Fluoxetine in Children and Adolescents With OCD: A Placebo-Controlled Trial MICHAEL R. LIEBOWITZ, M.D., SAMUEL M. TURNER, PH.D., JOHN PIACENTINI, PH.D., DEBORAH C. BEIDEL, PH.D., SUSAN R. CLARVIT, M.D., SHARON 0. DAVIES, R.N., FLEMMING GRAAE, M.D., MARGARET JAFFER, R.N., SHU-HSING LIN, PH.D., FLOYD R. SALLEE, M.D., PH.D., ANDREW B. SCHMIDT, C.S.W., AND H. BLAIR SIMPSON, M.D., PH.D. ABSTRACT Objective: To examine the safety and efficacy of fluoxetine in child and adolescent obsessive-compulsive disorder (OCD). Method: Between 1991 and 1998, 43 palients were randomly assigned to fluoxetine or placebo for 8 weeks. Dosing was fixed for the first 6 weeks (up to 60 mg/day) and then could be increased to 80 mg/day. Responders entered an 8-week maintenance phase. The primary outcome measures were the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) and the Clinical Global Impression-Improvement (CGI-l) scale. Analyses were done on the intent-to-treat sample. Results: Fluoxetine patients (n = 21) had significantly lower CY-BOCS scores than placebo patients (n = 22) after 16 (but not 8) weeks. Fluoxetine responders (n = 11) had significantly lower CY-BOCS scores than placebo respon- ders (n = 7) after an additional 8 weeks of treatment. After 16 weeks, 57% of fluoxetine (versus 27% of placebo) patients were much or very much improved on the CGI-I scale (p < .05). No patient terminated the study because of adverse medication effects. Conclusion: Fluoxetine was well tolerated and effective for the treatment ot child and adolescent OCD, but fluoxetine's full effect took more than 8 weeks to develop. J. Am. Acad. Child Adolesc. Psychiatry, 2002, 41(12):1431-1438. Key Words: obsessive-compulsive disorder, fluoxetine, selective serotonin reuptake inhibitors. Obsessive-compulsive disorder (OCD) is characterized by distressing, intrusive thoughts, images, or impulses (i.e., obsessions) and by repetitive mental or behavioral acts aimed to reduce distress (i.e., compulsions). The life- time prevalence of OCD is estimated to be 2% to 3% (Flament et al., 1988; Robins et al., 1984), its course is Accepted June 25, 2002. From the New York State Psychiatric Institute and Department of Psychiatry at Columbia University, New York (Liebowitz, Clarvit, Davies, Lin, Schmidt. Simpson); Department of Psychology, University of Maryland, College Park (Turner, Beidel); UCLA-Neuropsychiatric Institute, Los Angeles (Piacentini); Weill Medical College of Cornell University and New York-Presbyterian Hospital, Westchester Division, Westchester, NY (Graae, Jaffer); and Childrens Hospital Medical Center, University of Cincinnati (Sallee). Financialsupport wasprovided y NIMH (grant RO0 MH46439) and Eli Lilly and Company. Theauthors thankAndrea Giowand Dan DelBeneforresearch assistance, and Martin Franklin, Ph.D., for comments on an earlier draft. Correspondence to Dr. Simpson, Nev York State Pyhiatri Instintue, Unit 69, 1051 Riverside Drive, New York, NY 10032; e-nail: Simpson@nyspi.cpmc. columbia. edu. 0890-856710214112-1431 ©2002 by the American Academy of Child and Adolescent Psychiatry. DOI: 10.1097/01 .CHI.0000024862.60748. IA typically chronic (Skoog and Skoog, 1999), and OCD can cause significant functional impairment (Koran et al., 1996; Leonard et al., 1993). Up to 50% of OCD cases start in childhood or adolescence (Rasmussen and Eisen, 1990), making it critical to find safe and effective treat- ments for child and adolescent OCD. Two treatments have proven useful for adult OCD in randomized clinical trials (RCTs): cognitive-behavioral therapy consisting of exposure and response (or ritual) prevention (EX/RP) and pharmacotherapy with seroto- nin reuptake inhibitors (SRIs). Although EX/RP is com- monly used in children and adolescents, there is only one published RCT in this age group (DeHaan et al., 1998), although two others are nearing completion (March et al., 2001; Piacentini and Bergman, 2000). Clomipramine (CMI) was the first SRI examined for child and adoles- cent OCD, with two RCTs demonstrating superior effi- cacy to placebo (DeVeaugh-Geiss et al., 1992; Flament et al., 1985) and one demonstrating CMI's superiority to desipramine (Leonard et al., 1989). However, because J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 41:12, DECEMBER 2002 1431