Federal health officials are preparing stronger warnings for some antidepressants used in children after new analyses back a possible link to suicide.
Exactly what those warnings will say, and which drugs will be affected, hasn't been settled, according to Food and Drug Administration documents released Friday. The agency will ask its scientific advisers next month for help in deciding.
"While there remains a signal of risk ... for some drugs in some trials, it is important to note that the data are not black-and-white in providing a clear and definitive answer," FDA psychiatric drugs chief Dr. Thomas Laughren wrote the advisory panel this week.
The question is how strong the warnings will be, and whether any of the drugs will come with specific instructions not to use them in children and teenagers.
The controversy erupted last year, when British health authorities declared that most popular antidepressants might sometimes increase the risk of suicidal behavior in children and teenagers. They declared all but one — Prozac — unsuitable for depressed youth, but stopped short of a pediatric ban.
It's difficult to sort out because depression itself can lead to suicide, and studies show antidepressants can help adults recover.
Here, only Prozac is FDA-approved to treat pediatric depression, and a taxpayer-funded study earlier this week showed that Prozac plus talk therapy was more effective for depressed teenagers than either approach alone. The latest FDA analyses don't link Prozac to increased suicidal tendencies.
But while doctors widely prescribe antidepressants for children
which is legal despite the lack of FDA approval — there is little evidence that any other than Prozac work for pediatric depression, thus deepening concern about even potential risks.
The FDA in March urged close monitoring of patients for suicide warning signs, especially when they first start the pills or change a dose. The reason: The drugs may cause agitation, anxiety and hostility in a subset of patients unusually prone to rare side effects.
Now, FDA and Columbia University psychiatric specialists have re-evaluated 25 studies involving more than 4,000 young people and eight antidepressants.
There were no completed suicides. But, when all the results were lumped together, young antidepressant users were about 1.8 times more likely to have suicidal thoughts or behaviors than patients given dummy pills, say analyses released Friday.
Risk varied widely from drug to drug and among studies of the same drug, noted FDA's Dr. Tarek Hammad. Studies of Effexor showed particular risk; its maker warned doctors of those results last year. Also, suicidal tendencies were more common in studies that allowed patients to enroll despite a history of suicide attempt or behavior.
A total of 95 cases were deemed definitive suicidal behavior, noted FDA's Dr. Andrew Mosholder, who has urged the agency since February to discourage pediatric use of antidepressants other than Prozac until the issue is settled.
Because his bosses disagreed with his initial findings, the FDA didn't allow Mosholder to make his argument at its first public hearing on the antidepressant controversy, a move that has generated congressional investigations. The latest analyses validate Mosholder's original research.
Still, psychiatric specialists point to the low number of suicidal patients to say the overall risk appears small — and drugs routinely are used that bear rare but serious side effects.
Roughly 30 percent of patients don't respond to Prozac, said Dr. Darrel A. Regier of the American Psychiatric Association.
"What do you do with those kids, just say tough luck?" he asked. Having no alternative "would be, I think, inappropriate given the very low rates" of the suicide risk.
Instead, Regier favors strong FDA warnings for very close monitoring of depressed youth given the drugs.
But angry parents say at the very least, FDA should use its strongest type of warning — bold print in a black box on the label
to say antidepressants are only for children with the severest depression, and to spell out the suicide risk.
"The FDA is broken," said Jennifer Tierney of Kernersville, N.C., who has led calls for better warnings. "How could anybody sleep at night knowing they allowed the continued use of drugs that have such serious side effects that aren't even effective drugs?"
Tierney describes her daughter Jame as turning from a sweet, popular honor student into a raging loner after being prescribed Effexor for migraines, another unproven use, at age 14. She eventually recovered.