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Citalopram No Better Than Placebo Treatment for Children with Autism Spectrum Disorders

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Citalopram, a medication commonly prescribed to children with autism spectrum disorders (ASD), was no more effective than a placebo at reducing repetitive behaviors, according to researchers funded by the National Institute of Mental Health (NIMH) and other NIH institutes. The study was published in the June 2009 issue of Archives of General Psychiatry.

"Parents of children with autism spectrum disorders face an enormous number of treatment options, not all of which are research-based," said NIMH Director Thomas R. Insel, M.D. "Studies like this help us to better understand which treatments are likely to be beneficial and safe."

The researchers say their findings do not support using citalopram to treat repetitive behaviors in children with ASD. Also, the greater frequency of side effects from this particular medication compared to placebo illustrates the importance of placebo-controlled trials in evaluating medications currently prescribed to this population.

Citalopram is in a class of antidepressant medications called selective serotonin reuptake inhibitors (SSRIs) that is sometimes prescribed for children with ASD to reduce repetitive behaviors. These behaviors, a hallmark of ASD, include stereotypical hand flapping, repetitive complex whole body movements (such as spinning, swaying, or rocking over and over, with no clear purpose), repetitive play, and inflexible daily routines.

Past research suggested that some children with ASD have abnormalities in the brain system that makes serotonin, a brain chemical that, among many other functions, plays an important role in early brain development. Children with obsessive compulsive disorder (OCD) may also have serotonin abnormalities and have repetitive or inflexible behaviors. OCD is effectively treated with SSRIs, leading some researchers to wonder whether similar treatment may reduce repetitive behaviors in children with ASD. So far, studies have produced mixed results, but SSRIs remain among the most frequently prescribed medications for children with ASD.

Researchers in the Studies to Advance Autism Research and Treatment (STAART) network, funded by five NIH institutes, conducted a six-site, randomized controlled trial comparing the effectiveness and safety of using the SSRI citalopram (Celexa) versus placebo to treat repetitive behaviors in children with ASD. The study included 149 participants, ages 5–17, who had autism, Asperger disorder, or pervasive developmental disorder-not otherwise specified (PDD-NOS).

After 12 weeks of treatment, roughly 1 out of 3 children in both groups—32.9 percent of those treated with citalopram and 34.2 percent those treated with placebo—showed fewer or less severe repetitive symptoms.

"Adverse symptoms were common in both groups, probably reflecting common childhood ailments as well as the changing nature of symptoms associated with ASD," according to Bryan King, M.D., director of child and adolescent psychiatry at Seattle Children's Hospital and lead author on the study. "However, reports of increased energy, impulsiveness, decreased concentration, hyperactivity, diarrhea, insomnia, and dry skin were more common in the citalopram group."

According to the researchers, the study results may challenge the underlying premise that repetitive behaviors in children with ASD are similar to repetitive and inflexible behaviors in OCD.

The authors on the paper include Bryan H. King, M.D., Seattle Children's Hospital; Eric Hollander, M.D., Mount Sinai School of Medicine; Linmarie Sikich, M.D., University of North Carolina, Chapel Hill; James T. McCracken, M.D., University of California Los Angeles; Lawrence Scahill, M.S.N., Ph.D., Yale University; Joel D. Bregman, M.D., North Shore Long Island Jewish Health System; Craig L. Donnelly, M.D., Dartmouth Medical School; Evdokia Anagnostou, M.D., Mount Sinai School of Medicine (currently at the University of Toronto); Kimberly Dukes, Ph.D., DM-STAT; Lisa Sullivan, Ph.D., Boston University; Deborah Hirtz, M.D., National Institute of Neurological Disorders and Stroke (NINDS); Ann Wagner, Ph.D., NIMH; Louise Ritz, M.B.A., NIMH (currently at NINDS); and the STAART Psychopharmacology Network.

The STAART network is jointly funded by NIMH, NINDS, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Institute on Deafness and Other Communication Disorders (NIDCD), and the National Institute of Environmental Health Sciences (NIEHS), all part of the National Institutes of Health (NIH).

Reference

King BH, Hollander E, Sikich L, McCracken JT, Scahill L, Bregman JD, Donnelly CL, Anagnostou E, Dukes K, Sullivan L, Hirtz D, Wagner A, Ritz L; STAART Psychopharmacology Network. Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior: citalopram ineffective in children with autism . Arch Gen Psychiatry. 2009 Jun;66(6):583-90. PubMed PMID: 19487623.

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About the National Institute of Mental Health (NIMH): The mission of the NIMH  is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website .

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