'People Have a Right to Know'

The Woodwards will never know for sure if their daughter committed suicide last year because of an adverse reaction to an antidepressant. But Tom Woodward is convinced that if he had known then about the increased risk of suicide in some young patients, it could have saved their 17-year-old's life. "If we had been given that information in advance, I know Julie would still be here," he says.

Julie Woodward took her life in the summer of 2003. When her parents--and others whose children had killed themselves after starting to take antidepressants--began raising questions about the deaths, their concerns helped to prompt the Food and Drug Administration (FDA) to re-examine pharmaceutical companies' clinical trial data on antidepressants and adolescents this year. It found that, overall, children using antidepressants were nearly twice as likely to have suicidal tendencies than depressed children taking placebos. The agency announced this month that the risk was sufficient to require a "black box" warning label on all antidepressants. A black-box label is the government's strongest measure short of banning the drugs. The warning label describes the increased risk of suicidal thoughts and behavior in children and adolescents on antidepressant medications and notes what uses the drugs have been approved or not approved for in these patients (Prozac is currently the only medication approved to treat depression in children and adolescents.) The FDA is also developing a patient medication guide listing the risks and precautions that will be distributed by pharmacists to patients taking the drugs.

The next question: do adults on antidepressants face similar risks? On that, the jury's still out. "The child's brain is at a different developmental stage than an adult's, so you expect a different response in antidepressants, whether it's less improvement or worse or different side effects," says Dr. Wayne K. Goodman, who chaired the joint meeting of two federal advisory panels that called for the black-box warnings for children and teenagers. "But what's to say that there is something magic about being 18 versus 19 years old? What is the boundary between a child and an adult?"

That problem was underscored in February when one of the "healthy" adult participants--a 19-year-old bible-school student--hanged herself while enrolled in a clinical trial for Eli Lilly and Company's new antidepressant, Cymbalta. The FDA has since approved Cymbalta to treat depression and diabetes-related pain. Lilly pointed out that the drug, which increases serotonin and norepinephrine levels in the brain, was tested with more than 6,000 depressed adults worldwide, and was found to be "safe and effective" overall in clinical trials. (The company didn't study the safety or efficacy of Cymbalta in children.)

Last month, the FDA announced plans to re-examine clinical trial data for thousands of depressed adults as well to see if there's evidence that any suffered increased suicidal thoughts and behaviors while taking antidepressants. Most of the antidepressant drugs commonly used today--including Prozac, Zoloft, Paxil and Celexa--belong to a group called selective serotonin reuptake inhibitors (or SSRIs). They work by influencing levels of serotonin, the neurotransmitter that helps control moods in the brain. Others, like Serzone and Wellbutrin, target multiple receptors in the brain.

"These are serious medicines and should probably only be prescribed by practitioners willing to do the follow-up with patients and monitor them as closely as they need to be monitored," cautions Dr. Sandra Kweder, deputy director of the Office of New Drugs at the FDA's Center for Drug Evaluation and Research. "The risk isn't large and, by far, these medicines have helped people orders of magnitude beyond the harm they may have done. But no medicine is without risks--none."