FDA backs away from antidepressant warning
By Jim Polk
CNN
Wednesday, February 9, 2005 Posted: 8:50 PM EST (0150 GMT)
Change comes to light during murder trial of teen blaming Zoloft
CHARLESTON, South Carolina (CNN) -- The Food and Drug Administration has backed off its warning that antidepressants such as Zoloft, Paxil and Prozac can cause suicidal actions among children and teens taking those prescription drugs.
In a revised warning posted last week on its Web site, the FDA changed the wording to say only that the drugs "increased the risk of suicidal thinking and behavior in short-term studies of adolescents and children" with depression and other psychiatric disorders.
News of the FDA's warning change surfaced Wednesday in testimony in Charleston in the murder trial of 15-year-old Christopher Pittman.
The defense contends Zoloft drove him to kill his grandparents when he was 12.
The FDA has never suggested a link between Zoloft and other such drugs and violence against others -- the issue in the Pittman murder trial.
Dr. Steve Romano, a psychiatrist and a vice president of Pfizer, which makes Zoloft, mentioned the FDA change while testifying about the company's clinical trials for the drug. He was called by the defense in the Pittman case to testify about suicide-related warnings issued in Canada and the United States.
Limiting the warning language to a risk seen in studies, rather than saying the drugs actually could cause suicidal behavior in younger patients, was a significant retreat for the FDA -- and came after several months of lobbying by the pharmaceutical industry.
The agency has never approved Zoloft, Paxil or most similar drugs for use by younger patients with depression.
Even so, many doctors prescribe them for children and teens. Prozac is the only such antidepressant approved to treat depression in children.
The version of the warning that the agency posted on its Web site in October included this sentence: "A causal role for antidepressants in inducing suicidality has been established in pediatric patients."
The latest version omits that sentence.
The sentence was not part of the boldface black box warning placed at the start of the insert that accompanies any prescription, but instead appeared in the first paragraph of a separate section on "Suicide Risk," which appeared just below the black box.
The replacement sentence now appears as the first sentence inside the black box.
That first sentence was broader in the original version: "Antidepressants increase the risk of suicidal thinking and behavior in children." The new version qualifies that by inserting the phrase "in short-term studies."
Romano acknowledged that the wording change was preceded by an extended "dialogue" between his drug company and others and the FDA.
"They had a sentence in there that spoke to a causal link between the actual drugs and the events of suicide, and they took that out," he said.
"There was an increased risk of suicidal behavior and suicidal ideation, which are much more commonly encountered events in patients who are depressed, as you can imagine.
"There was no causal link to suicide established, and the FDA recognized that."
Romano testified that the change was "a big difference."
He was asked whether the new phrase meant that these drugs increase the risk of suicidal behavior.
"I think it means an increased risk was seen, but to what extent it was due to the drug or not is not yet confirmed, and that's why the FDA took out the 'causal' sentence before that," Romano responded.
Romano was referring to an FDA analysis that pooled the results of clinical trials by nine manufacturers and found the risk of suicidal behavior was twice as high for those on the drugs as for those taking placebos.
The FDA said the change was made February 3, after doctors and academics said causation could not be proved in any case; that only increased risk could be.
The Pittman trial was in its eighth day Wednesday and appears likely to spill over into a third week, rather than go to the jury by this weekend, as once predicted.