title: Searching for moderators and mediators of pharmacological treatment effects in children and adolescents with anxiety disorders.
abstract: OBJECTIVE
  To examine whether age, gender, ethnicity, type of anxiety disorder, severity of illness, comorbidity, intellectual level, family income, or parental education may function as moderators and whether treatment adherence, medication dose, adverse events, or blinded rater's guess of treatment assignment may function as mediators of pharmacological treatment effect in children and adolescents with anxiety disorders.
  
  
  METHODS
  The database of a recently reported double-blind placebo-controlled trial of fluvoxamine in 128 youths was analyzed. With a mixed-model random-effects regression analysis of the Pediatric Anxiety Rating Scale total score, moderators and mediators were searched by testing for a three-way interaction (strata by treatment by time). A two-way interaction (strata by time) identified predictors of treatment outcome.
  
  
  RESULTS
  No significant moderators of efficacy were identified, except for lower baseline depression scores, based on parent's (but not child's) report, being associated with greater improvement (p < .001). Patients with social phobia (p < .05) and greater severity of illness (p < .001) were less likely to improve, independently of treatment assignment. Blinded rater's guess of treatment assignment acted as a possible mediator (p < .001), but improvement was attributed to fluvoxamine, regardless of actual treatment assignment. Treatment adherence tended to be associated (p = .05) with improvement.
  
  
  CONCLUSIONS
  In this exploratory study, patient demographics, illness characteristics, family income, and parental education did not function as moderators of treatment effect. Social phobia and severity of illness predicted less favorable outcome. Attribution analyses indicated that study blindness remained intact. The presence of concomitant depressive symptoms deserves attention in future treatment studies of anxious children.
authors.affiliation: Johns Hopkins University, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Walkup
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Labellarte
authors.forename: Mark A
authors.initials: MA
authors.lastname: Riddle
authors.forename: Daniel
authors.initials: D
authors.lastname: Pine
authors.forename: Laurence
authors.initials: L
authors.lastname: Greenhill
authors.forename: Rachel
authors.initials: R
authors.lastname: Klein
authors.forename: Mark
authors.initials: M
authors.lastname: Davies
authors.forename: Michael
authors.initials: M
authors.lastname: Sweeney
authors.forename: Caifeng
authors.initials: C
authors.lastname: Fu
authors.forename: Howard
authors.initials: H
authors.lastname: Abikoff
authors.forename: Sabine
authors.initials: S
authors.lastname: Hack
authors.forename: Brain
authors.initials: B
authors.lastname: Klee
authors.forename: James
authors.initials: J
authors.lastname: McCracken
authors.forename: Lindsey
authors.initials: L
authors.lastname: Bergman
authors.forename: John
authors.initials: J
authors.lastname: Piacentini
authors.forename: John
authors.initials: J
authors.lastname: March
authors.forename: Scott
authors.initials: S
authors.lastname: Compton
authors.forename: James
authors.initials: J
authors.lastname: Robinson
authors.forename: Thomas
authors.initials: T
authors.lastname: O'Hara
authors.forename: Sheryl
authors.initials: S
authors.lastname: Baker
authors.forename: Benedetto
authors.initials: B
authors.lastname: Vitiello
authors.forename: Louise
authors.initials: L
authors.lastname: Ritz
authors.forename: Margaret
authors.initials: M
authors.lastname: Roper
mesh_terms: D000293:Adolescent; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001008:Anxiety Disorders / Q000188:drug therapy*; D002648:Child; D015981:Epidemiologic Factors; D005260:Female; D016666:Fluvoxamine / Q000494:pharmacology*; D006801:Humans; D008297:Male; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D016896:Treatment Outcome
chemical_list: D014151:Anti-Anxiety Agents; D016666:Fluvoxamine