arnings by drug regulators about the safety of
Paxil, one of the world's most 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 then endorsed the next
week by the Food and Drug Administration — that unpublished studies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 found 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
the first few weeks young patients are on the drug.
The concern that Paxil and drugs like it could cause suicide had
been weighed, and rejected, by regulators a dozen years ago, amid
early concerns about the group of antidepressants known as selective
serotonin reuptake inhibitors, or S.S.R.I.'s. In the meantime,
millions of people have taken the drugs, and many experts say that
they have prevented far more suicides by teenagers and children than
any reading of the new findings suggests they could have caused.
Almost no one suggests that Prozac, Zoloft, Paxil and their
cousins are not safe for the vast majority of adults, although
studies have shown them to be only modestly effective.
Still, the warnings have the early critics saying they feel
vindicated. Plaintiffs' lawyers who have uncovered evidence that
they say shows drug makers withheld evidence of the S.S.R.I.'s
suicide risk from regulators say the warnings give fresh urgency to
And the findings have unsettled some of the very experts who
absolved S.S.R.I.'s of a link to suicide a dozen years ago. Of the
10 American specialists who, as members of an ad hoc F.D.A. panel,
formally cleared the drugs of a link to suicide in 1991, seven now
say that the new information would prompt them to reconsider that
decision, if they were asked.
"In 1991, we said there wasn't sufficient evidence to support a
link between these drugs and suicide," said Dr. Jeffrey A.
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."
British health authorities have promised to "urgently" examine
the implications of their findings for adults. The F.D.A. is
considering whether to impose new restrictions on the use of the
antidepressants. The agency's warning emphasized that younger
patients "should not discontinue use of Paxil without first
consulting their physicians," adding, "it is important that Paxil
not be abruptly discontinued."
While the regulators' warnings address only Paxil, many of the
experts on the 1991 panel said all S.S.R.I.'s act similarly in the
body, so concerns about one could apply to all.
The drugs' manufacturers, which sell billions of dollars of
S.S.R.I.'s every year, have treaded carefully in responding to the
warnings. Without criticizing the regulators, they maintain that
there is no proof that their drugs have a link to suicidal thinking
in young patients — and they point out that the F.D.A. in the past
found no merit in such claims.
"We're trying right now to look at this issue with the F.D.A. and
come up with an understanding together of what the data mean," said
Dr. Philip Perera, a medical director of GlaxoSmithKline, the British company that makes Paxil. Pfizer, the maker of Zoloft, said that its drug
was different from Paxil and had passed all F.D.A. safety
evaluations, including one as recently as June 12. Eli Lilly & Company said that Prozac does not cause
So far, there is little evidence that the warnings have affected
doctors' prescribing practices. Teenagers and children account for
about 5 percent of S.S.R.I. prescriptions, and companies that track
the industry have detected no falloff in sales.
"I can hardly imagine working without these drugs," said Dr.
William Schreiber, a Louisville, Ky., internist. "These are good
drugs, and I think they're safe drugs."
But the warnings are beginning to seep into doctors' awareness.
Connecticut officials, for example, last month dropped Paxil from
their list of approved medications for foster children. And even
doctors who do not believe there is a link between S.S.R.I.'s and an
increased risk of suicide are emphasizing that patients need to be
closely monitored in their first weeks on the drugs.
"See them every day, if you need to," Dr. Perera of
The drugs are widely prescribed by general practitioners, who do
not have the same training in depression and treatment as