Paxil Birth Defect Litigation - Battle of the Decade
By Evelyn Pringle
28 December 2006
Sccop Independent News
A year ago, the FDA reclassified Paxil from a Category C drug to a Category D for pregnant women. Category C is for drugs that have been shown to harm the fetus in animals. Category D means a drug has been found to harm the human fetus.
In a December 1, 2006, news release, the American College of Obstetricians and Gynecologists' Committee on Obstetric Practice, advised that Paxil should be avoided "by pregnant women or women planning to become pregnant due to the potential risk of fetal heart defects, newborn persistent pulmonary hypertension, and other negative effects."
An interesting comment in the announcement states: "Unpublished data regarding the use of Paxil® during the first trimester of pregnancy have raised concerns about an increased risk of congenital heart malformations."
This discussion begs the question of exactly how much more "unpublished data" is out there about the dangers of Paxil that the public will hear about later, rather than sooner.
On December 8, 2005, the FDA issued a public advisory to report that a Swedish study showed women who received Paxil in early pregnancy had an approximately 2-fold increased risk of having an infant born with a cardiac defect compared to the general population.
The agency also reported that another study, of a US insurance claims database, found that infants born to women who received Paxil in the first trimester of pregnancy were at a 1.5-fold increased risk for cardiac malformations compared to women who received other antidepressants or women in the general population. Medical experts say Paxil exposure is especially harmful in the first trimester because fetal heart development occurs early in pregnancy. According to Dr Lara Jana, MD, FAAP, in Early Fetal Heart Development: 0-9 Weeks, published on the Dr Spock Web site, the most critical period in development is between three and seven weeks after fertilization, when a heart tube
It is always important to point out that because GlaxoSmithKline (GSK) promotes Paxil to treat a wide variety of "disorders," many pregnant women may be taking the drug, who are totally unaware of the risks because they have never been diagnosed with depression.
According to GSK, Paxil is indicated for the treatment of obsessive-compulsive disorder, major depressive disorder (MDD), panic disorder, social anxiety disorder, generalized anxiety disorder, and posttraumatic stress disorder; and Paxil CR is indicated for the treatment of panic disorder, social anxiety disorder, and premenstrual dysphoric disorder. Doctors are also too eager to prescribe Paxil off-label for everything from migraines to nail biting.
An important point to consider when weighing the risks and benefits of prescribing Paxil to pregnant women, is that most experts who have evaluated the study data on SSRIs, say the drugs do not work.
One of latest reviews in the July 2005, British Medical Journal, by Moncrieff & Kirsch, states in part: (1) Recent meta-analyses show [SSRIs] have no clinically meaningful advantage over placebo; (2) Methodological artefacts 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. .
Infant SSRI Withdrawal Syndrome
The fact that SSRIs can be extremely difficult to quit due to debilitating withdrawal reactions also adds to the dilemma that women face if they become pregnant. "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," Sandra Kweder, MD, deputy director of the FDA's Office of New Drugs, states in a March/April 2006 update about the risks of Paxil use by pregnant women on the FDA's Web site.
But on the other hand, staying on the SSRI places infants at risk. A February 2006, study in the Archives of Pediatrics & Adolescent Medicine reported that nearly one-third of babies born to mothers taking SSRIs showed severe symptoms of withdrawal, including high-pitched crying, tremors, gastrointestinal problems and disturbed sleep patterns.
Other Birth Defects
Over the past several years, in addition to heart defects, a variety of birth defects have been found to be associated with Paxil and the other SSRIs. A 2005 study in Teratology Society Abstracts, found that women who took Paxil were more likely to have an infant with omphalocele, a malformation where the abdominal contents protrude into the base of the umbilical cord, and craniosynostosis, an early closing of one or more of the sutures of an infant's head, causing a malformation of the skull.
A February 2004, study in the Pediatrics journal, linked abnormal heart rhythms, sleeping patterns, and levels of alertness to exposure to SSRIs in the womb. Dr Philip Zeskind, a professor of pediatrics at the University of North Carolina-Chapel Hill, and lead author, said the results were alarming.
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."
Earlier this year, 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.
In the US, preterm birth is reportedly the leading cause of infant mortality, 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 William M. Callaghan, MD, MPH., and colleagues, in the October 2006 issue of Pediatrics.
Five More Birth Defect Lawsuits
Earlier this month, five more lawsuits were filed on behalf of families of infants born with birth defects to mothers who were prescribed Paxil during pregnancy. Of the five cases, two are personal injury lawsuits and three are wrongful death cases. The lawsuits allege that GSK failed to warn doctors and consumers about the risk of birth defects and Paxil.
In the case of one West Virginia family, twin daughters were both born with heart defects. One daughter survived but the other died when she was 20-months-old. The parents have two older children who were born without birth defects. Their mother had not taken Paxil during pregnancy.
Another Paxil exposed infant with heart defects was born to an Omaha, Nebraska couple and lived only 24 days even after he underwent four surgeries in an attempt to save his life. There are three other normal children in this family, all born during times when their mother was not on Paxil.
A Toledo, Ohio, infant lived only 17 days after she was born with heart defects and underwent several surgeries in attempts to save her life. There is one older child in this family born without birth defects when the mother was not taking Paxil.
In Westerville, Ohio, another infant was born with heart defects to a mother who was prescribed Paxil during pregnancy and required two life-threatening surgeries during the first nine months after birth. The child is scheduled for an additional surgical procedure next year.
Less than five months ago, on July 28, 2006, a Texas couple filed suit against GSK. The lawsuit alleges that after the mother's use of Paxil caused their infant to be born with heart defects requiring multiple open-heart surgeries and the implantation of a pacemaker.
Baum Hedlund, a Los Angeles-based law firm that specializes in pharmaceutical product liability claims is handling these lawsuits, and has the longest track record of SSRI litigation in the country, representing over 3,000 antidepressant plaintiffs over the past 16 years. The firm currently represents families in dozens of birth defect cases and has five attorneys assigned specifically to SSRI litigation.
Karen Barth Menzies is a partner at Baum Hedlund and heads the Antidepressant Litigation Department. For more than a decade, she has been handling SSRI-induced suicide/violence litigation involving Prozac, Paxil and Zoloft and now also represents families in antidepressant birth defect cases.
Jennifer Liakos and Robert Brava-Partain are associate attorneys at the firm and members of the pharmaceutical products liability department handling all of the firm’s antidepressant birth defect cases and suicide and/or suicide attempt cases involving Paxil.
The firm is also being retained in birth defect cases for antidepressants other than Paxil.
Infant Lung Disorders
In July 2006, the FDA issued a Public Health Advisory on the latest type of birth defect believed to be associated with SSRIs, based on a study in the February 2006, New England Journal of Medicine. The study found an increased risk of a live-threatening lung disorder in infants exposed to SSRIs during pregnancy, 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."Infants with PPHN have difficulty making the transition from breathing inside the womb to normal breathing upon delivery causing respiratory failure that often requires mechanical ventilation. Even with treatment, between 10% to 20% of PPHN babies do not survive.
Although all the latest research clearly shows that the benefits of SSRI use by pregnant women could never outweigh the risks, the July 2006, FDA advisory titled "Treatment Challenges of Depression in Pregnancy," almost appears to be encouraging women to keep taking SSRIs, citing a study that warns that pregnant women who stop taking the drugs might relapse into depression.
Are Drug Manufacturers Selling Sickness?
In the research paper cited, the authors predicted that their findings would prompt some women to stay on antidepressants throughout pregnancy. However, the study ended up making frontpage news on July 11, 2006, after an investigation by the Wall Street Journal discovered that 9 of the 13 authors had undisclosed financial ties to the SSRI makers.
Which raises the question of whether SSRI makers are "selling sickness," using these so-called "experts" to convince doctors to keep prescribing drugs that are known to harm the fetus to increase profits.
By now, the industry's habit of planting bogus studies in medical journals and the media to promote drugs has become widely recognized. In the paper, "Selling sickness: the pharmaceutical industry and disease mongering," published in 2002, in the British Medical Journal, the authors describe how alliances of drug companies, doctors, and patient advocacy groups, use the media to portray conditions as being severe and widespread.
The paper notes that "in many cases the formula is the same: groups and/or campaigns are orchestrated, funded, and facilitated by corporate interests, often via their public relations and marketing infrastructure."
The authors could be discussing the study cited in the FDA advisory when they say: "A key strategy of the alliances is to target the news media with stories designed to create fears about the condition or disease and draw attention to the latest treatment."
The paper goes on to list the different components of this marketing technique. "Company sponsored advisory boards supply the "independent experts" for these stories, consumer groups provide the "victims," and public relations companies provide media outlets with the positive spin about the latest "breakthrough" medications.
Members of the medical profession are critical of medical journals that publish these "studies" and help make a mockery of "evidence-based medicine" with false claims about the safety and value of drugs whose lethal side effects are concealed from readers--i.e., physicians, health care policy officials, the judiciary, and the public at large, in "Research and Clinical Practice Guidelines: Can We Trust the Evidence in Evidence-Based Medicine?", by Dr. John Abramson, of Harvard, and Dr. Barbara Starfeld, a professor at Johns Hopkins, in the October 2005, Journal of the American Board of Family Practice.
According to Dr Abramson and Dr Starfeld: "Although one can make a case that the purpose of an industry is to make a profit and not necessarily to serve the public good, it is difficult to accept this as a justification for the behavior of medical scientists and regulatory agencies."
15-Year History of SSRI Litigation
Unbeknownst to most people, hundreds of SSRI suicide lawsuits have been ongoing behind the scenes for more than 15 years and Baum Hedlund has been involved from the start. The drug makers have done everything in their power to keep these cases from going to trial.
In one of the only three cases to ever go to trial, Eli Lilly was caught corrupting the judicial process by making a deal with the plaintiff's attorney to throw the case, in part by not disclosing damaging evidence to the jury.
The case involved a Kentucky man on Prozac, who went to his workplace and opened fire with an assault rifle killing 8 people, and injuring 12 others before turning the gun on himself. The jury returned a 9-to-3 verdict in favor of Lilly.
In the media, Lilly touted the verdict as a vindication for Prozac, but the judge in the case figured out what had happened and was outraged that a secret settlement occurred behind his back. He complained to a reporter from the British Broadcasting Company, stating:
"After the verdict came in, Eli Lilly gave it a great deal of publicity and various people went on television and on the radio and in newspapers proclaiming that this was a vindication of Prozac. "I think the public has a right to expect that a trial is a bona fide contest and not some sort of show that one side puts on with the consent of the other to influence public opinion. Because it was done to discourage other plaintiffs and to help settle the pending lawsuits for less money than they might have been settled otherwise."The judge, in the end, took the matter to the Kentucky Supreme Court, which found that "there was a serious lack of candor with the trial court and there may have been deception, bad faith conduct, abuse of judicial process and, perhaps even fraud."
The judge later revoked the verdict and instead, recorded the case as settled. The value of the secret settlement deal has been reported to be over $20 million.
Will Birth Defect Cases Follow Suit?
The few cases that have made it to a jury illustrate why the drug makers work so hard to get these cases dismissed or settled before trial. For instance, in a Paxil case in Wyoming in 2001, a jury awarded a surviving family member over $6 million after it determined that Paxil had caused a man to kill his wife, daughter and granddaughter before killing himself.
In addition, drug companies should be concerned over trial publicity because medical experts estimate that there are hundreds, if not thousands, of infants who were born with SSRI-related birth defects to mothers who do not know that the drugs could be to blame. After the PPHN study was published, the lead author, pediatric researcher, Dr Christina Chambers, told the Wall Street Journal that she heard from women all across the US who used SSRIs and gave birth to babies with PPHN.
In avoiding publicity, companies must consider that nagging little matter of profits. According to the Wall Street Journal, "Whether or not pregnant women continue or stop the use of antidepressants has big ramifications for makers of those drugs."
Citing US government estimates, the Journal reports that women are at a 25% risk for developing depression, with the highest risk period being in childbearing years.
As for industry influence on regulatory agencies, legal experts predict that GSK will file motions in an attempt to dismiss the birth defect cases using the FDA's new preemption policy announced in January 2006, which basically says that state failure-to-warn claims are barred against drug companies if a drug and its label were approved by the FDA.
"In essence," Ms. Menzies says, "the government’s position is that unless and until the FDA takes action regarding a safety risk associated with an approved drug, nobody else can -- not a drug company, not another state, and not a plaintiff in a lawsuit."
Before the Bush Administration took control of the FDA, the agency's consistent position was that the drug's label did not preempt state laws except in rare circumstances, precisely because the label would not reflect advances in knowledge about drugs once they were on the market. Critics point to the preemption policy as evidence of the administration's commitment to protect the profits of its largest political contributors.
It should be noted that, prior to his appointment as Chief Counsel at the FDA, Daniel Troy was a partner at Washington's Wiley Rein & Fielding, where he filed lawsuits against FDA regulations in support of the pharmaceutical industry. He left the FDA in late 2004, and is now back representing drug companies and applying the preemption policy that he put in place.
Up until now, most preemption cases have involved failure-to-warn claims about the association between suicide and SSRIs.
But the stakes are higher with birth defect cases and a massive filing of preemption motions is expected, aimed at keeping these families, considered to be extremely sympathetic plaintiffs, out of the sight of a jury.
However, when it comes to preemption motions, GSK could not be up against more formidable opponents than the attorneys at Baum Hedlund. Ms. Menzies and her Baum Hedlund associate, Robert Brava-Partain, have already soundly defeated preemption arguments by SSRI makers and the FDA in numerous cases, including Witczak v Pfizer, Cartwright v Pfizer, and Zikis v Pfizer.
According to Ms. Menzies, the use of the FDA to shield the industry from liability actually began in 2002, when Mr Troy began submitting briefs in private lawsuits on behalf of drug companies arguing that state tort failure-to-warn claims should be preempted because the FDA had the final word when it came to drug labeling.
In the first brief in Motus v Pfizer, Mr. Troy argued that even though Pfizer had never asked to strengthen Zoloft’s label, any warning would have been false and misleading. "Had Pfizer given a warning as to a causal relation between Zoloft and suicide, the FDA would have disapproved the warning," Mr. Troy wrote in the brief. The court never decided the preemption issue in Motus, because the case was concluded on other grounds.
In September 2002, Mr. Troy filed a brief with the same argument in another lawsuit that alleged that GSK failed to adequately warn about the withdrawal effects of Paxil. Ms. Menzies won that round when the judge held that the preemption argument "contravenes common sense" and "vitiates, rather than advances, the purpose of protecting the public."
Pfizer also tried to use Mr. Troy's brief from the Motus case, in support of a preemption motion in the Minnesota case of Witczak v Pfizer. The judge rejected it, stating:
"State consumer-protection law compliments, rather than frustrates, the FDA's protective regime. This is especially apparent when one considers that prescription drugs were once marketed primarily to trained health care providers -- sophisticated and discerning intermediaries. "Today, on the other hand, pill-rolling apothecaries and the mortar and pestle have disappeared. They have been replaced by drug manufacturers who urge the use of their drugs in mass-market print and television advertisements targeted directly at the public. Defendant, for example, advertises the drug involved in this case by personifying it as a happy, bouncing-oval cartoon character."Mr. Brava-Partain, who argued for Mrs. Witczak, praised the ruling. “The Court correctly recognized that drug manufacturers, like Pfizer," he stated, "cannot hide behind the rules and regulations of the FDA when they engage in conduct that harms the public."
The fact is, FDA regulations require drug makers to add a new safety warning whenever there is "reasonable evidence" of an association between a particular hazard and the drug, and that a "causal relationship need not have been proved."
"With respect to the SSRIs," Ms. Menzies states, "drug companies have utterly failed to add warnings to the labels despite far more than reasonable evidence of an association of a serious hazard.”
The claim that only the FDA can decide whether there is reasonable evidence to change the label is contradicted by its own inaction when it allowed Wyeth to strengthen the label with a warning about suicide and Effexor in August 2003, without prior approval.
According to Ms. Menzies, immunizing the pharmaceutical industry under the misplaced belief that the FDA is infallible is a threat to public health. "Recent regulatory failures," she states, "demonstrate that the agency is neither infallible nor does it have the capability of policing drug makers’ negligent misconduct."