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By Katherine Lutz, Globe Correspondent, 8/5/2003
Michelle Van Syckel was one of those teenagers who did everything — played the clarinet and basketball, loved to travel, was an honor-roll student for five years. But, after moving to a new town, Van Syckel had trouble making friends, became irritable, and eventually stopped eating.
Doctors diagnosed her with anorexia and depression, eventually prescribing Paxil, a close relative of Prozac and one of the most popular antidepressants on the market. Rather than improving, though, Van Syckel became suicidal, at one point cutting ”DIE” into her abdomen with a razor.
”I wasn’t always this insane,” Van Syckel wrote in a poem. ”I don’t see an end to this long and winding road. . . . Tomorrow doesn’t look too great but maybe I’ll be happier.”
Now, Van Syckel’s family is suing both her doctors and GlaxoSmithKline, the maker of Paxil, charging that her downward spiral into depression was made dramatically worse by the very medication prescribed to treat it. The case, part of a growing body of evidence linking Paxil to suicidial thoughts and actions in a small percentage of the children who take it, could have far-reaching implications for the treatment of depression in adolescents.
”I never felt helpless prior to Michelle being on medication,” said her mother, Lisa Van Syckel.
GlaxoSmithKline’s head of clinical development and medical affairs, Dr. Alan Metz, said ”we have some evidence” that Paxil is effective in children. Children on Paxil who experience suicidal thoughts ”is a relatively small number of patients,” said Mary Anne Rhyne, a spokeswoman for GlaxoSmithKline. ”We think there is more research that needs to be done.”
But the Van Syckel case and others like it have prompted regulators to act. In June, the US Food and Drug Administration, in an unprecedented decision, recommended that doctors stop prescribing Paxil to new patients under the age of 18 and advised parents to consult a doctor if their children are currently taking Paxil.
Not long before the FDA’s announcement, its British counterpart took a strong stance against Paxil, advising doctors not to prescribe it to children after reviewing clinical trial data of about 1,000 children on the drug who had a 1 1/2 to three times greater risk of having suicidal thoughts. But the FDA is more equivocal, waiting to deliver the final word on Paxil while it reviews the data, leaving parents and doctors agonizing over what to do next.
”This is something we are actively working on,” said an FDA spokesperson. ”Until we finish our review, we won’t have a final decision on this issue.”
But psychiatrists fear the controversy surrounding Paxil could scare families from getting what is sometimes the best possible treatment. ”This just puts families in a difficult spot,” said Dr. William Beardslee, chairman of the department of psychiatry at Children’s Hospital Boston.
Doctors may become more reluctant to prescribe Paxil to children as well, knowing that it could cost them personally if something goes wrong. A Wyoming family won a $6.4 million dollar lawsuit against GlaxoSmithKline in 2000 after a man taking Paxil shot his wife, daughter, and grandaughter. The jury found there was enough scientific evidence to find Paxil primarily responsible for the violence.
”Doctors I know felt more vulnerable [after FDA action],” Beardslee said. ”We’re prescribing medications for a terrible disease and suddenly the approval was withdrawn. It left us as physicians feeling very puzzled. If we can’t trust the FDA, what can we trust? No physician alone has resources to look at all medications. That’s what we have the FDA for.”
The controversy occurs at a time when Paxil has emerged as the drug of choice to treat teenage depression. Although the company says national figures are not available, in Massachusetts, about 1,000 children under MassHealth, the state’s Medicaid insurer for low-income people, are currently taking Paxil, out of about 3,700 children on Zoloft, Paxil, and Prozac.
”It seems like over the last few years I’ve encountered more and more kids coming into our practice that are on Paxil,” said Dr. Bruce Black, director of Comprehensive Psychiatric Associates in Wellesley and a paid speaker for GlaxoSmithKline five years ago. ”I’m sure [the FDA’s decision] is going to put a significant damper on this. It will pretty much shut it down.”
Paxil, a selective serotonin reuptake inhibitor, or SSRI, from the same family as Prozac and Zoloft, works by boosting concentrations in the brain of serotonin, a chemical that is key to mood regulation. Some doctors prefer it over Prozac because the body metabolizes it more quickly.
Paxil was celebrated upon its FDA approval in 1992, like other SSRIs, as the cure-all for depression, a debilitating disease affecting 18.8 million Americans, up to 2.5 percent of children and 8.3 percent of adolescents. It was one of the biggest sellers last year for GlaxoSmithKline with $2.5 billion in sales and the second most commonly prescribed antidepressant in the United States.
But drugs that boost serotonin levels in the brain could actually encourage the behaviors they are supposed to prevent. Soon after Prozac’s approval in 1987, doctors noticed their Prozac patients feeling so uncomfortable they wanted to jump out of their skins. This excessive physical and emotional agitation, called akathisia, some doctors believe could lead some patients to act on suicidal thoughts. In 1991, an FDA advisory panel decided there was no link between antidepressants like Prozac and suicide tendencies in adults.
Dr. Christopher Lamb, director of child psychopharmacology at Cambridge Health Alliance, said these side effects can happen with drugs like Prozac and Paxil early on in treatment or when the dosage is changed, although ”it’s hard to separate what is the side effect and what is just the illness.”
Some psychiatrists, however, say the side effects, while serious, are not reason enough to stop prescribing SSRIs to children.
”Medication can be extremely helpful and even lifesaving for some children,” said Dr. David Fassler, a child and adolescent psychiatrist in Burlington, Vt.
Far from saving Michelle Van Syckel’s life, however, the drug, her family said, nearly killed her. Within days of taking Paxil, Van Syckel felt ”extremely nervous and anxious,” according to court documents. Instead of withdrawing the medication, her doctors increased the dosage and within weeks Van Syckel became confrontational, verbally abusive, and started cutting herself. Her mother said the most striking change in the normally tolerant teenager was her rabid racism, ”calling kids s—s and using the n word.”
Understanding why youths like Van Syckel could be more susceptible to these side effects requires more data, doctors say, but companies rarely conduct clinical trials on children, leaving doctors to guess what drugs work best for young people.
In fact, Prozac is the only antidepressant approved for children, with studies demonstrating its effectiveness in young people. But even without approval, a drug like Paxil can still be prescribed to children. Once the FDA approves a drug for a certain group of patients with particular condition, doctors are free to prescribe it to whomever they feel might benefit, including children and conditions the FDA did not consider.
Parents should not take their children off Paxil or other antidepressants, according to the FDA, since patients can sustain severe withdrawal symptoms if the drugs are stopped abruptly. Psychiatrists have fielded more calls from concerned parents since the announcement, but Black sees this as medical progress.
”This is going to push people to be a little more thoughtful, and that’s a good thing,” Black said.
Doctors eventually took Van Syckel off Paxil. Three years later, her mother said she is almost completely back to normal and will be off to college soon.
But the scars remain. Van Syckel may not remember threatening her mother with an axe or screaming racial slurs, but the cuts on her body will not disappear.
”My advice to parents is, when you take your child to a psychiatrist and their first suggestion to you is, `We’ve got this new medication,’ run for the hills,” said Lisa Van Syckel. ”Because they have no desire to help a child; only to medicate them and get them out of their hair.”
Katherine Lutz can be reached at firstname.lastname@example.org.
This story ran on page D1 of the Boston Globe on 8/5/2003.