WASHINGTON — The Food and Drug Administration warned
doctors, patients and their families Monday that 10
popular antidepressants could cause deepening
depression and even suicide. It also directed the
manufacturers to put warnings of such possible side
effects on the drugs' labels. The agency also alerted
those involved with the drugs to look out for
agitation, hostility, mania and other forms of
sometimes violent behavior that have been associated
with them.
The drugs — Prozac, Zoloft, Paxil, Luvox, Celexa,
Lexapro, Effexor, Wellbutrin, Serzone and Remeron —
are taken by 30 million Americans, according to some
estimates. The first seven are in the drug category
known as "serotonin reuptake inhibitors,"
and their sales in 2003 exceeded those of any other
drug class except the group of painkillers that
includes codeine. The speed and scope of the FDA's
action reflected its concerns about the breadth of the
potential damage the drugs could cause. "Our hope
is that the new language and labeling will result in
closer observation of patients who are being
prescribed these drugs," said Dr. Thomas P.
Laughren, leader of the FDA's psychiatric drug
products team.
The warnings came after an FDA advisory panel heard
testimony last month from dozens of patients and
family members who blamed the drugs for suicide
attempts, suicides and violent acts by children among
patients taking them. Testimony at that meeting showed
that patients on the medications had become more
depressed or even suicidal or more agitated and
violent, and their doctors were doing nothing about
it, Laughren said.
The FDA hopes that with the new warnings, doctors will
know when to reassess treatments and possibly
discontinue the drugs, he added. The FDA said it was
not yet clear whether antidepressants contributed to
the emergence of suicidal tendencies and behavior. But
at the urging of the advisory panel, the agency
decided to issue the warnings now, before it completed
a reexamination of 25 clinical trials of various drugs
on children.
This summer, when that review is done, the FDA may
have more to say on the issue, Laughren said.Drug
companies played down the warnings and stressed that
the FDA had not shown a link between the drugs and
suicide. "Depression is a serious public health
issue — and it takes great courage for patients to
begin treatment in the first place," said
Jennifer Yoder, spokeswoman for Eli Lilly and Co.,
which makes Prozac. "Patents should not stop
treatment without first talking to their
doctors."
Dr. Cathryn Clary, a vice president of Pfizer, maker
of Zoloft, said her company was "working closely
with the FDA" to change the drug's labeling.
Concerns about a possible link between the drugs and
suicide were raised in the media and by some
psychiatrists in 1990. The FDA convened an advisory
panel on the topic but opted not to issue any
warnings. "It's 14 years later, and finally the
FDA — albeit tentatively — is doing the right
thing," said Dr. Joseph Glenmullen, a Harvard
Medical School psychiatrist, who wrote a book about
the side effects of antidepressants.
The FDA's warning is important, he said, because many
doctors and patients are not aware that suicidal and
violent behavior are possible side effects. Glenmullen,
who prescribes the drugs to his patients, said the
warning sent a direct message to doctors: "You
can't give a patient one of these drugs and tell them
to come back in two or three months. You have to
monitor them closely." Dr. Matthew Rudorfer, the
National Institute of Mental Health psychiatrist who
chairs the FDA advisory panel, said the group did not
believe that the risks of the medications ruled out
their use. "But we think such warnings are
required to elevate the level of concern and attention
that practitioners use in prescribing them,"
Rudorfer said.
The FDA said patients should be monitored especially
carefully at the beginning of treatment and when doses
are increased or decreased. Thomas J. Moore, a health
policy analyst at George Washington University, said
the FDA's warnings were more confusing than the
message from the British government, which in December
said children and teenagers should not take the drugs
because of the possible increased risk of suicide.
"The drawback to what the FDA did today is that
it still failed to acknowledge the relationship of the
suicidal, violent and manic behaviors to the
drug," Moore said. With the possible exception of
Prozac, there is not enough evidence that the drugs
are beneficial to children to justify the risks of
dangerous side effects, he said. Prozac is the only
antidepressant in the group that the FDA has approved
for use by children.
Neither the FDA nor the drug companies try to estimate
how many Americans take the drugs. Britain's North
Wales Department of Psychological Medicine estimates
that as many as 30 million Americans take
antidepressants. Generic drugs are available in the
U.S. for three of the drugs: fluoxetine for Prozac,
paroxetine for Paxil and bupropion for Wellbutrin.
