una segnalazione di Andrea Ventura
la "Food and Drug Administration" si servirà dei risultati di una ricerca che è stata commissionata alla Columbia University sui casi di suicidi di bambini e adolescenti che venivano trattati con una terapia antidepressiva per decidere se sconsigliare i medici dal prescrivere tali farmaci. Ma ci sono proteste.
New York Times, Published: June 20, 2004
Antidepressants Restudied for Relation to Child Suicide
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.
