Citalopram Ineffective in Children With Autism
King BH, Hollander E, Sikich L, et al
Arch Gen Psychiatry. 2009;66:583-590
Although no medications are currently approved by the US Food and Drug Administration for core symptoms of autism spectrum disorders (ASDs), selective serotonin reuptake inhibitors are widely prescribed for children with these conditions. The goal of this National Institutes of Health-sponsored, randomized, controlled trial was to evaluate the efficacy and safety of citalopram hydrobromide therapy for repetitive behavior in children with ASDs.
At 6 US academic centers, 149 children aged 5 to 17 years old with ASDs were randomly assigned to receive oral citalopram (10 mg/5 mL; n = 73) or placebo (n = 76) for 12 weeks. At baseline, illness severity ratings were at least moderate on the Clinical Global Impressions (CGI) severity of illness scale, as were compulsive behaviors measured with the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders. The mean maximum dosage of citalopram was 16.5 ± 6.5 mg/day (maximum, 20 mg/day).
A score of much improved or very much improved on the CGI improvement subscale constituted a positive response, and the score on the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders was the secondary endpoint. The Safety Monitoring Uniform Report Form allowed systematic determination of adverse events.
Neither the CGI improvement subscale nor the secondary endpoint showed any significant difference between groups. Positive response occurred in 32.9% of the citalopram group and in 34.2% of the placebo group. Adverse events were significantly more common with citalopram than with placebo; notably, increased energy level, impulsiveness, decreased concentration, hyperactivity, stereotypy, diarrhea, insomnia, and dry skin or pruritus.
Based on these findings, there is no support for citalopram treatment of repetitive behavior in children and adolescents with ASDs. This lack of effect is not explained by attrition, small sample size, or poor treatment compliance. Inadequate dosing is also unlikely because high rates of adverse events would have precluded use of higher citalopram dosing. A possible study limitation is the selection of repetitive behavior as the major treatment focus. Given the high positive response rate in the placebo group, other medications often used off-label for children with ASDs should also be tested in randomized, placebo-controlled trials to evaluate their risk-benefit ratio.
Abstract
Lack of Efficacy of Citalopram in Children With Autism Spectrum Disorders and High Levels of Repetitive Behavior: Citalopram Ineffective in Children With Autism
King BH, Hollander E, Sikich L, et al
Arch Gen Psychiatry. 2009;66:583-590
Summary
Although no medications are currently approved by the US Food and Drug Administration for core symptoms of autism spectrum disorders (ASDs), selective serotonin reuptake inhibitors are widely prescribed for children with these conditions. The goal of this National Institutes of Health-sponsored, randomized, controlled trial was to evaluate the efficacy and safety of citalopram hydrobromide therapy for repetitive behavior in children with ASDs.
At 6 US academic centers, 149 children aged 5 to 17 years old with ASDs were randomly assigned to receive oral citalopram (10 mg/5 mL; n = 73) or placebo (n = 76) for 12 weeks. At baseline, illness severity ratings were at least moderate on the Clinical Global Impressions (CGI) severity of illness scale, as were compulsive behaviors measured with the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders. The mean maximum dosage of citalopram was 16.5 ± 6.5 mg/day (maximum, 20 mg/day).
A score of much improved or very much improved on the CGI improvement subscale constituted a positive response, and the score on the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders was the secondary endpoint. The Safety Monitoring Uniform Report Form allowed systematic determination of adverse events.
Neither the CGI improvement subscale nor the secondary endpoint showed any significant difference between groups. Positive response occurred in 32.9% of the citalopram group and in 34.2% of the placebo group. Adverse events were significantly more common with citalopram than with placebo; notably, increased energy level, impulsiveness, decreased concentration, hyperactivity, stereotypy, diarrhea, insomnia, and dry skin or pruritus.
Viewpoint
Based on these findings, there is no support for citalopram treatment of repetitive behavior in children and adolescents with ASDs. This lack of effect is not explained by attrition, small sample size, or poor treatment compliance. Inadequate dosing is also unlikely because high rates of adverse events would have precluded use of higher citalopram dosing. A possible study limitation is the selection of repetitive behavior as the major treatment focus. Given the high positive response rate in the placebo group, other medications often used off-label for children with ASDs should also be tested in randomized, placebo-controlled trials to evaluate their risk-benefit ratio.
Abstract
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