Secret US report surfaces on antidepressants in children

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http://bmj.bmjjournals.com/cgi/reprint/329/7461/307

Secret US report surfaces on antidepressants in children

Jeanne Lenzer

New York

Internal memos and a secret government report about the negative effects of antidepressants in children—suppressed by the US Food and Drug Administration—have surfaced publicly.

The Alliance for Human Research Protection, a national network dedicated to ensuring ethical standards in medical research, published the documents on 26 July.

The published documents confirm earlier news accounts that a government expert with the FDA’s Office of Drug Safety, Dr Andrew Mosholder, found that children taking antidepressants were twice as likely to become suicidal as children taking placebo. He reportedly urged the agency to follow the lead of British health authorities by warning doctors that the risks of the newer antidepressants, except fluoxetine, might outweigh the benefits when used in children.

The leaked documents show his data and conclusions. The FDA has subsequently acknowledged to the BMJ that Dr Mosholder was prevented from presenting his report at an advisory committee meeting on 2 February and was told that if he was asked any questions during the meeting he could respond to queries only by using a prepared script approved by his supervisors.

Dr Mosholder had evaluated data from 22 studies using nine drugs in
4250 children and found that 74 of the 2298 children taking antidepressants had a “suicide related event” compared with 34 of the 1952 children taking placebos.

When questioned about the decision to suppress Dr Mosholder’s report, Dr Robert Temple, associate director for medical policy in the FDA’s drug evaluation centre, defended the agency’s actions. “We thought the analysis was premature,” he told the BMJ.

Both the raw data and Dr Mosholder’s interpretation were “imperfect” said Dr Temple, adding that some of the behaviours labelled “suicidal” were highly suspect and could have been accidents, such as a child “who hit her head with her hand.” FDA officials acknowledged, however, that some cases classified as “accidental injury” could be suicide related. Because of this, the FDA has contracted with Columbia University to further study and classify events that might be considered to be suicide related.

Some of these events, he added, such as superficial cutting, “might be due to anxiety” and not represent true suicidal intent.

Dr Thomas Laughren, the FDA’s team leader for psychiatric drug products, told the BMJ that he had reported the relative risk ratios of all the drugs evaluated at the advisory meeting and that it was Dr Mosholder’s conclusions, and not the data, that were withheld.

Responding to critics who say studies of antidepressants other than fluoxetine show little or no efficacy in children, Dr Temple said absence of proof should not be interpreted to mean the drugs are ineffective.

Dr Jerome Hoffman, an epidemiologist and professor of medicine at the
University of California at Los Angeles, told the BMJ that the flip side of Dr Temple’s claim that antidepressants in children could be life-saving is that they could be life threatening—as suggested by Dr Mosholder’s report.

“Most Americans undoubtedly believe that the FDA demands reasonable evidence that a drug is safe before it is allowed to be used,” said Professor Hoffman. “But this episode suggests that they reject this `precautionary principle’ in favour of the idea that no drug is dangerous unless it is `proven’ to be so.”

“The FDA… attempted to silence Dr Mosholder [but] repeatedly claimed to `support his concern’ for the safety of children,” added Professor Hoffman, “but this apparently didn’t extend to supporting his desire to express that concern publicly. That may be the most dangerous aspect of this entire affair.”

The FDA has launched a criminal investigation to find out which employees leaked Dr Mosholder’s report. Meanwhile the suppression of the report has triggered Congressional investigations by Senator Charles Grassley, who has interviewed employees in the agency’s Office of Drug Safety, where Dr Mosholder worked.

Submitted by Anonymous on Sat, 08/14/2004 - 6:49 PM

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Add that to the mercury/immunization issues… there are some very corrupt people our there. Three cheers for people like those who leak the information.

Submitted by victoria on Sat, 08/14/2004 - 8:33 PM

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Addendum: report on Canadian news (look at CBC, Canadian Broadcasting Corporation on the web for more details)

It was reported that pregnant women who are taking antidepressants such as Prozac and Paxil may have adverse effects on the baby during birth. BUT extreme caution is advised because rapidly cutting off the medication may cause even more problems, and depressed mothers not being treated may also harm the newborn. Therefore it is NOT advised to simply stop the drugs, but rather to get close medical supervision.

Submitted by Dad on Mon, 08/16/2004 - 12:05 PM

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It cannot be emphasized enough that patients taking SSRI’s, benzos or neuroleptics should not attempt to go cold turkey. All 3 classes of drugs have to be tapered off slowly or both the mother and the fetus will risk major adverse reactions.

That being said, there has been almost zero study at the effect of taking any of these medications while pregnant, and no long-term study of what in-utero exposure does to the child as they grow.

When you filter those two facts thru the growing realization that our Fed regulators are at least as concerned with the profitability of the companies the regulate as they are the safety and afficacy of the products being tested it makes for a very uncomfortable position for the people taking these medications.

Submitted by Anonymous on Wed, 08/18/2004 - 2:54 PM

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http://www.washingtonpost.com/wp-dyn/articles/A8876-2004Aug17.html

Prozac Plus Talk Is Best for Teen Depression
Government-Funded Study Says Cognitive Behavior Therapy Boosts Drug’s Benefits

By Shankar Vedantam
Washington Post Staff Writer
Wednesday, August 18, 2004; Page A02

The best treatment for depressed adolescents is a combination of Prozac and talk therapy, although the antidepressant does carry a risk that some patients might harm themselves or others, concluded a long-awaited study released yesterday.

Although the findings may seem contradictory, the study could begin to address the roiling controversy over the safety and effectiveness of antidepressants in children: Drugs such as Prozac might increase the risk that a minority of adolescents will harm themselves or others, even as they reduce depression among the majority.

The results will be weighed by regulators at the Food and Drug Administration, who have scheduled a meeting in September to discuss analyses of antidepressant trials. Two previous agency analyses found increased signs of suicidal behavior among children taking the drugs. British authorities warned doctors last year not to prescribe most drugs called selective serotonin reuptake inhibitors to depressed children.

The new study was eagerly anticipated by doctors, parents and regulators: Virtually all clinical trials of antidepressants to date have been conducted by pharmaceutical companies. Although several researchers who conducted the new study have done work for the pharmaceutical industry, the new study was paid for entirely by taxpayers.

Thomas Insel, director of the National Institute of Mental Health, which paid $17 million for the study, said the study strongly tilted the risk-benefit ratio in favor of employing Prozac to treat depression. At the same time, Insel said, the increased risk of harm among children who got Prozac was worrisome, and he indicated that the drug had to be used cautiously.

“You can’t write a prescription for Prozac the way you write a prescription for penicillin,” he said in an interview last week. “There is no question there is an increase of adverse events on the drug — there is more than a twofold increase in adverse events in those who are on the drug versus those who are not. That’s a lot.”

Critics of the drugs have seized on the signs of risk to demand the medications be more tightly regulated or even banned. Congressional investigations are underway into whether drug companies deliberately concealed information about dangerous side effects.

Most American psychiatrists, who generally favor the drugs, point to the risks of leaving depression untreated. Yesterday’s study indicated that Prozac was effective in treating depression and that it was superior to a form of psychotherapy called cognitive behavior therapy. Combining the medication with cognitive behavior therapy produced the best results.

The study hinted that adolescents who got both drug and talk therapy had a lower risk of harming themselves or others compared with those who got the drug alone.

The challenge for clinicians and researchers, Insel said, was to try to tease apart the subgroup of children who might be adversely affected from those who could be helped.

Although this particular study recruited a broader range of patients than trials conducted by drug companies, Insel and other researchers cautioned that adolescents at high risk of suicide were excluded. Questions have grown about whether such patients are the most likely to be helped by antidepressants or the most likely to harm themselves.

In the study published in this week’s Journal of the American Medical Association, seven adolescents among the 439 in the study attempted suicide during the 12-week trial. Four were getting Prozac and cognitive behavior therapy, two were getting Prozac alone, and one was receiving cognitive behavior therapy alone.

Insel, Susan Silva, an associate research professor of psychiatry and behavioral sciences at Duke University, and Richard Glass, a psychiatrist at the University of Chicago and deputy editor at JAMA who wrote an editorial accompanying the study, all warned against drawing broad conclusions from the small numbers of adolescents who harmed themselves or others.

Two internal FDA analyses of the pharmaceutical industry trials have suggested an increased risk of suicidal behavior among children getting antidepressants. But taken individually, the industry studies have been inconsistent, and pooling their results has proven complicated. Researchers have also struggled with whether harmful behaviors such as self-mutilation should be classified as suicide attempts. No child has committed suicide in any of the trials.

“At this point, the data is still equivocal and raises many more questions than it answers,” said David Fassler, a child psychiatrist who spoke on behalf of the American Psychiatric Association. “We need to take any risk of suicide very seriously, but we also need to weigh it against the risk of suicide in kids who are not treated.”

The study showed that about 61 percent of depressed 12- to 17-year-olds getting Prozac — and 71 percent of those getting Prozac and cognitive behavior therapy — improved significantly. About 43 percent of adolescents getting cognitive behavior therapy improved to the same extent. About 35 percent of adolescents getting sugar pills were rated as much improved.

Adolescents with suicidal thinking at the start of the trial showed declines in such behavior irrespective of whether they got medication, psychotherapy or sugar pills. Insel said this highlighted the importance of recognizing depression and treating it.

“Untreated depression is by itself fatal, and even placebo with usual care will confer some protection,” he said.

Critics say the drugs make patients suicidal by causing violent inner restlessness, but proponents advocate alternate theories about why an antidepressant might increase the risk of suicide: Some patients might not have depression but manic-depressive, or bipolar, disorder, and an antidepressant could push one into mania.

Or healing depression might itself briefly increase the risk of suicide. “I was taught that as a resident in 1976,” Insel said. “A person who is severely depressed is at greatest risk [for suicide] not at the deepest point of depression, but as they are coming out of it.”

The study found that 11.9 percent of adolescents given Prozac harmed themselves or others. The category included suicide attempts, suicidal thinking, self-harm without suicidal thinking and aggressive behavior. And 8.4 percent of those who got a combination of Prozac and cognitive behavior therapy, whereas 4.5 percent of those who got just cognitive behavior therapy, showed such adverse effects. In the comparison group, adolescents getting a placebo, 5.4 percent showed such harmful behaviors.

Submitted by Dad on Thu, 08/19/2004 - 12:30 PM

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Yes, I would have posted this had you not beaten me to it. This latest news blurb does little to quell my unease at our pill-popping culture. I find it interesting that our regulators express mild caution at the results of this, when regulators in other countries (Europe) have viewed similar study results and come to a diametrically opposite conclusion, and banned the use of SSRI’s in minors.

I am curious about a few things in this report…

“In the study published in this week’s Journal of the American Medical Association, seven adolescents among the 439 in the study attempted suicide during the 12-week trial. Four were getting Prozac and cognitive behavior therapy, two were getting Prozac alone, and one was receiving cognitive behavior therapy alone. ”

None of the teens taking sugar pills attempted suicide… I understand the reasoning of heightened risk as patients come out of depression, and this certainly would fall in line with that. However, it occurs to me that knowing this iatrogenic risk is present we should see a greater degree of care and monitoring take place than we sometimes see.

“The study found that 11.9 percent of adolescents given Prozac harmed themselves or others. The category included suicide attempts, suicidal thinking, self-harm without suicidal thinking and aggressive behavior. And 8.4 percent of those who got a combination of Prozac and cognitive behavior therapy, whereas 4.5 percent of those who got just cognitive behavior therapy, showed such adverse effects. In the comparison group, adolescents getting a placebo, 5.4 percent showed such harmful behaviors.”

So using SSRI’s alone more than doubled the risk of aggressive actions in teens… Not very comforting I should think to parents who must weigh the decisions of treatment options.

I do not think this matter has been satisfactorily settled with this latest report. The fact that the tax-funded study mirrors the studies industry conducted and suppressed is harldy a thumbs up for the SSRI industry.

I fully believe that some patients are greatly helped with these medications. That being said, the fact that some are also harmed should not be glossed over. What we need is a better understanding of why some patients respond favorably and some do not so that we can better ensure that powerful medications like these are dispensed appropriately.

And I do not like the rampant “off-label” usage of medications contrary to FDA approval.

Submitted by Anonymous on Thu, 08/19/2004 - 2:56 PM

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“The study found that 11.9 percent of adolescents given Prozac harmed themselves or others. The category included suicide attempts, suicidal thinking, self-harm without suicidal thinking and aggressive behavior. And 8.4 percent of those who got a combination of Prozac and cognitive behavior therapy, whereas 4.5 percent of those who got just cognitive behavior therapy, showed such adverse effects. In the comparison group, adolescents getting a placebo, 5.4 percent showed such harmful behaviors.”

Yes, but switch these numbers around and see how it sounds: 89.1% of the children taking Prozac alone did not harm themselves or others, 92.6 % of those who got Prozac plus CBT did not show suicdidal thinking, etc. Tbose are pretty large majorities. I completely agree that SSRI medication should only be used after great thought after fullly educating the patient and his family and with the patient under close supervision. What I think is misleading about many of the articles we see on this subject is that they tend to present the information is a sensationalistic manner and lead parents to think that suicidal behavior or agression is a likely result of taking these medications. That is simply not true and may end up harming children and teens who truly need the medication and don’t get it because their parents have been made overly fearful.

Submitted by Anonymous on Fri, 08/20/2004 - 2:51 PM

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[quote=”Dad”]Using your same way of looking at this, 94.6% of children receiving neither active medication or therapy did not harm themselves or others.

Perhaps we should be prescribing sugar pills to children…[/quote]

Well, the study did show that even a sugar pill had a positive effect. However, compare these numbers, also reported in the article:

“The study showed that about 61 percent of depressed 12- to 17-year-olds getting Prozac — and 71 percent of those getting Prozac and cognitive behavior therapy — improved significantly. About 43 percent of adolescents getting cognitive behavior therapy improved to the same extent. About 35 percent of adolescents getting sugar pills were rated as much improved. ”

The extent of improvement doubled when depressed adolescents received Prozac plus talk therapy vs. a placebo. On Prozac alone, 61 percent improved significantly vs. 35% for a sugar pill. Prozac treated patients also showed significantly more improvement than those treated only with CBT: 61% vs. 43%. In other words, the majority of patients receiving Prozac, alone or in combination with CBT, showed significant improvement while the majority of patients treated with CBT or placebo did not. That is important information for any parent of a depressed child and newspaper articles seldom highlight that kind of information. I posted this article because I thought it offered a balanced discussion of the risks and benefits that would be helpful to those who find themselves in the position of having to decide on the best course of treatment for a depressed child.

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