Antidepressants Restudied for Relation to Child Suicide
NY Times
June 20, 2004
By GARDINER HARRIS
A child stabs himself in the neck with a pencil. Another
slaps herself in the face. Is either suicidal? It is a
question that has divided psychiatrists and drug regulators
the world over and goes to the heart of a fierce
controversy over whether antidepressants lead some children
to become suicidal.
Now four researchers at Columbia University hope to provide
an answer. By reclassifying reports of suspect or
self-destructive behavior that occurred during tests of
antidepressants in youngsters, the research team hopes to
clarify whether antidepressants lead children and teenagers
to become suicidal. Officials at the Food and Drug
Administration say they will use results of the study to
help them decide, later this summer, whether the agency
should discourage doctors from prescribing the pills to
youngsters.
The study was commissioned by top F.D.A. officials after
they rejected an analysis by one of the agency’s top
experts that concluded that antidepressants could be
dangerous when given to teenagers and younger children.
With such a controversial beginning, the study is being met
by fierce criticism.
Senator Charles E. Grassley, Republican of Iowa, issued a
statement questioning whether the study was part of an
effort by the Food and Drug Administration to suppress the
truth about the risks of antidepressants. Mr. Grassley said
he was investigating the study as part of a larger inquiry
into the agency’s handling of the controversy involving
antidepressants and suicide.
Some prominent mental-health research has questioned the
study’s methodology.
“You’ve asked the Columbia group to take data that’s
suboptimal and try to come up with a conclusion, and I
really doubt that they will be able to do that,” said Dr.
Thomas R. Insel, director of the National Institute for
Mental Health.
The Columbia team plans to apply a consistent definition of
”suicidal” to a disparate collection of more than 400
reports of adverse behavior that occurred in 25 clinical
tests of nine antidepressants. The tests, undertaken by
drug companies, involved Prozac, Zoloft, Paxil, Luvox,
Celexa, Wellbutrin, Remeron, Serzone and Effexor.
One of the problems with the drug-company trials is that
they tend to confuse self-destructiveness with suicidal
attempts, team members said in an interview.
“Suicide research has come up with a specific definition of
suicide attempts: a self-injurious behavior where there is
some intent to die,” said Barbara Stanley, one of the
researchers.
The team will give nine independent reviewers the
descriptions that drug-company researchers used in
reporting the cases involving adverse behavior. . The
reviewers will label each event as suicidal, nonsuicidal or
indeterminate, and then give the data to federal drug
regulators for statistical analysis.
Discovering intent from the brief notes provided by the
drug companies could be difficult. In a speech before an
advisory panel in February, Dr. Thomas Laughren, leader of
the F.D.A.’s psychiatric drug products group, noted that
the drug companies’ descriptions were often poor. “We did
not have the level of detail in these cases that one would
have liked to do a rational classification,” Dr. Laughren
said.
Julie Magno Zito, an associate professor of pharmacy and
psychiatry at University of Maryland, Baltimore, predicted
the Columbia team would not be able to overcome this
problem. “If a kid pierces his neck with a pencil, that
could be a violent act of self-destruction or it could have
been nothing,” Dr. Zito said. “If the notes don’t make the
intent clear, how do you interpret that?”
Dr. Zito called the Columbia study “a fundamentally bad
idea.”
Dr. Alan Gelenberg, head of the department of psychiatry at
the University of Arizona, said the study would provide a
needed perspective. But even those who support the study
agree that it is unlikely to change many minds on the
question of whether antidepressants should be prescribed to
children.
“This question will never be settled,” said Dr. James
McGough, a professor of clinical psychiatry at the
University of California, Los Angeles. “Still, I’m eager to
see what their answer is.”
In tackling the issue, the researchers say they understand
that they are being thrust into a maelstrom rarely seen in
psychiatry.
“For all of us, our anxiety levels are higher because we
know that there are people invested in this one way or the
other,” said Dr. Madelyn Gould, professor of clinical
public health in psychiatry. “Anything that has to do with
drug treatment in kids is so emotionally charged.”
The study had its beginnings early last year when
GlaxoSmithKline submitted to federal drug regulators the
results of three trials of its Paxil antidepressant in
teenagers and other children. The company had undertaken
the studies to take advantage of a federal law that delays
by six months the introduction of cheaper, generic versions
of drugs when branded makers test medicines in children.
In GlaxoSmithKline’s trials, depressed young people given
Paxil fared no better than those given placebos. It was a
disappointing result for GlaxoSmithKline but had no effect
on its application for the six-month extension. Still, a
reviewer at the Food and Drug Administration noticed
something strange about the trials: teenagers given Paxil
suffered more problems of ”emotional lability,” or
instability, than those given a placebo.
The reviewer, Dr. Andrew Mosholder, thought ”emotional
lability” was overly broad. He asked the company to
resubmit its data, this time using a separate category for
suicide.
That report, given in May to both American and British
health authorities, was alarming. Teenagers and younger
children given Paxil were much more likely to become
suicidal than those given placebos. In June, both the
British and American authorities warned doctors against
prescribing Paxil to youngsters. Worried that the problem
could extend far beyond Paxil, the F.D.A. in July asked the
makers of eight other antidepressants to submit data from
their studies in youngsters.
In August, Wyeth issued a warning that doctors should avoid
prescribing Effexor to youngsters because it, too, seemed
to cause them to become more suicidal.
By September, the agency had received the other companies’
studies. Looking at them all, Dr. Mosholder concluded that
children given antidepressants were almost twice as likely
as those given placebos to become suicidal. He suggested
the agency discourage the drugs’ use in children.
It would have been a monumental step. Antidepressants are
among the biggest-selling drugs in the world and have long
been viewed by doctors as relatively safe. Their use in
children has been soaring.
Dr. Mosholder’s bosses at the Food and Drug Administration,
however, said the drug company data was inconsistent and
that some events termed ”possibly suicidal” seemed
innocent. Top agency officials hired the Columbia
researchers to review the data, and they forbade Dr.
Mosholder to speak about his conclusions to an advisory
panel reviewing the matter.
The silencing of Dr. Mosholder prompted outrage among
critics of antidepressants and the ongoing investigation by
Senator Grassley. It also has fostered skepticism about the
Columbia study. Already, Internet postings are questioning
the backgrounds of the Columbia researchers. One asks
whether Kelly Posner, the lead investigator, has
participated in trials financed by the drug industry.
In a group interview in a conference room in the New York
State Psychiatric Institute, the researchers said they were
unbiased.
Dr. Posner said that she had participated in some trials
sponsored by drug makers but never as a principal
investigator. All of the trials involved attention deficit
disorder, not depression or suicide, she said.
Her three colleagues said that they had never taken part in
a drug-company trial. And they said that their study, while
hugely controversial, was relatively simple: figuring out
the appropriate labels to place on the behaviors in the
individual cases.
“We’re just dealing with a lot of pieces of paper,” Dr.
Gould said. “We’re not dealing with people at all. And all
the interesting questions happen once we give the data over
to the F.D.A.,” where the statistical analysis will occur.
http://www.nytimes.com/2004/06/20/national/20depress.html?ex=1088722398&ei=1&en=0717b1524845d97e
Re: Columbia team to re-evaluate pediatric anti-depressants
[quote=”Anonymous”][quote]”If a kid pierces his neck with a pencil, that
could be a violent act of self-destruction or it could have
been nothing,” Dr. Zito said. “If the notes don’t make the
intent clear, how do you interpret that?”
What an absolutely idiotic and dangerous statement, and this from a doctor???
Well I don’t think it could be NOTHING. It might not be suicidal though. There are kids who hurt them selves (usually drawing on themselves with razors, etc.), sometimes called “cutters”. So it might not be clear what the intent was, but to say it would mean nothing, I’d agree that’s pretty idiotic. It is a serious behavior, but it is usually unrelated to suicide.
There are also kids who will make nonfatal “suicide” attempts. They have no intention of killing themselves but are generally attention seeking. What they do usually again with razors is mark themselves. Or sometimes they take a number of pills an overdose perhaps but it isn’t enough to kill themselves. I think though that sometimes these kids have made mistakes and killed themselves by accident (say not really knowing a fatal dose). Usually their actions don’t look like they have the intent to kill. I wouldn’t say that is NOTHING either.
I would think a serious study of this would need to differentiate such kids. Usually the above are long standing behaviors though.
—des
Re: Columbia team to re-evaluate pediatric anti-depressants
Des is absolutely right. There are many self-destructive behaviours that aren’t suicidal — serious and needing help, but a different issue and a different kind of help.
There is also another kind of self-inflicted damage that I don’t know a name for, but it is the “I didn’t know I was doing it” syndrome, where a person either performs a repetitive behaviour such as chewing nails or scratching until real injury results, or where a young person does something that looks incredibly stupid like making repeated stabbing motions with a pencil until one finally hits, and then he is as surprised as anyone else at the injury. Again, serious behaviour requiring serious help, but not suicidal.
Then the question comes up — and this is a most important question — whether the person had any of these behaviours before taking the medication. After all, the medication is given because there is some kind of problem. So is the previous problem continuing on the same level, being traded for a different problem, or getting worse? You need an answer to this before you start prescribing.
Re: Columbia team to re-evaluate pediatric anti-depressants
The problem I have with the use of medications such as SSRI’s is that too-often followed protocol is not what Victoria described (defining the problem thoroughly and determining appropriate course of action based upon weighing the options for treatment). Too often drs. will start with prescribing powerful medications, and to very young children contrary to FDA lisence which means in the absence of determined risk/benefit ratios. I have seen drs. on internet forums discuss treating children with various problems say things like “you have to mess around with meds until you hit one that works” as though it were a process akin to deciding whether to eat the green or red M&M’s first.
The practice of medicaine is supposed to be about best practices employed under the process of informed consent, and that is not the case in too many cases. What makes it worse is that because the FDA has allowed the pharmas to skew results and hide negative events, many people think that everything pharmaceutical is hunky dory, including a good number of drs., who are presumed to be knowledgable and really should be treating each patient as an individual, and not just a punchcard which gets a pre-dertermined regimen.
Re: Columbia team to re-evaluate pediatric anti-depressants
Amen to the Guest above, and thanx, Dad, for posting the article.
[quote]”If a kid pierces his neck with a pencil, that
could be a violent act of self-destruction or it could have
been nothing,” Dr. Zito said. “If the notes don’t make the
intent clear, how do you interpret that?”
What an absolutely idiotic and dangerous statement, and this from a doctor???
[/quote]The Columbia team plans to apply a consistent definition of
”suicidal” to a disparate collection of more than 400
reports of adverse behavior that occurred in 25 clinical
tests of nine antidepressants. The tests, undertaken by
drug companies, involved Prozac, Zoloft, Paxil, Luvox,
Celexa, Wellbutrin, Remeron, Serzone and Effexor.
How many different defintions of “suicidal” are necessary? That’s like Clinton’s wanting to define what “is” is. Only this is sinister and involves our children. Sounds to me like the big drug companies don’t want to lose their precious money, and nor do the doctors. How very frightening. I know I would never give that poison to my child.