Oct. 31, 2003 — The U.S. won’t join Canada in banning Serzone, the FDA says. The antidepressant rarely — but unpredictably — causes liver damage and death.

Since its introduction in 1994, 55 patients in the U.S. have had Serzone-related liver failure. Twenty of them died — and there likely have been 10 times as many unreported cases, according to the consumer group Public Citizen. Serzone is the brand name for nefazadone, which is available as a generic drug.

“Canada thought the drug was too dangerous to be on their market — and we think the drug is too dangerous to be on the U.S. market,” Sidney Wolfe, MD, director of the Public Citizen Health Research Group, tells WebMD.

Health Canada asked the drug’s manufacturer, Bristol-Myers Squibb, to stop selling the drug.

“We respectfully disagree with their view, but we want to be cooperative so we will discontinue sales in Canada on Nov. 27,” Bristol-Myers Squibb spokesman Rob Hutchinson tells WebMD.

The drug has already been withdrawn from the market in Europe. But the FDA does not intend to follow suit.

“We at one time had a much better regulatory system than Europe or Canada. Now that is not the case,” Wolfe says.

Deaths Continue Despite ‘Black Box’

In late 2001, the FDA required Bristol-Myers Squibb to put a “black box warning” — the most extreme possible safety warning — on all Serzone sold in the U.S. Sales plummeted. This means doctors take the warning seriously, suggests an official statement by Russell Katz, MD, director of the FDA’s division of neuropharmacological drug products.

“It also seems that some [doctors] still consider [Serzone] to be the right choice for their patients,” Katz says in the statement. “We have reviewed the data recently, and we see no reason to remove it from the market here.”

The FDA position is that as clinical depression is a very serious condition, doctors should have as many treatment options as possible. It seems likely that some patients helped by Serzone don’t get relief from other drugs — although there is no direct proof this is the case.

“There is no evidence Serzone is any better than any of half a dozen or more other antidepressants with less risk,” Wolfe says. “The FDA is making a reckless statement by saying something with no unique benefit — but with a unique risk — should stay on the market. They are giving the impression it is OK, and that will lead to more cases of liver failure and death.”

Low-Risk Russian Roulette

How risky is Serzone? It causes life-threatening liver failure only once in 250,000 patient-years. That means there will be one case of liver failure for every 250,000 patients who take the drug for one year. Since 1994, 11 million people worldwide have taken Serzone.

Public Citizen notes that Serzone deaths continue despite the black box warnings. That’s because it’s impossible to tell which patients will get liver damage from Serzone. So while a given patient has a very low risk of liver failure, those who do get liver failure may not see any warning signs until it’s too late.

Why Use Serzone

Even though it’s unpredictable, Serzone’s low risk makes it useful for some patients, says Mark I. Levy, MD, a private-practice psychiatrist and assistant clinical professor at the University of California, San Francisco.

“All drugs have side effects and liver toxicity is just one of them. It is a matter of balancing the benefits vs. the liabilities,” Levy tells WebMD. “Serzone obviously isn’t the first line of defense for depression. But it is a very good antidepressant. Is it better than others? Probably not. But it is useful when you are trying to find a drug that an individual patient responds to. The one-size-fits-all idea is a real problem in medicine.”

But Public Citizen disagrees that Serzone’s risks are worth even this benefit.

“There is no justification for the U.S. to continue marketing a drug that offers no advantage in efficacy over the existing drugs in its class … and that has, among its class, unique and unpredictable toxicity,” the Public Citizen petition states.