October 2, 2007
By Evelyn Pringle
A study of nearly 500,000 women by researchers at the University of Pittsburgh Medical Center, in the September 18, 2007, Annals of Internal Medicine, found that nearly 50% of women taking a prescription drug that could cause birth defects did not receive warnings to avoid pregnancy. The authors note that the pregnancy risks of a drug should be discussed with women before they begin taking it.
Experts say the seriousness of a life-threatening lung disorder found six times more often in infants born to mothers who take antidepressants during pregnancy is not being adequately conveyed to women while they are considering whether to use the drugs.
The disorder, persistent pulmonary hypertension (PPHN), occurs when a newborn does not adjust to breathing outside the womb. PPHN refers to high pressure in the lungs' blood vessels which prevents the body's oxygen-poor blood from entering the lungs to absorb oxygen, and leaves the infant with not enough oxygen into the bloodstream.
On July 19, 2006, the FDA ordered a PPHN warning for the labels of the selective serotonin reuptake inhibitor antidepressants (SSRI's), based on a February 9, 2006 study in the New England Journal of Medicine, and issued a Public Health Advisory that stated:
"A recently published case-control study has shown that infants born to mothers who took selective serotonin reuptake inhibitors (SSRI's) 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."
Two week later on August 1, 2006, the American College of Obstetricians and Gynecologist issued a press release warning that the use of SSRI's and selective norepinephrine reuptake inhibitors (SNRI's) during pregnancy should be individualized based on their respective risks and benefits, and specifically warned that Paxil should be avoided due to the potential risk of fetal heart defects, PPHN and other negative effects.
SSRI's sold in the US include Paxil marketed by GlaxoSmithKline, Prozac by Eli Lilly, Zoloft by Pfizer, and Celexa and Lexapro sold by Forest Laboratories, along with various generic versions of the drugs. The closely-related class of SNRI antidepressants also carry birth defects warnings and include Wyeth's Effexor and Lilly's Cymbalta.
In any given year in the US, at least eighty-thousand pregnant women are prescribed SSRI's, according to a study in the May 2005, Journal of American Medical Association. The CDC recently reported that antidepressants were the most prescribed class of drugs in the country in 2005. The fact that the overall prescribing rate is higher than for any other drugs indicates that a large number of pregnant women may be taking antidepressants without knowledge of the risks to the unborn fetus.
Overall, respiratory failure affects nearly 80,000 newborns per year, and it is responsible for as many as half of all infant deaths. Nearly one-third of all newborns with respiratory failure are born at term or near-term, and are at risk for PPHN, according to the April 2007 article, "Pulmonary Hypertension, Persistent-Newborn," by Dr Robin Steinhorn, head of the Division of Neonatology at Children's Memorial Hospital in Chicago and Professor at Northwestern University Medical School, in eMedicine from WebMD.
Dr Steinhorn also notes that an increased incidence of PPHN is reported for mothers who use SSRI's during the last half of their pregnancies.
As recently as 15 years ago, the reports says, the mortality rate for PPHN infants reached 40%, and the prevalence of major neurologic disability was 15-60%. However, the introduction of extracorporeal membrane oxygenation (ECMO) and other new therapies has had a major effect on reducing the mortality rate, yet the prevalence of major neurologic disabilities among surviving newborns remains approximately 15-20%.
Dr Steinhorn reports that Glass and colleagues compared the neurodevelopmental outcome of 103 neonates following ECMO and 37 without ECMO at age 5 and states:
"Major disability, which was defined as mental disability, motor disability, sensorineural impairment, or seizure disorder, was present in 17 of children in whom ECMO had been used. The mean full-scale, verbal, and performance intelligence quotient (IQ) scores of children who received ECMO treatment were within the normal range; however, as a group, the scores were significantly lower than in children who had not had ECMO (96 vs 115)."
According to the report, infants who survive following ECMO have a higher rate of rehospitalization for nonpulmonary and surgical conditions, and the rate of sensorineural disabilities in infants who survive averages 6% and developmental delay occurs in 9%.
Because the prevalence of hearing loss is high, the report recommends that an automated hearing test should be administered before discharging the baby and hearing should be reassessed when he or she is 6-months-old and again, as the results indicate.
Dr Steinhorn also notes that an increased frequency of social problems, academic difficulties at school age and higher rates of attention deficit disorder are reported in children who received ECMO.
Although the actual FDA warning about PPHN was not added to the antidepressant labels until August 2006, the drug makers were well aware of the risk of this birth defect for more than a decade, due to a long and steady line of studies that linked the drugs to serious respiratory problems in newborns dating back to 1996.
A study in the October 3, 1996, New England Journal of Medicine, lead by Dr Christina Chambers of the Department of Pediatrics at the University of California-San Diego, reported that PPHN developed in 2.7% of a group of infants whose mothers took Prozac throughout their pregnancy.
From 1989 through 1995, the California Teratogen Information Service and Clinical Research Program received approximately 1,500 calls requesting information on the potential teratogenic effects of Prozac (fluoxetine), and an estimated one-third of the calls were made by pregnant women who were currently taking Prozac.
For their study, the researchers selected 228 of these women. Because they hypothesized that birth size, gestational age, and neonatal adaptation were influenced by exposure to Prozac late in pregnancy, the women were divided into two groups.
One group was referred to as the exposed-early group because the women discontinued Prozac in the first or second trimester, and another group was referred to as the exposed-late group because the women continued to take Prozac in the third trimester.
A third group of 254 pregnant women who called the same California Information Program between 1989 through 1995, but with questions about other drugs and procedures that were not considered teratogenic, was enrolled as a control group.
The researchers determined that 73 infants in the exposed-late group had higher rates of premature delivery, admissions to special care nurseries, and poor neonatal adaptation, including respiratory difficulty, cyanosis on feeding and jitteriness. Birth weight was also lower and birth length shorter in the exposed-late infants, they found.
The study authors noted their concern over the 15.5% incidence of three or more minor anomalies in some infants exposed to Prozac in early pregnancy. "The combination of any three minor anomalies in a single child is an unusual finding," they wrote.
The 15.5 percent incidence, they said, indicates that exposure during the first trimester has an effect on embryonic development. "This finding raises the possibility of an associated defect in the development of the central nervous system that may become evident when the infant is older," the authors wrote.
In January 1998, a study in the international journal of medical science and practice, The Lancet, explained that the lungs act as a reservoir for antidepressants and this study suggests that SSRI's could play a pivotal role in infant respiratory conditions, such as PPHN. Another study, in the April 2002 Journal of Laboratory and Clinical Medicine, investigated the effects of SSRI's on pulmonary circulation and found that SSRI's affect the pulmonary smooth muscle cells and aggravate pulmonary hypertension.
In June 2004, a study in Prescrire International also reported that newborns exposed to SSRI's toward the end of pregnancy showed signs of altered muscle tone, breathing and suction problems, and agitation, with an estimated 20% to 30% of the infants affected.
The next month, after receiving hundreds of adverse event reports over a decade, in July 2004, the FDA finally revised the labels for all SSRI's and SNRI's, warning that some newborns exposed to the drugs had developed problems requiring prolonged hospitalizations, respiratory support and tube feeding.
Less than a year later, a study in the May 2005 Journal of the American Medical Association reported that women who took SSRI's or SNRI's late in pregnancy were at a 3 times higher risk of giving birth to infants suffering from serious respiratory problems, jitteriness and irritability. Lead author, Dr Eydie Moses-Kolko, reported that serious respiratory problems developed in about one out of every 100 infants.
According to Dr David Healy, a leading expert on pharmacology and author of "The Antidepressant Era," the doctors who prescribe SSRI's are often not able to spend enough time with patients to discuss their emotional issues in depth. "For some doctors," he notes, "SSRI's may appear to provide a quick solution for patient problems arising from normal life events such as bereavement, work stress, or marital conflict."
However, he says, a review of the actual SSRI studies shows that only one patient in 10 responds to these drugs, and he attributes the massive prescribing to successful marketing rather than benefits.
"Through educational and marketing campaigns," Dr Healy says, "the SSRI makers have produced a situation where people who would never have been given an antidepressant in the 1960s, 1970s and 1980s, are now given one after cursory questioning by a physician."
Another leading expert, Dr Peter Breggin, founder of The International Center for the Study of Psychiatry and Psychology (ICSPP), a nonprofit research and educational network, and the journal Ethical Human Sciences and Services, also says a thorough review of all the studies submitted to the FDA for the approval of the SSRI's showed that, when taken as a whole, the drugs do not work.
Dr Breggin also agrees that the high rate of prescribing to women indicates that women who may be experiencing minor symptoms of distress common with daily living are being convinced that they have a mental illness that requires drugs, most frequently an SSRI.
Proponents for the drug makers claim that depression itself poses a greater risk to the fetus than SSRI's. "The problem with this claim is that there is no consideration for the health of the baby and the immense stress a mother has to endure when her baby is sick," states Kate Gillespie, a Paxil injury lawyer from the Baum Hedlund law firm.
"Not to mention, the far greater stress that is created by having to constantly deal with life and death health issues, like the respiratory problems of an infant, that are caused by SSRI-induced PPHN," she adds.
"For these women," Ms Gillespie says, "it is clear that the risks far outweigh any benefit."
An August 2006 study in the Archives of General Psychiatry compared babies born to depressed mothers treated with SSRI's to those born to mothers who were not treated, and found a significantly greater incidence of respiratory distress, 13.9% vs 7.8%, and longer hospital stays for the infants exposed to SSRI's.
Another study, in the August 2007 American Journal of Psychiatry, examined the effects of depression and antidepressant use on fetal age and the risk of preterm birth with 90 women and found the drugs, rather than depression, to be associated with lower fetal age and an increased risk of preterm birth. The researchers noted that the presence of depression per se during pregnancy did not adversely affect outcomes.
According to Dr Breggin, SSRI's should never be used during pregnancy. "If pregnant women feel anxious or sad," he says, "they should seek counseling or family therapy involving the child's father, along with other sources of emotional support."
Families seeking legal advice regarding SSRI-antidepressant birth defects can contact the Baum, Hedlund, Aristei & Goldman Law Firm at: (800) 827-0087; http://www.baumhedlundlaw.com/