Washington Editor

Even though the risk of suicide is stated in warnings on many antidepressant drugs approved for adults, the FDA might consider requiring drug makers to strengthen the message by carrying "black box" warnings on labels for common selective serotonin reuptake inhibitors like Paxil, Zoloft and Prozac.

After two days of testimony from pharmacists, scientists, drug company executives and ordinary citizens about the positive and negative aspects of antidepressants, members of the FDA's Psychopharmacologic Drugs and Pediatric Advisory committees voted 15-8 in favor of requiring the strong "black box" warning on antidepressants used in children. The FDA is not bound by the panel's recommendation.

The FDA, as well as the House Energy Commerce Committee, initiated investigations into the use of antidepressants in children following a report released in June 2003 suggesting that paroxetine (generic for GlaxoSmithKline plc's Paxil) appeared to increase the risk of suicidal thoughts and actions in children. (See BioWorld Today, Sept. 10, 2004.)

In response to the panel's vote Tuesday, Eli Lilly and Co., of Indianapolis, said, "The recommendation of the FDA advisory committee does not change our belief that parents, in cooperation with health care professionals, must decide on the best treatment plan for their child.

"Lilly believes medication should be prescribed only after a careful diagnosis is made, and continued only if it clearly benefits the child. Because suicidal thinking is an inherent part of depression, we believe careful monitoring of patients is very important."

Lilly makes Prozac, the only selective serotonin reuptake inhibitor (SSRI) approved by the FDA for pediatric major depressive disorder (MDD). Lilly said it has never marketed Prozac in the pediatric indication.

Other drugs, such as Pfizer Inc.'s Zoloft, are being prescribed off-label in pediatric MDD. Zoloft is FDA approved for pediatric obsessive-compulsive disorder, as well as in several adult indications including MDD, obsessive-compulsive disorder, premenstrual dysphoric disorder and panic disorder.

Pfizer does not have plans to expand the Zoloft label to pediatric MDD, Susan Bro, a spokeswoman for New York-based Pfizer, told BioWorld Today. Zoloft's label acknowledges a long-standing concern that antidepressants might have a role in worsening depression and the emergence of suicidality in some patients. The label states that a causal role for antidepressants in inducing such behaviors has not been established, but, in bold print, it states that "nevertheless, patients being treated with antidepressants should be observed closely for clinical worsening and suicidality, especially at the beginning of a course or drug therapy, or at the time of dose changes, either increases or decreases."

Bro said Pfizer agrees with the FDA's concern about the need to identify and carefully treat patients with mental health issues. "From here, we plan to work closely with the FDA to achieve their ultimate objective, which is [to determine] the best way to communicate important information about monitoring patients [taking antidepressants]," she said.

Indeed, the Zoloft label also says, "Families and caregivers of patients being treated with antidepressants for MDD or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability and other symptoms [described in the label] as well as the emergence of suicidality and to report such symptoms immediately to health care providers."

Part of the controversy surrounding use of SSRIs is grounded in the charge that unpublished clinical data suggest a suicide or suicidality risk when the drugs are given to children.

Going forward, the medical journals have said they will not publish research findings unless all associated clinical trials are published in a public registry. Meanwhile, on Capitol Hill, Reps. Henry Waxman (D-Calif.) and Ed Markey (D-Mass.) said they would introduce legislation that would require drug companies to publish information on ongoing clinical trials and the results. The bill would expand the FDA's current clinical trial registry (www.clinicaltrials.gov) to include all trials.

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