Evelyn Pringle November 22, 2006
If Big Pharma cared one iota about the unborn fetus, at a bare minimum, it would call off its hired-guns traveling around the country peddling SSRI antidepressants to pregnant women by convincing doctors to prescribed the drugs and ignore the studies and FDA warnings that say SSRIs are associated with serious birth defects.
Less than a month ago, on October 16, 2006, the first lawsuit in the nation was filed against GlaxoSmithKline in which an infant charges that his life-threatening lung disorder was caused by exposure to the SSRI Paxil in the womb during his mother's pregnancy.
Eric Jackson was born in Denver, Colorado on October 28, 2004, with persistent pulmonary hypertension of the newborn (PPHN), a condition in which the infant’s arteries to the lungs remain constricted after birth and limit the amount of blood flow to the lungs and oxygen in the bloodstream.
Immediately after birth Eric had to be placed on a ventilator and eventually had to be placed on an oscillating ventilator for a month.
In his 2 short years on earth, Eric has undergone two cardiac catherizations, and another procedure to combat gastral reflux caused from being on a ventilator for so long. Since birth, he has remained on oxygen and medications to help him breathe and he continues to suffer with eating and digestive problems.
With their lawsuit, Eric's parents hope to recover the medical and other expenses incurred in treating, and attempting to cure Eric’s condition, as well as the related illnesses. Some of the related health problems may not even surface until Eric is a teenager.
A study in the October 3, 2006 Archives of Pediatrics and Adolescent Medicine by Dr Agnes Whitaker, MD, of Columbia University and the New York State Psychiatric Institute, and colleagues, reported that low birth weight infants who require mechanical ventilation, 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.
The research team said, two factors, male gender and days of ventilation were predictors of motor problems. For each additional week of mechanical ventilation, they said, total and oral motor problem scores were higher by 0.33 and 0.14 points, respectively.
Legal analysts predict that Glaxo will attempt to reach early settlements with the families of infants born with birth defects because the company in no way wants injured toddlers paraded in front of a jury.
Karen Barth Menzies is one of Eric's attorneys. She is a partner at Baum Hedlund, a national pharmaceutical products liability law firm with offices in Los Angeles, Washington, DC and Philadelphia, where she heads the Pharmaceutical Antidepressant Litigation Department.
Ms Menzies has been waging legal battles against the SSRI makers on behalf of injured consumers for more than a decade and she currently represents many other families in Paxil birth defect cases
Jennifer Liakos is an associate attorney at Baum Hedlund in Los Angeles, and she is also a member of the firm's Pharmaceutical Antidepressant Litigation Department, handling Paxil birth defect cases. She explains that between 10% to 20% of babies born with PPHN do not survive, even when they receive treatment.
Having been the leader in the Paxil litigation against Glaxo for years now, and through their intensive litigation and discovery, Baum Hedlund has evidence that reveals specifics relating to Paxil and birth defects. Eric's attorneys do not have to newly learn the inter-workings of Glaxo because they know how the company operates regarding Paxil and how they analyze or fail to analyze data.
According to Ms Menzies, studies have shown that infants who are exposed to selective serotonin reuptake inhibitor antidepressants (SSRIs), after the 20th week of gestation are more likely to develop PPHN than infants who were not exposed to an SSRI during pregnancy.
In addition to Paxil, the other SSRIs sold in the US include Prozac by Eli Lilly; Zoloft, from Pfizer; Celexa and Lexapro, from Forest Laboratories; and Luvox, from Solvay. Wyeth markets Effexor, a serotonin-norepinephrine inhibitor.
Adding to the problem of curtailing the prescribing of SSRIs to pregnant women, is the fact that SSRI makers have doctors prescribing the drugs for many other conditions besides depression, and often for off-label uses, meaning they are not approved by the FDA.
According to Dr Jay Cohen, author of, "Over Dose: The Case Against The Drug Companies," the "drug companies have marketed SSRI antidepressants vigorously not only to psychiatrists, who are supposed to have some expertise with these drugs, but also to family practitioners, pediatricians, gynecologists, internal medicine specialists, and anyone else who can pen a prescription."
"But this doesn't mean,” he says, “that they possess in-depth knowledge of SSRIs or their actions and toxicities.”
A study from the University of Georgia in the June 2006, Journal of Clinical Psychiatry, found that 75% of the people prescribed antidepressants received them for a reason not approved by the FDA.
Little Eric's lawsuit contends that when allowing Paxil to be prescribed to pregnant women, Glaxo has an ongoing duty of pharmacovigilance. The FDA describes the term pharmacovigilance to mean "all scientific and data gathering activities relating to the detection, assessment, and understanding of adverse events."
This includes, the agency notes, the use of pharmacoepidemiologic studies and activities "undertaken with the goal of identifying adverse events and understanding, to the extent possible, their nature, frequency, and potential risk factors."
"During the entire time Paxil has been on the market in the US," Ms Menzies says, "FDA regulations have required Glaxo to issue stronger warnings whenever there existed reasonable evidence of an association between a serious risk and Paxil."
"FDA regulations specifically state," she explains, "that a causal link need not have been proven before a new warning is issued and they explicitly allow Glaxo to issue a new warning without prior FDA approval."
Ms Menzies reports that research as far back as October 3, 1996 in the New England Journal of Medicine, by Dr Christina Chambers and colleagues, of the Department of Pediatrics, Division of Dysmorphology and Teratology, at the University of California–San Diego, indicated a risk of PPHN in babies born to mothers taking SSRIs.
For this study, the researchers identified 228 pregnant women taking Prozac between 1989 through 1995, and compared the outcomes of their pregnancies with those of 254 women who were not taking Prozac.
The study found that babies exposed to the Prozac, during the third trimester of pregnancy, had significantly higher rates of premature delivery, respiratory difficulties, admissions to special care nurseries, jitteriness, and poor neonatal adaptation including cyanosis on feeding.
There have also been studies specific to the use of Paxil during pregnancy that have shown respiratory problems in exposed infants upon delivery. For instance, 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 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.
In June 2004, the journal, Prescrire International, reported that newborns exposed to SSRIs toward the end of pregnancy had breathing and suction problems and showed signs of agitation, and altered muscle tone. The study estimated that 20% to 30% of infants were effected and warned that doctors should be aware of the risks when considering treatment during pregnancy with Paxil, Celexa, Prozac, Zoloft, and Lexapro.
The following month, on July 9, 2004, WebMd reported that over the past decade the FDA had received "hundreds" of reports of adverse effects with infants born to mothers taking SSRIs.
That same month, the FDA changed the labeling for all SSRIs, warning that upon delivery, some infants exposed to SSRIs required respiratory support, tube feeding and prolonged hospitalizations.
In May 2005, a University of Pittsburgh study in the Journal of American Medical Association, combined the previous research and found that women who took SSRIs late in pregnancy had a three times higher risk of giving birth to infants suffering from serious respiratory problems, jitteriness, and irritability in the first couple of weeks after birth.
The drugs involved in this study also included the serotonin norepinephrine reuptake inhibitor Effexor. The researchers estimated that in any given year in the US, at least 80,000 pregnant women are prescribed the drugs. According to psychiatrist, Dr Eydie Moses-Kolko, the lead author of the study, serious respiratory problems develop in about one out of 100 infants born to these women.
As a follow-up to her findings of breathing problems in the previous Prozac study in 1996, Dr Chambers, now an assistant professor of pediatrics at the University of California, San Diego, and colleagues, performed a case control study of women on SSRIs who gave birth between 1998 and 2003, to determine whether PPHN was associated with exposure to SSRIs in late pregnancy.
The results of the study published in the February 9, 2006, New England Journal of Medicine, reported that mothers who took SSRIs in the second half of their pregnancies were 6 times more likely to give birth to babies with PPHN.
The study found 14 infants with PPHN in the group who had been exposed to an SSRI, compared to 6 infants with the disorder in the group who were not exposed to the drugs.
The FDA found the study so alarming that it prompted the agency to hold a press 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.
She also told reporters that women of reproductive age are the "biggest users of antidepressant drugs."
Instead of immediately taking action to warn doctors and consumers of this development, the pharmaceutical industry went into all-out damage control to protect SSRI profits by encouraging pregnant women to keep taking SSRIs.
A corresponding study in the February 2006, Journal of the American Medical Association, warned that pregnant women who stopped taking the drugs could greatly increase their risk of a relapse of depression. The authors of the study predicted that their findings would prompt some women to stay on SSRIs throughout pregnancy.
The JAMA study got much more media attention than Dr Chambers, and included headlines warning about the dangers of relapse in pregnant women going off SSRIs. Many local television news broadcasts even ran an unedited video provided by JAMA, featuring a study author and one of his patients.
However, 5 months later, on July 11, 2006, the Wall Street Journal published an expose on the researchers involved in the study who were encouraging pregnant women to keep taking SSRIs. "But the study," it reported, "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."
Most of the authors, the WSJ noted, were leading psychiatrists at Massachusetts General Hospital, the University of California Los Angeles, and Emory University
The lead researcher, Dr Lee Cohen, a professor at Harvard Medical School, it reported, "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."
Among the most significant of the missing financial disclosures, the Journal said, were those of study author, Lori Altshuler, director of the Mood Disorders Research Program at UCLA, who was a speaker or consultant for at least 5 antidepressant makers.
Vivien Burt and Victoria Hendrick were also authors who did not report financial relationships with SSRI makers, and Dr Viguera, another author, did not disclose her paid speaking relationship with Glaxo.
All total, the Journal said, "the authors failed to disclose more than 60 different financial relationships with drug companies."
“The work of these academic researchers,” the article wrote, “highlights the role of "opinion" or "thought" leaders coveted by drug companies because of their ability to influence not only the practice of doctors, but popular opinion as well.”
In the case of SSRI use by pregnant women, the WJS said, the industry-paid opinion leaders have become dominant authorities in the field and stated:
“They help establish clinical guidelines, sit on editorial boards of medical journals, advise government agencies evaluating antidepressants and teach courses on the subject to other doctors. In some cases, the financial ties between industry and these leading researchers are not disclosed.”
According to the WSJ, as soon as their study was published, Dr Cohen and some the other authors went out on the lecture circuit, telling doctors about their findings and pointing out flaws in the studies that found an increased risks of birth defects with infants exposed to SSRIs.
For instance, the panel of experts who criticized the Chambers study during the May 17, 2006, continuing medical education lecture, "Psychotropic Drug Use During Pregnancy," sponsored by the Massachusetts General Hospital Psychiatry Academy, was comprised entirely of psychiatrists with financial ties to drug companies.
During the lecture, the panelists were also critical of the FDA for adding new warnings about birth defects to Paxil’s label. On December 8, 2005, the FDA issued a Public Health Advisory after US and Swedish studies showing that exposure to Paxil in the first trimester of pregnancy to be associated with an increased risk of heart birth defects.
With the warning, the agency for the first time placed an SSRI in the D category, its second highest for the risk of birth defects. Category D means that either controlled or observational studies of pregnant women "have demonstrated a risk to the fetus."
The agency did not ban Paxil from use with by pregnant women, but it did go so far as to say, "FDA is advising patients that this drug should usually not be taken during pregnancy."
At the May 17 conference, panelist, Zachary Stowe, from the women's mental health center at Emory University, described the FDA’s decision to change the label as "driven by a single set of data that is unpublished, non-peer reviewed, and somehow this trumps the very nicely done prospective investigations that have really failed to find this risk."
However, here once again, according to the WSJ, Dr Stowe has served as an paid adviser and speaker for several SSRI makers.
In July 2006, corresponding with the WSJ’s expose about the undisclosed financial relationships of the Cohen study authors with SSRI makers, JAMA published a correction to announce that 7 of the authors of the February 2006, study had failed to reveal their financial ties with drug companies.
Critics of Big Pharma‘s influence over studies published in medical journals were quick to respond to the disclosure. On July 11, 2006, Merrill Goozner, director of the Center for Science in the Public Interest, issued a statement saying: “It’s clear that the Journal of the American Medical Association does not evaluate conflict of interest disclosures when articles are submitted.”
“As a result,” Mr Goozner said, “some authors with blatant conflicts of interest apparently feel they can ignore the journal’s policy with impunity.”
“The only solution,” he added, “is for journals to adopt strong penalties for authors who fail to disclose – a three-year ban from publishing in the pages in the journal.”
A month later in August 2006, another study in the Archives of General Psychiatry, by Canadian researchers at the University of British Columbia, 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 Health on August 25, 2006, 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 determined that 14% of the mothers were diagnosed with depression. They then compared the outcomes of infants born to women treated with SSRIs to those born to depressed women who were not treated with SSRIs and found a significantly higher incidence of respiratory distress in infants exposed to SSRIs by a ratio of 13.9% to 7.8%.
The study reported longer hospitalizations for infants born to mothers on SSRIs, and found birth weight and gestational age were also significantly less in SSRI exposed infants.
"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 October, 2006, the journal, Pediatrics, reported that CDC researchers cited preterm birth as the leading cause of infant mortality in the US, accounting for at least one-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 pounds.
"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," the authors wrote in Pediatrics.
There are also studies showing infants born with symptoms of neurological damage associated with SSRI exposure in the womb. In February 2004 a study in the American Journal of Pediatrics reported abnormal sleeping patterns, heart rhythms and levels of alertness linked to SSRIs.
Dr Philip Zeskind, a developmental psychologist and research professor at the University of North Carolina, Chapel Hill, led the investigation and on February 22, 2006, told the Sunday Telegraph, "What we've found is that SSRIs disrupt the neurological systems of children, and that this is more than just a possibility, and we're talking about hundreds of thousands of babies being exposed to these drugs during pregnancy."
In reaching their results, the team of researchers compared 17 babies born to mothers who took the Prozac, Paxil, Zoloft or Celexa throughout their pregnancy, with 17 babies born to mothers who had never taken SSRIs.
According to Dr Zeskind, "These babies are bathed in serotonin during a key period of their development and we really don't know what it's doing to them or what the long-term effects might be."
"It could be that they go `cold turkey' when they are born,” he explained in the Telegraph, “or the serotonin could be having an effect on their brains, or it could be a bit of both."
“We're not saying that pregnant women should not take the drugs, because depression is itself a big problem,” he said. “But these drugs are being given away like smarties, and this is a big problem,” Dr Zeskind warned.
Legal analysts predict that this first PPHN lawsuit is just the tip of the proverbial iceberg because there are tens of thousands of infants exposed to SSRIs in the womb each year.
After the results of her PPHN study were made public, Dr. Chambers says she heard from women all across the country who took SSRIs during pregnancy and had babies born with PPHN.
The fact that Glaxo has not ordered its hired-guns to stop promoting the sale of Paxil to pregnant women, proves that the company plans to go on sacrificing the lives of babies in the name of profits and that should be a fairly easy point to get across to a jury.
(Written as part of the Paxil Litigation Monthly Round-Up series, Sponsored by Baum Hedlund's Pharmaceutical Antidepressant Litigation Department)