FDA Links Drugs to Being Suicidal

September 14, 2004
FDA Links Drugs to Being Suicidal
By GARDINER HARRIS, NY TIMES

BETHESDA, Md., Sept. 13 - Top officials of the Food and Drug
Administration acknowledged for the first time on Monday that
antidepressants appeared to lead some children and teenagers to become
suicidal.

Dr Robert Temple, director of the F.D.A.'s office of medical policy,
said after an emotional public hearing here that analyses of 15
clinical trials, some of which were hidden for years from the public
by the drug companies that sponsored them, showed a consistent link
with suicidal behavior.

"I think that we now all believe that there is an increase in suicidal
thinking and action that is consistent across all the drugs," Dr
Temple said, summarizing the agency's presentation to a special
advisory committee. "This looks like it's a true bill.''

The acknowledgement, made after the hearing, comes a year after the
agency suppressed the conclusions of its own drug-safety analyst, Dr
Andrew Mosholder, who first found a link between the drugs and suicide
in teenagers and children. Agency officials wrote in internal
memorandums that Dr Mosholder's analysis was unreliable, and they
hired researchers at Columbia University to re-analyze the same data.
That study recently reached conclusions nearly identical to Dr
Mosholder's.

The testimony came before an advisory committee of 31 independent
experts that the F.D.A. has charged with making a recommendation about
the labeling and use of antidepressants in children and teenagers.

Family members of suicide victims at the hearing angrily denounced
agency officials for the delay in admitting the risk of
antidepressants in children. The British health authorities decided in
December to ban the use of most antidepressants in children and
teenagers.

Mathy Milling Downing of Laytonsville, Md., whose 12-year-old daughter
hanged herself in January, said: "Candace's death was entirely
avoidable had we been given the appropriate warnings. The blood of
these children is on your hands."

Agency officials said that they had no regrets about the months of
study. "I don't think the data were at that time reliable," Dr Temple
said. "Scaring people needlessly" or overdoing a warning is
worrisome," he added.

The most popular pills are Zoloft, made by Pfizer; Paxil, made by
GlaxoSmithKline; and Prozac, made by Eli Lilly & Company. In 2002,
nearly 11 million children and teenagers were prescribed
antidepressants.

The risk of suicide among patients given the pills is very small. If
100 children and teenagers are given antidepressants, 2 or 3 will
become suicidal who otherwise would not have had they been given
placebos, agency officials said. None of the children in the trials
committed suicide, but some thought about or attempted suicide,
researchers found.

In March, the agency required antidepressant manufacturers to include
on labels a warning that therapy with antidepressants could lead some
patients, both adults and children, to become suicidal. The committee
must decide whether this warning is strong enough or whether the drugs
should be banned for children. The advisory committee is expected to
make a decision on Tuesday. The F.D.A. normally follows
recommendations of its advisory committees.

It is a complex task. Most studies of the drugs have failed to show
that they have any effect on depression in children and teenagers. But
the drugs have proven effective in adults, and studies suggest that
teenage suicide rates have dropped in countries where use of
antidepressants is widespread. A large study of depressed teenagers
conducted by the National Institute of Mental Health recently found
that Prozac was far more effective in treating depression in children
and teenagers than was talk therapy.

Several speakers noted that clinicians would have almost nothing to
offer depressed teenagers and children if antidepressants were banned.
Suicide is the third leading cause of death among teenagers, trailing
only homicide and accidents. Without treatment, many more teenagers
will die, several experts said. If the committee suggests an even
stronger warning, some patients will resist therapy and could perhaps
die, some speakers said.

The issue has roiled the agency and is likely to transform the way the
drug industry markets its products. Committees in both the House and
Senate have begun investigations following disclosures that Dr
Mosholder's analysis had been suppressed.

The New York State attorney general Eliot Spitzer, filed suit against
GlaxoSmithKline, charging the drug maker with fraud for failing to
disclose the results of clinical trials of Paxil that found no benefit
while promoting the drug to physicians. The company settled the suit
this summer by promising to disclose the results of all of its
clinical trials of its marketed products dating back to 2000.

Editors of the nation's top medical journals have said they will not
to accept for publication trials that have not been publicly
registered, and legislation is expected to be offered in both the
House and the Senate requiring the disclosure of the results of all
major drug tests on humans.

For some bereaved parents, Monday's hearing was a chance to take drug
makers and the F.D.A. to task.

Mark and Cheryl Miller of Overland Park, Kan.,, told the committee
that their 13-year-old son, Matthew, had committed suicide seven
months ago while taking Zoloft.

"Why haven't parents like Cheryl and myself and countless others been
told the truth?" Mr Miller asked.

But others said that antidepressants had helped millions. Dr Suzanne
Vogel-Sibilia of Beaver, Pa., said that she had brought her
15-year-old son, Tony, to the hearing to represent what she said were
the vast majority of patients who had been helped by the drugs.

"Please help me preserve my future," Tony told the committee. "Don't
take away my medication."

Claims that antidepressants cause patients to become acutely suicidal
have been made since 1991, just three years after Prozac was
introduced. But drug makers and regulators long dismissed these
claims, saying they were anecdotal reports without any basis in
rigorous clinical trials.

Then last year, GlaxoSmithKline announced that tests of Paxil had
found that teenagers and children who took the pill were more likely
to become suicidal than those given placebos. The announcement was
quickly followed by a similar one from Wyeth, the maker of Effexor,
another antidepressant. Suddenly, the anecdotal reports were being
confirmed by clinical trials.

Still, just how the drugs may lead some people to become suicidal
remains the subject of fierce debate. Many of those at the hearing
said that the pills had brought a change in the personalities of their
friends and relatives. Alice Erber said that Paxil caused her
21-year-old son, Jake Steinberg, to throw himself in June from the
24th floor of a Manhattan office building.

"If he had not taken Paxil, he would be alive today," Ms Erber said.

But Dr Temple speculated that some people taking the pills become
suicidal because they are actually getting better. As their depression
improves, he said, they gain the energy to act on suicidal thoughts
that their illness had suppressed.

"I think the work is cut out for us tomorrow," Dr Wayne Goodman,
chairman of the advisory committee, said at the end of Monday's
hearing.