FLUVOXAMINE IN CHILDREN &ADOLESCENTS WITH ANXIETY DISOR

Yale University, New Haven CT

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Abstract

The long-term goal of this project is to develop new and better treatments for children and adolescents with autism and related disorders. To this end, we plan to evaluate both pharmacological and psychosocial interventions to reduce target behavioral problems and/or core symptoms of autism. Another long-term goal is identify biological predictors (e.g., specific genotypes) of treatment outcome. The third long-term goal is to develop better outcome measures in order to improve the precision of assessing treatment effects. The first aim of the current project is to compare low dose fluvoxamine to placebo in children and adolescents with pervasive developmental disorders (PDDs) accompanied by prominent anxiety symptoms. This drug was recently shown to be effective in the treatment of typically developing children with anxiety, but has not been well studied in children with PDD. Exploratory aims include: to examine the effect of fluvoxamine on social functioning in children and adolescents with PDD and anxiety symptoms; to examine the relationships between fluvoxamine level, extent of transporter blockade and clinical response (therapeutic effects and adverse effects such as behavioral activation); to examine the relationship between serotonin transporter genotypes and treatment response; to examine the distribution of anxiety symptoms in a large sample of children and adolescents with higher functioning forms of PDD and compare to normative data in typically developing children. Sixty subjects with PDD and an anxiety disorder will be recruited (30 per group) over a 4 1/2 year period (approximately 1 per month) and randomly assigned to low dose fluvoxamine or placebo for 8 weeks. Placebo non-responders will be offered open-label treatment after the double-blind phase. The primary outcome measure will be the Pediatric Anxiety Rating Scale scored by a blinded clinician. All subjects will be genotyped in order to evaluate the association between the serotonin transporter and clinical response. To address Aim # 5, we will survey 100-200 children between the ages of 10 and 18 years with higher functioning forms of PDD with 2 commonly used childhood anxiety questionnaires. These subjects will be ascertained from other projects in this Center and from ongoing projects here at Yale. Aims #1-4 will be accomplished by a randomized, double-blind, placebo-controlled trial of parallel groups.