June 1, 2009
Antidepressant Do Not Stop Repetitive Behaviors In Autistic Children
The antidepressant citalopram does not appear to reduce the occurrence of repetitive behaviors in children and teens with autism spectrum disorders, according to a report in the June issue of Archives of General Psychiatry, one of the JAMA/Archives journals.
Although the U.S. Food and Drug Administration has not approved any drugs to treat the core symptoms of autism and related disorders, medications are increasingly being used in this population, according to background information in the article. Citalopram belongs to a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs), which interfere with the way the brain regulates the neurotransmitter serotonin.
"Because of suggested similarities between repetitive behavior in autism spectrum disorders and obsessive-compulsive disorder and the findings of serotonin system abnormalities in autism, anti-obsessional agents such as SSRIs have long been of interest," the authors write. Repetitive behaviors in children with autism"”including inflexible routines and repetitive play"”tend to persevere over time and predict the endurance of an early autism diagnosis. "Despite the relative dearth of evidence supporting their use, SSRIs are among the most frequently used medications for children with autism, partially because of their perceived safety."
Bryan H. King, M.D., of Seattle Children's Hospital and the University of Washington, Seattle, and colleagues conducted a randomized controlled trial to determine the safety and efficacy of citalopram in children with autism spectrum disorders who had at least moderate levels of repetitive behavior. Of 149 children age 5 to 17 (average age 9.4) with autism spectrum disorders who participated, 73 were randomly assigned to receive citalopram (at an average maximum dosage of 16.5 milligrams per day) and 76 to receive a placebo for 12 weeks. Most of the participants (82.6 percent) completed the 12-week trial.
At the end of the treatment period, there were no differences between the treatment group and the placebo group in the number of children who demonstrated improvements on scales measuring repetitive behavior (32.9 percent vs. 34.2 percent). "Citalopram use was significantly more likely to be associated with adverse events, particularly increased energy level, impulsiveness, decreased concentration, hyperactivity, stereotypy [mechanical repetition of the same posture or movement], diarrhea, insomnia and dry skin or pruritis," the authors write.
"There is growing recognition that children and adolescents with autism spectrum disorders have serious behavioral problems and psychiatric symptoms that may be appropriate targets for pharmacotherapy," they continue. "To date, there are few large-scale trials to guide clinical practice, so clinicians are left to address these problems with inadequate information. The results of this trial indicate that citalopram is not an effective treatment for children having autism spectrum disorders with moderate or greater repetitive behavior. The results also highlight the urgent need for placebo-controlled trials of medications commonly used for children with autism spectrum disorders to determine whether the risks of specific drugs substantially outweigh their benefits."
(Arch Gen Psychiatry. 2009;66:583-590. Available pre-embargo to the media at www.jamamedia.org.)
Editor's Note: This work was funded by National Institutes of Health via STAART center contracts. All of the study medications were purchased using National Institutes of Health grant funds. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Editorial: Data May Change Practice of Prescribing SSRIs to Children With Autism
"The use of selective serotonin reuptake inhibitors has prompted considerable interest regarding their possible application for treating children with autism," writes Fred R. Volkmar, M.D., of Yale Child Study Center, New Haven, Conn., in an accompanying editorial.
"Previous double-blind, placebo-controlled studies in adults with autism showed a reduction in levels of repetitive behaviors," Dr. Volkmar writes. "Given the frequency of such behaviors in children with autism and their association with other features such as anxiety, depression and rigidity, selective serotonin reuptake inhibitors would seem to have, at least in theory, some therapeutic potential."
"Although the findings in the study by King et al were negative, the results are not difficult to interpret," Dr. Volkmar concludes. "The medication does not appear to be useful for repetitive behaviors in children with autism and related conditions. We need more studies of this kind to advance research and guide clinical practice."
(Arch Gen Psychiatry. 2009;66:581-582. Available pre-embargo to the media at www.jamamedia.org.)
Editor's Note: Dr. Volkmar reports book royalty income and grant support from the National Institute of Mental Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development and Autism Speaks. He is also compensated for serving as editor of the Journal of Autism and Developmental Disorders. Please see the article for additional information, including author contributions and affiliations, financial disclosures, funding and support, etc.
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