|Patients taking antidepressants can become
suicidal in the first weeks of therapy, and
physicians should watch patients closely
when first giving the drugs or changing
dosages, federal regulators said yesterday.
The warnings are part of a public health
advisory issued by the Food and Drug
Administration and are a reminder that
antidepressants, taken by millions around
the world, are not without risks. The agency
is asking drug manufacturers to place
detailed caveats about the drugs' side
effects prominently on their labels.
The agency's decision to issue such a
broad warning was a surprise. Top F.D.A.
officials have long insisted that their
decisions are driven only by clear-cut
evidence from well-run clinical trials. But
in a conference call with reporters
yesterday, agency officials said that no
studies had shown a convincing link between
drug therapy and suicide. Suicide is such a
rare side effect that studies on the subject
have been difficult to interpret, the
Still, the agency issued the advisory
''It warns physicians that patients'
depression may become worse,'' said Dr.
Russell Katz, the agency's chief of
neurological drugs, ''that they may develop
suicidal thinking or behavior after the
initiation of treatment.''
A series of secret studies, which were
conducted by drug companies and became
public last year, seemed to show that
depressed children and teenagers given
antidepressants were more likely to become
suicidal than those given placebos. The
studies also showed that most
antidepressants were not effective in
treating depression in children and
teenagers. Those studies are still under
review at the agency.
Nevertheless, a scientific advisory panel
urged the agency last month to issue
stronger warnings about the possibility that
teenagers and children given the drugs could
become suicidal. Studies in adults have
found no link between the drugs and suicide,
but the agency included adults in the
warnings, in part because of anecdotal
stories at advisory meetings last month. Dr.
Katz said ''a number of witnesses said that
these were experiences that they had with
''We think this is good advice whether
the drugs did it or not,'' said Dr. Robert
Temple, associate director of medical policy
at the agency. ''If someone commits suicide,
it doesn't really matter whether it's the
drug or the underlying disease. In either
case, you need to pay attention.''
Some psychiatrists said the new warnings
were likely to slow sales, which amounted to
about $12 billion worldwide in 2002, and
would change how the drugs were prescribed.
Prozac, from Eli Lilly, is one of the most
widely prescribed drugs of all time. Zoloft,
from Pfizer, had $3.1 billion in sales last
year, making it one of the world's
Dr. Jeffrey Lieberman, a professor of
psychiatry and pharmacology at the
University of North Carolina, said that the
agency's action suggested that
antidepressants had become too popular and
physicians too casual about dispensing them.
''I think the effect of these warnings
will be to have physicians become a bit more
conservative in using these drugs,'' Dr.
Lieberman said. ''They'll start limiting
their use of them just to patients who are
clearly depressed with clinically
significant symptoms as opposed to those who
have very mild symptoms.''
Dr. Regina Casper, a professor of
psychiatry at Stanford, said that family
physicians had become far too confident in
the drugs' safety. Patients who are given
their first prescription for an
antidepressant should see their doctor at
least once a week and perhaps more
frequently, something family physicians
rarely have time for, she said.
''I think this will have a real sobering
effect among family practice doctors,'' Dr.
The warnings also tell physicians to be
particularly careful to evaluate whether
patients have bipolar illness, also known as
manic depression. Antidepressant therapy for
such patients can cause a manic episode, the