Teen SSRI Suicide

 

By ANNA WILDE MATHEWS

May 25, 2004

WASHINGTON -- Last December, drug-safety analyst Andrew Mosholder delivered a blunt message to his colleagues at the Food and

Drug Administration: Young people taking antidepressants were more likely to become suicidal.

That conclusion, based on Dr. Mosholder's analysis of clinical trials comparing youths who took the drugs with those who took a
placebo, set off a still-raging debate over whether the benefits of antidepressants outweigh the risks for children and teens. It's a
question of keen interest for the pharmaceutical industry and for American families, since the drugs are prescribed to millions of young
people.

Dr. Mosholder's bosses criticized his findings as premature and based on unreliable data. They barred him from reporting his
conclusion to an FDA advisory committee that met in February. Above all, they didn't want to drive people away from the medications
"when we weren't sure that was the right thing to do, and it may be the wrong thing to do," says Robert Temple, associate director for
medical policy in the FDA's drug-evaluation center.

The clash illustrates the FDA's challenge in balancing the need for prompt warnings about potential side effects from drugs against the
risk of discouraging the use of helpful medicine. Although critics have accused the FDA of a cover-up to protect a lucrative market for
drug makers, the events suggest a more complex situation, in which the agency took the initiative in uncovering much of the data but
hesitated to make a declaration that was sure to alarm many patients and doctors.

Antidepressants and suicide are particularly tough to analyze because it's hard to tease out whether suicide is a side effect or a
consequence of depression itself. Even defining a "suicidal event" -- crucial to figuring out whether an antidepressant induces suicidal
behavior -- is subjective.

In a rare glimpse of the FDA's struggle, a series of internal e-mails reviewed by The Wall Street Journal shows how one of Dr.
Mosholder's superiors was worried he would condemn the drugs too strongly before the advisory committee. Unlike most FDA
deliberations, the committee meetings are public. The superior, Anne Trontell, deputy director of the drug-safety office, sent Dr.
Mosholder a list of questions for which she wanted him to prepare and advised him "to acknowledge the limitations of your analyses."
She also offered to "provide guidance on how to finesse the likelihood of a shouting match at the table."

The FDA's handling of Dr. Mosholder's conclusions is drawing fire from Capitol Hill, and committees in both the House and Senate are
investigating. "You don't just ask someone to clam up," says Iowa Republican Charles Grassley, chairman of the Senate Finance
Committee. "If there's any doubt, they ought to put out the caution to the public at large, not try to muzzle it."

Mr. Grassley says his investigators are looking at other possible instances where FDA drug safety officials weren't allowed to make
their conclusions public. The investigators are interviewing Dr. Mosholder, who has hired a lawyer.