Date: 16/08/03

Time: 13:37:21

Suicide alert revives qualms on antidepressants
http://www.iht.com/cgi-bin/generic.cgi?template=articleprint.tmplh&ArticleId=105624

Gardiner Harris NYT Friday, August 8, 2003

Warnings by drug regulators about the safety of Paxil, one of the most widely prescribed
antidepressants, are reopening seemingly settled questions about a whole class of drugs that also
includes Prozac and Zoloft.

Doctors are just beginning to react to the finding - reported first by British drug authorities
in June and endorsed days later by the U.S. Food and Drug Administration - that unpublished
studies about Paxil show that it carries a substantial risk of prompting teenagers and children
to consider suicide.

Because the studies also showed that Paxil was no more effective than a placebo in treating young
people's depression, the regulators recommended that doctors write no new Paxil prescriptions for patients under 18. Experts say that the suicide risk is highest in young patients' first few
weeks on the drug.

In 1991 regulators weighed and rejected concern that drugs like Paxil - known as selective
serotonin reuptake inhibitors, or SSRI's - could cause suicide. Almost no one suggests that these
drugs, which include Prozac and Zoloft, are unsafe for most adults, although studies have shown
them to be only modestly effective.

Still, the warnings have the early critics saying they feel vindicated. And the findings have
unsettled some of the very experts who absolved SSRI's of a link to suicide in 1991. Seven of the

10 American specialists who served on a Food and Drug Administration panel that formally cleared the drugs of ties to suicide say that the new information would prompt them to reconsider.

"In 1991, we said there wasn't sufficient evidence to support a link," said Jeffrey Lieberman, a
professor of psychiatry and pharmacology at the University of North Carolina and a member of the panel. "Now there is evidence, at least in children, and I wouldn't rule out that it's in adults,
too."

While the regulators' recent warnings address only Paxil, many of the panel members said that
SSRI's act similarly, so the concerns could apply to all.

The Food and Drug Administration warned that younger patients "should not discontinue use of

Paxil without first consulting their physicians," adding, "It is important that Paxil not be
abruptly discontinued."

SSRI manufacturers, with billions of dollars of sales every year, have responded to the warnings
cautiously. Without criticizing the regulators, they maintain that there is no proof that the
drugs have a link to suicidal thinking in young patients, and they point out that the Food and

Drug Administration in the past found no merit in such claims.

"We're trying right now to look at this issue with the FDA and come up with an understanding
together of what the data mean," said Philip Perera, the medical director of GlaxoSmithKline, the
British company that makes Paxil.

Pfizer, the maker of Zoloft, said that its drug is different from Paxil and has passed the agency's safety evaluations, including one as recently as June 12.

Eli Lilly, the maker of Prozac, says its drug does not cause suicides.

In recent years, most debate among doctors and researchers about SSRI's has focused on whether they are effective, rather than whether they are safe.

Dr. David Shaffer, a researcher at Columbia University, noted that teenage suicides have fallen
significantly in every country where Prozac and its cousins are widely used.

"This amazing, undreamt-of and unhoped-for reduction in suicide rates is probably the result of
more liberal treatment of young people with SSRI's, and it's suggestive that these drugs may be
responsible for saving a lot of lives," Shaffer said.

Yet most studies have found that SSRI's are no more effective in fighting teenage depression than
sugar pills.

Even in adults, SSRI's have been found to offer only modest benefits. On average, they reduce symptoms of depression by about 41 percent on a widely used scale, versus a 31 percent reduction among those taking placebos, according to a survey done in 2000 of studies used by the Food and Drug Administration in approving the drugs.