Antidepressants will now come with double-barrel
warnings meant to get the attention of doctors and parents:
These drugs can and do cause some children to become suicidal.
The U.S. Food and Drug Administration on Friday acted on a
month-old recommendation from its own expert panel and will
require "black box" warnings for all antidepressants.
A black box warning is the government's strongest safety
alert. It's one step below a ban.
The label warnings will stress the importance of closely
monitoring children and adolescent patients started on these
drugs for the emergence of suicidal thoughts or behavior.
That message also will come in the form of a medical guide
that pharmacists will be required to give patients with all
antidepressant prescriptions. The guide will be required to be
distributed with sample packets.
Impact on Pittman case
Critics who've long fought for such warnings, including
attorneys for a boy facing double murder charges in Chester
County, called Friday's actions a step in the right direction.
Still, many questioned what took the FDA so long to act.
"It's taken far too long, but I'm thrilled by it," said
Karen Barth Menzies, an attorney from Los Angeles who
represents Christopher Pittman, the boy charged with killing
his grandparents at their Chester County home in 2001. "People
have just been buying the idea for so long that these drugs
are good for anything and everything. We now know that isn't
true. But it's just another example of the FDA failing to act
sooner."
Dr. Lester Crawford, the FDA's acting commissioner, said in
a written statement that Friday's actions "represent FDA's
conclusions about the increased risk of suicidal thoughts and
the necessary actions for physicians prescribing these
antidepressant drugs and for the children and adolescents
taking them."
"Our conclusions are based on the latest and best science,"
Crawford said.
The American Academy of Pediatrics applauded the FDA's
decision.
"Pediatricians support stronger warnings, including the
black box, as we now know there is definitely an increased
risk of suicidal thinking and behavior in children who are on
these drugs. The labels needed to change," said AAP President
Dr. Carol Berkowitz in a written statement "However, we still
believe that for the most serious cases of depression or other
psychiatric disorders, these medications can help adolescents
following appropriate diagnosis, an explanation of the risks
and benefits to the patient and family, and specific
guidelines for monitoring."
An official with GlaxoSmithKline, the British drug giant
that makes the antidepressant Paxil, told the Associated Press
that the company sees the warnings as a positive action.
"We agree with the FDA that providing additional
information to everyone -- from health care professionals to
parents and patients -- is one of the most positive steps that
can be taken to advance the diagnoses and treatment of
adolescents with depression," said Mary Anne Rhyne from the
company's office in Raleigh, N.C.
The end result left victims, scientists and advocates giddy
with happiness and claiming victory, but many strongly
disagreed with Crawford's assertion that the actions were
based on the latest and best science.
"The FDA fought every step along the way until they
couldn't hold out any longer," said Vera Hassner Sharav of the
Alliance for Human Research Protection. "I see this as a
victory, but the antidepressant issue is a demonstration of
how the system is dysfunctional."
The British government in December, using the same clinical
trial data provided to the FDA, all but banned antidepressants
from being used with children. In the 10 months since, the FDA
has held two advisory panel meetings to explore the issue of
antidepressants in children, including one in September that
led to the black box warning recommendation; a Congressional
investigation subcommittee has held two hearings looking into
what the FDA knew about the dangers of antidepressants and
when; and the New York attorney general sued Glaxo for
withholding data from clinical trials that demonstrated its
drug was either dangerous or not effective in treating
depression in children.
Questions about the safety of antidepressants first arose
in the early 1990s, just years after Prozac, the first of the
antidepressant "wonder drugs" known as selective serotonin
reuptake inhibitors, was approved. An FDA hearing in 1991
concluded that no credible evidence existed to show Prozac
could lead adult patients to become suicidal or homicidal.
Dr. Richard Kapit, a retired FDA scientist who reviewed
Prozac, Paxil and Zoloft in the late 1980s before the
antidepressants were approved to treat depression in adults,
said that he suspected the drugs could cause people to become
suicidal or homicidal from the beginning. Those risks,
however, did not outweigh the potential benefits of the drugs,
he said.
"I had always thought the drugs had the potential to cause
manic episodes, and manic episodes are frequently accompanied
by violence," said Kapit, who will testify for the defense at
Pittman's trial. "When I reviewed Prozac in the 1980s, I
accepted that in rare patients it could cause patients to
become manic, suicidal. I don't think I doubted, or anyone
doubted, in rare patients that could be true.
"Now we have hard data to back up what everyone sort of
believed, that these drugs are capable of causing manic
states."
Of the 24 antidepressant clinical trials involving
juveniles reviewed by the FDA, 22 failed to show the drugs
were any more effective than a placebo. A review of the same
trials by a Columbia University team hired by the FDA also
showed that antidepressants can cause 2 percent to 3 percent
of young patients who were not suicidal before taking the
drugs to become so during the early stages of treatment.
Only Prozac has been approved by the FDA to treat
depression in children. It was also the only drug not to be
included in the British government's virtual ban.
However, all antidepressants are given to children through
a legal practice known as "off-label" prescribing. Last year,
more than 11 million antidepressant prescriptions were written
for U.S. children, according to the FDA. A recent study showed
as many as 89 percent of those were written for off-label, or
non-approved, uses.
"In other words, almost 90 percent of the time children
receive antidepressants that are not approved by the FDA for
that child's condition," said Dr. Joseph Glenmullen, a
psychiatrist at Harvard University. "To give a child a drug
that can make them suicidal for conditions where there is
nonexistent or inadequate proof that the drugs work is
irresponsible and fails to protect our children.
"Surely, the FDA and the pharmaceutical industry know that
even a black box warning will not adequately curtail
prescribing unapproved antidepressants to children for
unapproved conditions."
Glenmullen, who prescribes antidepressants, said the FDA
should have banned doctors from prescribing the drugs for
non-approved uses. He also said the FDA still has much work to
do on the antidepressant issue.
Left to be explored, he said, is whether the drugs can
cause adults to become suicidal and the role the drugs play in
causing people to become violent and/or homicidal.
"And that goes right to the Christopher Pittman case,"
Glenmullen said.
Pittman is charged with shooting Joe Frank Pittman and Joy
Roberts Pittman while they were in bed in November 2001 before
setting the house on fire and fleeing in a family vehicle. He
was 12. Now 15, Pittman will be tried as an adult and could be
sentenced to life in prison if convicted. A trial date has not
been set.
The boy had been on a five-week regimen of Paxil and
Zoloft. His attorneys will contend an adverse reaction to his
antidepressant medication caused his violent behavior.
Friday's move by the FDA strengthens that position, they
said.
"We know it's been established that Zoloft causes kids to
commit suicide," said Andy Vickery, a Houston attorney
representing Pittman. "It's not a big leap to homicide. It's
the other side of the same coin. It's caused by the same
biological mechanism."
Vickery said he is encouraged by the FDA's action but
wondered whether things would have been different had the
warnings come three years ago.
"That would have been before Christopher got Zoloft from a
general practitioner for an unapproved use," he said. "Two
things might have happened. The doctor may not have given it
to him, or he might have provided them with the appropriate
warnings."
Jason Cato • 329-4071
jcato@heraldonline.com
