Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior: citalopram ineffective in children with autism.
BACKGROUND
Selective serotonin reuptake inhibitors are widely prescribed for children with autism spectrum disorders.


OBJECTIVE
To determine the efficacy and safety of citalopram hydrobromide therapy for repetitive behavior in children with autism spectrum disorders.


METHODS
National Institutes of Health-sponsored randomized controlled trial.


METHODS
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.


METHODS
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.


METHODS
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).


METHODS
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.


CONCLUSIONS
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.
King
Bryan H
BH
Seattle Children's Hospital, University of Washington, 4800 Sand Point Way NE, Seattle, WA 98105, USA. bhking@u.washington.edu
Hollander
Eric
E
Sikich
Linmarie
L
McCracken
James T
JT
Scahill
Lawrence
L
Bregman
Joel D
JD
Donnelly
Craig L
CL
Anagnostou
Evdokia
E
Dukes
Kimberly
K
Sullivan
Lisa
L
Hirtz
Deborah
D
Wagner
Ann
A
Ritz
Louise
L
D000293:Adolescent; D020817:Asperger Syndrome / Q000175:diagnosis / Q000188:drug therapy*; D001288:Attention / Q000187:drug effects; D001321:Autistic Disorder / Q000175:diagnosis / Q000188:drug therapy*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000175:diagnosis / Q000188:drug therapy*; D002675:Child, Preschool; D015283:Citalopram / Q000009:adverse effects / Q000627:therapeutic use*; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007175:Impulsive Behavior / Q000139:chemically induced; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced; D013239:Stereotyped Behavior / Q000187:drug effects*; D017211:Treatment Failure
D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors