Antidepressants Offer No Relief for Repetitive Behaviors in Children With Autism

The repetitive behaviors exhibited by some children and teens with autism spectrum disorders are not reduced with the antidepressant citalopram, according to a study in the June issue of Archives of General Psychiatry, one of the JAMA/Archives journals. Lawrence Scahill, professor at Yale University School of Nursing and the Child Study Center was the principal investigator at Yale for the multi-center study. Yale Child Study Center Director Fred R. Volkmar, M.D., authored an accompanying editorial.

Repetitive behaviors in children with autism—including inflexible routines and repetitive play—tend to persist over time and often interfere with everyday life. The United States Food and Drug Administration has not approved any drugs to treat the core symptoms of autism and related disorders, but medications like citalopram are increasingly being used in these populations, the authors write.

Citalopram is in the class of antidepressants called selective serotonin reuptake inhibitors (SSRIs), which alter how the brain regulates the neurotransmitter serotonin. Scahill said that citalopram has been prescribed because of similarities between the repetitive behavior of autism spectrum disorders and that of obsessive-compulsive disorder. There is also some evidence suggesting that there may be abnormalities of the serotonin system in autism. Because the SSRIs work for adults and children with obsessive-compulsive disorder, he noted, some believed it could also be adapted for use in children with autism.

“Despite the limited evidence supporting their use in children with autism, SSRIs are among the most frequently used medications in this population. This is due in part because of their perceived safety,” said Scahill.

Scahill, along with colleagues at various institutions 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 who participated, 73 were randomly assigned to receive citalopram and 76 received a placebo for 12 weeks.

At the end of the treatment period, there were no differences between the citalopram group and the placebo group in percentage of children showing overall improvement or on scales measuring repetitive behavior. Indeed, noted the researchers, citalopram was more likely than placebo to be associated with adverse events, such as hyperactivity, insomnia, impulsiveness, decreased concentration, stereotypy (abnormal repetitive movements), diarrhea and dry skin.

“These results highlight the importance of placebo-controlled trials of medications commonly used for children with autism spectrum disorders to determine whether risks of medications outweigh benefits,” said Scahill.

In the accompanying editorial on the study, Yale Child Study Center Director Fred R. Volkmar, M.D., said the data might change the practice of prescribing SSRIs to children with autism.

“Previous double-blind, placebo-controlled studies with SSRIs in adults with autism showed a reduction in levels of repetitive behaviors,” 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 the least in theory, some therapeutic potential.”

Volkmar added, “Although the findings in the study were negative, the results are not difficult to interpret. 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.”

The National Institutes of Health via STAART center contracts funded the study. The work was also funded in part by a Clinical and Translational Science Award (CTSA) from the National Center for Research Resources at the National Institutes of Health.

Other authors on the study include first author Bryan H. King, M.D., Eric Hollander, M.D., Linmarie Sikich, M.D., James T. McCracken, M.D., Joel D. Bregman, M.D., Craig L. Donnelly, M.D., Evdokia Anagnostou, M.D., Kimberly Dukes, Lisa Sullivan, Deborah Hirtz, M.D, Ann Wagner, and Louise Ritz.

Citation: Arch Gen Psychiatry Vol. 66 (no. 6)  492 (June 2009)

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