Clinical trials in the news

Tony Spirito on teens' suicide attempts; Kay Dickersin shapes debate on trials registries; Timothy Rivinus on antidepressants and kids

by Wendy Y. Lawton

Tony Spirito, a professor of psychiatry and human behavior at Brown Medical School and associate director of Brown's Center for Alcohol and Addiction Studies, has treated young suicide attempters and conducted research on teen suicide for more than 20 years.

But to say Spirito (left) has written the book on the subject would be wrong. He edited it.

"Evaluating and Treating Adolescent Suicide Attempters: From Research to Practice" is an overview of the feelings, thoughts and behaviors of teens who attempt suicide, one of the leading causes of death in young people. Published last year, the book is used by counselors and clinicians across the country.

The book led to Spirito landing an important behind-the-scenes role in the controversy over antidepressants and kids.

Kelly Posner, a research scientist at Columbia University, needed Spirito's help. The Food and Drug Administration had contracted with Columbia to conduct an independent review of 25 pediatric antidepressant clinical trials. The FDA's own review of these trials showed an alarming link between antidepressant medications and suicidal tendencies in children and teens. When these results were made public, debate over the drugsÕ safety started to swirl.

But what, exactly, are suicidal thoughts and behaviors? There is no hard and fast definition for researchers conducting trials. Without guidelines, researchers might classify some thoughts and actions as suicidal - or disregard others. Yet an accurate, consistent definition is critical. Without one, there is no way to tell whether the drugs being tested are safe.

Spirito agreed to serve on a nine-member expert panel that reviewed all 427 "adverse events" reported during the 25 drug trials in question. These events varied wildly - headaches, scraped knees, head-banging, cut wrists, swallowed pills. Using a classification system developed by Columbia, each panel member rated 125 adverse events. Experts did not know which study the event came from, nor did they know how it had been classified. Three experts reviewed each case.

The results: Of the 427 cases, the panel took issue with 40. Experts identified 26 new cases that were suicide related. Another 12 cases were originally reported as suicidal, but tossed out. And two new cases of self-injury Ð but not suicide attempts Ð were logged.

Bottom line: The panel did not uncover major discrepancies in drug company results. However, those results showed that antidepressants still posed a risk for kids. After an FDA advisory committee reviewed the panelÕs report last month, the agency is now adopting stricter drug warning labels.

Spirito noted that many more children and adolescents improve after taking antidepressants than the handful who get worse. But Spirito said the debate is healthy because it demonstrates the importance of carefully prescribing these medicines and the need for patients to be closely monitored.

"Child psychiatrists, who receive the most training in the use of these medicines, should be following the majority of children taking antidepressants," he said.