Fwd: Expert Psychiatrists Acknowledge Drug-Induced Brain Damage

[Guest guest]

ALLIANCE FOR HUMAN RESEARCH PROTECTION Promoting Openness, Full Disclosure, and Accountability http://www.ahrp.org and http://ahrp.blogspot.com FYIIn May and September, while my husband and I were traveling, twoilluminating articles (below) were published in the national press thatdeserve special attention.On May 18, NewsWeek asked leading neurologists, psychiatrists (from Harvard,Stanford, the National Institute of Mental Health) and Robert Whitaker, theauthor  of Mad in America: Bad Science, Bad Medicine, and the EnduringMistreatment of the Mentally Ill, what has been learned about the Biology ofBipolar Disorder--its possible genetic and neurological roots. NewsWeek reporter, Mary Carmichael posed two probing questions to theexperts:1. "What do we know about the genetics of bipolar disorder?"Dr. ROSS BALDESSARINI, Harvard: "People have tried genetic studies, but theyhaven't gotten all that far. It's been difficult in adults, and it's atleast that fuzzy in children."Dr. JANET WOZNIAK, Harvard: "In psychiatry all we have is the symptoms. Wedon't have the tests yet."Dr. KIKI CHANG, Stanford: "Right now, there's really no good way we have tointegrate what we've found so far regarding biological markers into ourclinical practice." Noting that "Children with bipolar disease are often given powerfulmedications," NewsWeek asked the experts:2. "How might psychoactive drugs affect a developing brain?"  Dr. ELLEN LEIBENLUFT, NIMH: "...we don't really have data as to what thesedrugs do to the brain."Dr. BALDESSARINI:  "Almost any psychotropic drug that's given for more thana few weeks leads to changes in brain function such that when you stop, thebrain has to reset its thermostat. If you withdraw abruptly or rapidlythere's a very high risk of recurrence of the illness that you're treating."Dr. WOZNIAK: "Our tools are not advanced enough to fully explain theextraordinary complexity of the brain. We have a general knowledge about,for example, dopamine: some drugs act as dopamine antagonists. But pleasedon't believe the idea that we understand everything that this medicine isdoing. I think part of our job as clinicians is to help parents understandhow little we know" ROBERT WHITAKER: "The frontal lobes are still developing when kids are 19 or20. Nature has honed that development over millions of years, and you muckwith that at some risk. When you put a kid on a psychotropic drug, the brainwill try to compensate and you will end up with a changed brain. Let's startwith the anti-psychotics-the standard ones block dopamine in the brain.There are three dopaminergic tracts, one that controls motor movement; onein the limbic system, related to emotions and paranoia; and one in thefrontal lobes. The drugs perturb normal function in these areas, and thebrain tries to compensate for that. Initially what will happen is theneurons release a bit of extra dopamine. That compensatory mechanism burnsout after a while, but people on anti-psychotics also end up with a dramaticincrease in dopamine receptors, and it may never come back to normal. Onceyou're in that unusual state, you're actually more vulnerable to psychosisthan you were in the first place. So when a kid is coming off his meds, it'snot the same as if he'd never been put on them."On September 16, The New York Times published a conversation with NancyAndreasen MD, PhD, a prominent neuroscientist /psychiatrist, who is thedirector of both the Iowa Mental Health Clinical Research Center and thePsychiatric Iowa Neuroimaging Consortium. She is regarded as one of theworld's foremost authorities on schizophrenia who is largely responsible fordeveloping  the concept of negative symptoms in schizophrenia. She served onboth the DSM III and DSM IV Task Forces and was the chair of theSchizophrenia Work Group for DSM IV. Dr. Andreasen is the author of  attrilogy: "The Broken Brain: The Biological Revolution in Psychiatry" (1984);"Brave New Brain: Conquering Mental Illness in the Era of the Genome"(2001); and "The Creating Brain: The Neuroscience of Genius" (2005).  The Times describes Dr. Andreasen as someone who "concentrates on the bigquestions."In the interview, Dr. Andreasen acknowledges that her 18-year follow-upstudy shows that the drugs used to treat psychotic symptoms cause the brainto shrink:"The big finding is that people with schizophrenia are losing brain tissueat a more rapid rate than healthy people of comparable age. Some are losingas 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 isthat 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 downby drugs. That reduces the psychotic symptoms. It also causes the prefrontalcortex to slowly atrophy.If I were developing new drugs, I'd switch targets. Till now it's beenchemically formulated targets. I believe we should be thinking moreanatomically and asking, "With schizophrenics, which brain regions arefunctioning abnormally?"*** These are the very drugs that are currently being widely andindiscriminately prescribed for children!Inexplicably-from a moral human perspective-both the Times reporter and Dr.Andreasen evade the essential question: What is the medical justification for prescribing toxic drugs forchildren--even after the damaging effects on adult brains have beendocumented?Instead, Claudia Dreifus asks Dr. Andreasen:  "ARE YOU WORRIED YOUR FINDINGSMIGHT BE MISUSED?"Dr. Andreasen's answer is mind boggling outside the field of psychiatry:A. "The reason I sat on these findings for a couple of years was that I justwanted to be absolutely sure it was true. My biggest fear is that people whoneed the drugs will stop taking them."Two questions that should have been asked of Dr. Andreasen: Why in the world should people prescribed brain damaging drugs NOT stoptaking them?Isn't it unethical to withhold publication of important negative findingsabout the hazards of currently prescribed drugs? Dr. Andreasen served as the Editor-in-Chief of the American Journal ofPsychiatry for 13 years. Her deputy editor, Dr. Jack Gorman, was a majorpharmaceutical industry promoter who was publicly discredited and barredfrom ever practicing medicine in Massachusetts. A noteworthy demonstration of psychiatry's head-in-the-sand denial ofreality is the following pronouncement by the APA:"The past 13 years have been perfect for Nancy and perfect for the Journal;the result has been perfect for Psychiatry."http://ajp.psychiatryonline.org/cgi/content/full/163/1/3  No doubt, these 13 years were PERFECT FOR PSYCHIATRY'S CASH FLOW.Reality Check: * This was the period during which psychiatry's diagnostic and therapeuticpractices have been shown to lack a validated scientific foundation. * Psychiatry's prescribing practices--e.g. TMAP, CMAP, TRAYY--have beeninfluenced by drug manufacturers--and their partners in academia. * Indeed, this was a period when psychiatry's academic leaders were shown tohave penned their name for cash to ghostwritten reports that polluted thescientific literature.* This was the period during which psychiatrists promoted off-label untesteduses of antidepressants and antipsychotics--singly and in untestedcocktails--for children--even when the drugs were known to be toxicresulting in serious harm.Contact: Vera Hassner Sharavveracare212-595-8974http://www.newsweek.com/id/137625Newsweek Web ExclusiveThe Biology of Bipolar DisorderWhat scientists have learned about the genetic and neurological roots ofthis complex illness.Mary CarmichaelMay 18, 2008 Bipolar disorder has come out of the shadows. Most people have heard of thedisease, which used to be shrouded in stigma and mystery. But there's stilla great deal unknown about how and why the disorder arises, what's happeningin the brains of those afflicted, and how best to treat it. NEWSWEEK's MaryCarmichael asked the psychiatrists and psychologists who are conductingcutting-edge research to explain what they do know. (Read more about howbipolar disease is diagnosed in children here and find out how parents ofbipolar children can get help here.)WHAT'S GOING ON IN A BIPOLAR CHILD'S BRAIN?Ellen Leibenluft, chief of the Section on Bipolar Spectrum Disorders,Emotion and Development Branch, Mood and Anxiety Disorders Program, NationalInstitute of Mental Health, Washington, DC: "We've begun to learn something about the brain mechanisms. There isevidence that the amygdala is involved in a number of disorders in bothchildren and adults, and bipolar disorder is one. The amygdala, whichprocesses emotions-it looks around the environment and says, 'what'simportant to me, what do I like, what do I not like, what am I afraidof?'-is smaller in kids with bipolar disorder, and it's also somewhathyperactive. We don't really know why the amygdala is smaller-we don't knowfor sure if that's a consequence of the disorder, or a cause of it. Onehypothesis would be there are neurotransmitters that are excitotoxic; theyfire too much and they can damage the tissue. There's also a regulatory loopbetween the amygdala and the prefrontal cortex. If the amygdala isoverreacting, it could be because the prefrontal cortex isn't doing a goodenough job of shutting it down. One of the ways that children both learn andare taught to regulate their emotions is by directing their attention awayfrom upsetting things. We have a paper from 2007 in the American Journal ofPsychiatry where we had children play a frustrating game, and what we foundwas that the bipolar children had difficulty with it when emotion was high.They could not redirect their attention. And attention is very muchcontrolled by the prefrontal cortex, among other places."Kiki Chang, associate professor of psychiatry and behavioral sciences at theStanford University School of Medicine: "When these kids are young, they're having to recruit extra brain areas todeal with hyperactivity in the amygdala. They're trying to stamp it down.But over time, if they're not treated, they're not able to do that. As theybecome adults, believe the prefrontal areas of their brain become less andless functional. We have evidence of neuronal loss. Eventually the brakeswear out. We believe that psychotherapy and medication boost those things.But we don't have it really nailed down yet. ... There are [treatment]centers that are using brain-imaging modalities to aid in diagnosis andtreatment. We're trying to spread the word that, 'hey, we're not ready forthat yet. A picture of your brain is not going to tell us what we want toknow.'"CHILDREN WITH BIPOLAR DISEASE ARE OFTEN GIVEN POWERFUL MEDICATIONS. HOWMIGHT PSYCHOACTIVE DRUGS AFFECT A DEVELOPING BRAIN ?Leibenluft: "We know about the side effects that people experience, but wedon't really have data as to what these drugs do to the brain. There is datain adults that lithium has growth-promoting effects on the brain, but wedon't know what effects there are in children. There are a few studies hereand there. You'll be seeing more and more of that in the future. Within thenext couple of years, we won't have all the answers, but we will haveprogress. ... We're always looking to develop better treatments. Everybodyworries about putting kids on medication. That's the rock and the hardplace: The first thing is, does it work or not? If you're a parent, that'swhat you want to know. You also want to know about long-term effects on thebrain, but you need to help your child today."Robert Whitaker, author, 'Mad in America: Bad Science, Bad Medicine, and theEnduring Mistreatment of the Mentally Ill:' "The brain is this incredibly complex thing, and it responds to theenvironment. The frontal lobes are still developing when kids are 19 or 20.Nature has honed that development over millions of years, and you muck withthat at some risk. When you put a kid on a psychotropic drug, the brain willtry to compensate and you will end up with a changed brain. Let's start withthe anti-psychotics-the standard ones block dopamine in the brain. There arethree dopaminergic tracts, one that controls motor movement; one in thelimbic system, related to emotions and paranoia; and one in the frontallobes. The drugs perturb normal function in these areas, and the brain triesto compensate for that. Initially what will happen is the neurons release abit of extra dopamine. That compensatory mechanism burns out after a while,but people on anti-psychotics also end up with a dramatic increase indopamine receptors, and it may never come back to normal. Once you're inthat unusual state, you're actually more vulnerable to psychosis than youwere in the first place. So when a kid is coming off his meds, it's not thesame as if he'd never been put on them. This is one of the real difficultiesfor parents. When they start down the path [of medicating], they're going tochange their child."Ross Baldessarini, professor of psychiatry, McLean Hospital, Boston: "Almost any psychotropic drug that's given for more than a few weeks leadsto changes in brain function such that when you stop, the brain has to resetits thermostat. If you withdraw abruptly or rapidly there's a very high riskof recurrence of the illness that you're treating. Some years ago we treateda young man who had been a very successful student and was just starting incollege and had a major psychotic breakdown. He got put on lithium and didvery, very well on it, but against medical advice he took himself off it.Everything was fine for a few weeks, and then all hell broke loose and hedeveloped a horrendous recurrence of psychotic mania. It was really likegetting Humpty Dumpty back together."Adelaide Robb, child psychiatrist, Children's National Medical Center,Washington, DC: "I think we don't know all the effects of medication. What we do know fromour adult work is that many of the adults who entered into treatment 10years ago never got treatment as children. And we know untreated bipolardisorder leads to a lot of bad outcomes-more symptoms, increased resistanceto treatment, less achievement, lost social interaction. It's really hard tofinish high school and it's very hard to keep a job or have anybody in yourfamily support you. We talk about medicines having side effects, but therisk of not treating also has side effects."Janet Wozniak, assistant professor of psychiatry, Harvard Medical School,Boston: "Our tools are not advanced enough to fully explain the extraordinarycomplexity of the brain. We have a general knowledge about, for example,dopamine: some drugs act as dopamine antagonists. But please don't believethe idea that we understand everything that this medicine is doing. I thinkpart of our job as clinicians is to help parents understand how little weknow. This is not an experiment or a wild guess. We are doing evidence-basedmedicine. But there is still very much that is unknown. The question is,what are the long-term effects of treatment vs. the long-term effects of notreatment? Part of making the decision of using a treatment that may haveunknown long-term effects is having some respect for how the disorder canwreak havoc. It's easy to talk about the miseries of treatment. And thetreatments are terrible. On the other hand, is life compatible with nottreating? For most of the kids I'm seeing, the answer is no."What do we know about the genetics of bipolar disorder?Baldessarini: "People have tried genetic studies, but they haven't gottenall that far. It's been difficult in adults, and it's at least that fuzzy inchildren. This illness probably has very subtle genetics, a lot like heartdisease and diabetes. It certainly runs in families, probably more than anyother psychiatric illness. But there's not a nice, crisp single gene."Wozniak: "In psychiatry all we have is the symptoms. We don't have the testsyet. One of the things we're trying to do is collect large enough samples tothoughtfully look for genes in the lab. But in general, with psychiatricillness, mapping the genome in and of itself hasn't provided us with easyanswers. We also need to figure out which genes might be protective againstbipolar disorder, and whether environmental factors determine which genesget expressed."Leibenluft: "Most children who are at risk for bipolar disorder by virtue ofhaving a parent with the illness will not themselves develop it. People havethe mistaken idea that most children of bipolar parents will develop itthemselves, and most don't. Somewhere between 15 and 30 percent, maybearound 20 percent, will develop it. But we do certainly know it's aheritable illness. We've identified a number of genes associated with smallincreases in risk, not big ones. There does appear to be some overlap inadult samples between genetics for bipolar disorder and the genetics forschizophrenia. It's a very, very rapidly evolving field. But there's a lotof work that still needs to be done."Chang: "Right now, there's really no good way we have to integrate whatwe've found so far regarding biological markers into our clinical practice.[but] it's starting to happen. John Kelsoe is marketing a test for a genethat may, in 3 to 6 percent of cases, have some relevance. He's awell-respected researcher. But this is such a complex disorder-there are somany genes that could contribute."~~~~~~~~~~~~http://www.nytimes.com/2008/09/16/health/research/16conv.htmlTHE NEW YORK TIMESSeptember 16, 2008A Conversation With Nancy C. AndreasenUsing Imaging to Look at Changes in the BrainBy CLAUDIA DREIFUSDr. Nancy C. Andreasen concentrates on the big questions. A neuroscientistand psychiatrist at the University of Iowa, she uses M.R.I. to ask questionslike: How do the nervous systems of extremely creative people differ fromthose of the rest of us? How is the brain physiology of the mentally illdifferent from that of normal people? For nearly two decades, she has beenconducting a study that tracks long-term changes in the brain. We spoke thissummer when she visited New York City. An edited version of a three-hourconversation follows:Q. HOW DID YOU BECOME A PSYCHIATRIST?A. I was an English professor in the early 1960s. I'd done a book on JohnDonne. Then, in 1964, I gave birth to my first child and nearly died from apostpartum infection - the very thing that had killed millions of birthingwomen in the centuries before antibiotics. As I recovered, I realized I hadbeen given back my life, and that caused me to rethink everything in it. Idecided 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 relish complexity, I chose psychiatry - it's more complicated thanneurology. And I chose brain research because the brain is the mostcomplicated organ in the body. I wanted to do something as important as thediscovery of penicillin, the thing that had saved me.Q. YOU PIONEERED THE USE OF IMAGING TECHNOLOGY FOR LEARNING ABOUT THEPHYSIOLOGY OF THE BRAIN. HOW DID THE IDEA OF USING CAT SCANS AND M.R.I.'S ASA RESEARCH TOOL COME TO YOU?A. My first patient was a schizophrenic. After working with him, I wanted tounderstand how this terrible disease developed, how to stop it and to findbetter treatments. Right away, I began searching for new tests to assaybrain activities. With the technology we had at that time, you couldn't seebrain differences easily. A lot of our information came from autopsies doneon patients, but that was of limited use because you had nothing to compareit to.But then, in the early 1970s, CT scans came along. They got pictures of theinside of a living patient's brain. I recognized the potential immediately.The problem was convincing my colleagues. CT scans involved exposingpatients to radiation. When I went to the human experimentation committee atmy medical school, they went, "We don't want you subjecting patients toradiation. Besides, you're not going to find anything that way, anyway." Ittook a long time to convince them.Q. TODAY, IMAGING STUDIES ARE ONE OF THE MAINSTAYS OF NEUROSCIENCE. WHEN DIDATTITUDES 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 brainstructures in exquisite detail. I decided to use it for a longitudinal studyof brain changes over a long period of time. We're asking: Is schizophreniaa 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, webegan seeing them at the first onset of their disease, which is usually ataround age 24. We recruited about 538 people with schizophrenia. Eighteenyears 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 publiclectures. The big finding is that people with schizophrenia are losing braintissue at a more rapid rate than healthy people of comparable age. Some arelosing as much as 1 percent per year. That's an awful lot over an 18-yearperiod. And then we're trying to figure out why. Another thing we'vediscovered is that the more drugs you've been given, the more brain tissueyou 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 downby drugs. That reduces the psychotic symptoms. It also causes the prefrontalcortex to slowly atrophy.If I were developing new drugs, I'd switch targets. Till now it's beenchemically formulated targets. I believe we should be thinking moreanatomically and asking, "With schizophrenics, which brain regions arefunctioning 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 justwanted to be absolutely sure it was true. My biggest fear is that people whoneed 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 possibledose, which often doesn't happen now. There's huge economic pressure tomedicate patients very rapidly and to get them out of the hospital rightaway. Implication 2: we need to find other drugs that work on other systemsand parts of the brain. Implication 3: whatever medications we use need tobe combined with more nonmedication-oriented treatments, like cognitive orsocial therapies.Q. IN YOUR LONGITUDINAL STUDY, ARE YOU ALSO LOOKING AT HOW THE NORMAL BRAINAGES?A. Yes. I've been asking, "At what point is human brain maturation completeand at what point do our brains naturally decline and lose tissue?" Theanswer 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 braintissue.But it's interesting: we lose brain tissue, but we don't necessarily losecognitive capacities. A lot of people at 50, 60, 70 or 80 are quite sharp. Ican quantify their brain tissue and see they've lost quite a bit from whatwould be normal for a 45-year-old, but their cognitive abilities are not atall impaired.~~~~~~  FAIR USE NOTICE: This may contain copyrighted (C ) material the use of whichhas not always been specifically authorized by the copyright owner. Suchmaterial is made available for educational purposes, to advanceunderstanding of human rights, democracy, scientific, moral, ethical, andsocial justice issues, etc. It is believed that this constitutes a 'fairuse' of any such copyrighted material as provided for in Title 17 U.S.C.section 107 of the US Copyright Law. This material is distributed withoutprofit. =====In accordance with Title 17 U.S.C. Section 107, this material is distributed without profit to those who have expressed a prior interest in receiving the included information for research and educational purposes.