Big Pharma hides unfavorable drug studies

Nearly one-third of antidepressant drug studies unpublished

A January 2008 study published in the New England Journal of Medicine reveals that nearly one-third of studies conducted on antidepressant drugs are not published. Nearly all of the unpublished studies show that the drugs being tested didn’t work. In addition, some of the studies on antidepressants that were published spun unfavorable results to make the drugs appear more effective than they really were.

The United States Food and Drug Administration (FDA) does not require companies to publish all data on clinical trials or to make those trials publicly available. However, “[s]elective publication can lead doctors to make inappropriate prescribing decisions that may not be in the best interest of their patients and, thus, the public health,” wrote the authors of the study.

The report focused on 74 studies conducted on 12 antidepressants. Thirty-eight of the studies had favorable results, all but one of which were published. But there were 36 studies that had negative or questionable results, and only three of those studies were published. An additional 11 studies with negative or questionable results were published, but were written as if there were positive results.

“Not only were positive results more likely to be published, but studies that were not positive, in our opinion, were often published in a way that conveyed a positive outcome,” wrote the authors.

For example, GlaxoSmithKline’s (GSK) antidepressant Paxil had seven negative studies, five of which were never published. In addition, GSK’s Wellbutrin had three studies, two of which were negative and never published.

Pfizer also had five studies conducted on its drug Zoloft, but three studies that showed the ineffectiveness of the drug were not published. A fourth questionable study was written and published to make it look like the drug worked.

The study is significant because allowing companies to publish only positive studies of antidepressants may allow them to make inflated claims about the efficacy of the drugs, thus making it virtually impossible for doctors and patients to know how effective or ineffective the drugs are. It can also hide data on side effects of drugs.

Dr. Thomas P. Laughren, director of the division of psychiatry products at the FDA, said the agency has known favorable studies are more likely to be published for a long time.

“It’s a problem we’ve been struggling with for years,” Laughren said.

Sources: Benedict Carey, “Antidepressant studies unpublished,” New York Times, January 17, 2008; Gene Emery, “Unfavorable drug studies don’t get into print: report,” Reuters.com, January 17, 2008; “Pharma companies hid antidepressant data,” Furious Seasons, January 17, 2008.

Antidepressant suicidiality warnings haven’t eliminated availability to youths

Rapid growth in antidepressant use curbed

On January 7, 2008, United States researchers said severe warnings of suicidiality in young persons taking antidepressants have curbed these drugs’ rapid increase in growth, however access to the drugs for youths seeking treatment has not been eliminated. Antidepressant use had been growing at a rate of 36 percent per year before warnings were first issued in 2003, but the growth rate has flattened since that time.

Some mental health professionals feared the warnings, which apply to children ages 6 to 17, would limit youth access to the medications. And some doctors have interpreted a spike in suicide rates in 2004 as being tied to a decline in the use of antidepressants among children.

Antidepressants are used to treat depression, the leading cause of suicide. But regulators issued warnings on use of the drugs after trials showed they could actually increase the risk of suicidal thoughts and behaviors in youth.

The Food and Drug Administration (FDA) issued a “black box” warning, the agency’s strongest, to highlight the risk associated with the drugs. This caused some to fear the medications wouldn’t be as available for the youth who use them, but the most recent study found this was not the case.

“What we found is the FDA warnings had a relatively moderate and targeted effect in slowing the growth of antidepressant use by children,” said Dr. Mark Offson of Columbia Medical Center. The FDA plans to continue to monitor youth suicide rates.

Source: Julie Steenhuysen, “Effect of antidepressant warnings moderate-US study,” Reuters, January 7, 2008.

FDA determines exposure to Paxil during the first trimester of pregnancy increases the risk of congenital malformations in infants

Particularly cardiac malformations

The FDA issued a Public Health Advisory today about Paxil (paroxetine), the prescription anti-depressant. The agency has determined that exposure to Paxil in the first trimester of pregnancy may increase the risk of congenital malformations in infants, particularly cardiac malformations.

Preliminary analysis of two unpublished studies bore this conclusion out. In a study using national registry data from Sweden, women who received Paxil in early pregnancy has an approximately two-fold increased risk for birthing an infant with a cardiac defect compared to the regular population. In a separate study of U.S. insurance claims data, infants of women on Paxil had a 1.5 times greater chance for cardiac malformations and a 1.8 times greater chance for congenital malfunctions in general. Paxil is manufactured by drugmaking giant GlaxoSmithKline plc.

The cardiac defects observed in these studies were atrial or ventricular septal defects, conditions in which the wall between the right and left sides of the heart is not completely developed. Septal defects are one of the most common type of congenital malformations. They range from those that are symptomatic and may require surgery to those that are asymptomatic and may resolve on their own.

Source: FDA Release, December 8, 2005.

Paxil birth defect lawsuit filed in South Carolina

No Paxil recall filed over birth defects

A South Carolina couple is filing a lawsuit against the maker of Paxil claiming that the drug caused their daughter’s birth defect. Paxil’s manufacturer, GlaxoSmithKline, has faced several thousand Paxil lawsuits in the United States since the drug’s introduction in 1992.

In 2000, Taylor Dismuke was born with a heart malformation that required open heart surgery during her first week of life. The birth defect will affect her for a lifetime, as doctors say she will require more surgeries as she grows and powerful prescription drug therapy that will prevent her from ever having children.

Shannon and Kimberly Dismuke did not realize their daughter Taylor’s heart defect could be the result of Kimberly taking Paxil while pregnant. The Dismukes claim they were never told that the anti-depressant Paxil can cause birth defects in pregnant women. During her pregnancy, Kimberly discontinued a heart medication but continued taking Paxil.

“When we found out she was pregnant,” Shannon Dismuke said, “she was on several medications”¦ one thing we did ask was do we need to stay on [Paxil] and we were told yes.”

In September 2005, GlaxoSmithKline released the results of a survey that found an increased risk for pregnant women on Paxil to have children born with heart malformations. The Dismuke’s personal injury attorney says that since neither parent has a family history of birth defects, he believes Taylor’s heart malformation was directly related to Paxil. The case is expected to go to trial sometime in 2007 in Greenville, SC.

Though most Paxil product liability lawsuits assert that people who took the drug were not sufficiently warned in advance of its side effects, GlaxoSmithKline has not issued a Paxil recall.

Source: Angela May, “First South Carolina Paxil Lawsuit,” ABC 4 News, Charleston, SC, December 28, 2006, accessed January 4, 2007.

Study sponsored by Paxil maker suggests that women taking Paxil are twice as likely to bear children with birth defects; FDA issues warning

The U.S. Food and Drug Administration issued a warning September 28, 2005, to pregnant women taking Paxil that they may be twice as likely as other women to bear children with birth defects. A study sponsored by Paxil’s manufacturer, GlaxoSmithKline, suggests that the children of women taking Paxil, especially during the first trimester of their pregnancy, were twice as likely to have birth defects. The prevalence of birth defects in this group was 4 percent, or 43.6% per 1000 births.

The most common birth defect suffered by children born to women taking Paxil were ventricular septal defects, where one or more holes are present in the muscular wall separating the right and left ventricles of the heart. The overall rate of heart birth defects in the general population is about 1 percent.

GlaxoSmithKline has said it will send a letter to physicians alerting them to their findings. Paxil already has a pregnancy precaution, belonging to the Category C of prescription drug warnings, meaning that comprehensive studies evaluating the drug’s effect on unborn fetuses have not been done. Citing another survey of births, GSK says it does not note a comparable increase among users of other anti-depressants, but will not admit a causal link between their drug and birth defects.

Source: “Study hints at Paxil tie to birth defects,” Associated Press, September 27, 2005; Amanda Gardner, “New Warning Issued on Paxil,” HealthDay News, September 28, 2005.

Antidepressants linked to low birth weights

Babies born to mothers on antidepressants at risk for low birth weights and respiratory distress

A study by researchers at the University of British Columbia in Vancouver has uncovered a higher risk for low birth weight and respiratory distress in infants born to mothers on SSRI antidepressants.

SSRIs, or selective serotonin reuptake inhibitors, work by preventing the reuptake, or re-absorption, or serotonin in the brain. Serotonin is considered a key ingredient in the chemical mix that affects mood levels. Dr. Tim F. Oberlander and colleagues examined population health data for nearly 120,000 live births between 1998 and 2001, of which 14 percent of children were born to mothers diagnosed with depression.

Researchers compared neonatal outcomes of 1451 children born to mothers diagnosed with depression and treated with SSRI medications to 14,234 children of mothers also diagnosed with depression but not treated with SSRIs. Children whose mothers took SSRIs suffered a 13.9 percent rate of respiratory distress, which is significantly greater than the 7.8 percent experienced by the children of mothers who did not take the drugs. In addition, infants whose mothers were on SSRIs experienced longer hospital stays, lower birth weights, and earlier gestational age. A larger proportion of babies born to mothers on SSRIs were born before 37 weeks.

“Our study may add another cautionary note to the use of SSRI medications during pregnancy,” Dr. Oberlander said, explaining that the study’s findings are contrary to an expectation that treating mothers for their depression would help lessen the adverse neonatal consequences associated with maternal depression, such as poorer cognitive performance, behavioral problems that can extend into adolescence, lower IQ scores, and disorders such as attention deficit/hyperactivity disorder (ADHD).

Sources: David Douglas, “Antidepressants during pregnancy may affect baby,” Reuters Health, August 25, 2006; Canadian Pediatric Society, “Maternal depression and child development,” Pediatrics & Child Health 9 (October 2004).

Lawsuit filed against Paxil maker

Child born with heart defects

No parent wants to hear the news that their child suffers severe birth defects. Lisa Collins Steele’s nine-month-old son, Chase, was born with half a heart. Since his birth, Chase has had to undergo one open heart surgery, a dozen emergency trips to the hospital for care, and is currently on life support. Ms. Steele now faces hundreds of thousands of dollars in medical bills that may never end. She believes her son’s suffering could have been prevented if she had been warned not to continue taking the anti-depressant Paxil while she was pregnant.

Ms. Steele has filed a lawsuit against GlaxoSmithKline and her physician, alleging product liability and negligence in her case.

Ms. Steele stopped taking Paxil a few months before a warning was issued in December 2005 by GlaxoSmithKline and the U.S. Food and Drug Administration that pregnant women taking Paxil faced a higher risk of their children being born with birth defects, especially cardiovascular defects. According to Ms. Steele’s personal injury attorney, if Ms. Steele had been aware of this risk, she would not have taken Paxil.

According to the attorney representing Ms. Steele, there may be as many as 50 additional personal injury cases being reviewed for potential litigation against GlaxoSmithKline involving similar defects in children born to women who took Paxil during their pregnancy.

Source: Chau Nguyen, “Litigation against Paxil begins,” KHOU.com, August 2, 2006.