CDC Leads SSRI Disinformation Media Blitz

Evelyn Pringle July 20, 2007

In a June 27, 2007 press release that made headlines all over the world the US Centers for Disease Control announced that birth defects associated with the use of antidepressants by pregnant women are rare. As proof for this claim, the CDC cited two new studies published in the New England Journal of Medicine.

Over the following 2 weeks hundreds of stories magically appeared in newspapers with headlines splashed all over the internet and “medical experts” appeared live on all the major television networks to tout the new studies as major health “news” in a well-coordinated media blitz clearly aimed at promoting the sale of selective serotonin reuptake inhibitor antidepressants (SSRIs) to pregnant women.

The well-coordinated blitz downplayed all the serious birth defects that have been reported in numerous studies over the past several years and all the warnings issued by the FDA over the past several years about the fetal harm known to be associated with the drugs.

The antidepressants included in the NEJM studies included Paxil by GlaxoSmithKline, Zoloft marketed by Pfizer; Prozac sold by Eli Lilly; Celexa and Lexapro by Forest Laboratories, Effexor marketed by Wyeth, Luvox by Solvay, and the generic makers of these drugs include Barr Pharmaceuticals, Ranbaxy Labs and Genpharm.

The public needs to know that the CDC study was funded in part by GlaxoSmithKline, the maker of Paxil, which carries the strongest FDA warnings about birth defects developing in infants exposed to the drug in the womb.

Experts point out that the hundreds of headlines failed to disclose the best kept secret about SSRIs – that the drugs do not work. “When tested in head-to-head competition it would take more space than a newspaper article will permit to explain how hard the researchers have to “work” to “prove” that these antidepressants work at all,” says SSRI expert, Dr Grace Jackson, author of “Rethinking Psychiatric Drugs: A Guide for Informed Consent.”

A fact also not mentioned in the headlines is that the studies were limited to women who took the drugs during the first trimester of pregnancy and the research consisted of mostly phone conversations that took place years ago with women who relied on their own memories without reviewing any medical records or actual pharmacy prescription data.

Most importantly, experts say, the researchers diluted the FDA warning about studies that found babies exposed to SSRIs after the 20th week of pregnancy, have a 6-fold increased risk of developing persistent pulmonary hypertension, a life-threatening lung disorder.

On July 19, 2006, the agency issued a Public Health Advisory and said, “the FDA has asked the sponsors of all SSRIs to change prescribing information to describe the potential risk for PPHN.”

The Advisory warned that: “Babies born with PPHN have abnormal blood flow through the heart and lungs and do not get enough oxygen to their bodies” and “Babies with PPHN can be very sick and may die.”

On October 16, 2006, the first PPHN related lawsuit was filed against Glaxo on behalf of the family of an infant born with the disorder after exposure to Paxil in the womb, by Attorney Karen Barth Menzies, a partner in the Baum Hedlund law firm and the leader of the firm’s Antidepressant Litigation Department.

According to Ms Menzies, “FDA regulations require Glaxo to issue stronger warnings whenever there is reasonable evidence of an association between a serious risk and Paxil.”

She points out that research indicated the risk of PPHN in a study published more than 10 years ago on October 3, 1996, in the New England Journal of Medicine, lead by Dr Christina Chambers of the Department of Pediatrics at the University of California-San Diego.

“FDA regulations specifically state that a causal link need not be proven and allow Glaxo to issue a new warning without prior FDA approval,” Ms Menzies notes.

She reports that infants born with PPHN often require mechanical assistance to breath but 10% to 20% of infants do not survive even when they receive treatment.

The PPHN babies that do survive often experience developmental delays, brain abnormalities and hearing loss, experts say.

The headlines about the NEJM studies in the media were also misleading because the researchers did find that Zoloft and Paxil were associated with “significant increases” in specific birth defects, and stated the “current study suggests that specific SSRIs may increase the risk of specific birth defects, and further studies will need sufficient power to pursue these important clinical questions.”

Heart birth defects in infants exposed to Paxil were found to occur 3 times more often and heart defects were 2 times higher in newborns exposed to Zoloft. The CDC researchers reported that by using an “embryologically based classification” of heart defects, “we found a doubling of the risk of septal defects” associated with Zoloft use, and “a tripling of the risk of right ventricular outflow tract obstruction defects” associated with Paxil.

The studies also found a nearly 6-fold rise in the risk of clubfoot in children of women who used Paxil and reported other birth defects including (1) anencephaly, (2) craniosynostosis; and (3) omphalocele.

Anencephaly, a neural tube defect where much of the brain does not develop, was found to be 2.4 times higher, and omphalocele, a condition in which the infant’s intestine or other abdominal organs protrude from the navel was 2.8 times more prevalent overall and 6.4 times higher with Paxil.

Craniosynostosis, an abnormality in which connections of the skull bones close prematurely, was found to be 2.5 times greater, and the neural tube defect, spina bifida, a condition where the spinal column does not completely close in the first month of pregnancy, was also noted.

Experts warn that far more infants will be born with birth defects in the coming years as a result of tens of thousands of infants being exposed to SSRIs in the womb every year.

In addition to birth defects, many other serious adverse events have been found to be associated with SSRIs over the past decade. Studies have shown the drugs to be linked to suicidality, violent and homicidal behavior, abnormal gastrointestinal and uterine bleeding, fertility problems, sexual dysfunction, a decrease in bone density, and a severe withdrawal syndrome in patients and infants born to mothers taking the drugs.

The risk associated with depression in pregnancy is suicidality. But one of the world’s leading authorities on SSRIs, Dr Peter Breggin, reports that SSRIs are known to increase the risks of suicide. “In fact,” he says, “the new FDA labels for antidepressants specifically warn about SSRI-induced suicidality in youth and in young adults, the very group most likely to become pregnant.”

“The SSRIs not only threaten to cause the death of the mother through suicide but the death of the child through lethal birth defects as well,” Dr Breggin advises.

As a direct result of the industry’s control over the mainstream media, the public is never properly warned about serious risks found to be associated with a drug because if the story gets told at all, it will only be in the news for a day or two, and then “medical experts” will suddenly show up on “news” programs for 2 or 3 days in a row to present what amounts to an infomercial to discount the risks reported in the study.

The industry’s control of the media began back in the late 1990s when the ban on direct-to-consumer advertising was lifted. Since then, the industry has invested so much money in advertising that all the media companies in the US are now dependent on drug money.

Due to this control, the industry paid shills are now dispatched on a regular basis to disseminate false information about the risks and benefits of a drug using the public airwaves even when an advertisement that contained the same bogus information would result in the sanction of a drug company for presenting false and misleading information to the public.

Drug companies basically bribe the medial journals to print their studies because the editors know the company will purchase thousands of copies for distribution to prescribing doctors, with full knowledge that most doctors will never read the whole study, but will remember the misleading headline because it was published in the “reputable” medical journal.

And Big Pharma funnels money to researchers in a variety of ways. Dr Marcia Angell, a nationally recognized authority on medical ethics and a former editor of the New England Journal of Medicine, had this to say in a the NEJM in 2000, about the financial ties between the industry and researchers:

“The ties between clinical researchers and industry include not only grant supports, but also a host of other financial arrangements.

“Researchers also serve as consultants to companies whose products they are studying, join advisory boards and speakers bureaus, enter into patent and royalty arrangements, agree to be the listed authors of articles ghostwritten by interested companies, promote drugs and devices at company sponsored symposiums, and allow themselves to be plied with expensive gifts and trips to luxurious settings”

After a rigged study is planted in a medical journal, the next step in the marketing scam is to provide a favorable report on the findings, also ghost-written by the drug maker or a PR firm, in a press release that is sent out to all the major news outlets which guarantees that headlines about the results will appear all over the world.

From there, the company uses the media to plant feature stories to reinforce the headline of the press release and in many cases, the news articles will quote the information verbatim from the drug maker’s press release.

In the final act, the media provides the company with a platform for the “medical experts” to reach consumers to tout the new study on all the major networks in “news” segments which in turn sends patients running to their doctors with news of the miraculous new findings and demanding a prescription for the drug.

In the book, “Trust Us We’re Experts,” by Sheldon Rampton and John Stauber, the authors document the many techniques used by PR firms hired to pump out propaganda through the press and refer to the mainstream media as the “disinfotainment industry.”

They report that the psychiatric manipulation industry is enormous and pays out about $10 billion a year to propaganda experts and that about 40% of all stories in the media are planted by PR firms.

Because most news stories on radio and TV are nothing more than a rehashing of stories published in newspapers, the book notes, the news Americans receive every day amounts to nothing but propaganda.

The success of the media backed campaign to sell SSRIs to pregnant women by discounting the years of studies showing serious harm to the fetus is clear evidence that “disinfotainment industry” is still paying high dividends to all shareholders in the US.

Taking Zoloft During Pregnancy Linked to Birth Defects

Evelyn Pringle June 7, 2007

Less than a year ago, in July 2006, the FDA issued a Public Health Advisory on a birth defect found to be associated with Zoloft and other selective serotonin reuptake inhibitor antidepressants by a study in the February 2006 New England Journal of Medicine that found a higher risk of a life-threatening lung disorder in infants exposed to SSRIs, stating:

“A recently published case-control study has shown that infants born to mothers who took selective serotonin reuptake inhibitors (SSRIs) after the 20th week of pregnancy were 6 times more likely to have persistent pulmonary hypertension (PPHN) than infants born to mothers who did not take antidepressants during pregnancy.”

PPHN infants have difficulty making the transition from breathing inside the womb to normal breathing after delivery, often leading to respiratory failure that requires mechanical ventilation. Even when treated, between 10% to 20% of babies born with PPHN do not survive.

Between 1998 and 2003, the research team interviewed 377 women who had recently given birth to a baby with PPHN, with questions about medical history and the drugs taken during pregnancy and found that 3.7% of the infants had been exposed SSRIs after the 20th week of pregnancy, or about 6 times the rate among healthy infants in a comparison group born at the same time.

Infants with PPHN typically show abnormal muscle cell growth in their respiratory system. Previous investigations have found that SSRIs tend to accumulate in adult users’ lungs and serotonin can promote the proliferation of certain muscle cells. This may explain how the drugs could have an effect on the developing fetus, according to the study authors in the NEJM.

This birth defect is also not as rare as once thought. After the results of the PPHN study were released in February 2006, the lead author and researcher, Dr Christina Chambers, told the Wall Street Journal that women contacted her from all over the US who had given birth to babies with PPHN after using SSRIs during pregnancy.

Medical experts say its important to recognize that Pfizer promotes Zoloft for many disorders besides depression, meaning women may be taking the drug even though they have never been diagnosed with depression. According to the FDA, in addition to depression, Zoloft is approved to treat obsessive-compulsive disorder, panic disorder, social anxiety disorder, post-traumatic stress disorder, and premenstrual dysphoric disorder.

In March 2006, Health Canada issued its own warning, “advising women who are taking antidepressants known as selective serotonin reuptake inhibitors and who are pregnant or intend to become pregnant to discuss the situation with their doctor, due to potential risks to the baby.”

On April 7, 2006, the BBC reported that a Canadian study from the University of Ottawa of almost 5,000 mothers found that SSRI use during pregnancy doubled the risk of delivering a stillborn baby and that women who took the drugs were also more likely to have a premature or low-birth-weight baby.

The study found almost 20% of women who used SSRIs gave birth prematurely, compared to 12% of those who did not use the drugs and that babies born to women using SSRIs were also more likely to have seizures.

On August 25, 2006, Reuters Health reported another Canadian study that found that babies born to women who took SSRIs during pregnancy appear to be at increased risk of having a low birth weight and to develop respiratory distress.

Lead investigator Dr Tim Oberlander told Reuters that “our study was undertaken to distinguish the effects of maternal mental illness — pregnancy-related depression — from its treatment — SSRIs — on neonatal outcomes.”

The research team at the University of British Columbia, Vancouver, examined data for almost 120,000 live births between 1998 and 2001, and found 14% of the mothers who were diagnosed with depression.

The study compared the outcomes of babies born to depressed mothers treated with SSRIs and of those born to depressed mothers who were not treated, and there was a significantly greater incidence of respiratory distress, 13.9% vs 7.8%, and longer hospital stays for infants born to mothers on SSRIs, the team reported in the Archives of General Psychiatry.

Birth weight and gestational age were also significantly less in SSRI infants, and a significantly greater proportion were born before 37 weeks. “These findings are contrary to an expectation that treating depressed mothers with SSRIs during pregnancy would be associated with lessening of the adverse neonatal consequences associated with maternal depression,” Dr Oberlander told Reuters.

Preterm birth is the leading cause of infant mortality in the US, accounting for at least a third of all infant deaths in 2002, and the contribution of prematurity to infant mortality may be twice as high as originally estimated, according to Dr William Callaghan and colleagues in the October 2006 Pediatrics journal.

For the study, the researchers looked at the top 20 causes of infant deaths in 2002 and found that 34% of the deaths occurred in preterm infants, 95% of whom were born before 32 weeks gestational age and weighed less than 3.3 lbs. Two-thirds of the deaths in preterm infants occurred in the first 24 hours of life, the research team found.

The fact that SSRIs are highly addictive also adds to the health risks that a pregnant woman faces if she is already taking Zoloft. “A lot of these medicines are associated with withdrawal syndromes, which can be very problematic for many patients, so stopping is something that needs to be monitored carefully by your doctor,” said Dr Sandra Kweder, deputy director of the FDA’s Office of New Drugs, in a March/April 2006 update on the FDA’s Web site.

But on the flip-side of the coin, continuing to take Zoloft places the infant at risk for withdrawal. A February 2006 study in the Archives of Pediatrics & Adolescent Medicine reports that nearly one-third of infants born to women taking SSRIs show symptoms of withdrawal including tremors, high-pitched crying, gastrointestinal problems and sleep disturbances. The researchers found that 13% of the 60 newborns exposed to SSRIs exhibited severe symptoms of withdrawal.

An earlier study in the February 2004 Pediatrics journal found abnormal heart rhythms, sleeping patterns, and levels of alertness in babies exposed to SSRIs in the womb. Dr Philip Zeskind, a professor of pediatrics at the University of North Carolina-Chapel Hill, and lead author, referred to the results as alarming.

The researchers compared one-day-old babies of mothers who took SSRIs with babies of mothers who did not and looked at sleeping and waking patterns, movements and heart rates. According to the study, infants exposed to SSRIs tended to be locked in one “sleep state” and showed “fewer of the smooth and predictable changes in heart rate that normally occur in newborn infants.”

In July 2004, the rising number of reports prompted the FDA to alter labeling for the entire SSRIs, warning that some newborns exposed to SSRIs and Effexor in the womb had developed problems requiring prolonged hospitalizations, respiratory support and tube feeding.

Critics also say, an important point to consider when weighing the risks and benefits of taking Zoloft during pregnancy, is that most experts who have evaluated all the clinical data on SSRIs say the benefits of the drugs are minimal.

In the July 2005 British Medical Journal, Moncrieff & Kirsch state in part: (1) Recent meta-analyses show [SSRIs] have no clinically meaningful advantage over placebo; (2) Methodological artifacts may account for the small degree of superiority over placebo; and (3) Given doubt about their benefits and concern about their risks, current recommendations for prescribing antidepressants should be reconsidered.

April 2007 Big Pharma Litigation Update – Drugs – Part I

Evelyn Pringle April 5, 2007

For the last two decades, illegal drug marketing schemes have paid off well for Big Pharma. However, as the old saying goes, all good things must come to an end, and every major drug company is currently involved in massive litigation.

Some companies are facing thousands of lawsuits with a common complaint that the drug maker deliberately concealed the side effects of their products while illegally promoting the drugs for off-label use.

Off-label refers to prescribing drugs to treat conditions other than those approved by the FDA and listed on the label. It can include prescribing drugs to unapproved populations, such as children or the elderly, or in higher doses than specified on the label.

It is illegal for drug companies to promote a drug for off-label uses, but doctors are allowed to prescribe a drug for any use they choose. Almost without exception, the lawsuits currently pending accuse the pharmaceutical companies of influencing doctors to prescribe the product for unapproved uses.

On August 18, 2006, Bloomberg News reported that Wyeth has accumulated more than 175,000 lawsuits since the Fen-Phen diet combination was removed from the market after studies revealed that the drugs caused heart valve damage, and primary pulmonary hypertension, or PPH, a life-threatening lung disorder. All total, Wyeth has set aside more than $21 billion to cover legal costs and settlements since the drugs were withdrawn, according to Reuters on May 24, 2006.

There was a national class-action settlement involving claims for heart valve damage, but it did not include claims for PPH which are proving to be costly. In one 2004 case alone, a Texas jury awarded over $1 billion to the family of a woman who died of PPH after taking Fen-Phen for about two years, including $113.4 million in compensatory damages and $900 million in punitive damages, according to Wyeth’s 2005 Annual Report. The case was later settled for an undisclosed amount.

PPH is a life-threatening condition that can require a heart-lung transplant. According to the FDA, PPH “results in death in about 40% of affected individuals within 4 years.”

The Fen-Phen combination was never FDA approved for any use, which means every prescription was off-label. Patients were able to get Fen-Phen on the internet, and Jenny Craig and Nutri-System set up weight-loss programs where doctors would prescribe the drugs to customers.

And there appears to be no end in sight for Fen-Phen lawsuits. On December 5, 2006, five more women who took the drugs in 1996 and 1997, filed lawsuits against Wyeth after being diagnosed with PPH. When it comes to liability, a plaintiff’s attorney, Paul Rheingold, in “Fen-Phen and Redux: A Tale of Two Drugs,” says, “there is blame enough to go around.”

The doctors who set up store-front Fen-Phen clinics and prescribed the drugs are obvious culprits, he says, and so are drug companies that profited financially from the fad and may have neglected to pass on information about deadly side effects.

On August 18, 2006, Bloomberg reported that Wyeth was facing 5,000 lawsuits over the menopause drug, Prempro, alleging that Wyeth misled the plaintiffs through deceptive marketing about the cancer risks associated with estrogen and progestin. As many as 6 million women took Prempro before it was linked to cancer in a 2002 study.

Financial analysts are predicting that, Merck in the end, will pay out as much as $50 billion for Vioxx litigation. On March 12, 2007, Reuters reported that a New Jersey jury found the drug was responsible for a plaintiff’s heart attack and awarded $20 million in damages.

According to Reuters, the jury also found that Merck committed consumer fraud by making misrepresentations concerning the heart risks, and intentionally concealing safety information from doctors prior to the plaintiff’s heart attack.

A large number of lawsuits have also been filed against Merck, over the osteoporosis drug Fosamax, and against Johnson and Johnson, over the Ortho-Evra birth control patch. The plaintiff’s allege that Fosamax causes jaw-bone death (OJN) and that the patch causes blood clots, which in turn lead to strokes.

Legal experts predict causation in cases involving Fosamax and the Ortho patch will be easy to prove because the plaintiffs have what is referred to as a “signature disease,” meaning a condition easily tied to the drug because it is rare.

The jaw-bone death occurring in people taking Fosamax is extremely uncommon. Kenneth Hargreaves of the University of Texas, noted the increasing cases in the April 3, 2006 LA Times. “We’ve uncovered about 1,000 patients in the past six to nine months alone,” he said, “so the magnitude of the problem is just starting to be recognized.”

FDA approved in 1995, Fosamax is a relatively new drug, and unreported cases may be higher than expected because doctors may attribute the pain caused by ONJ to osteoporosis, according to Diane Wysowski of the FDA’s Office of Drug Safety.

Dr Salvatore Ruggiero, an oral surgeon and one of the first doctors to notice the rise in ONJ in 2001, told the Times, “Even though the chances of getting this are small, considering there are 23 million women taking this drug, we could be talking about a significant number of people.”

The same goes for the Ortho patch. Blood clots seldom develop in young women of childbearing age. And legal experts say, for that reason, many Ortho patch lawsuits have already ended in confidential settlements with hardly a peep in the mainstream press, and J&J has made it clear to other plaintiffs’ attorneys that the company is willing to cut a deal.

Experts predict that many more lawsuits will be filed because there are thousands of young patch victims who are still unaware that the patch caused the health problems. In 2005 alone, more than 9.4 million prescriptions were written for the Ortho patch, according to IMS Health, an industry-tracking firm.

The FDA says it has received about 9,000 reports of adverse events related to the patch, but the agency also acknowledges that only between 1% and 10% of adverse events are ever get reported.

There are over a hundred more lawsuits filed against J&J involving the Duragesic pain patch. The device is supposed to deliver controlled doses of fentanyl, a drug so powerful that high doses can turn off the respiratory center in the brain.

On July 8, 2006, the Associated Press reported that a Houston jury had awarded $772,500 to the daughter of a woman who died after a leak on the patch increased the dose of the painkiller, and the jury found J&J negligent in the way the patch was made.

Another fentanyl product that legal experts say will bring a wave of lawsuits in the next couple of years, is Cephalon’s painkilling lollipop, Actiq. The product was only approved to treat cancer patients in chronic pain who are already on an opioid drug, because life-threatening conditions can occur at any dose in patients without a built-up tolerance for opioids. But a recent study by Prime Therapeutics found Actiq is being prescribed off-label nearly 90% of the time.

Fentanyl is reportedly 80 times stronger than morphine, and is a Schedule II narcotic drug, in the same category as cocaine, opium, methamphetamine and methadone, a class known to have the highest potential for abuse and overdose.

In 2004, there were an estimated 8,000 emergency-room visits for fentanyl overdoses, according the US Substance Abuse and Mental Health Services Administration. Overdose can result in sudden death through respiratory arrest, cardiac arrest, severe respiratory depression, cardiovascular collapse or severe anaphylactic reaction, according to the agency. As of November 16, 2006, there were 653 deaths confirmed in the US since 2005.

In November 2006, the Wall Street Journal, said evidence obtained in litigation showed Cephalon had set high sales quotas for its sales representatives that could not be reached without promoting Actiq off-label.

Internal company documents show sales reps were regularly sent to doctors who treated no cancer patients, with free coupons for doctors to pass out to patients. According to the Journal, Dr Stephen Leighton, a general practitioner with only 3 cancer patients at any given time, said a Cephalon saleswoman stop by once a month and gave him about 60 to 70 coupons to pass out to patients for 6 Actiq lollipops.

He told the Journal that the coupons led him to try the drug for migraines and back pain and said he prescribes Actiq 15 to 20 times a month to patients who do not have cancer.

According to the November 3, 2006, report in the Journal, Actiq sales increased from $15 million in 2000, to more than $400 million today.

The consequences of the off-label prescribing of this product are far reaching. On January 22, 2006, the Free Press reported that the wife of a minister, a former schoolteacher and mother of three, was charged with involuntary manslaughter because she gave Actiq to a friend for a migraine, and the friend died of a drug overdose.

More lawsuits are sure to be filed against Eli Lilly since secret internal documents obtained in litigation by attorney, Jim Gottstein, from Dr David Egilman, an expert in previous Zyprexa litigation, prove that the company concealed Zyprexa’s link to severe weight gain, high blood sugar, and diabetes for a decade, while Lilly promoted the drug for so many off-label uses that more than 20 million people have taken Zyprexa.

To date, Eli Lilly has spent well over $1 billion to settle about 26,000 Zyprexa lawsuits, with still more litigants waiting in line. Zyprexa has been linked to serious side effects, including diabetes, hyperglycemia and pancreatitis.

On January 14, 2005, a class-action lawsuit was filed in Canada with claims that Lilly also withheld information on the safety of Prozac. The plaintiffs allege that the reason Lilly failed to disclose the documents was because they showed a drastic increase in suicide attempts and other violent acts in patients taking Prozac, when compared to patients taking 4 other drugs.

All through the 1990s, Lilly swore that Prozac did not increase the risk of suicide or violence, while the company was quietly settling lawsuits out of court which made it possible to keep the incriminating evidence hidden with court orders, just as it has been doing with Zyprexa until the secret documents showed up in the press in December 2006.

Similar lawsuits are being filed against AstraZeneca over its antipsychotic drug, Seroquel, which reportedly has been used by more than 16 million people since it came on the market in 1997. The plaintiffs in those cases also claim that Astra downplayed the diabetes risks and concealed safety information.

No End in Sight for Fen-Phen Lawsuits

Evelyn Pringle January 29, 2007

On December 5, 2006, five women with ages ranging from 53 to 71, who took the appetite suppressants drugs known as fen-phen in 1996 and 1997, filed lawsuits against Wyeth Pharmaceuticals after being diagnosed with a life-threatening lung disorder.

These lawsuits demonstrate that the harm caused by fen-phen can surface many years after a person stops taking the drugs. For instance, plaintiff, Renee Tedesco, 53, of New Jersey, took fen-phen 10 years ago but was not diagnosed with primary pulmonary hypertension (PPH), until April 2006. She has undergone a double lung transplant to save her life.

In addition, studies released in November 2001, indicate that PPH in fen-phen users may be 7 times higher than originally predicted in 1997.

Fen-phen refers to a combination of the drug phentermine and the diet drugs Redux (dexfenfluramine) or Pondimin (fenfluramine). According to the FDA, these drugs were approved as appetite suppressants to be used separately in the treatment of obesity for short periods of time.

The fen-phen combination was never FDA approved for any indication so all prescriptions were written for off-label uses. Drug companies are prohibited from promoting drugs for off-label use but doctors may prescribe a drug that has been approved for one indication for any condition they deem appropriate. In recent years numerous drug makers have come under fire for illegally promoting their drugs for off-label uses.

Prescriptions written off-label for fen-phen were massive. Patients were able to get fen-phen over the internet, and Jenny Craig and Nutri-System set up weight loss programs where doctors would prescribe the drugs to patients.

Doctors prescribed fen-phen without doing a thorough examination, and in many cases without any exam at all. Most doctors prescribing the drugs had little or no training in obesity, according to One Half-Phen In the Morning/One Fen Before Dinner: A Proposal For FDA Regulation of Off-Label Uses of Drugs, by Maime Wilsker (1998).

One Illinois patient said that she obtained fen-phen from a weight-loss clinic without ever seeing a doctor and that a nurse gave her the prescriptions.

An estimated 6 million people have taken fen-phen and more than 18 million prescriptions were written for the combination in 1996 alone. From 1992 to 1997, new prescriptions for fen-phen increased by 442% for phentermine and 6390% for fenfluramine, according to a report in the March 24, 1997, Archives of Internal Medicine.

However, the run-away-train prescribing about came to a screeching halt on July 8, 1997, when the FDA issued a Public Health Advisory to 700,000 health care professionals and institutions warning that researchers at the Mayo Clinic had reported 24 cases of heart valve disease in previously healthy women who took fen-phen on average for 12 months.

Of the 24 women identified who had valve disease, eight also had moderate or severe pulmonary hypertension, which had not been previously identified.

The Advisory also noted that the agency had received additional reports of the same nature, and advised health care professionals to report any similar cases to the FDA through MedWatch. Subsequently, the FDA received 66 more reports of valve disease.

The lesions that formed on the heart valves of fen-phen users cause blood to flow backwards instead of forwards, which is called regurgitation. The Mayo Clinic study was reported in the August 28, 1997, New England Journal of Medicine and concluded by stating: “significant de-novo left-sided regurgitant valvular heart disease in a population less than 50 years old is rare. Thus, the association of valvular regurgitation with fenfluramine-phentermine is not likely due to chance.”

The researchers said that fen-phen users “should be informed about serious potential adverse effects, including pulmonary hypertension and valvular heart disease.”

Cardiologist, Dr Heidi Connolly led the study and was interviewed on PBS on August 27, 1997. At that time, she reported that five of the women in the study had required open heart surgery to repair or replace damaged heart valves.

Pulmonologist, Dr Lewis Rubin was also interviewed on the PBS program as part a member of the research team that linked PPH to fen-phen. Dr Rubin’s research found that people who took fen-phen for 3 months had a 9-fold increased risk for PPH, and 6-month users had a 23-fold increased risk of developing PPH.

After the Mayo Clinic report was published, the FDA conducted a study in five areas of the country, including Florida, Minnesota, Wisconsin, Indiana, and Pennsylvania and found a 32.8% presence of lesions causing valvular regurgitation, significantly higher than would be expected amongst the general population.

In addition to the FDA data supporting the link, Dr Mehmood Kahn performed a study in Minneapolis shortly after the July, 1997 announcement about valvular disease and found that approximately 25% of the 226 fen-phen users in his study had aortal regurgitation of mild or greater severity, compared with 1% in the 81 patients who did not take the drugs.

On August 27, 1997, acting FDA Commissioner, Dr Michael Friedman was interviewed on PBS and basically blamed the problems on the off-label prescribing explaining that “when these drugs are used in accordance with the labeled instructions, the number of side effects from pulmonary hypertension or from the valve abnormality are extremely rare.”

“When these medications are used outside of those labeled indications,” he advised, “at a higher dosage, for a longer period of time, or in combination with one another, then these side effects are seen more frequently.”

“But we’ve had very few, if any, valve abnormalities in patients who have used the products in an appropriately-labeled fashion,” Dr Friedman said in the interview.

He explained that the label indication “says to use these medications only for a short period of time, some few weeks, and in conjunction with dietary restrictions.”

On September 15, 1997, the FDA called for the removal Pondimin and Redux from the market, based on findings from patients evaluated with echocardiograms to test heart valve functioning. “These findings,” the FDA stated, “indicate that approximately 30 percent of patients who were evaluated had abnormal echocardiograms, even though they had no symptoms.”

The injuries resulting from the fen-phen debacle are reportedly one of the largest number of adverse drug reactions that the FDA has ever dealt with.

Since American Home Products Corporation, which became Wyeth in 2002, withdrew the drugs from the market, a massive number of lawsuits have been filed against the company alleging injuries of valvular heart disease and PPH caused by the drugs.

Heart valve damage is an extremely serious medical condition that is life-threatening. Experts note that there are no medications that can reverse valve damage and valve replacement surgery is often the only option available.

In a healthy heart the valves fit tightly when closed, preventing blood from flowing backwards. But in the hearts of the patients studied at the Mayo Clinic, a waxy substance prevented the valves from closing completely.

Valvular insufficiency occurs when the valves do not close properly, which forces the heart to work harder to circulate the blood and can lead to serious problems such as heart attack or heart failure, according to WebMD.

Valve replacement requires open heart surgery, according to the Texas Heart Institute. The 2 kinds of valves used are mechanical valves made of metal or plastic, and biological valves made from animal tissue or human tissue from a donated heart.

Mechanical valves are stronger but because blood tends to stick to them and create blood clots, patients need to take blood-thinning drugs for the rest of their lives. And because these drugs increase the risk of bleeding, patients must wear a medical alert bracelet so that medical professionals will know they are taking a blood-thinning drug.

Patients with biological valves usually do not have to take blood-thinning medications but because the valves are not as strong as mechanical valves, they may need to be replaced every 10 years.

PPH is also an extremely serious condition that may require a heart-lung transplant. In its simplest form, PPH means high blood pressure in the lungs and the constriction of the vessels makes it harder for the heart to pump blood through the lungs. According to the FDA, PPH “results in death in about 40% of affected individuals within 4 years.”

On November 22, 1999, the Philadelphia Inquirer interviewed a woman who was almost entirely housebound and on a waiting list for a double lung transplant. She was connected to oxygen tubes 24 hours a day and had an IV line connected to a pump to deliver drugs into her heart with her at all times. The woman said that as soon as she starts to move she gets weak and likened living with PPH to living on Mount Everest without oxygen.

Redux was FDA approved in April, 1996, even though there were already concerns about PPH. Reports of PPH with the drug had appeared in European literature in the 1980’s and 1990’s.

Two months after its approval, the International Primary Pulmonary Hypertension Study reported that the appetite suppressants (anorectic agents) increased the risk of PPH to between 23 and 46 cases per million, compared to the usual 1-2 cases per million. Redux and Pondimin represented 90% of the anorexigens in the study.

The IPPHS found that “the use of any anorexigen within the previous year was associated with a ten-fold risk of developing PPH, and the risk increased to more than 20-fold with use for longer than three months.”

There have also been reports of neuropsychological damage in fen-phen users that can include memory loss, behavioral changes, depression, psychotic breakdowns, and mood swings. A study reported in the September 1997, Journal of the American Medical Association, indicated that Redux and Pondimin can reduce the production of a key brain-signaling chemical and adversely affect memory, cognition and moods.

Critics say this too was a known risk at the time that Redux was FDA approved. In fact, after its approval, a group of neuroscientists sent a letter to the FDA criticizing the agency for ignoring animal tests that suggested that prolonged use of Redux damaged brain tissue.

In litigation, some plaintiffs are going after the doctors for their off-label prescribing. In a Philadelphia PPH jury trial, a doctor was held liable for half of the $8 million verdict for prescribing fen-phen for the plaintiff between 1995 and 1997.

The woman’s attorney stated that “the claim against [the prescribing doctor] was that he not only prescribed the drug beyond the two weeks recommended by the manufacturer, but he prescribed it for years . . . and he prescribed it until she [the plaintiff] called him and said that she had heard on CNN when she was in Italy touring that there were side effects,” according to Lori Litchman, in the February 24, 2000, Legal Intelligencer.

On the other hand, the drug maker can hardly argue that it was unaware of the widespread off-label use of fen-phen with record profits pouring in from the drugs.

According to one plaintiff’s attorney, Paul Rheingold, in Fen-Phen and Redux: A Tale of Two Drugs, “there is blame enough to go around.”

The doctors who set up store-front fen-phen clinics and prescribed the drugs are obvious culprits, he said, and so are drug companies that profited financially from the fad and may have neglected to pass on information about deadly side effects.

A national class action settlement has been reached involving claims for valvular heart disease, but the settlement did not include claims for PPH or neurological damage. Lawsuits with those claims are being tried individually.

Wyeth has reportedly allocated $21 billion to cover the costs and damages of fen-phen litigation.

Glaxo Writing Checks Left and Right to Settle Paxil Legal Battles

Evelyn Pringle December 6, 2006

GlaxoSmithKline is no doubt looking forward to the New Year because the end of this one is becoming costlier by the month.

On November 1, 2006, the Associated Press reported that Glaxo had agreed to pay $63.8 million to settle a class action lawsuit with allegations that Glaxo promoted Paxil for use with children and adolescents while withholding negative information about the drug’s safety and effectiveness.

Members of the class include all US residents who bought Paxil for their children, and those people who have records of their purchase can reportedly get a full refund.

According to the Associated Press, Madison County, Illinois, Judge Ralph Mendelsohn, approved the settlement on October 6, 2006, and unsealed the agreement on October 27. The judge has scheduled a hearing for March 9, 2007 to determine whether the settlement is fair and whether the plaintiffs’ attorneys are entitled to the fee they are requesting.

Another similar class action antitrust case filed against Glaxo, on behalf of consumers and third party payers, who paid all or part of the purchase price of Paxil, was settled on April 22, 2005 for $65 million.

In that case, the plaintiff’s alleged that they were forced to pay too much for Paxil because Glaxo unlawfully maintained a monopoly and excluded competition by (1) conducting sham patent infringement litigation against generic Paxil makers which triggered automatic 30 month stays of generic competition; (2) made intentional misrepresentations to the Patent and Trademark Office; and (3) made intentional misrepresentations to the FDA which enabled Glaxo to exclude generic competition.

However, although Glaxo doled out $65 million, it refused to admit guilt. Paragraph 22 of the final Order in that case, dated April 22, 2005 states:

“Neither this Final Order and Judgment, the Settlement Agreement, nor any of its terms or the negotiations or papers related thereto shall constitute evidence or an admission by Defendant, that any acts of wrongdoing have been committed, and they shall not be deemed to create any inference that there is any liability therefore.”

What this says is that Glaxo maintains it did nothing wrong but it wrote out a check for $65 million just to get the natty little plaintiffs off its back and furthermore, the court says no inference of guilt should be drawn by the $65 million pay-off.

Fair enough, never mind the inference of guilt, but how much does this not-guilty penalty cost consumers in terms of increased drug prices?

In settling the latest Madison County class action, Glaxo also denies all the allegations, and says it will pay the $63 million to keep the cost of litigation down. However, there are indications that this case might not end as smoothly as Glaxo planned because plaintiff’s attorneys in competing class actions have filed objections to the settlement.

Jim Gottstein, an attorney who recently won a landmark case in the Alaska Supreme Court that does away with forced drugging with psychiatric medications in state institution, sees major problems with the way this latest Glaxo settlement went down.

“One of the abuses in class actions,” he says, “is defendants finding lawyers supposedly representing the class who are willing to push settlements that are unfairly favorable to the defendants, thus allowing them to limit their liability.”

“The amount and other aspects of this proposed settlement,” he notes, “raise questions about whether that has happened here.”

“It still seems like a small amount,” Mr Gottstein points out, “assuming far more than $63 million was spent on Paxil prescribed to people under 18.”

He also says the settlement may result in a large payment to the lawyers for what may not be very much work, and notes that the first time this case surfaced was when a settlement had already been secretly negotiated with the immediate effort to kill the other class actions that seemed to be proceeding along a forthright path.

These on-going legal proceedings against Glaxo seem like one never-ending vicious cycle. Glaxo overcharges consumers, then runs up legal costs for years denying the charges, and then in the end, pays millions to settle the charges but is allowed to deny guilt, and then ups the prices on its products to cover the penalty.

The latest 2 settlements are eerily similar to the fraud case Glaxo settled in the summer of 2004, in which New York State Attorney General, Eliot Spitzer, charged the company with hiding studies that “not only failed to show any benefit for the drug in children but demonstrated that children taking Paxil were more likely to become suicidal than those taking a placebo.”

According to Mr Spitzer, the company had conducted at least 5 studies on the use of Paxil with children, but only published one, and even it revealed questionable results. Glaxo ended up paying more than $2 million to settle those charges and also had to agree to publish all of its clinical trials online.

How many get out of jail free cards does Glaxo get? In that case, Mr Spitzer estimated that by suppressing the studies showing that Paxil was not effective with children and that it may cause them to commit suicide, Glaxo made $55 million off prescriptions written for children in 2002 alone.

Glaxo was also recently busted for another overcharging racket across the globe. On November 9, 2006, the Comet reported that “BRITAIN’S largest drugs company is facing a bitter pill in the form of a bill from Whitehall that could be for over �1 billion.”

“An independent report on behalf of the Department of Health has revealed that GalxoSmithKline,” the Comet said, “may have over-charged the NHS by a staggering �280 million a year for at least five years.”

It seems Glaxo agreed to price cuts in talks with the British government in 1999, but the Pharmaceutical Price Regulation Scheme independent arbitration panel, set up by the Department of Health, has now determined that the company continued to bill the government the full price for 5 years after agreeing to the lower prices.

Less than 2 months earlier, on September 11, 2006, Glaxo announced that it has settled its tax dispute with the US Internal Revenue Service, in a statement to the London Stock Exchange. “This settlement resolves all the issues which were in dispute in this case,” the company said.

“Under the agreement,” Glaxo stated, “the final net cash cost to GSK will be approximately 3.1 billion dollars which covers federal, state and local taxes, interest and also the benefit of tax relief on the payments made.”

According to Glaxo, the settlement covered the dispute for the years between 1989 and 2000, which was set to go to trial in February 2007, and also covers the subsequent years of 2001 to 2005.

At the end of the statement, came the customary denial of wrongdoing. “GSK was confident of the strength of its position,” it stated, “but in view of the size of the potential financial exposure, as well as the continued level of resource being applied to the case, GSK concluded that it was in the best interests of its shareholders to reach this settlement, thereby removing the costs and uncertainty of future litigation.”

For its part, the IRS said that Glaxo will pay $3.4 billion all total, once interest is included, making it the largest single payment ever to resolve a US tax dispute.

In another potentially troublesome legal development, last month Glaxo was hit with the first of likely many more lawsuits to come, filed on behalf of an infant who was born with persistent pulmonary hypertension, a life-threatening lung disorder, following exposure to Paxil in the womb during his mother’s pregnancy.

Attorney, Karen Barth-Menzies, a partner at Baum Hedlund, a national law firm with offices in Los Angeles, Washington, DC and Philadelphia, is the lead attorney on the case, and says a study published in the New England Journal of Medicine, back on October 3, 1996, led by Dr Christina Chambers, of the Department of Pediatrics, at the University of California-San Diego, indicated an increased risk of the lung disorder in infants born to mothers who were prescribed SSRI antidepressants like Paxil.

As a follow-up, Dr Chambers and colleagues performed a study of women who gave birth between 1998 and 2003, published in the February 9, 2006, New England Journal of Medicine, that found mothers who took SSRIs in the second half of their pregnancies were 6 times more likely to give birth to babies with the lung disorder.

According to Jennifer Liakos, an associate attorney at Baum Hedlund in Los Angeles and a member of the firm’s Antidepressant Litigation Department involved in Paxil birth defect cases, between 10% to 20% of infants born with persistent pulmonary hypertension do not survive, even after they receive treatment.

Glaxo Gets Hit With Another Paxil Birth Defects Lawsuit

Evelyn Pringle October 17, 2006

Two years ago, little Eric Jackson was born with persistent pulmonary hypertension, a life-threatening lung disorder in which an infant’s arteries to the lungs remain constricted after birth, limiting the amount of blood flow to the lungs and oxygen in the bloodstream.

Persistent pulmonary hypertension (PPHN) is associated with substantial infant mortality and morbidity and between 10 and 20 percent of infants born with the disorder end up dying even when they receive treatment.

Several life-saving medical procedures have already been performed on Eric. At birth he was placed on a ventilator, and eventually had to be placed on an oscillating ventilator for a month. He then had to undergo two cardiac catherizations, and another procedure to correct additional medical problems caused from being on a ventilator for so long.

Eric still needs oxygen and medications to help him breathe and he also suffers with eating and digestive problems.

Eric’s mother, Lisa Boden of Denver, Colorado was prescribed the selective serotonin reuptake inhibitor antidepressant, Paxil (SSRI), while pregnant and took the drug right up until Eric was born. Paxil use by pregnant women has been found to associated with a 6 times increased risk of PPHN in newborns.

On October 16, 2006, Eric’s mother and father, Christopher Jackson, filed a lawsuit against Paxil maker, GlaxoSmithKline, in a state court in Pennsylvania alleging that Ms Boden’s use of Paxil during her pregnancy resulted in Eric being born with PPHN due to Glaxo’s failure to warn about the risk of PPHN associated with Paxil.

In the lawsuit, Eric is represented by Baum Hedlund, a national pharmaceutical products liability law firm in Los Angeles, Washington, DC and Philadelphia. Baum Hedlund attorney, Karen Barth Menzies, says the family has endured “a terrible ordeal.”

Based in part, on the company’s long history of concealing the adverse side effects of Paxil, Ms Menzies says she believes that Glaxo has known about the risk of PPHN, or at the least should have known, and therefore should have warned medical professionals and consumers about the risk of the lung disorder.

Attorney Menzies has been battling Glaxo and the makers of other SSRIs for a decade. Besides representing clients against the drug giants, she has been writing articles and giving speeches around the world warning about the risks of SSRI.

She has testified before lawmakers, and the FDA, about the harmful effects of SSRIs and the failure of the drug companies to come clean about their dangers. In one appearance before the FDA, she ended her testimony by saying, “Put me out of business for the right reasons. Warn about these drugs.”

FDA regulations require Glaxo to issue a warning to medical professionals and consumers whenever there is reasonable evidence of an association between Paxil and a serious risk. The regulations specifically say that a causal link need not be proven before adding a warnings. In fact, they explicitly allow Glaxo to issue a warning about a risk without prior approval from the FDA.

Ms Menzies will have no problem showing a jury that Glaxo was aware of the risk of respiratory problems in infants born to mothers taking SSRIs because researchers have been reporting breathing problems in newborns associated with the use of SSRIs during pregnancy for more than a decade.

As far back as 1996 a study published in the New England Journal of Medicine found that babies exposed to the SSRI, Prozac, during the third trimester of pregnancy had significantly higher rates of premature delivery, admissions to special-care nurseries, jitteriness, and poor neonatal adaptation including respiratory difficulty and cyanosis on feeding. The study also found that the birth weight of infants exposed to Prozac was lower, and their birth length was shorter.

To reach its results, the NEJM study identified 228 women on who took Prozac while pregnant during the period of 1989 through 1995, and compared the outcomes of their pregnancies to 254 women who were not taking the SSRI.

In 2003, researchers at the Motherisk Program at the University of Toronto reported that exposure to Paxil in late pregnancy was associated with a significantly higher rate of transient neonatal complications among 55 exposed newborns, when compared to infants exposed to Paxil in early pregnancy or to newborns with no exposure, and respiratory distress was the most commonly reported adverse reaction.

Also in 2003, a study in the American Journal of Psychiatry reported that SSRIs readily cross the placental barrier and expose the infant to increased serotonin levels during early development.

In February 2004, a study in Pediatrics reported that “first-trimester use of SSRIs has been associated with higher rates minor physical anomalies and miscarriages, thus suggesting possible early effects of SSRI exposure on embryonic development.”

Five months later, in June 2004, the journal Prescrire International reported neonatal complications after intrauterine exposure to SSRIs and said newborns exposed toward the end of pregnancy showed signs of agitation, altered muscle tone, and breathing and suction problems. The study found that an estimated 20% to 30% of infants were effected and said doctors should be aware of these risks when considering SSRI treatment for pregnant women.

On July 9, 2004, WebMd reported that the FDA was concerned by reports that SSRIs may cause adverse effects in newborns when mothers take the drugs late in pregnancy and that over the past decade the FDA had received “hundreds” of reports of adverse effects in newborns.

As a result of the numerous reports, in July 2004, the FDA changed the labeling for all SSRI, warning that upon delivery some infants exposed to SSRIs required prolonged hospitalizations, respiratory support, and tube feeding.

In December 2005, the FDA issued a warning about two studies that found an increased risk of heart birth defects in babies born to Paxil users and moved the drug into the D category which means definite harm has been shown to occur by maternal use of the drug to the unborn fetus.

Paxil (paroxetine) was approved for use in the US by the FDA in 1993. In large part due to extremely aggressive and creative marketing campaigns, the drug quickly became one of the world’s most widely prescribed drugs.

Glaxo has doctors in just about every field of medicine prescribing the drug for a wide variety of ailments including generalized anxiety disorder (GAD), social anxiety disorder (SAD), obsessive-compulsive disorder (OCD), and depression.

Critics, including court certified experts on SSRIs, say that most of these so-called “mental disorders” do not even exist. Rather, they are inventions of Glaxo and other drug companies used to justify the sale of these high priced SSRIs. According to the August 2002 Mother Jones Magazines, “Pharmaceutical companies have come up with a new strategy to market their drugs: First go out and find a new mental illness, then push the pills to cure it.”

Jonathan Leo, associate professor of anatomy at Western University of Health Sciences, and author of, “The Biology of Mental Illness,” says, “The basic tenet of biological psychiatry is that mental illness is an “organic” disease, meaning that the patient has too much or too little of a neurotransmitter, too much or too little of a receptor, or an overactive or underactive neuronal circuit.”

“Never,” he says, “has a theory with so little scientific evidence been so well accepted by the American public-three of the seven most commonly prescribed drugs are now mood elevators.”

By implementing creative marketing schemes, SSRIs have become the easiest drugs to push. Drug companies now offer and advertise free depression screening surveys in high schools, colleges, and on web sites online.

The industry has even designated October 5, as “National Depression Screening Day,” in the US and Canada, complete with TV and newspapers ads telling people where to go to find the free screening sites in their community on that day.

This blatant drug pushing has gotten so out of hand, that according to Mr Leo, this chapter in the history of psychiatry goes beyond the issue of whether there is a link between SSRIs and side effects. “The entire affair calls into question the behavior of the profession over the past decade;” he states, “years from now historians will be writing about how during the past decade academic psychiatry sold itself to the pharmaceutical companies.”

“Ghostwritten papers, company written papers, editors refusing to publish articles critical of the “science”, NIMH press releases announcing the latest new research findings while ignoring contrary data, and psychiatrists calling their critics “quacks,” he writes, “all point to major problems with the profession-not just a minor glitch.”

This is exactly what happened when the Chambers study on PPHN was released in February 2006. As a follow-up to her previous study in 1996 that suggested a possible association between use of the SSRI, Prozac, late in pregnancy and the risk of PPHN, Dr Christina Chambers and her team of researchers performed a case control study to determine whether PPHN was associated with exposure to SSRIs during late pregnancy.

The results of the study were published in the February 9, 2006, New England Journal of Medicine and reported that mothers who took SSRIs, in the second half of their pregnancies were nearly 6 times more likely to give birth to infants with PPHN.

The study found 14 infants with PPHN in the group who had been exposed to an SSRI after the 20th week of pregnancy, compared to 6 infants with PPHN in the control group who were not exposed to the drugs.

That means that PPHN “occurred about six times more frequently in women taking SSRIs,” said lead author Dr Chambers, an assistant professor of pediatrics at the University of California, San Diego.

The study was so alarming that it prompted the FDA to hold a news conference. “This appears to be a very well-conducted study and we find the results to be very concerning,” said Dr Sandra Kweder, deputy director of the office of new drugs at the FDA.

The same month the study was published the industry went into full damage control and took active steps to encourage pregnant women to keep taking SSRIs. A widely publicized study in the February 2006 issue of the Journal of the American Medical Association, warned that stopping SSRIs greatly increased the risk of pregnant women relapsing into depression.

In the article, the authors predicted that their findings would prompt some women to stay on their medication throughout pregnancy. “That was good news for the makers of big-selling antidepressants who have recently faced growing questions about the safety of their medications when used during pregnancy,” the July 11, 2006 Wall Street Journal said,

Six months after the study’s publication in JAMA, the WSJ provided a little background information about the researchers who encouraged pregnant women to keep taking SSRIs.

“But the study,” it wrote, “and resulting television and newspaper reports of the research failed to note that most of the 13 authors are paid as consultants or lecturers by the makers of antidepressants.”

The lead author, Dr Lee Cohen, the WSJ said, “is a longtime consultant to three antidepressant makers, a paid speaker for seven of them and has his research work funded by four drug makers.”

According to the WSJ, as soon as the study was published, Dr Cohen and some the other authors hit the lecture circuit, telling doctors about their findings and pointing out the flaws in the recent studies that had found increased risks to newborn of mothers who used SSRIs.

All total, the Journal said, “the authors failed to disclose more than 60 different financial relationships with drug companies.”

According to JAMA, its policies require that authors disclose financial ties to the industry. Its editor-in-chief, Catherine DeAngelis, told the WSJ that JAMA was not aware of the financial relationships between Dr Cohen and his co-authors and the drug companies.

After being made aware of the situation, in July 2006, JAMA published a correction to report that 7 of the authors of the February 2006 study failed to reveal that they had financial relationships with the SSRI makers.

With all the bogus free screening programs in place, depression has become the top money-maker and the pharmaceutical industry is trying to cash in every way possible even gaining approval for treatment with a device that is implanted and was developed for the treatment of epilepsy, followed up by another planted promotional article in a medical journal.

On July 18, 2006, Bloomberg News reported that the journal, Neuropsychopharmacology, would correct a review of Cyberonics’ depression treatment device to disclose that the scientists who wrote the article had financial ties to the company.

The links not disclosed in this journal involved 8 of the nine authors who were paid members of a scientific advisory committee for Cyberonics.

The study’s lead author, Charles Nemeroff, is also chairman of the Cyberonics advisory board and on top of that, he is the editor-in-chief of the Neuropsychopharmacology journal itself.

The reviewing article called the epilepsy treatment device “a promising and well-tolerated intervention” for people with depression who are not helped by other treatments. The FDA approved this highly controversial treatment in July 2005, over the objections of “more than 20” FDA scientists, according to a report by the Senate Finance Committee.

Failing to report the connections violated the journal’s policy, Kenneth Davis, the journal’s publisher and president of the American College of Neuropsychopharmacology, told Bloomberg in an interview.

The acknowledgements for the article did thank Sally Laden for “editorial support in developing early drafts of this manuscript.”

However, according to the July 18, 2006 Wall Street Journal, “Ms. Laden is a professional medical writer who was hired by Cyberonics to help compile the review article.” The WSJ described her admitted involvement in the article as:

“She said the company provided her with materials from the company’s advisory board meetings to help draft the review article. Ms. Laden said she prepared the first draft of the review piece which then went through many revisions based on edits and suggestions by the listed authors. All of the authors were involved in preparing the final version of the review article, she said.”

“This was not a ghostwritten project,” Ms. Laden told the WSJ. “I was just a facilitator.”

But she declined to tell the WSJ how much she was paid by Cyberonics for her work.

“This is about as classic an example as you’ll ever find of conflict of interest and manipulation by thought leaders who are beholden to corporations,” said Bernard Carroll, a member of the neuropsychopharmacology group who is the retired chairman of the department of psychiatry at Duke University, in a phone interview with Bloomberg.

“This article is a piece of a slick, skillfully coordinated PR campaign directed by the corporation,” he said in the interview.

Mr Carroll and Robert Rubin, a professor of psychiatry at the University of California, Los Angeles, told Bloomberg that in 2003, Mr Nemeroff also failed to disclose his financial interests in depression treatments in a review he wrote for the journal, Nature Neuroscience, including that he held ownership of a patent on one product.

Back then they wrote and complained to the editors of Nature, and their letter and an article in the New York Times prompted the publishers to change their policy and require that authors of reviews disclose all their financial links to products they write about.

In a rare turn of events for a case of wrongdoing involving the pharmaceutical industry, Mr Nemeroff apparently could not take the heat because on August 29, 2006, News Target, reported that “the editor of the medical journal Neuropsychopharmacology, Charles B. Nemeroff, has resigned his position after drawing criticism for failing to disclose his financial ties to a medical company whose device he endorsed in his journal.”

“The surprise is not that Nemeroff lacks fundamental ethics and abused his power as a medical journal editor to pad his own pockets; the surprise is that he got caught,” says Mike Adams, a consumer health advocate and critic of unethical practices in conventional medicine.

“Notice,” he points out, “how he only published a correction after being exposed by the Wall Street Journal?”

“You have to remember,” Mr Adams explains, “that virtually everyone in conventional medicine — from doctors to journal editors to FDA advisory panel members — claim they operate with such supreme intellect that they are immune to financial influence, and thus there is no need for them to even disclose conflicts of interest.”

“They seem to demand, ‘How dare you question our judgment?’ while simultaneously pocketing cash from pharmaceutical companies or medical device manufacturers,” Mr Adams notes.

“The arrogance is astonishing,” he says.

Until stepping down in July 2004, Richard Smith was an editor for the British Medical Journal for 25 years. For the last 13 of those years, he was the editor and chief executive of the BMJ Publishing Group, responsible not only for the profits of the BMJ, but for the whole group which published some 25 other journals.

In a 2005 paper in the Public Library of Science, Mr Smith says that more than paid advertisements in medical journals influencing doctors and consumers, he sees a bigger problem with these studies, and particularly clinical trials, being published in medical journals.

According to Mr Smith, “readers see randomised controlled trials as one of the highest forms of evidence.”

Unlike advertising he says, a large trial in a major journal has that journal’s stamp of approval, will be distributed around the world, and “may well receive global media coverage, particularly if promoted simultaneously by press releases from both the journal and the expensive public-relations firm hired by the pharmaceutical company that sponsored the trial.”

For a drug company, he says, a favorable trial is worth thousands of pages of advertising, “which is why a company will sometimes spend upwards of a million dollars on reprints of the trial for worldwide distribution,” he explains in the paper.

The doctors receiving the reprints may not read them, he acknowledges, but they will be impressed by the name of the journal. “The quality of the journal will bless the quality of the drug,” he says.

Since the embarrassing disclosure about the drug companies’ hidden involvement in the pregnancy related SSRI studies in mid-summer, more health problems have been reported in infants born to women taking SSRIs. On August 25, 2006, Reuters Health reported a study published in the Archives of General Psychiatry, conducted by Canadian researchers at the University of British Columbia, that found babies born to women who took SSRIs during pregnancy to be at an increased risk of having respiratory distress and low birth weight.

Lead investigator, Dr Tim Oberlander, told Reuters that “our study was undertaken to distinguish the effects of maternal mental illness — pregnancy-related depression — from its treatment — SSRIs — on neonatal outcomes.”

The researcher reviewed health records for almost 120,000 live births between 1998 and 2001 and found that 14% of the mothers were diagnosed with depression. They then compared the outcomes of babies born to 1451 depressed mothers treated with SSRIs during pregnancy to those born to 14,234 depressed mothers who were not treated with SSRIs and found a significantly greater incidence of respiratory distress, 13.9% verses 7.8%, and longer hospitalization for infants born to mothers on SSRIs. Birth weight and gestational age were also significantly less in SSRI-exposed infants and a significantly greater proportion of babies were born before 37 weeks.

“These findings are contrary to an expectation that treating depressed mothers with SSRIs during pregnancy would be associated with lessening of the adverse neonatal consequences associated with maternal depression,” Dr Oberlander told Reuters.

In the October, 2006, issue of Pediatrics, CDC researchers reported that preterm birth is the leading cause of infant mortality in the US, accounting for at least a third of all infant deaths in 2002.

The contribution of prematurity to infant mortality may be twice as high as originally estimated, reported Dr William Callaghan, MD, MPH, and colleagues.

The research team looked at the top 20 causes of infant deaths in 2002, and found that 34% occurred in preterm infants, 95% of whom were born before 32 weeks gestational age of 32 weeks and weighed less than 3.3 lbs.

“On the basis of this evaluation, preterm birth is the most frequent cause of infant death in the United States, accounting for at least one third of infant deaths in 2002,” the authors wrote in Pediatrics. “The extreme prematurity of most of the infants and their short survival indicate that reducing infant mortality rates requires a comprehensive agenda to identify, to test, and to implement effective strategies for the prevention of preterm birth.”

Finally, a study in the October 3, 2006 Archives of Pediatrics and Adolescent Medicine reported that low birth weight infants with no obvious disability early on can have subtle and cognitive deficits discernable at age 16. The study sample represented a cohort of babies who were born at or admitted to one of three hospitals in New Jersey between September 1, 1984 and June 30, 1987.

Scores on the Wechsler Abbreviated Scales of Intelligence test were generally within the normal range but showed an overall downward shift, so that on average they were lower for the 474 adolescents who weighed less than 2,000 grams at birth, according to Dr Agnes Whitaker, MD, of Columbia University and the New York State Psychiatric Institute, and colleagues.

Two factors, male gender and days of ventilation, were independent predictors of motor problems, the team said. For each additional week of mechanical ventilation, total and oral motor problem scores were higher by 0.33 and 0.14 points, respectively.

Legal analysts say to look to Glaxo attorneys to try and attempt to reach early settlements with the families of children born with birth defects because they in no way want those injured children showing up in court in front of a jury.

Fen-Phen May Cause Rummage Sale of Wyeth Assets

Evelyn Pringle August 23, 2006

On August 18, 2006, Bloomberg News reported that Wyeth has faced more than 175,000 claims since fen-phen was removed from the market, and that over the past 9 years, the company has settled many claims without forcing fen-phen users to file a lawsuit.

All total, the company has set aside more than $21 billion to cover legal costs and settlements since the diet drugs were withdrawn, according to Reuters News on May 24, 2006. As for how long Wyeth can stay afloat under the tidal wave of fen-phen lawsuits, financial experts say the answer could boil down to insurance coverage.

If this is true, the future looks bleak for Wyeth shareholders because according to, “The $22 Billion Gold Rush,” by Robert Lenzner & Michael Maiello, on on April 10, 2006:

“Insurance covered only $400 million of the damage costs, forcing Wyeth to fund the rest by selling $8 billion in assets and giving up a merger with Warner-Lambert to get a $2 billion kill fee; it warns it may have to sell more assets to fund still more claims.”

Well then maybe its time for Wyeth to put up signs for a rummage sale because on August 10, 2006, in the most recent fen-phen trial, a jury in a Philadelphia returned a $300,000 verdict in favor of 41-year-old, Jodi Wier, after deliberating only 6 hours. Ms Wier took fen-phen for about three months starting in October 1996, and was diagnosed with primary pulmonary hypertension 5 years later.

“She has an incurable disease and has to be treated for the rest of her life,” her attorney, Edward Freidberg, told the jury in closing arguments.

The lawsuit was filed in 2004 by attorney, Theodore Holt, of the California firm of Hackard & Holt, and was the first fen-phen-related PPH case to go to trial in Philadelphia. In a July 27, 2006, press release at the onset of the trial, Mr Holt, stated that “PPH is a serious incurable disease that can take years to develop.”

“We suspect,” he said, “there are still many undiagnosed victims and that PPH litigation will continue well into the future.”

In the fall of 1997, American Home Products Corporation (renamed Wyeth in 2002), withdrew the diet drugs Pondimin and Redux, which in many cases were being prescribed together with phentermine, in the combination commonly referred to as “fen-phen.”

“Fen” is short for fenfluramine, marketed as Pondimin, since it gained FDA approval in 1973, and its chemical cousin, dexfenfluramine, marketed as Redux, since it was approved in 1996.

“Phen” is short for phentermine, which is marketed under various trade names such as Ionamin and Fastin, as well as several generic forms.

According to the FDA, phentermine and fenfluramine were approved to be used as separate appetite suppressants for short periods of time of a few weeks in the management of obesity.

Nonetheless, doctors prescribed the drugs together and for extended periods of time in what the FDA referred to as “off label” use because there have been no studies submitted to the FDA to demonstrate the effectiveness or safety of the drugs taken together or for longer than a few weeks.

It is estimated that more than 6 million people took fen-phen and Pondimin and Redux became two of the most widely prescribed drugs in the US. In 1996 alone, their sales totaled over 20 million prescriptions.

Things began to head downhill for Wyeth in July 1997, when researchers at the Mayo Clinic reported 24 cases of a rare valvular disease in women who took fen-phen. On July 8, 1997, the FDA issued a Public Health Advisory describing the Mayo findings.

The FDA also revealed that it had received additional reports of the same kind, and requested that all health care professionals report any similar cases through MedWatch or the respective drug makers. Subsequently, the FDA received 66 additional reports.

The findings of the Mayo Clinic were also reported in the August 28, 1997, New England Journal of Medicine, along with an FDA letter to the editor describing additional known cases of valve disease.

At that point, the FDA asked Wyeth to stress the risk to the heart in the drugs’ labeling and package inserts. But on September 15, 1997, citing new evidence about significant side-effects, the FDA asked the company to remove both Pondimin and Redux, from the market. The action, it said, was based on findings by doctors who had evaluated patients taking the drugs with echocardiograms, a procedure that can test the functioning of heart valves.

“These findings,” the FDA stated, “indicate that approximately 30 percent of patients who were evaluated had abnormal echocardiograms, even though they had no symptoms.”

“The data we have obtained indicate that fenfluramine, and the chemically closely related dexfenfluramine,” the agency warned, “present an unacceptable risk at this time to patients who take them.”

These new findings suggest fenfluramine and dexfenfluramine are the likely cause of heart valve problems of the type that prompted FDA’s two earlier warnings concerning fen-phen, the agency advised.

The reports of cases of heart valve disease in patients taking Pondimin or Redux alone prompted the FDA to advise patients using either of the drugs to stop taking them and contact their doctors to discuss treatment.

“These findings call for prompt action,” said Michael Friedman, MD, the Lead Deputy Commissioner of the FDA at the time.

However, internal FDA documents have since surfaced in litigation that shows the FDA could have acted much sooner. As it turns out, a doctor from Fargo, North Dakota sent the FDA reports of valve damage associated with the diet drugs in February and March of 1997, and when he got no response, the doctor called the FDA in May of 1997, and had his assistant fax 25 reports to the official he spoke with.

But the official who received the information, did not alert her superiors and in fact, did nothing about the situation for a month, until she mentioned in a routine report that there was a doctor in Fargo who discovered problems with the drugs that should be tracked.

In describing valvular disease, the FDA’s web site states: “There are four major valves controlling the flow of blood into, out of, and between the four chambers of the heart.”

“Several disease processes,” it explains, “including infection and toxicity, may damage the valves, causing them to malfunction, and may produce severe heart and/or lung disease.”

Symptoms of the condition can include shortness of breath, swelling in the legs, chest pain and heart palpitations.

In some cases, the FDA says, medication can control heart failure associated with valvular damage but in others, surgery may be necessary to replace the valves with artificial valves.

Mass litigation followed the removal of the drugs from the market and continued as more studies confirmed their association with valve damage. By 1999, Wyeth faced nearly 20,000 personal injury lawsuits in state and federal courts, and more than 100 putative class actions, with some moving quickly toward certification.

The injuries alleged by plaintiffs included: heart valve regurgitation, valvular heart disease, or an increased risk of developing these conditions.

The plaintiffs claimed that Wyeth not only failed to do the testing that would have revealed the dangers of the drugs but that the company was fully aware that the fen-phen cocktail was being prescribed and sought to profit from the pairing of the two drugs. One complaint states:

“As a result of Defendants’ promotions, there was an enormous increase in sales revenues and profits for Defendants, their affiliates, and other commercial entities involved in the manufacturing and distribution chains of these anorectic pharmaceuticals.”

The complaint also alleges that Wyeth’s gross sales of Pondimin in the US increased from $3.7 million in 1993 to $150 million in 1996.

The lawsuit charges that the defendants knew that there were at least 41 reports of PPH associated with fenfluramine by the spring of 1994, and knew that the drug’s label describing only four cases of PPH was false and misleading and that they intentionally concealed information, “in order to maximize sales and profits of Pondimin.”

By 1996, the complaint says, defendants knew of at least 71 cases of PPH, including twelve deaths, while the Pondimin PDR entry continued to falsely state that there had been only four PPH cases, and only one case was fatal.

The complaint also alleges that the defendants deliberately decided not to submit proposed labeling changes to the FDA about the risk of PPH with Pondimin, to avoid any negative impact on the New Drug Application for Redux, pending before the FDA in 1995-96.

Defendants knew, it says, that PPH risks associated with Pondimin were relevant to the FDA’s consideration of Redux because both drugs had the same active ingredient.

On December 10, 1997, the Judicial Panel on Multidistrict Litigation transferred all federal fen-phen lawsuits to the US District Court for the Eastern District of Pennsylvania for consolidated pretrial proceedings before the Honorable Louis Bechtle, Chief Judge Emeritus, and upon his retirement, on June 29, 2001, the litigation was reassigned to Judge Harvey Bartle III.

The first two fen-phen cases to go to trial turned out to be a disasters for Wyeth. One settled after several plaintiffs in Mississippi won over $100 million in compensatory damages and a Texas case resulted in a verdict that included high punitive damages.

On August 7, 1999, a Texas jury awarded 36-year-old Debbie Stone Lovett, $23 million. Legal experts said the verdict was significant being Wyeth tried the case believing that the facts were their favor. The case was reportedly settled during an appeal for $2.2 million.

In another 1999 trial in Oregon, Wyeth lost a $29.2 million verdict that eventually was settled for $15.5 million. In this case, Mary Linnen, took fen-phen for just 23 days before developing PPH.

A few months after she was diagnosed, Ms Linnen had to undergo surgery to insert a tube in her heart, so that she could inject a medication into her heart several times a day. Less than 3 months later she died and her family filed the first fen-phen wrongful death lawsuit against the company.

Legal experts say Wyeth was so alarmed over the large punitive damage awards that it was desperate to find a way to set a limit on what fen-phen litigation would cost the company.

Wyeth believed that a class action could alleviate the threat of enormous punitive damage awards providing that only a small number of patients decided to opt out of the class. Under the rules, people who rejected the class action outright could sue for punitive damages, but victims who did not opt out at the first stage, would be barred from seeking punitive damages if they later decided to sue Wyeth.

The company offered the plaintiffs a good reason to remain in the class by conceding causation so that class members who stayed would not have to prove that Pondimin or Redux caused their heart valve damage, only that they had valve damage after taking the drugs.

Wyeth also offered generous compensation to class members. At the high end of the payment schedule, plaintiffs with valve damage so severe that they had strokes, heart transplants or died could receive upwards of $1.3 million.

The low end of the schedule was about $7,500 for claimants whose medical testing showed evidence of significant valve damage but no other indication of serious heart disease.

To cover its end of the deal, Wyeth agreed to ante up $2.55 billion for claimants who qualified for the larger payments, and another $1 billion for the smaller cash benefits and medical services for people with less severe heart damage.

On May 2, 2000, the US District Court in Pennsylvania held a hearing to determine whether the proposed Settlement Agreement was fair, adequate, and reasonable and held another hearing on August 10, 2000, to hear evidence on the fairness of changes contained in the Agreement.

On August 28, 2000, Judge Bechtle issued Memorandum and Pretrial Order approving the Agreement and the four amendments. A Settlement Trust was established on September 1, 2000, to administer the provisions of the Agreement, and to process the claims of class members.

In the end, Wyeth put up $3.75 billion to manage the litigation and was forced to add another $1.3 billion to the pot in 2004.

However, before the ink even had a chance to dry on the class action agreement, a new nightmare began for Wyeth when about 50,000 victims decided to opt out. The prospect of 50,000 punitive damage awards was an extremely frightening thought for Wyeth, given the results of the jury trials in 1999.

Legal experts say this looming threat prompted Wyeth to attempt settle the opt out cases as quickly as possible for whatever amount necessary and when the word got out, the whole mess quickly turned into a feeding frenzy for litigants.

Experts say news about previous large settlements may have prompted many victims to opt out. For instance, on July 22, 1999, the Dallas Morning News reported a case where the company paid more than $3 million to settle a lawsuit with a 70-year-old Texas woman. The agreement, the newspaper said, was at least the 12th settlement involving former fen-phen users, but was the first in a Dallas County court case.

A month before the $3 million settlement was reported, the article said, the company agreed to pay between $6 and $7 million to settle a case in Harris County, Texas that linked a woman’s death to fen-phen.

Adding to the risk of trying cases before a jury, is the fact that more documents keep surfacing that prove useful in court. For instance, an internal FDA e-mail dated about a year before the agency issued the fen-phen advisory, written by former FDA reviewer, Leo Lutwak, to a colleague says the serious side effects linked to fen phen and the drugs’ marginal benefits “should be brought out.”

“The company has gotten away with much manipulation these past 3 years, of the public, of the press, of the FDA,” Mr Lutwak wrote. “I started getting upset about this drug in ’93 or ’94 and was running into a lot of blocks from the FDA and from the drug company,” he said.

Although other injuries associated with fen-phen include PPH and neuropsychological damage, only persons with heart valve damage are allowed to participate in a national class action settlement.

Persons suffering from neuropsychological damage that can include depression, mood swings, memory loss, behavioral changes, and psychotic breakdowns, must sue separately.

According to the FDA, PPH has been reported to occur in about 1 in 25,000 people using the appetite suppressants for more than 3 months. Close to half of all PPH cases result in death. The Pulmonary Hypertension Association defines the condition as:

“Pulmonary hypertension (“PH”) is a rare blood vessel disorder of the lung in which the pressure in the pulmonary artery (the blood vessel that leads from the heart to the lungs) rises above normal levels and may become life threatening.

“Symptoms of pulmonary hypertension include shortness of breath with minimal exertion, fatigue, chest pain, dizzy spells and fainting.

“When pulmonary hypertension occurs in the absence of a known cause, it is referred to as primary pulmonary hypertension (PPH). This term should not be construed to mean that because it has a single name it is a single disease. There are likely many unknown causes of PPH. PPH is extremely rare, occurring in about two persons per million population per year.”

“This disorder,” the FDA web site says, “results in death in about 40% of affected individuals within 4 years.”

Studies released in November 2001 suggest that the occurrence of PPH may be 7 times higher than anticipated in 1997, when the diet drug were removed from the market.

According to the FDA, the disorder can also occur in association with valvular heart disease, but the class action settlement still does not apply even in those cases. However, this ruling may turn out to be the nail in the coffin for Wyeth.

On April 27, 2004, a Texas jury awarded over $1 billion to the family members of a woman who died of PPH after taking fen-phen for about two years. The verdict included $113.4 million in compensatory damages, and $900 million in punitive damages, according to Wyeth’s 2005 Annual Report filed with the SEC. The case was later settled for an undisclosed amount.

As of July 24, 2006, Wyeth told shareholders in its latest SEC filing, the company is listed as a defendant in 103 lawsuits that allege a claim of PPH, alone or with other injuries, and in approximately two additional lawsuits pleaded as valvular regurgitation cases, the plaintiff’s attorneys have advised the company that the plaintiffs will allege a claim of PPH.

Back in February 2006, at the Merrill Lynch health-care conference in New York, Kenneth Martin, chief financial officer of Wyeth, said he was hopeful that the remaining lawsuits may be “wrapped up” within 12 to 24 months.

However, according to Fen-Phen e-Resource, Natexis Bleichroeder analyst, Jon LeCroy, said Wyeth may be able to eliminate “the bulk” of the cases within the next 24 months, but predicted it will take at least 4 more years to eliminate cases involving serious heart-valve damage and cases involving fen-phen users who developed PPH.

“So we are assuming Wyeth will need to take another $4 billion in fen-phen charges through 2010,” Mr LeCroy said.

Jury selection for the next state court trial is set to begin on September 1, 2006, in a PPH case brought by Beverly “Kim” Tilmon of Palestine, Texas, seeking a combined total of $180 million in compensatory and punitive damages, according to the June 15, 2006 Palestine Herald.

Ms Tilmon alleges she developed PPH, after taking fen-phen for four months in 1997. This case ended in a mistrial on January 31, 2006, when Texas Judge, Jim Parsons, ruled that defense attorneys “exceeded the boundaries” during opening statements.