A team of researchers from the Johns Hopkins Children's Center and four other medical centers have found that the antidepressant drug fluvoxamine significantly lowers anxiety without major side effects in most children who take it. The finding, reported in this week's New England Journal of Medicine, is the result of the first large-scale study of an anti-anxiety drug treatment in children.

The work is also the first published report to come from the Research Units on Pediatric Psychopharmacology (RUPP) project established by the National Institute of Mental Health (NIMH) in 1999. NIMH directed five medical research centers across the country to work together to provide the public with much-needed information about the efficacy and safety of mood-altering drugs used in children, a population largely excluded from scientific drug trials.

"Fluvoxamine and other drugs are widely prescribed for use in anxious children who don't respond to psychotherapy," says Children's Center psychiatrist John Walkup, M.D., a principal investigator and co-author of the research. "But until now, we've had no scientific information about their safety and usefulness."

In a randomized, double-blind study, Walkup, along with Hopkins pediatric psychiatrists Mark Riddle, M.D., Michael Labellarte, M.D., and researchers at the other four RUPP centers followed 128 children ages 6 to 17 years, all of whom were diagnosed with at least one anxiety disorder, including social phobia, separation anxiety or generalized anxiety. The subjects had not responded to psychotherapy and had no other major psychological conditions. Fluvoxamine was chosen for the study because it was the only drug approved for use in children by the Food and Drug Administration at the time of the study's design. A selective serotonin reuptake inhibitor (SSRI), fluvoxamine causes the neurotransmitter serotonin to accumulate in the synapses between neurons, which in turn affects brain chemistry related to depression and anxiety.

About half of the children received increasing doses of fluvoxamine over the course of the eight-week trial; the rest of the children received a placebo. Anxiety and impairment were monitored weekly by clinicians using a rating scale developed jointly by Johns Hopkins and Columbia University doctors, and at intervals by the child and parents themselves. During each visit to the clinician, children in both groups also underwent psychotherapy.

Five of the 63 children in the fluvoxamine group dropped out of the study due to apparent adverse reactions to the drug. No major side effects were reported among the other 58 children, though children in the fluvoxamine group said they'd experienced more stomach aches and were more active than children in the control group. In the fluvoxamine group, 76 percent of children showed improvement, compared with 29 percent in the placebo group.

Pediatric anxiety disorders are relatively common, says Walkup, affecting as many as one in seven American children and adolescents. Pediatric anxiety disorders are associated with a two- to five-fold increased risk for adult anxiety disorder, major depression, suicidal tendencies and psychiatric hospitalization later in life.

The RUPP Anxiety Study is supported by grants from the National Institute of Mental Health and the Research Foundation for Mental Hygiene. Fluvoxamine was supplied by Solvay Pharmaceuticals. The centers selected by the NIMH to conduct the drug studies are New York University, Columbia University, Duke University, the University of California, Los Angeles, and Johns Hopkins Children's Center.

RUPP researchers at Hopkins and other RUPP centers receive some research support from Solvay Pharmaceuticals.

---Johns Hopkins

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