Experts Say Birth Defect Risks Outweigh Benefits

Drug makers looking to increase profits with the sale of selective serotonin reuptake inhibitor antidepressants to pregnant women claim that untreated depression poses a grave risk to the unborn fetus, but a new study reports that the use of antidepressants, and not the depression itself, increases the risk of lower fetal age and preterm birth.

The study in the August 2007 American Journal of Psychiatry examined the effects of depression and antidepressant use on fetal age and risk of preterm birth in 90 women who were divided into three groups: (1) forty-nine women treated with antidepressants for more than 50% of their pregnancy; (2) twenty-two briefly treated or not treated with the drugs during pregnancy; and (3) a comparison group of 19 healthy pregnant women.

The researchers found that the average fetal age at birth was 38.5, 39.4 and 39.7 weeks in the three groups, respectively, and that the rates of preterm birth were 14.3 percent, 0 percent and 5.3 percent, respectively.

The study showed that the rate of admission to the special-care nursery more than doubled at 21% for newborns exposed to antidepressants, compared to 9% of infants born to mothers who were not treated with the drugs and 0% in the control group. "This result was surprising to us, as we had anticipated that depression and anxiety during pregnancy would be associated with an increased risk of preterm birth," wrote Dr Rita Suri and colleagues from the University of California, Los Angeles.

"The two groups of women with depression -- those who were treated with antidepressants and those who were not -- had similar degrees of depression and anxiety during pregnancy," the authors of the study note.

The new study is alarming because, in May 2005, researchers at the University of Pittsburgh reported that, in any given year, at least 80,000 pregnant women in the US are prescribed SSRIs which include Paxil marketed by GlaxoSmithKline; Zoloft from Pfizer; Prozac and Cymbalta marketed by Eli Lilly, and Celexa and Lexapro from Forest Labs.

The drugs are still being prescribed to pregnant women despite the fact that more than 4 years ago, in June 2004, the FDA revised the SSRI labels to warn that infants exposed to the drugs in the womb can develop problems requiring prolonged hospitalization, respiratory support and tube feeding.

When issuing the warning, the agency said it had received hundreds of preliminary reports of adverse effects in newborns over the last decade and that the most common were trouble eating, irritability, body rigidity and respiratory problems. More SSRI-related birth defects have surfaced in every year since that FDA warning in 2004.

In September 2005, Glaxo sent a “Dear Doctor” letter about a Paxil label change based on data from the National Birth Defects Prevention Study, which found that women who took SSRIs were more likely to have an infant with omphalocele, an abnormality in which the infant's intestine or other abdominal organs protrude from the navel, with the strongest effect reported with Paxil, accounting for 36% of all SSRI exposures.

In addition, the "Dear Doctor" letter advised of an association between mothers taking SSRI's and giving birth to an infant with craniosynostosis, a congenital defect present at birth in which the connections betweensutures-skullbones prematurely close during the first year of life, which causes an abnormally-shaped skull.

In December 2005, Glaxo notified doctors of a new warning added to the Paxil label about the risk of major congenital malformations in infants born to women taking Paxil during the first trimester of pregnancy and the FDA also issued an advisory warning about the risk of congenital malformations, especially of the heart, and changed Paxil's category from C to D. Category D means a drug has been found to harm the human fetus.

In July 2006, the FDA issued another public advisory, this time warning that infants exposed to SSRI's were six times more likely to develop the life-threatening lung disorder persistent pulmonary hypertension (PPHN) than infants who were not exposed.

The warning was based on a study in the February 9, 2006, New England Journal. After the study was released, lead author Dr Christina Chambers told the Wall Street Journal that she heard from women all over the country who had babies born with PPHN after taking SSRI's during pregnancy.

According to Dr Robin Steinhorn, Head, Division of Neonatology; Children's Memorial Hospital of Chicago, Department of Pediatrics, Professor, Northwestern University Medical School in eMedicine from WebMD, accessed on August 15, 2007:

"Recent data suggest that the PPHN syndrome may occur as often as 2-6 cases per 1000 live births. PPHN is a frequent complicating factor in the term or near-term newborn with parenchymal lung disease, such as MAS (meconium aspiration syndrome) or pneumonia. An increased incidence of PPHN is reported for mothers who use selective serotonin reuptake inhibitors (SSRI's) during the last half of their pregnancies."

Dr Steinhorn explains that, during fetal life, pulmonary blood flow is low, with less than 10% of the combined cardiac output directed to the lungs. In fetal life, numerous factors, including hypoxia, maintain high pulmonary vascular resistance (PVR) and after birth, PVR decreases and pulmonary blood flow increases dramatically as the lungs assume the function of gas exchange, he says.

However, in some newborns, Dr Steinborn notes, the normal decrease in pulmonary vascular tone does not occur, and the result is PPHN. "This syndrome causes substantial morbidity and mortality in otherwise healthy, term newborns," he states.

PPHN is the failure of the normal circulatory transition that occurs after birth, and mechanical ventilation is usually needed to maintain adequate oxygenation. Because of their lability and ability to fight the ventilator, newborns with PPHN nearly always require sedation and paralysis is sometimes required in newborns whose condition remains unstable despite adequate sedation, Dr Steinborn says.

According to Michael Baum, a pharmaceutical drug product liability attorney and senior partner of Baum Hedlund law firm, who has been handling SSRI cases for 17 years against defendants such as, Glaxo, Pfizer and Eli Lilly in cases involving antidepressant-induced suicide, birth defects and various other injuries, the increased risk of lower fetal age and pre-term birth is likely linked to the mechanism causing higher rates of fetal heart and lung defects amongst babies whose mothers took SSRI's during pregnancy.

It is well known that SSRIs cross the placental barrier, he says, leading to exposure of the developing fetus to the SSRI itself or exposure to excess serotonin caused by the SSRI's during fetal organ formation, which then leads to cellular and organic malformation.

"While the administration of the SSRI is supposedly intended to "correct" a chemical imbalance in the depressed pregnant mother," Mr Baum explains, "its crossing the placental barrier may itself cause a chemical imbalance for a developing fetus--the presence of the SSRI may interfere with the proper balance of serotonin and serotonin re-uptake needed for normal cellular development."

"This link should have been analyzed and placed on SSRI warning labels long before pregnant women were advised to take SSRIs--now these children and their families are dealing with the tragic aftermath that could have and should have been avoided," he says.

Experts say the benefit of prescribing any drug must be weighed against its risks. According to Harvard-trained psychiatrist Dr Stefan Kruszewski, "This is never more important than when two lives are at stake as with a pregnant mom and her unborn child."

He notes that the serious risks for moms taking SSRI's may include an inability to stop taking the drug, akathisia-induced suicidality and rapid mood swings. "For the newborn," he says, "the overwhelming concern is the risk of major congenital malformations that can require life-long medical care for the child."

Dr Grace Jackson, a recognized authority on psychotropic drugs, also warns that women often find they can never return to living without the drugs – not because they develop a "craving," she says, but because the withdrawal effects they experience are intolerable and are misinterpreted by physicians as "proof" of depressive relapse for which "lifelong therapy" is mandated.

One of the world's best-known experts on SSRI's, Dr Peter Breggin, says, "the worst hazards of depression in pregnancy are those of suicidality and, very rarely, infanticide."

However, he points out that SSRI's are implicated in increasing the risks of both suicide and violence and that the newest FDA labels specifically warn about SSRI-induced suicidality in young adults, the age group most likely to become pregnant. "Now we know," he says, "that the SSRI's not only threaten to cause the death of the mother through suicide but also the death of the child through lethal birth defects."

The drug makers have known for years that SSRI's increase the risk of suicide. Dr Arif Khan conducted an analysis of clinical trial data for SSRI's approved by the FDA between 1985 and 2000 and reported a finding of a higher rate of completed suicides during the trials, in Clinical Psychiatric News, August 2002.

When compared to the rate of 11 per 100,000 suicides for the general population, Dr Khan found there were 718 completed suicides per 100,000 in the clinical trials, and rates were higher among patients receiving SSRI's than with patients taking a placebo. These findings were particularly surprising, Dr Khan said, because most clinical trials try to exclude patients who are actively suicidal.

On the benefits side of the equation, a review of 38 studies on SSRI's including Zoloft, Prozac, Paxil, Serzone, Celexa and Effexor, conducted during 1987-1999, showed an average 10-point improvement in mood for patients who took the drugs, and an 8-point improvement in patients on a placebo (Kirsch, Moore, Scoboria & Nicholls, 2002).

Another leading expert on SSRI's, Dr David Healy, author of, "The Antidepressant Era," says that the efficacy of SSRI's has been greatly exaggerated, and a review of the actual clinical trials reveal that only one in ten patients responds specifically to an SSRI rather than a nonspecific factor or placebo.

Dr Jackson also notes that SSRI's barely out-performed sugar pills in head-to-head trials. Dr Healy and Dr Jackson both say that the risks of the neonatal withdrawal syndrome and serious birth defects far outweigh any benefits of SSRI use by pregnant women.

Critics point out that, if SSRI's worked, suicide rates would be declining, especially since patients are kept on the drugs indefinitely. But suicide rates have not dropped at all, and in fact, suicides have increased in some age groups.

The April 19, 2006, National Vital Statistic Report shows the overall suicide rate in the US has remained basically unchanged since 1999 when the rate was 10.5 suicides per 100,000. In 2000, the rate was 10.4, and in 2001 it dipped to 10.1; but in 2002, the rate was back up to 11.0. In 2003, the suicide rate was 10.8 per 100,000, and in 2004 it was back up to 11.0.

Going back to 1980, a year in the pre-SSRI era, in persons aged 25 to 44, death by suicide was ranked the 5th leading cause of death. In 2004, however, when SSRI's were close to being the most prescribed class of drugs in the US, suicide rates were higher, and it became the 4th leading cause of death for persons in this age group.

Yet the Centers for Disease Control recently reported that antidepressants were the most prescribed drugs in the US in 2005, with higher prescription rates than drugs used to treat high blood pressure, high cholesterol, diabetes or headaches.

Experts say people are being misdiagnosed with depression as a result of normal responses to stressful events or an important loss, or in the case of pregnant women, worries that naturally occur with becoming a new mother. According to Dr Timothy Scott, author of "America Fooled," there is an abundance of research indicating that depression can stem from many issues that are downplayed by drug-industry-funded ads and literature.

"The fact that physicians rarely go over the many factors which we know can move us away from joyfulness and toward depression," he says, "is a clear indication of the success of the industry's marketing strategy."

Dr Scott says he is frustrated and angered by the industry's essential disregard for the financial costs these ineffective drugs impose on families and the physical harm they inflict on millions of users who consume them year in and year out.

Families seeking legal advice regarding SSRI birth defects can contact the Baum, Hedlund, Aristei, Goldman & Menzies Law Firm at: (800) 827-0087; http://www.baumhedlundlaw.com/

Evelyn Pringle
evelyn-pringle@sbcglobal.net

(Written as part of the Antidepressant Birth Defect Litigation Monthly Round-Up, Sponsored by Baum Hedlund's Pharmaceutical Antidepressant Litigation Department)
www.paxilbirthdefect.com/
www.pphnlawyers.com

(Evelyn Pringle is a regular columnist for OpEd News and investigative journalist focused on exposing corruption in government and corporate America)

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