By Aaron Reiss
By Angelica Leicht
By Dianna Wray
By Aaron Reiss
By Camilo Smith
By Craig Malisow
By Jeff Balke
By Angelica Leicht
Dark blue splotches stained Lisa Collins's newborn son's mouth as if he'd gotten messy with a lollipop.
Mom scrubbed Baby clean in the bathtub, but the blemishes would not go away.
The discoloration soon spread to Chase's tiny fingernail beds -- the sign doctors had warned about.
Midway through her pregnancy, doctors told the 27-year-old Friendswood resident to expect complications.
The same ultrasound that revealed she was having a boy also showed the fetus was missing part of his heart. A more detailed X-ray image taken a week later revealed an underdeveloped heart chamber.
Doctors predicted Chase would require surgery within two weeks after delivery, if he survived that long.
Nobody could explain why the baby had congenital heart defects. Neither the mother's nor the father's family had any history with such problems.
Months later Collins caught a TV news segment warning pregnant women against using antidepressants. Studies showed they may cause birth defects in developing fetuses.
Collins doesn't suffer from severe depression or any other mental illness. But six months before becoming pregnant, she complained to her general practitioner in Pearland of irritable bowel syndrome and at times feeling claustrophobic.
After becoming pregnant, Collins asked Snell if she should stop.
"She assured me it was perfectly safe," the mom says. "I trusted my doctor."
Collins popped the oval-shaped pills through the end of her first trimester.
On November 2, 2005, Collins had a cesarean delivery at St. Luke's Hospital. Nurses immediately rushed the baby to the neonatal intensive care unit. For two weeks Chase was hooked to a ventilator and fed through a tube.
"I was tripping over cords trying to hold my baby," Collins recalls.
Able to breathe on his own, he was allowed to go home.
Here he was, nearly three months old, doing fine. A happy, alert infant with a mop of black hair, he ate slowly but rarely fussed and already slept through the night.
Mom held out hope that the doctors were wrong.
Then Baby turned blue.
In March Collins sued GlaxoSmithKline, the pharmaceutical giant that manufactures Paxil. The suit alleges the London-based company concealed studies and manipulated statistics that revealed the drug's risks for pregnant women.
"We cannot discuss pending litigation around our products," says GlaxoSmithKline spokeswoman Gaile Renegar.
Snell is also named in the suit. The 35-year-old general practitioner, currently on sabbatical after giving birth to her own child, contends she did not know about the hazards until the U.S. Food and Drug Administration's advisory late last year.
Since December 2005, the FDA has issued three public health advisories concerning Paxil and the threat of congenital heart defects. The regulatory agency changed Paxil's pregnancy category from C to D, which indicates that there is "positive evidence of fetal risk."
In addition to heart defects, several medical studies published in the last year have shown antidepressants taken during pregnancy significantly increase the risk of potentially fatal lung conditions and abdominal wall defects in newborns.
The FDA has not approved Paxil or other similar drugs for pregnant women, though they are commonly prescribed to treat depression. More than 40,000 pregnant women in the United States take antidepressants, according to the American Medical Association.
Though it remains too early to know how many families may be affected, the potential result is a new generation of deformed children and guilt-ridden mothers not seen since the thousands of thalidomide babies born in the early '60s.
Antidepressants such as Paxil were widely touted as wonder drugs with no serious side effects when they entered the market nearly two decades ago. "Sunshine in a bottle," proponents called them. They have since become increasingly controversial, prompting thousands of lawsuits.
These suits have fallen into two main camps. One alleges the drugs are addictive and can produce severe withdrawal symptoms including hallucinations, extreme mania and electric-shock sensations. The other claims they may actually cause depression and trigger suicidal and homicidal behavior.
Collins's case is among the first of its kind and marks the start of a new trend in litigation against antidepressant makers.
Dallas-area residents Anthony and Matilda Vasquez have filed the only other similar lawsuit in Texas. Their two-year-old son, Adrian, has undergone three open-heart surgeries and has a pacemaker. The mom took Paxil during her entire pregnancy.
These cases may attract international attention; the Collins suit is the first in the country to already have a trial date, set for next summer.
The FDA approved Paxil to treat depression in 1992 as part of a new class of antidepressants called selective serotonin reuptake inhibitors, or SSRIs.
It has long been believed that SSRIs work by boosting serotonin levels, the brain chemical most closely associated with depression. Drug makers and several leading scientists say this helps normalize cell-to-cell communication in the brain, stabilizing the chemical imbalance thought to cause depression.
Recent studies cast doubt on this theory, suggesting that scientists have never understood the drugs' effects on the brain.
A growing number of medical researchers say while increasing serotonin retention, SSRIs also indirectly inhibit the neurotransmitter dopamine, causing a chemical imbalance in some users. This has been linked to serious side effects such as akathisia, a severe inner restlessness associated with violent behavior.
Illegal hallucinogens such as ecstasy, LSD and PCP similarly increase serotonin levels and decrease serotonin metabolism.
SSRIs were considered a vast improvement over previous generations of antidepressants, developed in the '50s and '70s, which were found to elevate moods but later deemed acutely toxic with a high risk of overdose.
The first SSRI introduced in the United States was Eli Lilly's Prozac in 1988. Its immediate popularity led to a host of brand-name imitators, from Paxil to Pfizer's Zoloft, Forest Laboratories' Celexa, Solvay Pharmaceuticals' Luvox, Wyeth Pharmaceuticals' Effexor and many others.
All are marketed to treat a range of mental illnesses, including severe depression, post-traumatic stress disorder, social anxiety and obsessive-compulsive disorder. Doctors prescribe them for everything from eating disorders to bed wetting, low self-esteem, nail biting and shyness.
More than 20 million Americans take antidepressants. Last year doctors dispensed 150 million prescriptions in the United States, according to IMS Health, a Connecticut-based health care information company. As much as 70 percent of the drugs are prescribed not by psychiatrists but by general practitioners with no special training in complex mental disorders.
The overall market for antidepressants in the United States exceeds $12.5 billion annually. Sales of Paxil earn GlaxoSmithKline $3 billion a year worldwide.
The debate over SSRIs has raged for 20 years. Drug companies and countless patients who swear by them have been quick to dismiss any suggestion that they may be harmful. Then there are doctors and attorneys who blame the drugs for virtually every seemingly unexplainable violent rampage.
Harvard Medical School psychiatrists were the first to identify a link between SSRIs and aggressive behavior, reporting in 1990 that six adults experienced "intense, violent suicidal preoccupation" within a couple of months of starting Prozac.
An FDA panel dismissed the study. It took 15 years for the agency -- which some criticize as more lapdog than watchdog -- to change its thinking.
FDA drug-safety analyst Andrew Mosholder in 2003 discovered several suicide attempts reported in Paxil trials under the euphemistic heading "emotional liability." Mosholder conducted his own analysis of Paxil and other antidepressants. He found they doubled the risk of suicidal thoughts or behavior in children and adolescents compared to a placebo. Several trials further showed they performed no better than a sugar pill.
The FDA blocked Mosholder from going public, claiming that his study had not been finalized. But his findings were soon leaked to the media.
Based on these revelations, the FDA in the summer of 2003 issued a public health advisory warning that Paxil and other SSRIs may worsen depression and cause suicidal tendencies in kids under 18.
In June 2004, New York Attorney General Eliot Spitzer sued GlaxoSmithKline for allegedly burying studies showing Paxil increased suicidal thoughts and behavior in kids. Central to the case was an internal GlaxoSmithKline document showing the company intended to "manage the dissemination of data in order to minimize any potential negative commercial impact." GlaxoSmithKline denied the charges but settled the suit in August 2004 for $2.5 million and agreed to post its clinical results on the Web.
Later that year the FDA required all antidepressants to carry a black box warning on labels, the agency's strongest kind, to warn of suicide risk in children. Then in May 2006, GlaxoSmithKline issued a statement warning doctors of a heightened risk of suicide in young adults, ages 18 through 30. It marked the first study released by a drug company that showed a connection between antidepressants and suicidal behavior.
This debate has been argued in scores of lawsuits since the late '80s, when Prozac hit the market. Antidepressants have been blamed for prompting the Columbine shootings and countless other killing sprees.
Many of these suits were resolved in 11th-hour settlements, enabling drug companies to avoid the publicity of going to court and nix the risk of confronting a guilty verdict.
One high-profile case pitted the family of Joseph Westbecker against Eli Lilly, claiming the Kentucky man's four-week use of Prozac in 1989 led him to kill eight people. Lilly won the case. But it was later discovered that the drug company doled out huge settlements to all the attack survivors and their attorneys. The judge later changed the official record from a jury verdict in Lilly's favor to dismissal of a settled case.
In 2001 relatives of Donald Schell sued GlaxoSmithKline, claiming the Wyoming man's 48-hour use of Paxil in 1998 led him to kill his wife, daughter and nine-month-old granddaughter. The jury found Paxil was a "substantial factor" and ordered the drug company to pay $6.5 million to surviving relatives. It marked the first and only case won by a plaintiff.
Houston trial lawyer Andy Vickery represented the Schell family. He enjoys a national reputation as the lone attorney to stick it to GlaxoSmithKline on the suicide issue.
Vickery and associate Paul Waldner already have consulted with about 70 women who are convinced that taking Paxil during pregnancy caused serious birth defects.
The most commonly reported malformations have been atrial and ventricular septal defects. These are holes in the membrane that separates the chambers of the heart, and often can be surgically repaired.
Vickery and Waldner are in the preliminary stages of filing several lawsuits against GlaxoSmithKline. They are selecting the most extreme and unique cases, all of which required multiple surgeries. In one instance, a baby was born without heart chambers. In another, the aorta and pulmonary artery were conjoined as one vessel.
Vickery points to revelations that GlaxoSmithKline selectively used clinical trial data to play down the risks of violent behavior in Paxil users. He predicts similar information will emerge regarding the dangers to fetuses.
"We gained access to a lot of GlaxoSmithKline documents that are not in the public domain," says Vickery, whose firm is devoted entirely to antidepressant cases. "We're not some wild-eyed crazy lawyers blowing smoke."
Vickery says the first claim linking Paxil with heart defects in fetuses appeared in a 1998 report filed in the FDA's "adverse effects" database.
In 2003 GlaxoSmithKline began the first major study on the subject, performing a retrospective analysis of pregnant women, dating back to 1995, who had taken antidepressants in the first trimester and had given birth to children with major congenital malformations. The analysis showed a more than twofold increase in women taking Paxil compared to other antidepressants.
At about the same time researchers analyzed data from Sweden's birth registry, which collects information on pregnant women and offspring, and found birth defects were twice as common among Paxil users.
Based on these studies, the FDA changed Paxil's labeling.
Meanwhile, new reports continued to surface showing a wider array of health risks for pregnant women taking Paxil and similar antidepressants.
A 2005 study published in The Teratology Society reported women who took Paxil were more likely to have infants with birth defects such as omphalocele, in which the intestines or other abdominal organs protrude from the navel, and craniosynostosis, the early closing of one or more of the sutures of an infant's head, resulting in malformation of the skull as well as mental retardation and blindness.
A February 2006 study published in The Archives of Pediatrics & Adolescent Medicine examined 60 newborns exposed in utero to SSRIs. Of these, 18 showed mild to severe signs of "neonatal abstinence syndrome," or withdrawal from the drugs at birth. Symptoms included tremors, high-pitched crying and feeding difficulties.
One week later a study published in The New England Journal of Medicine showed taking antidepressants such as Paxil after 20 weeks of pregnancy greatly increases the risk of having a baby born with persistent pulmonary hypertension. As much as 20 percent of babies born with the disease die soon after birth, while others will have developmental delays, hearing loss and brain abnormalities.
And a report last month in the Archives of General Psychiatry found that babies born to women who took SSRIs during pregnancy face an increased risk of having a low birth weight and developing respiratory distress.
These studies and several others still awaiting publication would seem to offer ample proof that SSRIs and pregnancy should not mix. But many doctors remain unconvinced.
Chambers led a study ten years ago showing neonatal problems in infants born to mothers using SSRIS but says the risks were not statistically significant compared to the general population. Chambers and many others say the sample sizes in most studies have been too small to be considered definitive.
They face the difficult task of proving the antidepressants caused the deformations in much the same way attorneys had to show the drugs and not the depression were causing violent behavior.
Renegar, the GlaxoSmithKline spokeswoman, is quick to point out that congenital heart defects affect 3 percent of the general population and often have no discernible cause.
Kwok believes there will be strength in numbers.
"The drug company's not going to be able to deny causation," he says, "when I have 100 babies lined up with the same problem."
So what's a depressed woman in her childbearing years to do?
Doctors remain divided on this question, since depression during pregnancy carries its own risks. Several studies have linked the illness to higher rates of miscarriage, stillbirths, premature deliveries and developmental delays.
"Someone who is severely depressed, who is not getting out of bed, not eating, not tending to prenatal care -- I'm going to medicate her," says Dr. Margaret Spinelli, director of the Maternal Mental Health Program at the New York State Psychiatric Institute.
But Spinelli and others say they may be more inclined to prescribe tricyclics, a previous generation of antidepressants developed in the '70s not found to cause birth defects.
Psychiatrist and author Peter Breggin, a longtime critic of SSRIs, says it's hard to get unbiased information about treatment options for depressed pregnant women because of what he perceives as the incestuous relationship between drug companies and the FDA.
In the '60s the FDA won praise for rejecting approval of thalidomide, a sedative marketed to pregnant women that became infamous for producing birth defects such as flipperlike arms. But that was a different agency, he says, from the one that took 15 years to succumb to evidence of a suicide risk in SSRIs.
In fiscal year 2004 the FDA collected some $250 million from drug companies, nearly half its drug-review budget. At the federal level, congressional committees and the Government Accountability Office recently have criticized the agency for failing to scrutinize drug safety. This summer the FDA announced plans to write new guidelines specifying when scientists and doctors serving on advisory panels should be disqualified because of conflicts of interest.
Further complicating the issue are recent revelations that several doctors considered opinion leaders on the risks of antidepressants have financial ties to drug companies.
In July, The Wall Street Journalrevealed that a study published in the Journal of the American Medical Association, which warned that pregnant women who stop taking SSRIs are more likely to relapse into depression, was created by authors paid as consultants and lecturers by makers of antidepressants.
According to Breggin, it should come as no surprise that SSRIs are harmful to fetuses, since the drugs cross the placenta barrier and even enter the breast milk. Paxil, he says, is particularly toxic.
"The drug should not be given to pregnant women, period," Breggin says. "The fetus is bathed in Paxil. The developing brain and the developing lungs are growing in response to the drug, and that can't be good."
A faint, thin scar extends from the base of Chase's neck to his bellybutton, covering one quarter of his pale little body.
On January 27, 2006, three days after his nail beds turned blue, Chase underwent open-heart surgery at Texas Children's Hospital. The operation went as well as could be expected.
Two weeks later he unleashed a hair-raising scream from his crib unlike anything his mother had ever heard.
Chase had suffered three consecutive strokes due to a blood clot caused by the operation, a cardiologist later discovered.
Following the strokes, seizures gripped his body, causing his eyes to roll back and his head and limbs to fold forward and convulse. He has since experienced seizures on a near-daily basis.
The surgery saved his life. But it changed him.
Blame it on the stroke, the half-dozen medications he takes daily or a combination of the two, but Chase today often appears catatonic. His facial features drag; his motor skills are delayed, his breathing labored.
Doctors warn he will need repeated heart surgeries. He may one day require artificial replacement valves and a heart transplant.
He is examined monthly by a cardiologist, a hematologist and physical and occupational therapists. He has been rushed to the ER ten times in nine months.
Lisa Collins quit her job as an office manager to take care of Chase full-time. She and the child's father, 29-year-old Radford Steele, agree that stress over the baby dissolved their five-year relationship.
Last month Collins moved in with her grandparents across from Friendswood High School. A poster hangs in the kitchen, demonstrating how to perform CPR on an infant.
Collins has warned other pregnant women against using Paxil. Since she began publicizing her experiences, several Houston-area women have come out of the woodwork with similar stories and are now working to file their own suits against GlaxoSmithKline.
Cassandra Burdick, a 41-year-old Galveston resident and taxi driver, took Paxil during her first trimester to help level out her mood. Burdick's doctor assured there was no risk involved. Last June she delivered a boy with no pulmonary artery, among other deformities. Never allowed to leave the hospital, Nicholas died two months later.
"Tubes," she says. "That's all he knew his whole life was tubes."
Despite their better judgment, Collins, Burdick and others hold themselves responsible.
"My baby was cut from top to bottom," Collins says, "and I may have taken something that caused him to go through all of this."