Did FDA Include Evidence of Brain Damage Caused by Antipsychotics?

The new generation antipsychotic drugs were all approved without proof of efficacy–they were approved to treat psychosis in adults merely on the speculative basis, "proof in principle."

Since their marketing approval, a mountain of evidence documents the measurable, severe hazards of these drugs–including debilitating chronic disease and cardiac arrest.  The drugs induce obesity, type II diabetes, metabolic syndrome, hormonal and sexual malfunction, hyperglycemia, cardiovascular and liver abnormalities, and sudden death.

These toxic drugs have become the pharmaceutical industry’s most profitable products, primarily due to deceptive marketing practices and collusion by psychiatry’s academic leaders and professional institutions who are financially indebted to psychopharmacologic drug manufacturers.

Evidence demonstrates that the hazards of antipsychotics are even more damaging for children. Nevertheless, they are irresponsibly being prescribed for children who are not even psychotic. Indeed, as documented by a Vanderbilt University study, only one-third of the antipsychotic prescriptions for use in children were for bipolar or schizophrenia.
Instead, nearly 30% were prescribed to kids diagnosed with attention deficit hyperactivity disorder–and nearly 15% were prescribed for children and adolescents with no psychiatric diagnosis at all.

Given the hazards and documented misuse of these toxic drugs, why is the FDA even considering lending the government seal of approval for these largely misused drugs for children?

Among the most damaging scientific evidence against the use of antipsychotic drugs is empirical evidence that they cause brain damage. The evidence of brain damage has been documented by pillars of biological psychiatry, including Dr. Nancy Andreasen, the former editor-in-chief of the American Journal of Psychiatry. In a 2008 interview in the New York Times (below), Dr. Nancy Andreasen revealed that her exhaustive brain imaging research documented brain damage:

"The big finding is that people with schizophrenia are losing brain tissue at a more rapid rate than healthy people of comparable age. Some are losing as much as 1 percent per year. That’s an awful lot over an 18-year period…Another thing we’ve discovered is that the more drugs you’ve been given, the more brain tissue you lose." 

Q. WHY DO YOU THINK THIS IS HAPPENING?

A. "Well, what exactly do these drugs do? They block basal ganglia activity. The prefrontal cortex doesn’t get the input it needs and is being shut down by drugs. That reduces the psychotic symptoms. It also causes the prefrontal cortex to slowly atrophy."

If I were developing new drugs, I’d switch targets. Till now it’s been chemically formulated targets. I believe we should be thinking more anatomically and asking, "With schizophrenics, which brain regions are functioning abnormally?"

Q. ARE YOU WORRIED YOUR FINDINGS MIGHT BE MISUSED?

A. "The reason I sat on these findings for a couple of years was that I just wanted to be absolutely sure it was true. My biggest fear is that people who need the drugs will stop taking them. "

Q. WHAT ARE THE POLICY IMPLICATIONS OF THIS FINDING?

Implication 1: these drugs have to be used at the lowest possible dose, which often doesn’t happen now.
Implication 2: we need to find other drugs that work on other systems and parts of the brain.
Implication 3: whatever medications we use need to be combined with more nonmedication-oriented treatments, like cognitive or social therapies.

Did the FDA invite presentations to the advisory panel from any of the scientists who have documented evidence of a causal relationship between these drugs and brain damage?

U.S. law permits a physician to prescribe any FDA-approved drug for any medically supportable purpose. The physician bears greater responsibility when prescribing a drug off-label: he / she must become fully informed about the risks before prescribing a drug for an unapproved use–as such a use is experimental. 

If the FDA lends the government seal of approval for marketing antipsychotics for children, doctors will assume–wrongly–that the drugs are safe.  Drug manufacturers will reap the benefit in measurable increased sales, while children will suffer the consequences for years to come.
 

Posted by  Vera Hassner Sharav

 

NATIONAL PUBLIC RADIO
FDA Debates Safety Of Antipsychotic Drugs In Kids
by Joseph Shapiro

Listen Now [3 min 33 sec] add to playlist | download

Morning Edition, June 9, 2009 . A panel of medical experts for the federal Food and Drug Administration is being asked to approve three powerful and expensive antipsychotic drugs for use in children. The FDA panel begins a two-day meeting outside Washington on Tuesday and is scheduled to vote Wednesday on whether to approve the drugs.

The hearing and the vote highlight growing use of these drugs by children, even as questions remain about their side effects.

The medications – Seroquel, Zyprexa and Geodon – are already approved for adults. Many doctors and parents say they can also be life-changing for children and adolescents with schizophrenia and bipolar disorder. Doctors already prescribe them to kids, even without FDA approval.

A Daughter’s Milestone

Christina Bagno, of Brooklyn, N.Y., will testify about her 7-year-old daughter, who has been diagnosed with pediatric bipolar disorder.

"Back when she was 3 and before we tried medication, I wondered if she would be alive, frankly, you know, or at least living in our home," says Bagno, "because her own rages were so very scary and destructive. She would bite herself – to the point of bite marks up and down her arm, and banging her head. And now she doesn’t have the rages that she once had."

Until her daughter began those medications, she had hallucinations of explosions and dangerous things that kept her in a frequent state of anxiety and terror, Bagno says. Now she’s able to settle down in school. She’s learning to read and do basic math this year.

And there was another milestone this past weekend: her first sleepover with a friend.

"It was tremendous, and she was just so happy," says Bagno, who belongs to a group called Families for Depression Awareness. "It was a joy to watch – just to see her have a friend like that and have her be able to sit and watch a movie with a friend and have a pillow fight and just do all these things that kids do is just, really, a blessing."

Measuring Side Effects

Last week, FDA staff members released reports saying the three drugs do help kids, but that there are serious side effects. They can cause sedation, heavy weight gain and other problems that can lead to heart disease and diabetes.

"If these children are starting these medications at very young ages, they’re likely to be on them for many years," says Dr. William Cooper, a professor of pediatrics at Vanderbilt University School of Medicine. "So the adverse effects, such as weight gain, increased lipids, increased blood sugar are likely to have potentially long-term and important side effects for these children."

Cooper says bad outcomes may be worse in kids than they are in adults, and there needs to be more study of the side effects in children.

After seeing a lot of kids coming to his clinic who had been prescribed these expensive and heavily marketed medications designed for adults, Cooper did a national survey. He found that the number of prescriptions to children had increased five times over a recent seven-year period.

Over a similar period, another study found, the number of children diagnosed with bipolar disorder had increased 40 times. Still, Cooper says that doesn’t explain all of the increase in the use of antipsychotics among children and adolescents.

Cooper says he was surprised that, in most cases in his survey, doctors weren’t prescribing the drugs for serious mental illness. "Only one-third of the use was for bipolar or schizophrenia," says Cooper.

Instead, nearly 30 percent were prescribed to kids diagnosed with attention deficit hyperactivity disorder; nearly 15 percent went to children and adolescents with no psychiatric diagnosis at all.

Mental Health Groups Urge Approval

Still, Cooper thinks these medications are important tools to help children with bipolar disorder and schizophrenia. Most pediatricians and child psychiatrists agree. The FDA has already approved two similar antipsychotic drugs for children.

On the eve of the hearing, a coalition of nine national mental health and suicide prevention organizations released a letter urging the FDA committee to keep the drugs available.

"Like cancer, aggressive treatment may be needed for some patients with bipolar disorder and schizophrenia, diseases with a higher risk of death than some forms of cancer," the groups said in the letter. They added that "no one treatment option works for all children," and that physicians and families need "a full range of medications and treatment options." The groups also called for more long-term research about the risks and benefits of these drugs to children.
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THE NEW YORK TIMES
September 16, 2008
A Conversation With Nancy C. Andreasen
Using Imaging to Look at Changes in the Brain
By CLAUDIA DREIFUS

Dr. Nancy C. Andreasen concentrates on the big questions. A neuroscientist and psychiatrist at the University of Iowa, she uses M.R.I. to ask questions
like: How do the nervous systems of extremely creative people differ from those of the rest of us? How is the brain physiology of the mentally ill different from that of normal people? For nearly two decades, she has been conducting a study that tracks long-term changes in the brain. We spoke this summer when she visited New York City. An edited version of a three-hour conversation follows:

Q. HOW DID YOU BECOME A PSYCHIATRIST?
A. I was an English professor in the early 1960s. I’d done a book on John Donne. Then, in 1964, I gave birth to my first child and nearly died from a postpartum infection – the very thing that had killed millions of birthing women in the centuries before antibiotics. As I recovered, I realized I had been given back my life, and that caused me to rethink everything in it. I decided to quit literature studies and go back to school to become a doctor.

From the outset, I knew I wanted to do research and patient care.
Because I elish complexity, I chose psychiatry – it’s more complicated than neurology. And I chose brain research because the brain is the most complicated organ in the body. I wanted to do something as important as the discovery of penicillin, the thing that had saved me.

Q. YOU PIONEERED THE USE OF IMAGING TECHNOLOGY FOR LEARNING ABOUT THE PHYSIOLOGY OF THE BRAIN. HOW DID THE IDEA OF USING CAT SCANS AND M.R.I.’S AS A RESEARCH TOOL COME TO YOU?
A. My first patient was a schizophrenic. After working with him, I wanted to understand how this terrible disease developed, how to stop it and to find better treatments. Right away, I began searching for new tests to assay brain activities. With the technology we had at that time, you couldn’t see brain differences easily. A lot of our information came from autopsies done on patients, but that was of limited use because you had nothing to compare it to. But then, in the early 1970s, CT scans came along. They got pictures of the inside of a living patient’s brain. I recognized the potential immediately.

The problem was convincing my colleagues. CT scans involved exposing patients to radiation. When I went to the human experimentation committee at my medical school, they went, "We don’t want you subjecting patients to radiation. Besides, you’re not going to find anything that way, anyway." It took a long time to convince them.

Q. TODAY, IMAGING STUDIES ARE ONE OF THE MAINSTAYS OF NEUROSCIENCE. WHEN DID ATTITUDES CHANGE?
A. In the early 1980s, when magnetic resonance imaging came on line.
M.R.I.’s did not expose patients to radiation, and you could see brain structures in exquisite detail. I decided to use it for a longitudinal study of brain changes over a long period of time. We’re asking: Is schizophrenia a neurodegenerative disease like Alzheimer’s?

In 1989, I began to collect subjects – some with schizophrenia and some not- and began taking pictures of their brains. With the schizophrenics, we began seeing them at the first onset of their disease, which is usually at around age 24. We recruited about 538 people with schizophrenia. Eighteen years later, we’re still following 305.

Q. AND WHAT HAVE YOU FOUND?
A. I haven’t published this yet. But I have spoken about it in public lectures. The big finding is that people with schizophrenia are losing brain tissue at a more rapid rate than healthy people of comparable age. Some are losing as much as 1 percent per year. That’s an awful lot over an 18-year period. And then we’re trying to figure out why. Another thing we’ve discovered is that the more drugs you’ve been given, the more brain tissue you lose.

Q. WHY DO YOU THINK THIS IS HAPPENING?
A. Well, what exactly do these drugs do? They block basal ganglia activity.
The prefrontal cortex doesn’t get the input it needs and is being shut down by drugs. That reduces the psychotic symptoms. It also causes the prefrontal cortex to slowly atrophy.
If I were developing new drugs, I’d switch targets. Till now it’s been chemically formulated targets. I believe we should be thinking more anatomically and asking, "With schizophrenics, which brain regions are functioning abnormally?"

Q. ARE YOU WORRIED YOUR FINDINGS MIGHT BE MISUSED?
A. The reason I sat on these findings for a couple of years was that I just wanted to be absolutely sure it was true. My biggest fear is that people who need the drugs will stop taking them.

Q. WHAT ARE THE POLICY IMPLICATIONS OF THIS FINDING?
A. Implication 1: that these drugs have to be used at the lowest possible dose, which often doesn’t happen now. There’s huge economic pressure to medicate patients very rapidly and to get them out of the hospital right away. Implication 2: we need to find other drugs that work on other systems and parts of the brain. Implication 3: whatever medications we use need to be combined with more nonmedication-oriented treatments, like cognitive or social therapies.

Q. IN YOUR LONGITUDINAL STUDY, ARE YOU ALSO LOOKING AT HOW THE NORMAL BRAIN AGES?
A. Yes. I’ve been asking, "At what point is human brain maturation complete and at what point do our brains naturally decline and lose tissue?" The answer is: the human brain continues to mature till about 25. At about 25, it plateaus for about 20 years, and at about 45, we start to lose brain tissue.

But it’s interesting: we lose brain tissue, but we don’t necessarily lose cognitive capacities. A lot of people at 50, 60, 70 or 80 are quite sharp. I can quantify their brain tissue and see they’ve lost quite a bit from what would be normal for a 45-year-old, but their cognitive abilities are not at all impaired.

Copyright 2008 The New York Times Company
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