Lack of Efficacy of Citalopram in Children With Autism Spectrum Disorders and High Levels of Repetitive Behavior

Abstract

Context Selective serotonin reuptake inhibitors are widely prescribed for children with autism spectrum disorders. Objectives To determine the efficacy and safety of citalopram hydrobromide therapy for repetitive behavior in children with autism spectrum disorders. Design National Institutes of Health–sponsored randomized controlled trial. Setting Six academic centers, including Mount Sinai School of Medicine, North Shore–Long Island Jewish Health System, University of North Carolina at Chapel Hill, University of California at Los Angeles, Yale University, and Dartmouth Medical School. Participants One hundred forty-nine volunteers 5 to 17 years old (mean [SD] age, 9.4 [3.1] years) were randomized to receive citalopram (n = 73) or placebo (n = 76). Participants had autistic spectrum disorders, Asperger disorder, or pervasive developmental disorder, not otherwise specified; had illness severity ratings of at least moderate on the Clinical Global Impressions, Severity of Illness Scale; and scored at least moderate on compulsive behaviors measured with the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders. Interventions Twelve weeks of citalopram hydrobromide (10 mg/5 mL) or placebo. The mean (SD) maximum dosage of citalopram hydrobromide was 16.5 (6.5) mg/d by mouth (maximum, 20 mg/d). Main Outcome Measures Positive response was defined by a score of much improved or very much improved on the Clinical Global Impressions, Improvement subscale. An important secondary outcome was the score on the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders. Adverse events were systematically elicited using the Safety Monitoring Uniform Report Form. Results There was no significant difference in the rate of positive response on the Clinical Global Impressions, Improvement subscale between the citalopram-treated group (32.9%) and the placebo group (34.2%) (relative risk, 0.96; 95% confidence interval, 0.61-1.51; P> .99). There was no difference in score reduction on the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders from baseline (mean [SD], −2.0 [3.4] points for the citalopram-treated group and −1.9 [2.5] points for the placebo group; P=.81). Citalopram use was significantly more likely to be associated with adverse events, particularly increased energy level, impulsiveness, decreased concentration, hyperactivity, stereotypy, diarrhea, insomnia, and dry skin or pruritus. Conclusion Results of this trial do not support the use of citalopram for the treatment of repetitive behavior in children and adolescents with autism spectrum disorders. Trial Registration clinicaltrials.gov Identifier: NCT00086645

Complementary and Alternative Medicine in Autism: An Evidence-Based Approach to Negotiating Safe and Efficacious Interventions with Families

“…Multisite research networks have been established, 13,14 and clinical practice guidelines for the identification and treatment of children with ASD have recently clarified the role of the primary care provider. 6,15 Additionally, a stronger evidence base is emerging for educational and behavioral treatments.…”

“…16,17 Recently, several very well-designed medication trials have begun to clarify the evidence base for medications that physicians use for some of the most problematic associated symptoms of ASD. 13,14,18,19 For many families, however, geographic and economic barriers continue to limit access to high-quality behavioral and educational interventions, 20,21 and many concerns endorsed by families of children with ASD remain difficult to treat. 6,9,13 Additionally, despite increasing use of conventional psychiatric medications in children with ASD, 14,19 the evidence base supporting such use remains limited, and well-designed studies have found increased adverse effects and no clinical benefit from some medications that have been widely prescribed to children with ASD.…”

“…6,9,13 Additionally, despite increasing use of conventional psychiatric medications in children with ASD, 14,19 the evidence base supporting such use remains limited, and well-designed studies have found increased adverse effects and no clinical benefit from some medications that have been widely prescribed to children with ASD. 14 These inconsistencies can be challenging for families and contribute to the increased levels of treatment uncertainty reported by parents of children with ASD. 22.…”

Cognitive-Behavioral Therapy for Anxiety in Children With High-Functioning Autism: A Meta-analysis

“…[10][11][12] Results of a recent trial indicate that citalopram is not effective for repetitive behavior in youth with ASD. 13 Atypical antipsychotics risperidone 14,15 and aripiprazole [16][17][18] have been reported to reduce irritability in children with ASD. However, side effects such as weight gain and metabolic abnormalities 19 underscore the value of nonpharmacological treatments in ASD.…”

Improving the Prediction of Response to Therapy in Autism

“…Children treated with citalopram in this study also had no greater improvement than a placebo in a standard measure of obsessive-compulsive symptoms. 8 In another randomized, controlled trial (n ϭ 158), fluoxetine was found to be no better than a placebo for improving repetitive behaviors. 9 The full details of this study have yet to be published.…”