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

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.

Figure 1

Consolidated Standards for Reporting of Trials (CONSORT) chart. ITT indicates intent to treat.

Figure 2

Percentage of children with a rating of much improved or very much improved on the Clinical Global Impressions, Improvement subscale during the 12-week trial. All children assigned to citalopram hydrobromide (n=73) and to placebo (n=76) are included. Week 2 is the first opportunity to assess change from baseline. Using the generalized estimating equation method, there was no statistical difference between groups over time.

Figure 3

The mean scores on the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders (CYBOCS-PDD) over time. Scores reflect frequency and intensity of repetitive behaviors and are shown with the standard error. All children assigned to citalopram hydrobromide (n=73) and to placebo (n=76) are included. Using the generalized estimating equation method, there was no statistical difference between groups over time.