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.

• Authors: Bryan H King, Eric Hollander, Linmarie Sikich, James T McCracken, Lawrence Scahill, Joel D Bregman, Craig L Donnelly, Evdokia Anagnostou, Kimberly Dukes, Lisa Sullivan, Deborah Hirtz, Ann Wagner, Louise Ritz, STAART Psychopharmacology Network
• Journal: Archives of general psychiatry (Arch Gen Psychiatry) Vol. 66 Issue 6 Pg. 583-90 (Jun 2009) ISSN: 1538-3636 [Electronic] United States
• PMID: 19487623 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• Serotonin Uptake Inhibitors
• Citalopram

Topics

• Adolescent
• Asperger Syndrome (diagnosis, drug therapy)
• Attention (drug effects)
• Autistic Disorder (diagnosis, drug therapy)
• Child
• Child Development Disorders, Pervasive (diagnosis, drug therapy)
• Child, Preschool
• Citalopram (adverse effects, 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, therapeutic use)
• Sleep Initiation and Maintenance Disorders (chemically induced)
• Stereotyped Behavior (drug effects)
• Treatment Failure