Sept. 13, 2004 — Children and adolescents taking a range of popular prescription medications for depression appear to be at higher risk for suicide attempts than patients who don’t take the drugs, a pair of FDA analyses have concluded.

The drugs of concern are all newer-generation antidepressants: Prozac, Paxil, Zoloft, Effexor, Celexa, Remeron, Lexapro, Luvox, Serzone, and Wellbutrin. Most are known to affect the brain chemical serotonin. Only Prozac is FDA-approved to treat depression in children.

Overall, these medications may increase the risk of suicidal thoughts or attempts by 2% to 3%, the reviews show.

Officials stress that no completed suicides were recorded in the 23 drug company studies making up the reviews. But they also say that a potentially dangerous elevated risk of childhood suicidal behavior is consistent in seven drugs in the group.

“That’s beyond the risk that occurs with the disease” alone, says Tarek A. Hammad, MD, an FDA senior medical officer who conducted one of the reviews, tells a panel of outside experts advising the agency.

Hammad’s analysis showed children with a variety of disorders who used some of these drugs, including Zoloft, Remeron, Luvox, and Wellbutrin, were 1.4 to 5.5 more likely to have suicidal thoughts or behaviors than similarly ill children taking a placebo.

Despite the elevated risk, suicidal behavior was rare in the studies. Potentially suicidal events were reported in 109 out of nearly 2,500 patients.

But the effect persisted when analysts limited their review to children taking the drugs only for depression. Children with depression taking one popular drug, Effexor XR, showed self-harming behavior or considered suicide nearly nine times as often as children not taking medication.

“It is important to put in mind that these are just estimates,” says Hammad, stressing that his audit was retrospective in nature and looked at studies not specifically designed to pick up on a heightened risk of suicide.

Consistent Findings

The study confirms similar findings in another FDA review conducted last year by Andrew D. Mosholder, MD. That review became a subject of heated controversy when Mosholder’s FDA superiors barred him from presenting his conclusions at an agency hearing in February of this year.

As late as last week, lawmakers accused FDA officials of working to suppress key data on the efficacy and safety of antidepressant drugs. Several drug company executives told a House committee on Thursday that the FDA encouraged them to withhold data undermining the drugs’ effectiveness for fear of scaring doctors and the public.

Robert Temple, MD, head of the FDA’s scientific investigations division, tells reporters that he does not regret withholding Mosholder’s determination last winter even in light of Monday’s confirmatory review. His conclusions were premature given what was known at the time about performance of antidepressant medications, he says.

Temple now calls attention to the consistency of elevated suicide behavior across most drugs in the class. “What’s interesting and pervasive is that they all lean the same way,” he says.

Three percent to 5% of children under 18 years of age are thought to suffer from depression, according to the American Psychiatric Association.

The reviews are part of a government evaluation of antidepressants in children, spurred by reports that the drugs may lack effectiveness or pose some elevated risks to children with depression and other mental disorders.

The FDA warned doctors in March that these drugs could be associated with elevated suicide risk in children and urged close monitoring of patients.

Officials are now considering issuing warnings on many antidepressant labels to alert doctors and patients to the potentially elevated suicide risk. More than 20 family members of children and adults who killed themselves while taking the drugs urged the FDA to issue strong warnings or to pull the drugs off the market altogether.

“These drugs did not help her. They made her suicidal and abusive to herself and her family,” says Marian Goth, whose 9-year-old daughter was prescribed Zoloft and Paxil for an eating disorder in 2002. “We almost lost our daughter twice.”

Drug manufacturers and many clinicians stress that that no children or adolescents succeeded in killing themselves in any of the studies and that antidepressants have helped far more patients than they have harmed.

Jeffrey Jonas, MD, vice president of Forest Laboratories Inc., argues that that the drugs don’t cause increases in suicidal behavior but that some patients become suicidal when the drugs fail to work.

“It is a lack of response that may be responsible,” says Jonas, whose company makes Celexa.

The FDA’s advisory panel is expected to issue recommendations Tuesday on how officials should proceed on concerns over the drugs.