Antidepressant Labeling Should Reflect Negative Pediatric Studies

With study results for several drugs failing to show pediatric efficacy, an FDA advisory committee suggests revising a standard labeling statement that efficacy "has not been established" in children. The committee also recommends that labeling highlight the need for suicide monitoring.

Antidepressant labeling should be revised to reflect negative efficacy data for pediatric patients, a joint FDA advisory committee suggested Feb. 2.

The Pediatric Subcommittee met with the Psychopharmacologic Drugs Advisory Committee to discuss reports of suicidality in children taking antidepressants off-label.

"Looking through most of the labels, it says simply that efficacy has not been established" in children, Anti-Infective Drugs/ Pediatric Subcommittee member Robert Nelson, MD/PhD, Children's Hospital of Philadelphia, said.

"Even though that's a true statement, I think most general physicians and pediatricians have been socialized into thinking that means the studies have not been done, where the reality here is they were done and did not show efficacy."

"I would say you need to actually say that, in fact, the studies were done and didn't show efficacy," he concluded.

In seven drugs evaluated for pediatric major depressive disorder, fluoxetine (Lilly's Prozac and generics) showed efficacy with two positive studies. Citalopram (Forest's Celexa ) resulted in one positive and one negative study. None of the other drugs - Wyeth's Effexor (vanlafaxine), GlaxoSmithKline's Paxil (paroxetine), Pfizer's Zoloft (sertraline), Bristol-Myers Squibb's Serzone (nefazodone), and Organon's Remeron (mirtazapine) - had statistically significant positive study results.

Wyeth revised Effexor labeling in August to state that efficacy was not established in pediatric clinical trials. Effexor labeling also notes increased reports of "suicide-related adverse events" in children on the drug versus placebo.

The committee also suggested an update to the standard warning on suicide.

"The way that [selective serotonin reuptake inhibitors] and other antidepressants are being used now is such that the warnings as they exist in the current labeling are not adequate and/or not being taken seriously," Psychopharmacologic Drugs Advisory Committee Chair Matthew Rudorfer, MD, National Institute of Mental Health, said.

Rudorfer suggested eliminating a sentence in the current labeling that states antidepressant prescriptions "should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose."

"I'm wondering if instead we should have a statement that encompasses two thoughts. One, that patients should be monitored frequently early in treatment, and two, that any change in behavior, particularly early in treatment, should be reported to the clinician promptly."

Such wording would highlight the need for monitoring but "avoid getting into issues of causality" between the medications and suicide, for which data is still being analyzed, Rudorfer noted.

The committee also recommended that strengthened warnings about the risk of suicidality in children be communicated to physicians and consumers as soon as possible. FDA is in the process of re-analyzing pediatric data for suicide-related events.

- Elizabeth Walker