Friday, January 30, 2004

Four years ago, Michelle Van Syckel was losing weight and having trouble adjusting to her new school.

Doctors diagnosed the then-14-year-old with depression and prescribed different drugs over the next few months, her mother said. One was Paxil, a widely used antidepressant.

Later that year, though, she said her daughter became violent and attempted suicide. She blames the drug and its manufacturer, GlaxoSmithkline, arguing that such serious side effects can be caused by a group of medicines used by millions of American each year.

"She used knives, scissors, razor blades. Her personality changed," said her mother, Lisa Van Syckel, a Flemington resident, who filed a lawsuit against Glaxo. "You don't go from being an honor-roll student, who gives you hugs, to someone who's violent and thinks you're the devil within a few weeks.

"Glaxo had clinical studies that indicated people can become suicidal on the drugs, but didn't give them to anyone. They should have placed warnings on the label. Instead, they placed my child at risk for financial gain. And I feel betrayed," she said, adding that her daughter is now in college and doing better.

Numerous other lawsuits making similar allegations have been filed against several drug makers that sell antidepressants. Also known as SSRIs -- selective serotonin reuptake inhibitors -- these pills include Pfizer's Zoloft, Eli Lilly's Prozac and Wyeth's Effexor. Last year, the retail market for the drugs was $11.3 billion, according to Verispan, a market research firm.

Concerns have lingered ever since a 1990 study in the American Journal of Psychiatry reported that some patients became suicidal after taking Prozac. But the companies deny a link exists between their drugs and a risk of suicidal thoughts among youngsters.

"There's really no established cause and effect at this point," said Philip Perera, a Glaxo medical director. "What we have, potentially, is a signal that needs to be looked at more carefully. It's a terribly difficult and muddled area to be conclusive about."

The controversy erupted again recently, when U.K. regulators warned doctors not to prescribe the pills, except Prozac, to children under 18. They also pointed to newly disclosed data about Paxil that showed the drug wasn't effective, but could increase the risk of suicide.

On Monday, the issue will undergo further scrutiny when the U.S. Food and Drug Administration holds a meeting to review years of data about antidepressants and any link to suicide. The session won't yield a recommendation, until after a second meeting that is scheduled for the summer.

"We don't think we're in a position to give a definitive answer, but the idea is to let the public know where we are," said Robert Temple, the FDA's director of medical policy, who added that none of the SSRIs have, so far, shown to be effective for children.

The review began because drug makers labeled suicidal thoughts differently in their studies, sometimes citing emotional liability, which is a catch-all term for instability. This made it difficult to determine the extent to which suicide may be a problem, according to Russell Katz, the FDA director of neuropharmacology.

Beyond science and statistics, the highly charged debate is also something of a paradox. Over the years, many other families and their doctors say this same group of pills has saved lives. The medicines are widely used to treat depression, which if untreated, may lead to suicide, in some cases.

"Most of the depressed kids I see have suicidal thoughts to begin with, and these drugs have often been a valuable treatment," said Roy Boorady, an assistant psychiatry professor at the New York University School of Medicine's Child Study Center. "But I think this meeting is a great idea, because it will, hopefully, help us make sense of these recent warnings."

There's little debate that antidepressants are prescribed regularly for children and adolescents. Between 1987 and 1996, such usage tripled, according to a recent study in the Archives of Pediatric and Adolescent Medicine.

This occurred even though the FDA approved only Prozac for anyone younger than 18, and that occurred only two years ago. But doctors are free to prescribe medicines if they believe patients will benefit, a practice known as off-label usage.

Glaxo and other companies, though, never published all of the available clinical-trial data involving depressed children, including studies showing negative results. This means that doctors who prescribed the pills to children did so with incomplete knowledge.

Glaxo's Perera acknowledged not every study was published in a medical journal, because the results may appear inconclusive. But he also maintained that results were not suppressed, because summary findings were circulated at scientific conferences.

"Like it or not, those studies belong to the companies," said Graham Emslie, a psychiatry professor at the University of Texas Southwestern Medical Center, who has conducted several trials for drug makers.

He is also a member of the American College of Neuropsychopharmacology task force, which last week issued a preliminary report saying a link between SSRI's and suicide does not seem to exist. However, the task force also called for drug makers to release all studies.

Meanwhile, Bernard Poussot, a Wyeth executive vice president, said the Madison-based company had no suicides reported in its Effexor studies or side-effect database. In August, Wyeth warned doctors not to prescribe Effexor to anyone under 18.

A Pfizer spokeswoman denied any link between Zoloft and suicide. But a 1998 paper published by Pfizer scientist Roger Lane noted that "all SSRIs have the rare potential to cause akathisia," an agitated state that can sometimes be confused with worsening depression.

"As a result, it's very difficult to see any other reason for a patient's condition," said David Healy, a psychopharmacologist at University of Wales College of Medicine and an industry critic. "The drugs offer no warnings at all. The FDA needs to go into reverse gear."