A Danish study of over 400,00 children born from 1996 to 2003, found that the risk increased when expectant mothers either take more than one selective serotonin reuptake inhibitor (SSRI) or switch SSRIs in early trimesters, said WebMD.  Popular SSRIs include Prozac, Paxil, Zoloft, Celexa, and Lexapro, and are often prescribed to pregnant women suffering from depression, WebMD pointed out.

According to the study, when pregnant women took more than one SSRI, their babies experienced a four-fold increase in septal heart defects, a defect in the wall that divides the heart’s left and right sides, explained WebMD.

As we've reported previously, in late 2005, the  U.S. Food & Drug Administration (FDA),  sent an alert to physicians about early studies suggesting Paxil could be a contributor to heart defects in babies when taken by expectant mothers in the first trimester. WebMD noted that not only was Paxil singled out by the agency, but also since the warning, doctors are routinely known to switch pregnant women’s medication from Paxil to a different SSRI when pregnant or discussing become pregnant. That early switching has been linked to the infant heart defect. Also, said WebMD, citing recent studies, Paxil does not increase the risk of the specific heart defect versus other antidepressants; the Danish study found that Celexa and Zoloft in early trimesters was associated with the heart defect while the risk was not seen with Paxil or Prozac.

Septal heart defects occurred in 0.5 percent of children born to women not on SSRIs, while 0.9 percent of children born to mothers taking SSRIs were diagnosed with the defect. Lars H. Pedersen of Aarhus University called for larger studies to determine the safety of any one SSRI versus any others during pregnancy.

In a joint statement from the American College of Obstetricians and Gynecologists (ACOG) and the American Psychiatric Association (APA), the groups recommended that women who experience psychotic episodes, have bipolar disorder, are suicidal or have a history of suicide attempts should remain on antidepressants; women suffering from mild depression or who experienced few symptoms for six months or more could consider gradually reducing or stopping SSRI use under close physician supervision; and psychotherapy and other treatments might be an appropriate alternative in some, not all, pregnant women with depression, reported WebMD.

A prior study found that patients taking the clot reducer Plavix (Generic: Clopidogrel bisulfate) experienced more than 12 times as many ulcers as those patients who were treated with aspirin plus a heartburn pill.  It is believed that up to half of those patients who are now taking Plavix do so because their doctors assume that Plavix is safer on the stomach than aspirin, said that study's lead author, Dr. Francis K. L. Chan.  Of note, the American College of Cardiology and the American Heart Association recommends Plavix therapy instead of aspirin therapy for those heart and stroke patients at risk of developing ulcers.

The study also suggested that the drug’s guidelines should be changed, and that many of those patients taking Plavix should consider switching to aspirin plus a heartburn pill, Dr. Chan said.  Dr. Chan’s study looked at 320 patients whose ulcers had healed.  He treated half with Plavix and half with aspirin plus Nexium, a heartburn pill. Thirteen of the patients taking Plavix, or 8.6 percent, experienced renewed ulcer bleeding during the year; just one patient, or 0.7 percent, of those taking aspirin and Nexium developed an ulcer bleed.

The FDA advised healthcare professionals this week that it ordered the makers of Plavix—Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership—to collaborate with the agency on studies that are hoped to reveal deeper information on the possible effects of genetic factors, said MedWatch and on possible drug interactions, said the LA Times.  In particular, the study will be looking at the effect of PPIs—proton pump inhibitors—on Plavix, since it is unclear which, either, or both of these factors are involved, reported MedWatch.  PPIs, which are taken for the treatment of acid reflux, are described by the LA Times as medications which suppress stomach acid production.  Nexium, Prevacid, Aciphex, and Protonix are some examples of prescription PPIs and Prilosec OTC is an over-the-counter PPI.

Medwatch confirmed that the FDA knows of reports which indicate that clopidogrel efficacy is uneven, with results differing in some patients over others.  The FDA expects that it could take several months to conduct the studies.  MedWatch urged healthcare providers to re-evaluate the need to start or continue PPIs in those patients being treated with clopidogrel; likewise, patients taking the combination or considering the combination are advised to speak to their healthcare providers, and to bear in mind that Prilosec OTC can be taken without a prescription.

The LA Times reported that the FDA move came about because of reports that clopidogrel’s cholesterol reducing efficacy seemed to be compromised in some patients.  The FDA also noted that genetic factors might be involved and other drugs could also affect how the drug is metabolized in the body, said the LA Times.  PPIs seem to reduce the breakdown of some drugs by the liver and may increase the concentration of diazepam (Valium), phenytoin (Dilantin), and warfarin (Coumadin), said the LA Times.

Universities are supposed to monitor conflicts when their researchers receive government grants.  According to a report published by The New York Times in October, Grassley has been asking some of the nation’s leading researchers to provide their conflict-of-interest disclosures, and is comparing those documents with records of actual payments from drug companies.

The Emory faculty member in question is Dr. Charles B. Nemeroff, one of the nation’s top psychiatric researchers.  In October, we reported that documents released by Emory to Grassley's investigators indicated that Nemeroff was paid more than $2 million by pharmaceutical companies, but failed to report more than $1 million of that income to the school while working on government-funded drug researcher. Those documents include a letter from Nemeroff dated July 15, 2004 in which he promises Emory administrators that he would earn less than $10,000 a year from GlaxoSmithKline to comply with federal rules.  But in that same year, Nemeroff actually earned $170,000 from Glaxo for giving talks about Paxil and other drugs the company made.  

According to The Wall Street Journal, Emory has tried to explain the Glaxo payments by claiming they were for talks that weren’t promotional in nature but instead were “CME-like” (a term for continuing medical education).  Emory claims that the distinction led Nemeroff to believe he didn’t need to disclose those payments, the Journal said.

But Grassley isn’t buying it.  In a letter dated Dec. 17, Grassley chided Emory’s president.  “Neither anyone on my staff, nor any medical expert that they have contacted, have ever heard of the term ‘CME-like,’ ” he wrote. “It appears to be a new term created at Emory University.”

The Wall Street Journal also reports that Nemeroff himself is facing criticism for a letter he wrote 2000 when he was also serving as editor in chief of the journal Depression and Anxiety.  According to the Journal, which termed the missive a “Dear Me” letter, Nemeroff wrote it on the journal’s letterhead, and indicated he being paid $3,000 by the publication to write an article about Wyeth Pharmaceutical’s antidepressant, Effexor.  But Nemeroff also billed Emory that exact amount for the article.  It’s not clear if Nemeroff received two payments of $3,000, one from Emory and one from the journal.

According to the Journal, 14 other Emory faculty members received similar payments to write Effexor articles for the same issue of Depression and Anxiety.  Grassley says their payments, and the $3,000 Nemeroff received from Emory actually, came from a grant furnished by Wyeth.  According to the senator, the issue of Depression and Anxiety where the articles appeared fails to mention that any of the authors, including Nemeroff, were paid out of an account funded by Wyeth.

Among  the documents obtained by congressional investigators is a letter signed by Nemeroff dated July 15, 2004 in which he promises Emory administrators that he would earn less than $10,000 a year from GlaxoSmithKline to comply with federal rules.  But in that same year, Nemeroff actually earned $170,000 from Glaxo for giving talks about Paxil and other drugs the company made.  

Nemeroff's failure to fully disclose his financial relationship with the drug industry is just the latest revelation in a probe led by Senator Charles Grassley (R-Iowa).  Universities are supposed to monitor conflicts when their researchers receive government grants.  According to The New York Times, Grassley has been asking some of the nation’s leading researchers to provide their conflict-of-interest disclosures, and is comparing those documents with records of actual payments from drug companies.  

Grassley is a sponsor of  the Physician Payment Sunshine Act, which would require drug and device companies to publicly list payments to doctors that exceed $500.  The Senator has already discovered many instances where researchers' disclosures did not match the drug companies' records.   Harvard, Brown and Standford universities are just a few of the institutions where discrepancies have been found.

In a letter to Emory President James W. Wagner dated last Thursday, Grassley said that from 2000 through 2006, Nemeroff received just over $960,000 from Glaxo, but reported to the university that he received no more than $35,000. From 2003 until this past summer, Nemeroff was the  primary investigator on a federally-funded research project conducted jointly by Emory, Glaxo and the National Institute of Mental health that examined five Glaxo drugs considered for use as possible antidepressants.

According to federal research rules, universities are supposed to inform the National Institutes of Health (NIH) when a researcher receives annual income from a drug company totaling more than $10,000.  According to documents obtained by congressional investigators, Nemeroff would have exceeded the NIH's $10,000 limit in 2003, 2004, 2005 and 2006.  Emory should have either taken steps to deal with the conflict or to remove Nemeroff as the investigator.  

But Emory took Nemeroff's word that his drug company income did not exceed NIH limits.  This despite the fact that Emory’s conflict of interest committee investigated Nemeroff in 2004, and submitted a report to the university that detailed multiple “serious” and “significant” violations of university procedures intended to protect patients.  At the time, he had consulting arrangements with about a dozen companies, including Merck & Co., Bristol-Myers Squibb Co. and Eli Lilly & Co.  Even then, Emory took no action against Nemeroff, nor did it subject his financial ties with drug companies to further scrutiny.

This is not the first time that Nemeroff's ties to the pharmaceutical industry have raised questions.  In 2006, he stepped down as editor of the journal Neuropsychopharmacology after failing to disclose financial ties to Cyberonic's Inc., the maker of a depression-treating device that received a favorable review in a paper he co-authored.  At the time, Nemeroff blamed the omission on a "clerical error".  

On Friday night, the day after Grassley's letter to the university's president was made public, Emory announced that Nemeroff would “voluntarily step down as chairman of the department, effective immediately, pending resolution of these issues.”

Keywords:  Paxil ASD Lawyer VSD Heart Lawsuit Birth Defects

The lawyers and attorneys at our firm are currently offering free case evaluations to families whose children were born with heart defects, specifically Atrial Septal Defects (ASD) and Ventricular Septal Defects (VSD), due to their mother's use of Paxil while pregnant.  While several studies have linked the antidepressant Paxil to a number of birth defects, by far the most common problems associated with Paxil use during pregnancy are ASD and VSD.  These heart defects, which involve holes between the heart's pumping chambers, can be devastating, and often babies with these problems must undergo painful surgeries to correct them.  Our Paxil heart defect lawyers will make sure that infants and  families coping with ASD or VSD are compensated for these injuries.

Ventricular Septal Defects

A ventricular septal defect (VSD) is a hole between the right and left pumping chambers of the heart.  VSD is among the most common congenital heart defects, occurring in 0.1 to 0.4 percent of all live births and making up about 20 to 30 percent of congenital heart lesions. VSD is probably one of the most common reasons for referral of an infant to a cardiologist.

Although babies with large VSDs may do very well in the first weeks of life,  such defects eventually become dangerous.  In these cases, VSD will gradually lead to symptoms of congestive heart failure and must be treated.  Medium or moderate VSD is  more challenging to predict. Sometimes babies born with moderate VSD will have problems with congestive heart failure like babies with large VSD. Others will have no problems at all and just need to be watched.

VSD has can have a very characteristic heart murmur, however, a murmur is often not heard at birth, especially in a large VSD. It is only when there is excessive flow across the hole into the lungs that a murmur can be appreciated.  Babies who do have moderate or large VSD with excessive blood flow to the lungs will have signs of congestive heart failure. The most important sign will be the baby's growth.  In older children, lower energy levels compared to other children the same age may be a symptom of VSD.

Babies who have shown some signs of congestive heart failure from VSD will typically be placed on medication, usually a diuretic to help get rid of extra fluid in the lungs. A medication like digoxin might be used to stabilize heart rhythm.  In babies who are failing to thrive because it is too difficult for them to eat, a high calorie formula or fortified breast milk will be added to help the baby grow.   A nasogastric feeding tube may be necessary to deliver the food if a baby is too weak. The point of such treatments is to control the symptoms of heart failure, and  help the baby achieve normal growth.

Hopefully, the VSD will close and no other treatment will be needed. When the symptoms of VSD are hard to control with medicines or there is persistent evidence that the heart is doing extra work, surgical closure of the defect is often recommended.

In September 2005, the Food & Drug Administration (FDA) and GlaxoSmithKline, the maker of Paxil,  alerted doctors about a new study on major birth defects seen in babies born to women who took the antidepressant during the first trimester of pregnancy. In the study of more than 3,500 pregnant women, Paxil was linked to twice as many major birth defects as other antidepressants.  Most of these defects were heart related, and the most common heart problem seen in the study was VSD.  At that time, the label of Paxil was modified to include information on this study.

The Paxil birth defect lawyers at our firm know that VSD can take an enormous toll on babies and their families.  The medications and treatments used to stave off heart failure are expensive, and often carry other dangerous side effects.  Surgery is always a painful and traumatic experience for infants. Our Paxil birth defect lawyers will do everything they can to make sure families victimized by this drug get their lives back on track.

Atrial Septal Defects

An atrial septal defect (ASD) is a hole in the wall between the two upper chambers of the heart.   In some cases, the hole may close on its own, but often infants with ASD must undergo surgery to correct the problem.  While ASD is sometimes diagnosed at birth, it is not unusual for the defect to be discovered later in life.  An adult who has had an undetected atrial septal defect for decades may have a shortened life span from heart failure or high blood pressure in the lungs.

In December 2005, the FDA again announced that it was requiring GlaxoSmithKline to add additional warnings about Paxil birth defects to the drug's prescribing information.  The FDA took the action because the early results of two more studies showed that women who took Paxil during the first three months of pregnancy were about one and a half to two times as likely to have a baby with a heart defect as women who received other antidepressants or women in the general population.  In addition to VSD, the studies indicated that Paxil use during the early months of pregnancy put infants at risk of ASD. In addition to the label change, the FDA also moved Paxil to another pregnancy category.  The FDA had previously classified the Paxil birth defect  risk as Category C (Risk of Fetal Harm Cannot be Ruled Out).  The new Paxil labeling now classified the birth defect risk as Category D (Positive Evidence of Fetal Risk).

Infants with large atrial septal defects may have a poor appetite, and they often do not grow at a normal rate.  In some cases, they may also exhibit signs of heart failure or arrhythmias.  But very often, symptoms do not appear for years - when a person is in their 20s, 30s, or 40s - after  ASD has done significant damage to the heart and lungs.  Paxil was first approved in 1992, and thousands of pregnant women have taken the drug since then.  Because the symptoms of ASD often take time to appear, our Paxil heart defect lawyers expect many cases of Paxil-related ASD will be diagnosed in adults in the coming years.

The symptoms of long-standing ASD include shortness of breath, fatigue, swelling of legs, feet or abdomen, and heat palpitations.  Large ASDs can cause a range of life-threatening problems if they are not treated.  These include right-sided heart failure, a higher risk of heart attack and stroke, and heart rhythm abnormalities. 

In a child, doctors may observe the atrial septal defect for a period of time to see if it closes on its own. If a hole hasn't closed early in childhood, it usually will never close on its own and requires surgery to correct.  For adults and children, surgery involves plugging or patching the abnormal opening between the atria. Doctors can do this through two methods: open heart surgery or cardiac catheterization.  For children, both procedures involve a great deal of trauma and pain.  Our Paxil injury lawyers want to make sure that GlaxoSmithKline is held accountable for the pain and suffering inflicted on Paxil birth defect victims.

Legal Help for Victims of Paxil-related ASD or VSD

If you or someone you know used Paxil during pregnancy and gave birth to a child with ASD, VSD or other heart defects, you have valuable legal rights.  Please fill out our online form or call 1-800-LAW-INFO (1-800-529-4636) to discuss your case with an experienced Paxil birth defect lawyer.

The study examined the question of whether a person's response to these anti-depressant medications was dependent on how depressed the patients were before they received treatment for their depression.  All four medications studied are the so-called selective serotonin reuptake inhibitors—commonly known as SSRIs—and were specifically Eli Lilly and Company’s Prozac, which is also known as fluoxetine; Wyeth's Effexor, which is also called venlafaxine; GlaxoSmithKline's Paxil, which goes by both Seroxat and paroxetine; and Bristol-Myers Squibb Company’s drug Serzone, which is also called nefazodone.  Bristol-Meyer’s Serzone is no longer marketed in the United States.

The research group discovered that when compared with placebo, these new-generation SSRI antidepressant medications did not provide any measurable, clinically significant improvements in depression in those patients who initially suffered from moderate or even very severe depression.  The study did reveal, though, that the most significant benefits occurred only in the very severely of depressed patients.  "Drug-placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients.  The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication," the researchers wrote.

As part of their study, the researchers also obtained data on all of the clinical trials submitted to the U.S. Food and Drug Administration (FDA) for the licensing of the four antidepressant SSRI drugs.  "Although patients get better when they take antidepressants, they also get better when they take a placebo, and the difference in improvement is not very great.  This means that depressed people can improve without chemical treatments," Kirsch said in a statement concerning the findings of the study.  But, Mary Ann Rhyne, a spokeswoman for Paxil maker GlaxoSmithKline, argued that the study only looked at data submitted prior to the drug's U.S. approval.  "The authors have failed to acknowledge the very positive benefit these treatments have provided to patients and their families who are dealing with depression and they are at odds with what has been seen in actual clinical practice," Rhyne said.  "This analysis has only examined a small subset of the total data available, while regulatory bodies around the world have conducted extensive reviews and evaluations of all of the data available," she added.

Doug Petkus, a spokesman for Wyeth, the maker of Effexor, said he had not yet seen the recent study and could not comment on its contents.

They are being advised to discuss the situation with their doctor due to potential life-threatening risks to their babies.
Equally important is the fact that patients taking SSRIs should not stop taking them without first consulting their doctors, as abrupt termination of these medications can cause them to experience serious side effects.

According to the advisory: “Generally, SSRI treatment should only be continued if the benefits to the individual patient are thought to outweigh the risks to the unborn child, while also considering the benefits and risks of switching to another treatment option or stopping treatment altogether.”

SSRIs and other newer antidepressants prescribed for the treatment of depression include the following drugs: Wellbutrin (bupropion), Celexa (citalopram), Cipralex (escitalopram), Prozac (fluoxetine), Luvox (fluvoxamine), Remeron (mirtazapine), Paxil (paroxetine), Zoloft (sertraline) and Effexor (venlafaxine), and Zyban (bupropion) for smoking cessation.

A recent study published in the New England Journal of Medicine suggests that “use of SSRIs during the second half of pregnancy may be associated with a serious condition called persistent pulmonary hypertension of the newborn.”

Newborns with this rare but life-threatening condition do not receive enough oxygen in the blood and require intensive-care treatment to survive.

According to the study, babies born with this condition were six times more likely than healthy babies to have been exposed to SSRIs. This information is still considered to be preliminary.

Numerous reports in Canada and abroad have already indicated that some children exposed to SSRIs and other newer antidepressants during pregnancy may develop serious complications at birth.

“An increase in the overall risk of major birth defects has also been associated with SSRI use.”

Health Canada intends to “vigilantly” monitor the situation and issue additional advisories “if new concerns arise.”

Health Canada advisories on other SSRI-related complications in newborns are available on the Health Canada website (see August 9, 2004, October 6, 2005 and December 22, 2005).

Health Canada stresses that: “Managing the adverse reactions of marketed health products depends on the active participation of both healthcare professionals and consumers in reporting these reactions. The spontaneous reporting of adverse reactions generally underestimates the risks associated with the use of marketed health products.”

To report a suspected adverse reaction to SSRIs or other newer antidepressants, please contact the Canadian Adverse Drug Reaction Monitoring Program (CADRMP) of Health Canada by one of the following methods:

Telephone: 866-234-2345; Facsimile: 866-678-6789; CADRMP, Marketed Health Products Directorate, Health Protection Building, Tunney’s Pasture, AL 0701C; Email: cadrmp@hc-sc.gc.ca

Consumers requiring more information about this advisory can contact the Health Canada public inquiries line at (613) 957-2991, or toll free at 1-866-225-0709.

• Wellbutrin (bupropion)
• Celexa (citalopram)
• Cipralex (escitalopram)
• Prozac (fluoxetine)
• Luvox (fluvoxamine)
• Remeron (mirtazapine)
• Paxil (paroxetine)
• Zoloft (sertraline)
• Effexor (venlafaxine)
• Zyban (bupropion) for smoking cessation

Injured by Paxil?