Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior: citalopram ineffective in children with autism

Arch Gen Psychiatry. 2009 Jun;66(6):583-90. doi: 10.1001/archgenpsychiatry.2009.30.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Asperger Syndrome / diagnosis
  • Asperger Syndrome / drug therapy*
  • Attention / drug effects
  • Autistic Disorder / diagnosis
  • Autistic Disorder / drug therapy*
  • Child
  • Child Development Disorders, Pervasive / diagnosis
  • Child Development Disorders, Pervasive / drug therapy*
  • Child, Preschool
  • Citalopram / adverse effects
  • Citalopram / therapeutic use*
  • Diarrhea / chemically induced
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Impulsive Behavior / chemically induced
  • Male
  • Motor Activity / drug effects
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Sleep Initiation and Maintenance Disorders / chemically induced
  • Stereotyped Behavior / drug effects*
  • Treatment Failure

Substances

  • Serotonin Uptake Inhibitors
  • Citalopram

Associated data

  • ClinicalTrials.gov/NCT00086645