and adjunct associate professor of medicine at Duke University Medical Center.

"Although not demonstrated, one could infer that rimonabant might cause depression or anxiety to worsen in patients who already experience these symptoms," said Kroll.

And evidence suggests that obese people may, on the whole, be even more prone to depression in the first place. In a combined written testimony of the FDA advisory committee on rimonabant earlier this year, Dr. Sidney Wolfe, director of the health research group for the consumer advocacy group Public Citizen, and his colleagues noted an underlying increased risk of depression — up to 20 percent — in the obese population.

Also of interest in the report was the fact that 30 percent of patients taking other diet pills between 2004 and 2006 were concurrently taking antidepressant medication.

"This strongly suggests that patients would, if this drug is approved, end up taking antidepressants and rimonabant in tandem, with unknown consequences," Wolfe noted in the testimony.

Wolfe and his colleagues are not the only ones concerned about the use of the drug in the general population.

"I agree that there is likely to be an even larger group affected," said Dr. Marc Siegel, clinical associate professor at the New York University department of general internal medicine.

"Rimonabant has several intended actions, including appetite suppression, lowering cholesterol, smoking cessation, and an aid in treating chemical substance abuse," noted Paul Doering, professor of pharmacy at the University of Florida in Gainesville.

"While this list is on the 'good side' of the pharmacologic ledger, we need to look at the whole balance sheet before unleashing this drug on the trusting, yet vulnerable, public," said Doering.

Do Benefits Outweigh the Risk?

Both the study released Thursday and the testimony by Wolfe at the FDA advisory meeting, found a modest 5 percent to 10 percent decrease in weight in patients taking rimonabant. Study authors note that this weight loss would most likely not be sustained once treatment ended, and the patient would need to continue taking the drug for life to see lasting improvement in obesity-related risk factors.

"Given this fact, the complete lack of data on rimonabant use in humans over an extended period of time, is cause for significant concern," Wolfe reported, adding that more long-term studies are needed to "fully evaluate the benefit risk ratio of this new drug."

Dr. Domenic Sica, a professor of medicine and pharmacology at Virginia Commonwealth University, agrees that more studies are needed to evaluate the safety of this drug, especially in the high risk population, for depression.

But as the obesity epidemic continues to increase worldwide, Doering noted, the search for better pharmacological interventions to control obesity will likely continue.

"We desperately need a drug that will effectively suppress appetite, not lead to tolerance and dependence, and has few side effects," Doering said.

"The search for the elusive 'silver bullet' goes on."