Medication Nation

http://www.opednews.com/articles/Pediatric-Zyprexa-Brochure-by-Martha-Rosenberg-091118-587.html

By Martha Rosenberg

“Your medicine is called Olanzapine. Pronounced ‘o-lan-za-peen,’” says the lime green kids’ brochure for the antipsychotic Zyprexa, published by Britain’s National Health Service (NHS). “Many children, teenagers and young people need to take medicines prescribed by doctors to help them stay well and healthy,” says the text amid cartoons of happy children skating, roller blading and playing soccer.

Similar brochures educate children about “ris-perry-done” (Risperdal), another antipsychotic and “ato-mox-e-teen” (Strattera), an ADHD drug. But when mental health advocate Ben Hansen tried to “educate” US children further by posting the brochures on his web site bonkersinstitute.org, he got a love letter from the NHS.

“I have been informed that you are using our leaflets on your web-site,” wrote Deputy Chief Pharmacist with the Central and North West London NHS Trust Sue Eccles in an email this month. “Our objective is [sic] provide written materials to support the verbal counselling given by healthcare professionals – they are not meant to stand alone as sources of information,” says Eccles requesting that only the “front page and our contact details,” be shown.

Unfortunately, the NHS caught Hansen on a day he didn’t take his meds. “We posted the NHS leaflets to stimulate public scrutiny of your agency,” replied Hansen, who writes under the pseudonym Methodius Isaac Bonkers, MD. “We call upon the NHS to stop promoting harmful psychotropic drugs for children. In a spirit of full disclosure and transparency, we have now posted your letter as well.”

No wonder Hansen’s four-year-old site, the Bonkers Institute, is considered a leader in sunshine activism. Hansen’s zeal for unearthing and posting pharma sleight-of-hand even landed him on the front page of the New York Times two years ago in an article called,

“In Some States, Maker Oversees Use of Its Drug.”

Twenty states take advantage of the Pharmacy Quality Improvement Project, a “free” program from Eli Lilly that shows states how to save money on…drugs from Eli Lilly. But Hansen, says the Times “obtained documents through a Freedom of Information request that showed a Lilly account executive had asked to take part in planning sessions and offered to have Lilly representatives brief doctors.”

Lilly dropped the program in states daring to require doctors to seek permission to prescribe Zyprexa which at $300 a month is the single biggest drug cost for state Medicaid budgets according to the Times.

Hansen also received FOIA documents from the state of Michigan showing the number of psychiatric drugs prescribed to children under 6 and the number of Medicaid patients on 5 or more psychiatric drugs but they did not name the drugs.

How does pharma vault a drug only indicated for the one percent of the population with schizophrenia and four percent with bipolar disorder to be the biggest line item in the Medicaid budget? As in your tax dollars? Just good off-label marketing–promoting a drug for a non-FDA approved use which is illegal in the US.

And speaking of non-approved uses, how can Britain’s National Health Service produce a brochure for kids taking Zyprexa when kids are not supposed to take Zyprexa? “ZYPREXA is not for patients who are under 18 years,” says the prescribing information. “Keep out of the reach and sight of children.”

Are the healthy, active kids shown in the cartoons “befores” since 30 percent of Zyprexa patients gain 22 pounds or more, 16 percent, 66 pounds or more and some gain over 100 pounds according to Lilly’s own published data? Zyprexa “may make you feel like eating more food,” says the NHS brochure in what might be considered classic British understatement. “If this happens, try not to eat more than usual and talk to an adult or your doctor about this.” Any questions?

And how about Zyprexa’s notorious soporific effect or zombie factor? “It is a good [sic] to take olanzapine at bedtime, as it can make some people feel sleepy,” says the brochure.

Hansen’s war on pharma disease mongering comes from first hand experience. He was misdiagnosed with “bipolar disorder” and denied release in a Michigan hospital after a reaction to the death of his father and a suicide of a friend on the same day. “The psychiatrist refused to treat me without drugs,” says Hansen and “I was held in the hospital involuntarily for the next 39 days, totaling a bill of $23,000.”

Take one look at the Bonkers Institute’s gallery of vintage psychiatric drug advertising, the Nearly Genuine and Truly Marvelous Mental Medicine Show–one of the best on the web–and you see the roots of today’s pediatric bipolar/depression/ADD/ADHD “epidemic” decades ago. Thorazine syrup was given for vomiting in kids, antidepressants for bedwetting and Ritalin for “mischief” and “juvenile pranks.” Like the NHS brochures, kids are shown happy and playing with soccer balls.

Martha Rosenberg is columnist and cartoonist based in Chicago.

_________________________________________________________________

Psychiatry is to medicine what astrology is to astronomy. ~ Leonard Roy Frank

http://www.miamiherald.com/news/5min/story/1056520.html

Miami Herald
Lawsuit says too many psychiatric drugs killed boy

A disabled boy was lethally overmedicated, a lawsuit contends, as outrage continues over a child’s suicide while on several drugs last month.
BY CAROL MARBIN MILLER

Amid a wide-ranging debate over the proper use of mental health drugs on troubled children, the mother of a disabled boy who died in 2007 is claiming in a lawsuit the boy was overdosed by a cocktail of psychiatric drugs, including two powerful anti-psychotics.

Martha Quesada, the mother of 12-year-old Denis Maltez, filed a wrongful death and medical malpractice lawsuit Monday in Miami-Dade circuit court, claiming Denis’ psychiatrist, Dr. Steven L. Kaplan, and the now-shuttered Rainbow Ranch group home overmedicated Denis and failed to properly monitor his condition …

Quesada’s lawsuit was filed amid a high-profile investigation by the Department of Children & Families into the death last month of Gabriel Myers, a 7-year-old foster child who had been taking a cocktail of mental health drugs. DCF Secretary George Sheldon appointed a task force to study Gabriel’s case, and the use of psychiatric drugs on foster kids.

‘TOUGH’ TO HANDLE

Kaplan did not return calls for comment. In a June 2007 article in The Miami Herald, Kaplan said ‘’it’s possible'’ Denis would have been sleepy at school if he had not been given his medications at the right times. But, Kaplan added, “I never saw him dopey or sleepy.'’…

According to the 28-page lawsuit, Glatt stopped taking Denis to doctors at Jackson Memorial Hospital after he arrived at the group home in May 2006, and substituted Kaplan ‘’without the consent of [Denis’s] mother.'’ Kaplan was treating several group home clients, the suit claims.

Kaplan prescribed and refilled four mental health drugs: Seroquel and Zyprexa, both anti-psychotic medications; Depakote, an anti-seizure drug sometimes used to stabilize moods; and Clonazepam, a tranquilizer. The lawsuit says the drugs were used “as chemical restraints to control Denis’s behavior.'’

Though some of the medications are not approved by the Food and Drug Administration for use on children and carry strong warnings about possible side-effects, Kaplan ‘’took no steps to ensure that Denis was not suffering any adverse effects from these medications,'’ the suit claims.

In fact, the suit claims, Kaplan examined the boy only once between between May 26, 2006 and May 23, 2007, the day Denis died.
There were warning signs that the drugs may have been harming the boy, according to the suit, filed by by Fort Lauderdale attorneys Maria Elena Abate and Howard Talenfeld.
In June 2006, teachers at Denis’s school, Ruth Owens Kruse Educational Center, reported the boy was sleeping through class. …

DCF would not discuss the investigation with a reporter Tuesday.

http://nymag.com/news/features/43892/

I’d heard it was the most effective stop-smoking drug yet. So I took it. Then those reports of suicidal ideation began washing in.

By Derek de Koff
Published Feb 10, 2008

Things were looking good. My doctor had gone through the test results and told me I was perfectly healthy—except my breathing was a little shallow. That didn’t surprise me. I’d been smoking for twelve of my 32 years, and my father died of lung cancer in his early fifties. That’s why I was having my first physical in five years: I’d decided it was time to stop for good.

I’d heard about Chantix, a relatively new drug from Pfizer that blocks nicotine from attaching to your brain receptors. That way, you stop receiving any pleasure from cigarettes at all—even as the drug, snuggling up to those receptors the same way nicotine does, reduces withdrawal cravings and unleashes a happy little wash of dopamine to boot. Wonderful things they can do nowadays.

My doctor wished me luck as he wrote out the prescription, telling me it was the single most important decision I’d ever make in my life. I had the medication that night, 35 minutes after dropping into Duane Reade. While waiting, I gleefully chain-smoked Parliament Lights. One of Chantix’s big perks is that you can smoke for the first seven days you’re on it (most people take it for twelve weeks)—more than enough time, I thought, to say good-bye to an old friend.

I swallowed my first pill the next day before work. It was a beautiful fall morning, an almost obnoxiously cinematic day to turn over a new leaf. But by the time I was halfway to the office, I started to feel a slight nausea coming on. Of course, that is a common side effect, as are constipation, gas, vomiting, and changes in dreaming. These five symptoms were emblazoned in a large font on the patient-information sheet.

My stomach settled as I finished my first cup of coffee. I slipped into my boss’s office, proudly announcing that I’d just started taking Chantix. “You’ve probably seen the commercial,” I said. A CGI tortoise races against a sprightly CGI hare, while a paternal voice-over reminds us that quitting smoking “isn’t for sprinters … it’s all about getting there!” Clinical trials demonstrated a whopping 44 percent of patients were still off cigarettes after twelve weeks, the ad says. The tortoise winks knowingly.

“You know, I saw something about Chantix,” my boss said, sounding vaguely concerned. He tracked down the story on a CBS Website. It was a sensational report on Carter Albrecht, a Dallas musician formerly with Edie Brickell & New Bohemians. Albrecht had started taking Chantix with his fiancée, with seemingly dramatic side effects. She claimed he had had bizarre hallucinations that worsened when he drank. One evening, he attacked her, something he’d never done before. He then ran to his neighbor’s house and kicked at the door, screaming incomprehensibly. The neighbor was so panicked he wound up shooting Albrecht through the door, killing him.

I tried not to roll my eyes. It seemed obvious this was nothing more than scaremongering—perhaps Big Tobacco had launched a spin campaign. Millions of Americans were on Chantix. Why focus on the negative?

The next night, I nodded off listening to Radiohead’s In Rainbows, feeling a little guilty that I’d paid zero dollars for it. I had a quick blip of a dream: A dark, inky fluid was jolting violently from the corners of my ceiling, zigzagging its way across the walls and wooden floor in jerky sync to the music.

It was only a dream, though it seemed more immediate and visceral than my usual fare, which I rarely remember after waking up. The following night, things got even stranger. I fell asleep with Bravo blaring on my TV and dreamed that a red-faced Tim Gunn was pushing me against the wall. “But I always thought you were so nice,” I said.

By night four, my dreams began to take on characteristics of a David Cronenberg movie. Every time I’d drift off, I’d dream that an invisible, malevolent entity was emanating from my air conditioner, which seemed to be rattling even more than usual. I’d nap for twenty minutes or so before bolting awake with an involuntary gasp. I had the uneasy sense that I wasn’t alone.

I smoked a cigarette, then tried going back to sleep. But each time I started napping, I’d dream that something increasingly ominous—carbon monoxide? Vampires?—was sucking vital essence out of me. Soon the clock on my desk read 3:20 a.m.

The most unsettling thing about sleeping on Chantix is that I never felt like I was truly asleep. Some part of me remained on guard. It was more like lucid dreaming, what I thought it might feel like to be hypnotized. And it didn’t entirely go away come morning. As I showered, shaved, and scrambled into clothes, I tried to shake a weird, paranoid sense that I’d just been psychically raped by a household appliance.

Pages: 1 · 2

http://www.bloomberg.com/apps/news?pid=20601124&sid=a4V6UEpXf_mY&refer=home

Bloomberg News
Grassley Probes Financing of Advocacy Group for Mental Health
By Nicole Gaouette
April 6

U.S. Senator Charles Grassley expanded his investigation into drug company influence on the practice of medicine by asking a nonprofit mental-health- advocacy group about its funding.

In a letter sent today to the National Alliance for Mental Illness, based in Arlington, Virginia, Grassley asked the nonprofit group to disclose any financial backing from drug companies or from foundations created by the industry.

The Iowa Republican, in a series of hearings and investigations, has focused on financial ties between the drug industry, doctors and academic institutions. His efforts have led New York-based Pfizer Inc. to begin disclosing consulting payments to U.S. doctors, and Harvard Medical School in Boston to reexamine its conflict-of-interest policies. Now Grassley is expanding his inquiries to nonprofit groups.

“I have come to understand that money from the pharmaceutical industry shapes the practices of nonprofit organizations which purport to be independent in their viewpoints and actions,” Grassley wrote in his letter.

Officials at the National Alliance for Mental Illness didn’t return calls for comment.

The group identifies itself as the largest grassroots organization in the U.S. for people with mental illness and their families. The group came under scrutiny in 1999, when the magazine Mother Jones reported that 18 drug companies gave the group $11.7 million from 1996 to mid-1999. The article reported that at one point an executive of Indianapolis-based Eli Lilly & Co. worked out of the nonprofit group’s headquarters.

A 2007 annual report showed that the group’s corporate partners at that time included Madison, New Jersey-based Wyeth; London-based GlaxoSmithKline Plc; Eli Lilly, which makes Prozac; and the Washington-based trade group Pharmaceutical Research and Manufacturers of America.

Financial Report

A separate financial report shows the National Alliance for Mental Illness brought in $10.5 million in contributions in the year that ended June 30, 2007. The donors aren’t broken out.

Vera Sharav, president of the Alliance for Human Research Protection, a New York-based nonprofit that promotes ethical research, said the National Alliance for Mental Illness may have drawn Grassley’s attention because it lobbies Congress for mental-health funding.

“Academics and physicians give an appearance of authority,” Sharav said by telephone. “Industry gives them the money. Grassley has been going after each group systematically, and the dots are being connected.”

In January, Grassley and Senator Herb Kohl, a Wisconsin Democrat, reintroduced the Physician Payment Sunshine Act, which would require manufacturers to report on payments to doctors and any physician-owned facility.

Pfizer Announcement

Grassley’s investigations have led to changes in industry and academia. Pfizer made its announcement about disclosing physician payments in February. In March, the American Psychiatric Association said it would no longer accept industry support for symposiums and meals at its annual meetings.

On April 1, Stanford University School of Medicine, near Palo Alto, California, said it would post on a Web site all income faculty earned from royalty payments and outside consulting.

In the March 31 issue of the Journal of the American Medical Association, a group of researchers and physicians called for professional medical associations to transform their operations to avoid conflicts of interest posed by “extensive funding from pharmaceutical and device companies.” The group included Steven Nissen, a Cleveland Clinic cardiologist.

http://www.google.com/hostednews/ap/article/ALeqM5gZKV2jQ28z5DgCou7jApK7RUHqMQD96IRMOG1

18 hours ago

BOSTON (AP) — Drugmaker Forest Laboratories Inc. offered kickbacks to doctors for prescribing its antidepressants Celexa and Lexapro and pushed the drugs for unapproved use on children, according to a complaint filed Wednesday by federal prosecutors.

The New York-based drugmaker offered cash payments, expensive meals and entertainment to induce doctors and others to prescribe the drugs, the complaint said. It also accused Forest of promoting Celexa for pediatric use, even though a study showed it was no more effective than a placebo for children.

The allegations were contained in a suit the Department of Justice filed in federal court alleging Forest triggered thousands of fraudulent claims to federal health care programs like Medicaid.

Forest executive Frank Murdolo said he hasn’t seen the complaint and could not comment on it. But he said it stemmed from a federal government investigation into his company’s marketing practices that dates back to 2004.

The vice president of investor relations said Forest has disclosed this investigation in filings with the Securities and Exchange Commission.

“It’s the formalization of that investigation, basically, but it’s not new as far as a disclosure issue to the company,” he said.

The complaint also said the Celexa study found that more patients taking the drug attempted suicide or reported suicidal thoughts than those taking the placebo. The Food and Drug Administration denied Forest’s request to sell the drug for children, but that failed to dissuade the drugmaker.

“Over the course of more than half a decade, Forest illegally marketed two related antidepressant drugs, Celexa and Lexapro, for off-label use in pediatric patients when both drugs had been approved only for adult use,” the complaint states.

Pharmaceutical companies are prohibited from promoting drugs for uses not approved by the Food and Drug Administration.

Shares of Forest Laboratories fell $1.29, or 5.3 percent, Wednesday.

Copyright © 2009 The Associated Press. All rights reserved.

This is just the first of eight pages, please read the full article: http://www.rollingstone.com/politics/story/25569107/bitter_pill

Created to treat schizophrenia, Zyprexa wound up being used on misbehaving kids. How the pharmaceutical industry turned a flawed and dangerous drug into a $16 billion bonanza

BEN WALLACE-WELLSPosted Jan 28, 2009 3:10 PM

In June 1992, not long after the place closed down, a Harvard-trained psychologist named Sergio Pirrotta walked out of Danvers State Hospital for the last time. The psychiatric facility, at this late date, was a baggy old thing, rectangled into a field just north of Boston; whole wings were barely occupied, and vandals had already begun to rip out the mantelpieces and furniture. The hospital had been slowly, incrementally shutting down for a decade, and the patients that remained were the hardest cases, mostly schizophrenics and those with disorders too dense and weird to classify. But now, as Pirrotta took a walk around the campus, even those patients were gone: released into the larger world to fend for themselves or bused to hospitals where the staffs had little psychiatric training.

Pirrotta had come to Danvers in the mid-1970s to rehabilitate children whom the courts had declared insane. Back then the place was overpopulated, the halls packed with madmen who would wander around smoking cigarettes, leering and lunging at the kids. In those days, the drugs used to treat mental illness were crude and ugly things. Thorazine was the best, and it made you into a ghouled and lifeless ogre — your face seized up involuntarily, you kept shuffling around, you were an emotional drone. But gradually the medications got a little bit better, the pharmacology more precise. First there was haloperidol, similar to Thorazine but with less-vivid side effects. Then clozapine, which had at first seemed a wonder drug, before it turned out to trigger a potentially fatal immune deficiency in two cases out of a hundred.

The patients at Danvers, their symptoms softened by the new medications, began to venture forth, almost miraculously, into the world beyond the hospital. Pirrotta took a group that included schizophrenics to a children’s camp in New Hampshire, off-season, where they spent a week cleaning and grooming the grounds. “For most of them, it was the first time they’d been out of an institution in their adult lives,” he recalls. But the state’s budget crunchers had wanted to close places like Danvers for years — pills, after all, were far cheaper than hospitals — and the new drugs made the move clinically defensible. To the staff at Danvers, it seemed as if the state had abandoned its responsibilities to the mentally ill. “It felt like we’d been sold a bill of goods,” Pirrotta says. “It felt like a betrayal.”

By 1992, when Danvers closed, something even more vivid and hopeful was looming: A whole new class of drugs, called atypical antipsychotics, were being tested in clinical trials. The atypicals held the promise of a more perfect tranquilizer, one that would calm the storms of schizophrenia while eliminating the side effects that made the older drugs so despised. Psychiatrists reserved their greatest excitement for a molecule being developed by Eli Lilly, a pharmaceutical company based in Indianapolis. The new chemical mirrored the powers of clozapine but without its fatal flaw. It was called olanzapine, and the scientists working on it believed it might be the One.

Dr. William Wirshing, a UCLA psychiatrist who had a grant from Lilly to conduct clinical trials on olanzapine, was one of those enthused by the early results. He believed the hype was warranted, and Lilly was flying him around the country to brief other psychiatrists on his work and to seed excitement for the coming medication. Then one morning in 1995, as Wirshing was driving to LAX to catch a pre-dawn flight, a story came on the radio about olanzapine. Wirshing listened in astonishment as a top Lilly executive announced the company’s plans for the new drug, which it was preparing to market under the name Zyprexa.

“He says it’s got the potential to be a billion-dollar-a-year drug,” Wirshing recalls. “I almost pulled off the road and crashed into the side rail.” At the time, the entire market for atypical antipsychotics was only $170 million. “How the hell do you make $1 billion?” Wirshing thought. “I mean, who are we gonna give it to? It’s not like we’re making any more schizophrenic brains.”

There is a well-known feature of medical science called the placebo effect, which suggests that, in a clinical trial, patients who are told they are being medicated but are in fact given only a sugar pill will see their symptoms improve, merely out of the misplaced conviction that they are being healed. During the late 1990s, and then with increasing speed during the current decade, Wirshing and other psychiatrists watched as the market for atypical antipsychotics swelled well beyond its marked territory, far exceeding the country’s supply of schizophrenic brains — past $2 billion a year, $5 billion, $10 billion, all the way to $16 billion. What had begun as niche drugs are now the third-largest class of medication in the world, their sales greater than those of the antidepressants. The mechanisms used to leverage this growth were in some ways the most modern and perfect the pharmaceutical industry had developed, but they were also, according to state and federal prosecutors, illegal. Lilly has already agreed to pay $2.6 billion to settle charges that it built the market for Zyprexa first by concealing its side effects, and then by marketing it “off-label,” for diseases for which it had not been approved.

“It was a very clever sort of con,” says Dr. Peter Tyrer, a leading psychiatric researcher at Imperial College in London who wrote in the latest issue of the respected medical journal The Lancet about a new study that debunks the effectiveness of the atypicals. “Almost the whole scientific community was conned into thinking — as a consequence of good marketing — that this was a different and better set of drugs. The evidence, as it’s all added up, has shown this to be untrue.”

Eli Lilly insists that it has not marketed Zyprexa off-label and that it has accurately represented the drug’s side effects. But some medical researchers who have studied the atypical antipsychotics say that, in the final tally, the drugs, which have already been linked to some deaths, may eventually be responsible for tens of thousands of cases of diabetes and other potentially fatal diseases. And despite their early promise for treating schizophrenia, the drugs have not even performed any better than the crude and imprecise earlier medications that preceded them. “We have been paying $16 billion a year instead of $2 billion a year for drugs that seem to be no better and might be worse,” says Douglas Leslie, a researcher at the Medical University of South Carolina who contributed to an extensive federal study of the drugs. The story of how Zyprexa and other atypicals became a multibillion-dollar market suggests that the medical community — doctors, researchers, the institutions that back them — may be themselves prone to a placebo effect: the willed conviction that a new drug, presented as a breakthrough, must in fact be one, that a product sold as healing must in fact do good.

http://www.naturalnews.com/025732.html

Antipsychotic Drugs Boost Risk of Stroke in All Patients, Researchers Warn
Friday, February 27, 2009 by: David Gutierrez, staff writer

(NaturalNews) Antipsychotic drugs are significantly more dangerous than researchers had previously thought, according to a new study conducted by researchers from the London School of Hygiene and Tropical Medicine and published in the British Medical Journal.

Antipsychotic drugs come in two classes: an older variety known as “typical antipsychotics,” and a newer variety ("atypical antipsychotics") that became popular in the 1990s. In 2002, researchers became aware that atypical antipsychotics significantly increased the risk of stroke among elderly dementia patients, but believed that the older drugs did not carry the same risk.

In the new study, however, researchers found that taking an antipsychotic drug of either class was associated with a 40 percent higher risk of stroke in patients that did not have any form of dementia. Among those with dementia, taking either variety of antipsychotic was correlated with a more than 200 percent increase in risk.

The study was based on the medical records of 6,700 elderly patients.

“This is another warning that all antipsychotics should be prescribed with great thought and care and be subject to rigorous follow-up,” said Marjorie Wallace, chief executive of the nonprofit organization Sane

Neal Hunt of the Alzheimer’s Society said that the findings only make it more urgent that the drugs no longer be given to people with dementia.

“The over-prescription of antipsychotics is a serious breach of human rights,” he said. “These drugs should only be a last resort.

Antipsychotic drugs are designed for the treatment of people with schizophrenia and severe depression, and are not licensed for use on dementia patients. Nevertheless, they are widely used in nursing homes as sedatives, particularly on patients who exhibit aggression. Many nursing homes have been accused of using the drugs merely to make life easier for their own staff, even at great risk to their patients’ lives.

Sources for this story include: news.bbc.co.uk.

http://www.tampabay.com/news/health/article979974.ece

St. Petersburg Times
Facing numerous Seroquel lawsuits, drugmaker AstraZeneca releases documents
By Kris Hundley
In Print: Saturday, February 28, 2009

The public got a glimpse into the inner workings of a global pharmaceutical company Friday when AstraZeneca released more than 100 sealed documents in a tsunami of lawsuits claiming its powerful antipsychotic Seroquel caused diabetes, weight gain and other health problems.

Among the documents:

A Chicago psychiatrist who claimed patients lost weight on Seroquel had his research touted in AstraZeneca’s marketing materials — then trashed in interoffice memos.

Seroquel marketing managers discussed “burying” the results of three unfavorable clinical trials and “cherry-picking” useful data from a fourth. Even before the drug received FDA approval in September 1997, an AstraZeneca employee was praising a co-worker’s great “smoke-and-mirrors” job on a key study.

When physicians asked about the link between Seroquel, diabetes and weight gain — a link the company’s safety manager warned about as early as 2000 — Christine Ney, AstraZeneca’s “scientific alignment manager,” had this advice in a voice mail to sales reps in August 2005: “neutralize customer objections” and “refocus” on the positive by referring to a handy “Weight and Diabetes Sell Sheet.”

“Thanks everyone and good selling!” Ney said.

Seroquel, approved for schizophrenia and bipolar disorder but prescribed for everything from insomnia and depression to ADHD in kids, is one of the world’s bestselling drugs, with $4.45 billion in sales last year.

But like another leading antipsychotic, Eli Lilly & Co.’s Zyprexa, Seroquel has been blamed for causing diabetes, weight gain and other health problems. Lilly has agreed to pay $1.2 billion to settle patients’ lawsuits and $1.4 billion to settle criminal charges of illegal marketing.

AstraZeneca, a U.K.-based company, says the FDA has repeatedly upheld the safety of Seroquel, and the company plans to vigorously defend itself against thousands of patient lawsuits.

Regarding Friday’s disclosures, company spokesman Tony Jewell said: “Selected documents produced in connection with the Seroquel product liability litigation do not provide a fair and accurate picture. The evidence will show that AstraZeneca acted reasonably and responsibly with regard to the development and marketing of Seroquel.”

About 6,000 personal injury complaints have been consolidated in U.S. District Court in Orlando for pretrial proceedings. In a victory for the drugmaker, the judge dismissed the first two cases set for trial. Another 3,000 cases are pending in state courts.

In addition to the personal injury cases, AstraZeneca is being sued by four states for off-label marketing of Seroquel. The company said the U.S. Attorney’s Office in Philadelphia is investigating its marketing practices.

AstraZeneca had resisted efforts to unseal hundreds of company documents produced in the Orlando proceedings. “This (disclosure) could jeopardize public safety by causing confusion and alarm in patients, who may then discontinue their medication without seeking the guidance of a medical professional,” the company’s lawyers said in a court filing.

But just hours before a hearing Thursday, AstraZeneca and plaintiffs’ attorneys hammered out a compromise: All but a handful of documents would be released.

Steve McConnell, AstraZeneca’s attorney, argued that the remaining papers must remain confidential because they contain trade secrets and other proprietary information. Among the sealed documents are results of two clinical studies, sales’ reps call notes since January 2004 and correspondence with foreign regulatory authorities.

McConnell also insisted that communication between AstraZeneca and the FDA regarding expanded use of Seroquel should remain under wraps because the “negotiating process” is ongoing.

But U.S. Magistrate Judge David Baker was skeptical. “What about the public interest in reviewing the integrity of the FDA’s administrative process?” he asked from the bench.

“The public might want to know if the FDA is running a slipshod operation.”

The judge ordered the agreed-upon material to be made public by Wednesday. The first batch hit the court’s electronic files Friday.

Among the documents was harsh criticism from an AstraZeneca executive of Dr. Michael J. Reinstein, a Chicago psychiatrist who was one of the company’s paid consultants for Seroquel. In a note in October 2001, Georgia Tugend, U.S. brand manager for Seroquel, slammed the quality of research performed by the doctor’s group.

“Our clinical colleagues have significant and numerous issues in the past with the quality of research that this group has produced,'’ she said in the internal memo. “There is little confidence that Good Clinical Practices can be adhered to.”

This is surprising because the documents also included a Seroquel marketing piece featuring Reinstein’s research showing that the drug had led to weight loss in a patient.

Reinstein said Friday that AstraZeneca paid him about $40,000 a year for 10 years to promote Seroquel among doctors. Reinstein, who said AstraZeneca ended his contract at the end of 2007, described the company’s negative comments as “sour grapes.”

http://www.philly.com/inquirer/breaking/business_breaking/20090225_Ruling_near_on_privacy_issues_in_Seroquel_case.html

Letters to the editor: pmazurek@phillynews.com

Philadelphia Inquirer
Ruling near on privacy issues in Seroquel case
By Miriam Hill
Feb. 25, 2009

Does the world have the right to know about negative studies on AstraZeneca’s potent antipsychotic drug Seroquel?

Or whether company representatives promoted the drug for unapproved uses?

And what about details of sexual relationships between Wayne Macfadden, AstraZeneca’s former U.S. medical director for Seroquel, and two women who researched and wrote papers supporting the drug’s safety and efficacy?

A federal judge in Orlando may answer those questions as soon as tomorrow in a case stemming from personal-injury claims by 15,000 people that Seroquel triggered weight gain, diabetes, and other health problems.

Plaintiffs’ attorneys and Bloomberg News, the news organization, have sued to force London-based AstraZeneca P.L.C. to make public documents discovered in the litigation. AstraZeneca’s U.S. headquarters are in Wilmington.

“This is, first and foremost, a public-safety issue,” said Howard Nations, chairman of the Seroquel litigation group of the American Association for Justice (formerly the Association of Trial Lawyers of America).

Patients, Nations said, have the right to know about safety concerns raised in discussions between AstraZeneca and the U.S. Food and Drug Administration or in unpublished research on the drug.

Seroquel belongs to a class of drugs known as atypical antipsychotics. The drug is approved to treat bipolar disorder and schizophrenia, but doctors have been prescribing it and similar drugs for conditions including attention-deficit disorder and sleeplessness.

Seroquel is now one of AstraZeneca’s best-selling drugs, with $4.5 billion in sales last year.

AstraZeneca has asked the FDA to approve an extended-release version of the drug, Seroquel XR, to treat major depression and generalized anxiety disorder.

In December, the FDA asked for more information on that application. AstraZeneca said today that the FDA had scheduled a meeting in April to review the safety and efficacy of Seroquel XR for depression and anxiety.

Last month, the Philadelphia U.S. Attorney’s Office completed a $1.4 billion settlement with Eli Lilly & Co., the maker of Zyprexa, also an atypical antipsychotic, over allegations that the Indianapolis drug company illegally promoted Zyprexa to treat dementia in the elderly. AstraZeneca has said the U.S. attorney was looking into its marketing of Seroquel.

Lilly also paid $1.2 billion to settle several thousand personal-injury suits over allegations that Zyprexa caused weight gain and led to diabetes.

Last month, U.S. District Judge Anne Conway threw out the first two Seroquel personal-injury cases for lack of evidence.

Nations and other lawyers, along with Bloomberg, have asked Conway to unseal documents discovered in the dismissed cases.

They want to unseal correspondence and other documents stemming from AstraZeneca’s initial application for FDA approval of Seroquel.

They are also asking that Conway make public so-called call notes from Seroquel representatives that may reveal whether AstraZeneca sales pitches focused on prescribing the drug for uses not approved by the FDA. If that happened, it would be illegal. Plaintiffs’ attorneys and Bloomberg have also requested that correspondence between Macfadden and people who researched or wrote about Seroquel be made public.

AstraZeneca spokesman Tony Jewell said the hearing tomorrow is about the confidentiality of 111 documents, and of those documents, AstraZeneca is arguing that only 65 documents should remain confidential. The company also is worried that documents released in litigation may cause undue concern among patients.

“AstraZeneca believes the best way for physicians and patients to understand benefits and risks of medicines is through communications from the FDA, not in discovery as part of litigation or through the media,” Jewell said.

The company also said that while it did not condone Macfadden’s behavior, details of his relationships are irrelevant. He no longer works for AstraZeneca and could not be reached for comment.

http://www.tampabay.com/opinion/editorials/article976463.ece

St. Petersburg Times
Editorial
Patients deserve facts about drug
In Print: Tuesday, February 17, 2009

Pharmaceutical companies spend millions each year to market drugs to doctors and potential patients. That makes it all the more outrageous that AstraZeneca is asking an Orlando court to keep information about the performance of its lucrative antipsychotic drug Seroquel secret.

The company is claiming public safety, saying it shouldn’t be required to release information about the drug that could cause a panic among “a vulnerable patient population” that might stop taking the drug without a doctor’s oversight. But the real public safety issue is one of public health and whether the company hid findings that Seroquel causes weight gain and diabetes. The legal system must put public health — and a patient’s right to know — above a company’s interest in secrecy.

Seroquel has been approved for treatment of schizophrenia and bipolar disorder, but the drug is widely prescribed for other health problems such as depression and insomnia. Last year, this blockbuster drug racked up $4.5 billion in sales and was prescribed to more than 22 million people.

But there have been serious questions about potential side effects. AstraZeneca is facing more than 9,000 personal injury lawsuits filed by at least 15,000 patients. Forty percent of these cases have been consolidated in federal court in Orlando.

The lawyers for patients say that AstraZeneca knew for nearly a decade that Seroquel caused weight gain and diabetes. As Times staff writer Kris Hundley reported Sunday, a hearing is scheduled for Feb. 26 on the public disclosure of documents produced during the trial’s discovery phase, including unpublished results of drug studies and notes of company sales representatives on marketing strategies.

The plaintiffs’ lawyers want the court to unseal the documents. AstraZeneca wants the seal to remain and the hearing to be closed to the public. The company claims that disclosure could jeopardize public safety by causing “confusion and alarm” and prompting patients to end treatment.

What the company really means is that disclosure could make drug consumers more aware of any downside risks of taking Seroquel — which might take a bite out of revenues.

It would not be the first time a drug company is suspected of putting profits before public health. Internal documents on the Eli Lilly drug Zyprexa, also an antipsychotic, indicated that the drugmaker ignored evidence that its drug was causing weight gain and diabetes. Those documents were put under seal, and had it not been for an expert witness who disseminated them against court orders, the public may never have been sufficiently warned. Since then Lilly pleaded guilty to marketing Zyprexa illegally and paid a record $1.4 billion in fines.

AstraZeneca points out it won its first two cases, with the judge finding that the patients had not successfully linked their health problems to Seroquel. That doesn’t lessen the public’s interest in the results of clinical trials and what the company’s sales representatives were saying about the drug.

There is altogether too much secrecy in court cases that implicate public health. If the records being held back contain information that the judge would like to know before taking Seroquel, then the public should know as well. No other interest should take precedence.

http://www.tampabay.com/news/health/article976067.ece

St. Petersburg Times
Seroquel maker wants to seal info from you, “for” you
By Kris Hundley
In Print: Sunday, February 15, 2009

AstraZeneca, maker of the blockbuster anti­psychotic Seroquel, is battling to keep information about the drug out of the public’s view … for the public’s own good.

Later this month in Orlando, lawyers for the drugmaker will argue that unsealing company documents, including unpublished clinical trial data and letters from the FDA, could harm “a vulnerable patient population.”

“This (disclosure) could jeopardize public safety by causing confusion and alarm in patients, who may then discontinue their medication without seeking the guidance of a medical professional,'’ lawyers for the drugmaker said in a recent filing in federal court.

Seroquel is approved only for schizophrenia and bipolar disorder, but its use for everything from depression to insomnia to ADHD in kids is so widespread that the drug has been prescribed for more than 22 million patients. Its $4.5 billion in sales last year put it among the top-selling drugs in the world.

In light of Seroquel’s popularity, the argument that hiding information protects patients has public health advocates nearly swinging from the rafters.

“They don’t want anybody to know about the side effects of their drug, and they’re keeping secret the results of studies from patients, their doctors and the FDA,'’ said Dr. David Egilman, clinical associate professor at Brown University’s Department of Community Health.

“Saying they’re protecting the patient is a self-serving, fraudulent argument.”

---

Though Egilman is merely an observer of the Seroquel proceedings, he knows the power of sealed documents in drug liability cases. He played a key role when similar lawsuits were lodged against another mega-selling antipsychotic, Eli Lilly’s drug Zyprexa. As in the Seroquel cases, thousands upon thousands of patients claimed Zyprexa caused weight gain and diabetes.

Hired as an expert witness for the plaintiffs in Zyprexa cases, Egilman was given access to reams of internal Lilly documents that had been sealed by the court. The documents showed that the drugmaker had ignored evidence of diabetes among patients while pushing Zyprexa’s off-label use for anxiety and dementia.

Egilman defied the judge’s orders and helped leak thousands of damaging Lilly documents to the New York Times. Egilman ended up paying a $100,000 fine to Lilly for releasing the sealed documents.

The leaked documents, meanwhile, helped the U.S. Department of Justice build a criminal case against Lilly. The company pleaded guilty to marketing Zyprexa illegally and last month paid a record $1.4 billion fine. Though a landmark amount, Lilly’s fine amounts to about 3.5 percent of the $39 billion in revenues Zyprexa has posted since the FDA approved it 1996.

---

Seroquel’s parent, Astra­Zeneca, has a similarly valuable franchise to protect. The anti­psychotic accounted for 14 percent of AstraZeneca’s sales of $31.6 billion last year. Avoiding negative publicity — one of the reasons the company wants to seal documents in the Orlando cases — is critical as it seeks to maximize sales before Seroquel loses patent protection in about three years.

The skirmish over document disclosure in Orlando is part of a hornet’s nest of litigation against AstraZeneca, a British company with U.S. headquarters in Wilmington, Del. More than 15,000 patients have filed over 9,000 personal injury lawsuits. About 40 percent of these claims have been consolidated for pretrial motions in U.S. District Court for the Middle District of Florida.

Plaintiffs say the company knew as early as 2000 that Seroquel caused diabetes, weight gain and other health problems, but failed to adequately warn patients and doctors.

Dr. William C. Wirshing, a California psychiatrist, has lectured doctors on AstraZeneca’s behalf and has prescribed Seroquel to as many as 5,000 patients. Though he has been a paid consultant for the drugmaker, in a pretrial deposition he left no question about the links he sees between the drug, weight gain and diabetes.

“You literally just got to watch them get bigger … it was riveting to me,” said Wirshing who estimated that several hundred of his patients developed diabetes.

AstraZeneca denies the allegations and has spent more than $500 million defending itself against Seroquel claims. Key to the company’s strategy has been its insistence that millions of pages of documents produced in discovery should remain under seal, out of the public eye.

To Egilman, such blanket agreements in drug liability cases are outrageous. “Confidentiality agreements that prohibit disclosure of important information that may impact public health to state and federal authorities should be illegal,'’ he said. “The court should at least send all discovery in drug cases to the FDA and DOJ (Department of Justice) for review if they intend to seal them.”

The upcoming hearing is expected to focus on specific items that the plaintiffs’ lawyers say have no legal right to secrecy. Among them: unpublished results of several drug studies, sales reps’ notes on Seroquel’s marketing strategies and letters from the FDA.

The drugmaker also hopes to keep under seal information about sexual relationships that Dr. Wayne MacFadden, AstraZeneca’s former U.S. medical director for Seroquel, had with an independent researcher as well as with a woman who wrote papers supporting the drug’s safety and efficacy. Correspondence shows that MacFadden, who was also director of clinical research for neuroscience drugs, “promised sexual favors in exchange for intelligence on AstraZeneca’s competitors.”

The plaintiffs say the affairs “can create bias which can affect the integrity of the science.'’

Lawyers for the drugmaker counter that the affairs are not relevant to the lawsuits. Other disputed documents, they say, contain trade secrets, could taint the jury pool and could “harm public health.”

AstraZeneca’s lawyers say the information to be discussed at the hearing scheduled Feb. 26 is so sensitive that the court should be closed to the public. “The potential harm of dissemination of documents at this stage in the litigation far outweighs the public’s right of access, particularly when trials in these cases are on the near horizon,'’ company lawyers said in a filing Feb. 6. “The whole picture will be presented to the public at once.”

The judge has not ruled on the request.

There’s a good chance that many of these cases will never come to trial, and the underlying documents will never become public. In a victory for Astra­Zeneca, the judge dismissed the first two cases in late January, saying plaintiffs had not sufficiently established that their health problems were caused by Seroquel. Up to nine trials are slated for 2009.

In the Zyprexa litigation, Lilly paid $1.2 billion to settle injury claims involving 31,000 patients. Damaging company documents were never released by the court, though they were available on the Internet after Egilman leaked them and excerpts appeared in the New York Times.

Egilman is well aware of the big money in liability lawsuits, having made $2.3 million as an expert witness in Vioxx cases. He contends that patients’ lawyers are motivated by maximizing their share of any settlement, which can be 30 percent or more. He says attorneys should be required to get their client’s approval before agreeing to seal documents.

“The client may be more interested in making sure that health information gets to their doctor than money,” he said. “They have a real interest and it’s called their health.”

Gary Farmer, a Fort Lauderdale lawyer who represents more than 100 Seroquel patients, said Egilman has a point.

“If we can get the documents to win the case and get compensation, you have to ask yourself, ‘Is it necessary to make that information public?’ ” he said.

Whether the mountains of Seroquel material now sealed in Orlando’s federal court ever see the light of day may depend on the progress of related cases. Four states — Pennsylvania, Montana, Arkansas and South Carolina — are suing Astra­Zeneca for off-label marketing of Seroquel.

The company said it is aware that the U.S. Attorney’s Office in Philadelphia is investigating Seroquel’s marketing practices, most likely based on whistle blower complaints.

Regulators also seem to be taking note. In December, the FDA sent AstraZeneca a warning letter after learning a sales rep had pitched Seroquel to a doctor as a treatment for depression. Though doctors can prescribe a drug for any use, it is illegal for pharmaceutical companies to promote such uses.

The FDA also reportedly sent AstraZeneca two letters in late December, telling the company to strengthen Seroquel’s warnings about diabetes. The drugmaker declined to comment, saying its communications with the FDA are confidential. The letters remain sealed in Orlando’s federal court.

http://uk.reuters.com/article/healthNewsMolt/idUKTRE51717X20090208?sp=true

Psychiatrists may cut some ties to drug firms
Sun Feb 8, 2009 5:17pm GMT

By Julie Steenhuysen

CHICAGO (Reuters) - Dr. Daniel Carlat knows all too well how easy it is for doctors to be seduced by drug industry money.

In 2002, he earned $30,000 in speaking fees to promote Wyeth’s antidepressant Effexor XR to fellow doctors.

“I quit doing it because I felt I was beginning to push some ethical boundaries in terms of what I was saying and what I was not saying,” said Carlat, a psychiatry professor at Tufts University in Boston who believes doctors need to cut their financial ties with drug companies.

“My own story was really nothing special,” he said in a telephone interview. “I made $30,000 for the year, which is less than some of these doctors make in a weekend.”

Carlat and other psychiatrists have been studying the issue and have proposed that the American Psychiatric Association cut back on medical education seminars funded by drug companies.

Dr. Nada Stotland, president of the group that represents 38,000 doctors, said the proposal is one of several the association’s board will take up next month to address concerns that psychiatrists have become too cozy with drugmakers.

The APA and some prominent psychiatrists have been targeted in a probe by Iowa Republican Senator Charles Grassley. He has faulted several noted child psychiatrists, including Dr. Joseph Biederman of Harvard University in Boston, for failing to disclose hefty payments from drug companies.

Psychiatric drugs represent billions of dollars in global sales, with Wyeth’s Effexor alone generating sales of $4 billion last year.

Several drugmakers last month stopped passing out pens and other items as part of a set of voluntary ethics guidelines, but getting U.S. doctors to give up free medical education, often at fancy resorts, will be a harder sell.

“Most people see the ban on trinkets as being a small step in the right direction but not really the major source of worry or concern,” said Carlat, editor of The Carlat Psychiatry Report, a continuing medical education publication supported by subscriptions alone.

“I think much more important is the fact that companies are paying for legitimacy in different ways by hiring doctors to give talks and hiring companies to put on continuing medical education,” he said.

“As long as that continues, it is really hard to see that medical practice won’t continue to be biased toward always prescribing the newest and most expensive drugs, even when we don’t have much clinical experience with them.”

‘INTEGRITY OF INFORMATION’

The drugmakers’ new ethics guidelines do specify that industry-funded seminars are intended to cover “a full range of treatment options, and not to promote a certain medicine.”

And they recommend that medical education grants should not come from a company’s marketing budget.

“Doctors rely on accurate and appropriate information about new medicines in order to provide the best possible care to patients,” David Norton, a Johnson & Johnson executive who worked on the new code, said in a statement announcing the changes.

“We take this responsibility seriously and are constantly re-examining ways we can enhance these essential company-physician interactions and reinforce the integrity of information about our medicines.”

Still, many doctors think the model of drug company money paying to educate doctors is patently flawed.

“It is self-evidently absurd to look to a company for information about a product it makes,” Dr. Marcia Angell of Harvard Medical School and former editor of the New England Journal of Medicine, said in a telephone interview.

“Why can’t doctors, who are among the most privileged members of society, pay for their own continuing medical education?” Angell said. “Why have they abdicated that responsibility to the companies who make drugs?”

Stotland has heard a range of opinions on whether to ban industry-sponsored talks but she said the APA board will likely cut out at least some of the seminars during their meetings.

“There are still those who feel strongly that they can hear things but it doesn’t influence their practice,” she said. “But the evidence points the other way.”

(Editing by Maggie Fox and John O’Callaghan)

http://www.tampabay.com/news/health/article976067.ece

St. Petersburg Times

By Kris Hundley
In Print: Sunday, February 15, 2009

AstraZeneca, maker of the blockbuster anti­psychotic Seroquel, is battling to keep information about the drug out of the public’s view … for the public’s own good.

Later this month in Orlando, lawyers for the drugmaker will argue that unsealing company documents, including unpublished clinical trial data and letters from the FDA, could harm “a vulnerable patient population.”

“This (disclosure) could jeopardize public safety by causing confusion and alarm in patients, who may then discontinue their medication without seeking the guidance of a medical professional,'’ lawyers for the drugmaker said in a recent filing in federal court.

Seroquel is approved only for schizophrenia and bipolar disorder, but its use for everything from depression to insomnia to ADHD in kids is so widespread that the drug has been prescribed for more than 22 million patients. Its $4.5 billion in sales last year put it among the top-selling drugs in the world.

In light of Seroquel’s popularity, the argument that hiding information protects patients has public health advocates nearly swinging from the rafters.

“They don’t want anybody to know about the side effects of their drug, and they’re keeping secret the results of studies from patients, their doctors and the FDA,'’ said Dr. David Egilman, clinical associate professor at Brown University’s Department of Community Health.

“Saying they’re protecting the patient is a self-serving, fraudulent argument.”

• • •

Though Egilman is merely an observer of the Seroquel proceedings, he knows the power of sealed documents in drug liability cases. He played a key role when similar lawsuits were lodged against another mega-selling antipsychotic, Eli Lilly’s drug Zyprexa. As in the Seroquel cases, thousands upon thousands of patients claimed Zyprexa caused weight gain and diabetes.

Hired as an expert witness for the plaintiffs in Zyprexa cases, Egilman was given access to reams of internal Lilly documents that had been sealed by the court. The documents showed that the drugmaker had ignored evidence of diabetes among patients while pushing Zyprexa’s off-label use for anxiety and dementia.

Egilman defied the judge’s orders and helped leak thousands of damaging Lilly documents to the New York Times. Egilman ended up paying a $100,000 fine to Lilly for releasing the sealed documents.

The leaked documents, meanwhile, helped the U.S. Department of Justice build a criminal case against Lilly. The company pleaded guilty to marketing Zyprexa illegally and last month paid a record $1.4 billion fine. Though a landmark amount, Lilly’s fine amounts to about 3.5 percent of the $39 billion in revenues Zyprexa has posted since the FDA approved it 1996.

• • •

Seroquel’s parent, Astra­Zeneca, has a similarly valuable franchise to protect. The anti­psychotic accounted for 14 percent of AstraZeneca’s sales of $31.6 billion last year. Avoiding negative publicity — one of the reasons the company wants to seal documents in the Orlando cases — is critical as it seeks to maximize sales before Seroquel loses patent protection in about three years.

The skirmish over document disclosure in Orlando is part of a hornet’s nest of litigation against AstraZeneca, a British company with U.S. headquarters in Wilmington, Del. More than 15,000 patients have filed over 9,000 personal injury lawsuits. About 40 percent of these claims have been consolidated for pretrial motions in U.S. District Court for the Middle District of Florida.

Plaintiffs say the company knew as early as 2000 that Seroquel caused diabetes, weight gain and other health problems, but failed to adequately warn patients and doctors.

Dr. William C. Wirshing, a California psychiatrist, has lectured doctors on AstraZeneca’s behalf and has prescribed Seroquel to as many as 5,000 patients. Though he has been a paid consultant for the drugmaker, in a pretrial deposition he left no question about the links he sees between the drug, weight gain and diabetes.

“You literally just got to watch them get bigger … it was riveting to me,” said Wirshing who estimated that several hundred of his patients developed diabetes.

AstraZeneca denies the allegations and has spent more than $500 million defending itself against Seroquel claims. Key to the company’s strategy has been its insistence that millions of pages of documents produced in discovery should remain under seal, out of the public eye.

To Egilman, such blanket agreements in drug liability cases are outrageous. “Confidentiality agreements that prohibit disclosure of important information that may impact public health to state and federal authorities should be illegal,'’ he said. “The court should at least send all discovery in drug cases to the FDA and DOJ (Department of Justice) for review if they intend to seal them.”

The upcoming hearing is expected to focus on specific items that the plaintiffs’ lawyers say have no legal right to secrecy. Among them: unpublished results of several drug studies, sales reps’ notes on Seroquel’s marketing strategies and letters from the FDA.

The drugmaker also hopes to keep under seal information about sexual relationships that Dr. Wayne MacFadden, AstraZeneca’s former U.S. medical director for Seroquel, had with an independent researcher as well as with a woman who wrote papers supporting the drug’s safety and efficacy. Correspondence shows that MacFadden, who was also director of clinical research for neuroscience drugs, “promised sexual favors in exchange for intelligence on AstraZeneca’s competitors.”

The plaintiffs say the affairs “can create bias which can affect the integrity of the science.'’

Lawyers for the drugmaker counter that the affairs are not relevant to the lawsuits. Other disputed documents, they say, contain trade secrets, could taint the jury pool and could “harm public health.”

AstraZeneca’s lawyers say the information to be discussed at the hearing scheduled Feb. 26 is so sensitive that the court should be closed to the public. “The potential harm of dissemination of documents at this stage in the litigation far outweighs the public’s right of access, particularly when trials in these cases are on the near horizon,'’ company lawyers said in a filing Feb. 6. “The whole picture will be presented to the public at once.”

The judge has not ruled on the request.

There’s a good chance that many of these cases will never come to trial, and the underlying documents will never become public. In a victory for Astra­Zeneca, the judge dismissed the first two cases in late January, saying plaintiffs had not sufficiently established that their health problems were caused by Seroquel. Up to nine trials are slated for 2009.

In the Zyprexa litigation, Lilly paid $1.2 billion to settle injury claims involving 31,000 patients. Damaging company documents were never released by the court, though they were available on the Internet after Egilman leaked them and excerpts appeared in the New York Times.

Egilman is well aware of the big money in liability lawsuits, having made $2.3 million as an expert witness in Vioxx cases. He contends that patients’ lawyers are motivated by maximizing their share of any settlement, which can be 30 percent or more. He says attorneys should be required to get their client’s approval before agreeing to seal documents.

“The client may be more interested in making sure that health information gets to their doctor than money,” he said. “They have a real interest and it’s called their health.”

Gary Farmer, a Fort Lauderdale lawyer who represents more than 100 Seroquel patients, said Egilman has a point.

“If we can get the documents to win the case and get compensation, you have to ask yourself, ‘Is it necessary to make that information public?’ ” he said.

Whether the mountains of Seroquel material now sealed in Orlando’s federal court ever see the light of day may depend on the progress of related cases. Four states — Pennsylvania, Montana, Arkansas and South Carolina — are suing Astra­Zeneca for off-label marketing of Seroquel.

The company said it is aware that the U.S. Attorney’s Office in Philadelphia is investigating Seroquel’s marketing practices, most likely based on whistle blower complaints.

Regulators also seem to be taking note. In December, the FDA sent AstraZeneca a warning letter after learning a sales rep had pitched Seroquel to a doctor as a treatment for depression. Though doctors can prescribe a drug for any use, it is illegal for pharmaceutical companies to promote such uses.

The FDA also reportedly sent AstraZeneca two letters in late December, telling the company to strengthen Seroquel’s warnings about diabetes. The drugmaker declined to comment, saying its communications with the FDA are confidential. The letters remain sealed in Orlando’s federal court.

By TOM MURPHY and MARLEY SEAMAN, AP Business Writers

INDIANAPOLIS – Eli Lilly & Co. said Thursday it pleaded guilty to a charge that it illegally marketed the anti-psychotic drug Zyprexa for an unapproved use, and will pay $1.42 billion to settle civil suits and end the criminal investigation.

The Indianapolis-based company said it will pay $800 million to settle civil suits, including $438 million to the federal government and $362 million to states. It will pay $615 million to resolve the criminal probe, and plead guilty to a misdemeanor violation of the Food, Drug and Cosmetic Act for promoting Zyprexa as a dementia treatment.

The company did not acknowledge any wrongdoing in the civil cases.

The misdemeanor plea resolves charges related to Lilly’s marketing of Zyprexa between September 1999 and March 2001. It states that Lilly marketed the drug for the treatment of dementia, including Alzheimer’s-related dementia, even though the drug is not approved for that use.

Zyprexa is approved to treat schizophrenia and bipolar disorder. Doctors are allowed to prescribe it for other uses, but Lilly is not allowed to market the drug for any other illnesses because it lacks Food and Drug Administration approval.

The case began in 2004 and was led by the U.S. attorney for the Eastern District of Pennsylvania and the Office of Consumer Litigation of the Department of Justice.

Laurie Magid, U.S. Attorney for the Eastern District of Pennsylvania, said they hoped cases like this put an end to a pharmaceutical practice known as “off-label” marketing.

“The company made hundreds of millions of dollars by trying to convince health care providers that Zyprexa was safe for unapproved uses,” Magid said, noting that they hold the drugmaker “responsible for putting thousands and thousands of patients at risk.” She added that off-label marketing circumvents “the very process put in place to protect the public.”

Lilly also said it agreed to resolve civil investigations brought by the Medicaid fraud-control units of the states involved in the settlement. The states were looking into rebate agreements between Lilly and pharmacy benefits managers related to Zyprexa and other drugs.

A company spokesman said about 30 states are involved.

Zyprexa was approved in 1996 and has been Lilly’s top seller for years. It brought in $3.5 billion in revenue through the first three quarters of 2008, or roughly $1.5 billion more than the company’s second-best seller, the antidepressant Cymbalta.

But the company has spent roughly $1.2 billion to resolve 32,000 claims related to Zyprexa product liability. About 125 cases are still pending.

For instance, a group of insurance companies, unions and others are suing Lilly for billions, saying it broke marketing laws and overcharged for the drug.

Lilly in October said it expected to pay the additional $1.42 billion to end the investigations. It set aside that amount, or $1.29 per share, in the third quarter, which resulted in the company’s first quarterly loss in three years.

Earlier the same month, Lilly agreed to pay $62 million to 32 states and the District of Columbia to resolve accusations it marketed Zyprexa for pediatric care, for use in high doses and for dementia.

Lilly shares fell 66 cents, or nearly 2 percent, to $36.81 in Thursday morning trading.

___

Associated Press writer Maryclaire Dale contributed to this report from Philadelpia.

http://www.washingtontimes.com/news/2008/nov/13/veterans-kin-demands-answers-on-ptsd-drugs/

Help the families of these soldiers. Send the below article to everyone you know. And also send it to your local legislators and veteran’s groups.

“I believe there are many more soldiers and Marines who have died in their sleep just like the four in West Virginia,” said Mr. White, a retired high school principal. “I think what we have found is just the tip of the iceberg, but we need more national publicity to help us find others who have lost loved ones and are looking for answers.”

“Our veterans - particularly those suffering from mental health injuries - should have the very best health care and support in the world; they should never be needlessly exposed to drugs without proper notification of the dangers involved or effective monitoring of the side effects,” said Mr. Obama, now the president-elect.”

Washington Times

EXCLUSIVE: After death of son, dad takes cases to Capitol Hill
HURRICANE, W.Va.
Andrea Billups and Audrey Hudson
Thursday, November 13, 2008

A West Virginia man whose son survived the battlefields of Iraq only to die in his sleep at home is crusading to find other military families whose loved ones also have died after taking drugs prescribed for post-traumatic stress disorder (PTSD).

Stan White’s son Andrew, who was found dead in bed at the family’s Cross Lanes, W.Va., home on Feb. 12, 2007, is one among a cluster of young veterans in the state who have died in their sleep with little explanation. Now Mr. White wants the federal government to monitor the drugs it prescribes to some 375,000 soldiers who have been diagnosed with mental trauma.

Shirley White of Cross Lanes, Andrew’s mother, says she and her husband want an investigation into the medications prescribed to their son and other veterans who died.

So far, he has identified nine veterans across the country - including four in West Virginia - who have died in their sleep after taking antidepressant and antipsychotic medications.

Mr. White has met with members of Congress and asked for Capitol Hill hearings to investigate the deaths. His research prompted a Department of Veterans Affairs (VA) investigation into Andrew’s and one other death, which were found to have been caused by “combined drug intoxication.” But the investigation could not determine whether the prescribed medications were at fault.

The father is taking up the crusade amid increased criticism of VA medical treatment of veterans suffering PTSD upon their return from Iraq or Afghanistan, including media and government reports that several VA centers failed to adequately care for patients and inform them of potentially dangerous drug side effects.

Finding out why his son died and keeping others from suffering a similar fate has become a personal cause for Mr. White.

“Our goal was to find out if the medications are safe,” said Mr. White, who, with his wife, continues to grieve the loss of his son. “If they are, that needs to be publicized. But if they are not, that also needs to be publicized as well.

“I believe there are many more soldiers and Marines who have died in their sleep just like the four in West Virginia,” said Mr. White, a retired high school principal. “I think what we have found is just the tip of the iceberg, but we need more national publicity to help us find others who have lost loved ones and are looking for answers.”

The VA’s Office of Inspector General conducted a review of the quality of care received by Marine Cpl. Andrew White and another veteran whose name was not made public but whom The Washington Times was able to identify as Army National Guard Sgt. Eric Layne, an Iraq war veteran.

According to the Aug. 14 findings, the two combat veterans were taking three prescribed psychiatric medications:

• Paroxetine (Paxil) - an antidepressant that can produce panic attacks, sleeping problems and suicidal thoughts.

• Clonazepam (Klonopin) - an anticonvulsive that should not be used with alcohol or other drugs, including narcotics or barbiturates.

• Quetiapine (Seroquel) - an antipsychotic used to treat schizophrenia but, combined with clonazepam, can increase sedative effects.

“The medical examiner found that these patients died from combined drug intoxication involving prescribed and nonprescribed medications,” the report said. “In the presence of PTSD, other mental health conditions, and uncertain use of medications by patients, we are unable to draw conclusions about the relationship between medication regimens and these deaths.”

The report said Cpl. White “died as a result of combined drug intoxication,” including a nonprescribed medication that the IG declined to identify. “No contributory natural diseases or physical injuries were identified,” the report said.

Sgt. Layne died as a result of the VA-prescribed drugs and two unidentified nonprescribed medications, “under circumstances significant for fatal over-use of prescribed paroxetine” along with “apparent misuse of nonprescribed medications of uncertain intentionality.”

The VA conducted an agencywide analysis of all cases of death among veterans who were taking a combination of the same drugs and “found no high mortality rate in veterans in the referenced group compared to those taking other similar psychotropic combinations or veterans taking the single agents,” said VA spokeswoman Alison Aikele, who did not specify the death rate.

Nevertheless, a California neurologist who contacted Mr. White after reading about his efforts to investigate the veterans’ deaths in a local newspaper article, expressed alarm over seemingly healthy young veterans suddenly dying in their sleep.

“The drugs and the occurrence there in the four vets in West Virginia really jumps out at you,” said Dr. Fred Baughman of El Cajon, Calif. “They are seemingly OK, and then they go to bed and they die in their sleep.

“The constant drugs that all four of them are on are the Paxil [paroxetine] and Seroquel [quetiapine],” said Dr. Baughman, who has long had his own concerns about PTSD drug prescriptions in the military.

Miss Aikele said it is not unusual for veterans suffering PTSD to be prescribed several psychotropic drugs for various symptoms, including sleep disturbance, nightmares and anxiety.

However, the Food and Drug Administration (FDA) is re-evaluating whether there are safety issues with recommended doses of quetiapine and possibilities of “overdose due to sample pack labeling confusion.”

The VA, meanwhile, has consented to review all drugs it prescribes to veterans who suffer PTSD.

At the urging of Mr. White, Rep. Shelley Moore Capito, West Virginia Republican, met with four victims’ families in mid-July to hear their frustrations with the VA system.

Mrs. Capito said afterward that it was important for the families to learn whether there is any relation between the medications and the deaths of the young veterans.

“These are returning veterans, and we want to make sure we take as good of care as possible,” she said.

VA Secretary James B. Peake, in an interview with The Times in June, shared Mrs. Capito’s concerns.

“My concern is that there is a perception that we don’t care about our veterans, but that is just the opposite,” he said during the 90-minute interview. “Our first responsibility is to our veterans. My whole life has been about taking care of them.”

The VA was plagued with controversies this year, including its own acknowledgment of “failures” in numerous human subject experiments and tests involving new drugs.

A joint investigation by The Times and ABC News of a behavioral study of veterans suffering from PTSD who also were taking the smoking-cessastion drug Chantix exposed “unacceptable failures” in ensuring safeguards for soldiers in the experiment, according to an internal agency report.

VA officials took anywhere from two weeks to 134 days to warn veterans that the FDA had issued new warnings that the drug could cause suicidal behavior and that more than 40 suicides had been reported among people taking the drug.

Sen. Barack Obama was the first lawmaker to demand an investigation just days after The Times’ story ran June 16, and Rep. Bob Filner, California Democrat and chairman of the House Veterans Affairs’ Committee, held an investigative hearing into the matter weeks later.

“Our veterans - particularly those suffering from mental health injuries - should have the very best health care and support in the world; they should never be needlessly exposed to drugs without proper notification of the dangers involved or effective monitoring of the side effects,” said Mr. Obama, now the president-elect.

According to the VA, more than 83,000 veterans who have served in Iraq or Afghanistan had received diagnoses of actual or suspected PTSD as of Aug. 15.

“Without going through each patient’s medical record, we don’t have a way of knowing exactly how many have persistent symptoms or confirmed diagnosis of PTSD for which specific treatment is needed,” Miss Aikele said.

Letters to the editor: letters@washingtontimes.com

http://www.adn.com/news/alaska/story/589914.html

http://tinyurl.com/6o747r —a few videos where Texas foster kids are speaking out.

Letters to the Editor: http://www.adn.com/help/letters/

Anchorage Daily News
Foster kids say medication is overprescribed
LEGISLATIVE MEETING: Youths and graduates of the system offer alternatives.
By LISA DEMER
November 15th, 2008

Before a roomful of important adults, foster kids and graduates of the system talked about being put on powerful psychiatric drugs and undergoing “treatment” when what might have helped more was a chance for a regular life with sports and clubs and jobs.

Friday’s day-long legislative meeting drew a number of state officials, lawmakers and advocates, and focused on how to improve Alaska foster care.

In May, a group of foster care youth and those who have aged out came up with eight ways to improve the system. Among the identified problems: Overprescribed psychiatric drugs.

Too many foster children are prescribed psychiatric drugs, the kids said. They are labeled as disturbed, defiant or anxious when in reality they are just reacting to the trauma of their broken families and the difficulties of living in state custody.

Candice Tucker remembered when she first went into foster care two years ago, at age 15, because her mother couldn’t take care of her.

“I was freaking out because I had just gotten into care. I was having a hard time so they thought I needed residential,” Tucker, now 17, said.

For her, the treatment center helped, but she questions all the drugs doctors put her on.

“There are natural things in life that stress you out. You get depressed. You get sad or you get angry or anxious. They are natural emotions. I feel being in foster care and being on as many anti-psychotics and anti-depressants that I’ve been on – they see me for a week and they assume that’s the way I’ve always been,” Tucker said, her voice soft but her manner open. Later she explained that she’s shy, but wants to make life better for other foster children if she can.

Now, as she’s preparing to start at the University of Alaska Anchorage in January, Tucker wants to ease off the powerful medications.

“I need to have my mind with me. I need to be alert,” she said.

Slade Martin is 20 now, but he spent 15 years in Alaska’s foster care system and shuffled through, by his count, 21 different foster homes, emergency placements and treatment centers. He once was treated at a local psychiatric hospital and said every kid there is put on psychiatric drugs.

The kids want the medications cut back and think that will help them focus better on school and function better in the world.

“I don’t think meds are always the best option,” Martin said.

A NEED TO BE NORMAL

Counseling is traumatic to some kids – telling your story to one stranger and then another, said Becca Shier, now 18 and a UAA student in social work who has been in foster care nearly six years.

Some, like her, will never open up. Instead of making them feel like something is wrong with them, Shier told the legislators, why not get them involved in extra curricular activities so they can be part of a regular school experience?

“So they could be normal.”

Teens in foster care too often end up in treatment centers because the state has no other home for them; they are the “foster homeless,” Shier said.

Martin said he spent 2 1/2 years at an Anchorage treatment center because no foster family would take him in. “Some crazy people up in there,” he told legislators.

He said he was “diagnosed with everything under the rainbow” but doesn’t think anything was really wrong with him. Other kids stabbed people and punched holes in the walls and were scary, he said during a break.

Tammy Sandoval, director of the state Office of Children’s Services, said later that she was taken with what the youths had to say. The idea of kids spending months or years in residential treatment centers for lack of a family is troubling and she wants to look into the matter.

But the fact is, the state doesn’t have enough foster homes, especially for teenagers, she said.

Sandoval said she planned to discuss the medication issues with the state’s director of behavioral health.

The foster kids and alumni at the meeting are especially articulate and successful, said state Rep. Les Gara, an Anchorage Democrat who grew up in foster care in New York state and was one of the main organizers of Friday’s session. Foster kids too often struggle in school, end up homeless and are unemployed as young adults, according to studies presented at the meeting.

The kids who spoke Friday have been finding their voice through an advocacy group called Facing Foster Care in Alaska that now numbers about 140 statewide, said its president, Amanda Metivier, who at 24 helped organize the conference and is weeks away from graduating from UAA with a social work degree.

She’ll be one of the first to graduate on a special tuition waiver specifically for foster kids. The foster care group wants all foster kids to be offered that benefit. Now just 10 foster kids a year get that at UAA.

At their May meeting, they also agreed to push for Medicaid health benefits to age 21, Medicaid-paid braces, and money to help older foster kids live on their own.

But state Sen. Johnny Ellis, an Anchorage Democrat at the meeting, said even sympathetic legislators may have trouble getting new programs into the state budget with the recent dramatic drop in the price of oil.

http://www.aboutlawsuits.com/fda-panel-to-review-zyprexa-side-effects-for-children-1774/

November 18th, 2008

At a meeting of the FDA’s Pediatric Advisory Committee today, potential label changes will be considered for Eli Lilly’s antipsychotic drug Zyprexa. The Committee will evaluate whether new warnings are necessary about the risk of potential Zyprexa side effects for children, such as severe weight gain, hyperglycemia or other metabolic effects…

It is manufactured and marketed by Eli Lilly & Co., and was first approved in the United States in 1996 for treatment of schizophrenia and bipolar disorder in adults. It has also been widely prescribed off-label for other unapproved uses, such as treatment of dementia and mild forms of bipolar disorder.

Although Zyprexa is only approved by the FDA for use by those 18 years or older, it is commonly prescribed off-label to children, and Lilly has been seeking approval to market the drug for children between 13 and 17 years of age.

In documents released in advance of the advisory meeting today, FDA staffers suggested that new language should be considered to specifically warn about the potential side effects of Zyprexa for children. This could include information about the risk of weight gain and other metabolic changes that are already noted on the label for adults.

As a result of Lilly’s failure to adequately warn about these side effects in the past, the drug maker has already paid about $1.2 billion to settle over 30,000 Zyprexa lawsuits filed by users who suffered diabetes, hyperglycemia, pancreatitis and other injuries.

Lilly has also paid millions to settle claims over their marketing practices, which included claims that they marketed the drug for unapproved uses and downplayed the risk of Zyprexa side effects.

According to the New York Times, Eli Lilly is also expected to pay at least another $1 billion in restitution and fines to resolve federal criminal investigations related to their marketing of Zyprexa…

The Best Pharmaceuticals for Children Act of 2002 requires drug reviews for all drugs recently tested in children. The FDA advisory panel consists of outside experts who will discuss the reports and make recommendations to the FDA about adding warnings to the drug labels about potential side effects in children.

Only 51 More Signatures Needed to reach 28,000 Against TeenScreen!
Petition: http://www.petitiononline.com/TScreen/petition.html
Video: http://www.youtube.com/watch?v=RfU9puZQKBY

Minnesota becomes latest to sue Lilly over Zyprexa

November 03, 2008: 03:57 PM EST

NEW YORK (Associated Press) - Minnesota has joined a long line of states aiming to wrangle money from Eli Lilly and Co. with a lawsuit over the drugmaker’s top seller, the anti-psychotic Zyprexa.

The state attorney general’s office filed a complaint in federal court last week echoing claims of other lawsuits that say Lilly downplayed the drug’s side effects and marketed it for uses not approved by federal regulators.

Lilly has spent more than $1.1 billion since 2005 to settle product liability claims regarding the drug, which brought in more than $4.7 billion in revenue last year. It announced last month a $62 million settlement with 32 states and Washington, D.C., over Zyprexa marketing practices.

Minnesota was not part of that case but has been engaged in settlement talks, said Ben Wogsland, a spokesman for the attorney general’s office.

“We weren’t frankly … comfortable with the amount of money that was being offered to Minnesota, and we communicated that to the company and what our concerns were there,” Wogsland said.

He declined to elaborate on the amount or the talks, citing their confidential nature. Minnesota spent more than $175 million through public health programs on Zyprexa prescriptions between 2000 and 2007. Wogsland said the lawsuit helps the state learn more about the drug’s impact on Minnesota through the discovery process.

Lilly’s Zyprexa legal woes also include an investigation by the U.S. attorney’s office for the Eastern District of Pennsylvania. The company recorded a loss in the recently completed third quarter largely due to a $1.4 billion charge related to the investigation of Zyprexa marketing practices.

Lilly said late last month it was taking the charge because it was in advanced discussions with that U.S. attorney’s office over the investigation.

Lilly has long maintained that it promotes its medications only for approved uses. Company spokesman Jamaison Schuler said in an e-mail Monday Lilly is committed “to the highest ethical standards and to promoting our medications only for approved uses.”

“We have clear guidelines and extensive training for our sales representatives to help assure that they provide appropriate promotional information that is within the scope of prescribing information approved by the FDA,” he wrote.

http://en.wikipedia.org/wiki/Inositol

Highly Recommended Reading: Nutritional therapies for mental disorders
by Shaheen E Lakhan and Karen F Vieira who link choline deficiency to bipolar disorder and report efficacy in lecithin supplementation based on a double-blind, placebo controlled trial. (wikipedia)

Inositol as a treatment for psychiatric disorders: a scientific evaluation of its clinical effectiveness

Townsend Letter for Doctors and Patients, Oct, 2004 by Gina L. Nick

Inositol is a naturally occurring isomer of glucose, though it is generally considered to be a member of the B vitamin family. It is a key intermediate in the intracellular phosphatidyl inositol second messenger pathway activated by numerous serotonergic, cholinergic, and noradrenergic receptors. (1) In this capacity it serves as an important signal transduction molecule, but inositol is also a structural component of cellular membrane phospholipids. (2) Research indicates that inositol is an effective and safe option in the treatment of panic disorder, obsessive-compulsive disorder (OCD), bulimia nervosa, binge eating and/or depression. (3-9) Inositol’s efficacy, in the absence of side effects, makes this nutrient an attractive addition to treatment plans for specific mood disorders. Following is a scientific review of inositol for the treatment of mood disorders, including a discussion of its anecdotal use for the treatment of insomnia and its cautioned use by pregnant women for the prevention of neural tube defects and embryopathies.

Inositol occurs naturally as phytic acid in the fiber component of numerous plant foods, especially whole grains, citrus fruit, nuts, and seeds, and as myoinositol in meat. In the intestinal tract, bacteria break down phytic acid into bioavailable inositol that is easily absorbed via the intestinal epithelium. Myoinositol is found to bioaccumulate most abundantly in the central nervous system, supporting a role for it in neurological function.

Depression

Depressive patients generally have decreased levels of inositol in their cerebrospinal fluid. (3) Researchers now theorize that inositol produces positive clinical results in patients with depression due to intracellular phosphatidyl inositol serving as a second messenger for 5-hydroxytryptamine (5-H[T.sub.2]) receptor signaling mechanisms. Serotonin selective reuptake inhibitors (SSRIs), a family of drugs commonly used to treat depression, have a similar therapeutic profile to inositol in that they inhibit serotonin reuptake in the synaptic cleft. (10)

Levine et al. (4) performed a double-blind, placebo-controlled trial for 28 days on 28 depressed patients using a large dose (12 grams per day) of inositol. The Hamilton Depression (HAMD) Scale was used to evaluate patients after the 28-day trial period, and a significant overall benefit was confirmed in the inositol group compared to the placebo group (Table 1). No changes were noted in liver, kidney, or hematological function as a result of the high-dose inositol supplementation.

Bipolar Depression

Statistically nonsignificant differences favored inositol in 22 subjects treated for 6 weeks for bipolar depression. (11) This study noted the appeal of minimal side effects and the agent’s ‘natural substance’ aspect.

Obsessive-Compulsive Disorder

Levine (3) completed a review of research studies using inositol on psychiatric patients. The review highlighted some interesting findings with OCD patients. Serotonin plays a definitive role in obsessive-compulsive disorder as confirmed by the effectiveness of SSRIs in OCD patients and the fact that serotonin agonists exacerbate the syndrome. Rahman and Neuman (12) effectively reduced serotonin receptor desensitization via the administration of myo-inositol.

These research findings, coupled with the knowledge that SSRIs have proven beneficial in the treatment of OCD, (13) influenced Fux et al. (9) to complete a double-blind, placebo-controlled, random, crossover treatment trial of inositol on OCD. Thirteen patients, all of whom met DSM-III-R criteria for OCD, completed the trial. Six patients began the trial on placebo and seven began the trial on inositol (18 grams per day) for a total of six weeks for the first phase and six weeks for the crossover phase. The researchers administered 18 grams of inositol rather than 12 grams (typical dose for depressive patients) because OCD patients generally respond to higher relative doses of SSRIs than is needed to effect change in most depressives. The OCD patients were free of drug and alcohol abuse and had no evidence of diabetes or GI disorder. OCD was assessed using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and depression and anxiety were assessed using the Hamilton Depression Scale (HDS) and Hamilton Anxiety Scale (HAS). The mean improvement in OCD symptoms from baseline to six weeks was 5.9[+ or -]5.0 for inositol versus 3.5[+ or -]2.8 for placebo (p=0.04; t-test). This indicates a measurable positive response of OCD patients to inositol. Table 2 further details the results of this study with respect to inositol’s effect on subscale obsession, subscale compulsion, anxiety, and depression, all of which showed marked improvement with the administration of inositol versus the placebo.

Panic Disorder

Panic attacks are recurring attacks of severe anxiety without an apparent cause. Agoraphobia (irrational fear and avoidance of crowds, travel, and multiple situations), depression, alcohol abuse, and suicide are common symptoms and may be exacerbated by post-traumatic stress. Current treatments usually consist of antidepressant drugs and cognitive-behavioral therapy.

Antidepressant medications affecting serotonin metabolism are effective about 70% of the time for dramatic, short-term improvement of anxiety symptoms. However, chronic residual symptoms often persist in the long term. 25-75% of patients with panic disorder discontinue drug treatment because of side effects, and these patients quickly relapse. (8) This has led researchers to study the effects of inositol on patients suffering from this condition.

In one study, (5) twenty-one patients diagnosed with panic disorder with or without agoraphobia were given 12 grams of inositol per day or placebo. In the treatment group, the severity and frequency of panic attacks declined significantly with minimal associated side effects. The average number of panic attacks per week in patients treated with inositol fell from 10 to 3.5 per week. The researchers concluded that these results were “clinically meaningful” in the management of panic attacks.

More recently, inositol was compared with the antidepressant fluvoxamine in the treatment of panic disorder. (8) This study represents a more stringent test of the effects of inositol in treating panic disorder because it is the first to compare inositol with an established antidepressant drug. In this study of 20 patients with panic disorder, inositol was found to be slightly but significantly more effective than fluvoxamine in reducing the number of panic attacks (p<0.049). Otherwise, it was comparable to fluvoxamine on all other measures (HAS, phobia, and Clinical Global Impression (CGI) Scale). Since inositol appears to be as effective as fluvoxamine, patients may prefer it and continue to take it for the long term because side effects are extremely rare and mild.

Bulimia nervosa and Binge Eating

Gelber et al. (7) conducted a double-blind crossover trial comparing 18 g inositol to placebo in 12 patients with bulimia nervosa and binge eating. They took each test substance for 6 weeks. Inositol was significantly better than placebo on the Global Clinical Impression, the Visual Analogue Scale, and the Eating Disorders Inventory. The study concluded, “Inositol is as therapeutic in patients with bulimia nervosa and binge eating as it is in patients with depression and panic and obsessive-compulsive disorders.”

Insomnia

Extreme situational stress can have a major impact on sleep rhythm and dreaming. (14) As of yet, there are no clinically valid controlled studies confirming the use of inositol in stimulating sleep in insomniacs. However, based on what is known about the role of inositol in regulating serotonin levels, researchers have speculated that inositol may assist people suffering with insomnia. Because it has no known side effects and is present in healthy whole foods, a diet rich in inositol may improve disrupted sleep patterns.

Retinopathy of Prematurity

In a completely different vein, Friedman et al. (15) demonstrated that infants receiving high inositol formula supplements and with higher serum inositol concentrations at birth and after 30 days had a significantly lower incidence of severe retinopathy of prematurity than those receiving the lower inositol formula and with lower serum concentrations. The p value was <.05), and the odds ratio was 4.7.

Not for Use During Pregnancy

Researchers have documented the preventive effect of inositol in folate-resistant neural tube defects in rats and mice, (16,17) as well as its positive effect in treating hyperglycemia-induced embryopathy. (18) However, inositol may cause dose-related uterine contractions because it has an intimate relationship with oxytocin, a key uterine stimulator. Oxytocin activates phospholipase C to produce inositol-1,4,5-triphosphate, which causes the release of calcium from intracellular stores and stimulates uterine contractions. (19,20) Thus, it is possible that inositol in high doses may stimulate uterine contractions via its role in the oxytocin stimulatory pathway, making it potentially dangerous for pregnant women.

Inositol in Food

Inositol in the form of phytic acid has been proposed as a possible agent in the cancer-fighting potential of whole grains. (21) The compound is heat- and acid-stable and is found in high concentration in many food items, including cereal grains, nuts, and seeds. Phytic acid is a metal chelator that can suppress damaging metal-catalyzed redox reactions, making it a natural antioxidant. Indeed, a high concentration of phytic acid in fruits and vegetables prevents oxidative browning and putrefaction by inhibiting polyphenol oxidase. (22)

The foods in which phytic acid is found are typically high in numerous other antioxidants, including quercetin and flavonoids. Phytic acid is also a major source of dietary phosphorus. (23) It is unclear if physiologically effective doses of inositol for treating mood can be achieved through diet alone.

In the Lab

Carey (24) has recently demonstrated in 14 patients with OCD that improvement during inositol treatment parallels specific single photon emission computed tomography (SPECT) changes in certain areas of the brain. These findings suggest inositol’s clinical effects are mediated through neuronal circuitry that is different from those involved with the SSRIs, implying an “overlapping but distinct mechanism of action.”

Brink et al., (25) exploring the mechanism of action of mI in depression and related anxiety disorders, found both similarities and differences in the effects of myo-inositol (mI), fluoxetine and imipramine on serotonin 5HT2A and muscarinic acetylcholine receptors in human neuroblastoma cells. These findings may help to explain why mI seems to be effective exclusively in selective serotonin reuptake inhibitor-sensitive disorders.

Conclusion

Inositol’s clinical efficacy coupled with the absence of significant side effects suggests that this nutrient may be an attractive addition to treatment plans for patients suffering from panic disorder, clinical depression, and/or obsessive-compulsive disorder. While inositol has shown benefit in some SSRI responsive conditions, it is not indicated as a replacement for SSRIs or as a treatment for all SSRI responsive conditions. Further research is necessary to elucidate the full potential of this natural compound in the treatment of mental illnesses and other conditions.

Statistical Data on next page…

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Nutritional Supplements: Amino Acids

By Kimberly Read & Marcia Purse, About.com

Updated: July 30, 2006

Research indicates there are a number of supplements which may be beneficial for those with this disorder. I have categorized these into amino acids, vitamins and minerals. In this first article we will explore the amino acids. However, a note of caution before we begin.

The purpose of this article is to bring these supplements to your attention so that you may be aware of some additional tools available for your well-being. This article is intended as a source of information to discuss with your doctor and not as a replacement for your doctor. These supplements are just that - supplements. They can in no way replace your prescription medications for manic depression.

Amino Acid Defined

A literal definition of an Amino acid is an organic compound containing an amino group (-NH2) and a carboxyl group (-COOH). So what does this mean? It means they are literally the building blocks for all life, in that they are the chemical basis for all protein. Protein is one of the biggest components of our bodies (as well as the bodies of all living things). Our bodies use amino acids to form the proteins which build everything from muscles and bones, skin and hair, to internal organs and fluids. These amino acids also play an active role in our nervous system, where they function as neurotransmitters carrying messages from cell to cell. In short, amino acids are absolutely essential for our well-being. (For additional reading about the science of amino acids, take a look at The Amino Acid Collection and Amino Acids - An Overview.)

There are about 20 natural amino acids. These can be divided into two basic groups: essential and nonessential. The essential amino acids are those which your body cannot synthesize. Your body only gets these through your diet. The nonessential amino acids are just as important, but your liver can manufacture them.

Amino Acids and Bipolar Disorder

As it relates to Bipolar Disorder, an overall balance of amino acids is very important. This gives the body a healthy supply of protein which is necessary for normal brain function as well as helping combat depression. In the book Prescription for Nutritional Healing, the authors recommend taking, as directed on the label, a free-form amino acid complex twice daily on an empty stomach.

Two in Particular

In considering specific amino acids as supplements for those with Bipolar Disorder, two in particular may be of some help. Tyrosine transmits nerve impulses to the brain, helps overcome depression, improves memory and increases mental alertness among other things. Tyrosine supports the formation of the bulk of neurotransmitters in the body. A reduction in neurotransmitters such as dopamine, norepinephrine and epinephrine can lead to fatigue and even depression.

Athletic Nutrition.com (link no longer available) pointed out that there are no definitive studies as to an effective dosage for Tyrosine. However, Prescription for Nutritional Healing recommends 500 mg three times a day on an empty stomach. This book also warns that Tyrosine should NOT be taken if you are taking an MAO inhibitor.

Taurine is another which has possibilities for helping with Bipolar Disorder, in that it can reduce hyperactivity and anxiety. Taurine is an inhibitory neurotransmitter and therefore functions as a mild sedative. The Natural Health Consultants recommend one 1,000 mg dose a day. AMNI (Advanced Medical Nutrition) [link no longer available] stated that 500 mg up to 3 times a day may be taken. You should be aware that excessive levels can lead to depression and short term memory loss.

In closing, I just want to remind you to consult your doctor before taking any nutritional supplements. The individual amino acids in particular should only be taken under the supervision of a medical professional.