Antidepressant No Help for Autism Behaviors

Celexa for Autism No More Effective Than Placebo at Reducing Repetitive Behaviors, Study Shows

By Kathleen Doheny
WebMD Health News

Reviewed by Louise Chang, MD

June 1, 2009 --The antidepressant Celexa, often prescribed for children with autism and autism spectrum disorders (ASD) to reduce repetitive behaviors, works no better than a placebo, according to a new study.

Even worse, the medication was more likely than the placebo to produce adverse side effects such as increased energy, impulsiveness, and decreased concentration, the researchers found.

The study findings were a surprise, says the study's lead author Bryan H. King, MD, director of child and adolescent psychiatry at Seattle Children's Hospital and professor and vice-chairman of psychiatry at the University of Washington School of Medicine. "We were fully expecting to demonstrate the value of this drug," he tells WebMD.

"A medication that we thought would be helpful for these repetitive behaviors was no better than placebo," he says. "That calls into question how or if we should use [Celexa] or even related medications for this purpose."

Repetitive behaviors in children with autism or ASD include asking the same question over and over; repeating body movements, such as swaying or spinning; or insisting on inflexible daily routines, such as taking the same route to school.

The study is published in the Archives of General Psychiatry and was funded by the National Institutes of Health.

Celexa for Autism: Study Background

Although antidepressant drugs such as Celexa aren't approved by the FDA to treat the repetitive behaviors of children with autism or ASD, they are widely prescribed "off-label", a common and legal practice.

"Surveys suggest about a third of the kids with autism treated with medication are on one of the SSRIs for a variety of symptoms," King says. SSRIs, or selective serotonin reuptake inhibitors, are a family of drugs such as Celexa that work by increasing the level of the brain chemical serotonin, associated with mood and behavior. The SSRIs have been shown to help reduce repetitive behavior in children with obsessive-compulsive disorder, King says.

Celexa for Autism: Study Details

King and his colleagues evaluated 149 children, aged 5 to 17, all diagnosed with autism or other ASD and being treated at six academic medical centers across the country. They were enrolled from April 2004 through October 2006 and randomly assigned to get either placebo or an average of 16.5 milligrams a day of liquid Celexa.

"Most had autism," King says. All the children had at least a moderate level of repetitive behaviors. The researchers focused on how well the drug reduced these behaviors, evaluating the results by using commonly used scales to show improvement in the behaviors.

Celexa for Autism: Study Results

After 12 weeks, about one of three children in each group -- 32.9% of those on Celexa and 34.2% of those on placebo -- showed fewer or less severe repetitive symptoms.

Side effects were more common in the children taking Celexa, the researchers found. Those on Celexa were more likely to have increased energy levels, impulsiveness, decreased concentration, hyperactivity, mechanical repetition of the same movement or posture, and sleep problems.

Treating Repetitive Behaviors: Other Opinions

In a commentary accompanying the study, Fred R. Volkmar, MD, of the Yale Child Study Center, speculates that the findings may change the widespread practice of prescribing antidepressants for children with autism and ASD.

Although the researchers note in the report of the study that different results might have been obtained with larger numbers of children, Volkmar says the King study is believed to be the largest such trial of the SSRIs in children with autism or ASD.

''It's important to realize the door is not necessarily closed on SSRIs,'' Volkmar tells WebMD. Other SSRI drugs may be found to help, says Volkmar, the Irving B. Harris Professor at Yale.

The study finding also suggests that researchers should explore why the SSRI drugs seem to work well overall in adults but not always in children, he says.

Forest Laboratories, which makes Celexa, says in a statement, "Forest Laboratories was not involved in this study and therefore cannot provide comment."

The results are ''disappointing," says Thomas Insel, MD, director of the National Institute of Mental Health. "The bottom line is, it doesn't sound like the medication is any better than placebo."

Because repetitive behaviors can be a significant problem, he says, "The question is, is there something else that can be used?"

Because Celexa didn't work for the autism-related repetitive behaviors but does work for those associated with obsessive-compulsive disorder, Insel says the findings may yield a clue that the behaviors are fundamentally different in some way.

Another expert, Geraldine Dawson, PhD, chief science officer for Autism Speaks, an advocacy and research organization, agreed that the study suggests the "underlying biology" is different for obsessive-compulsive disorder and autistic behaviors. The study finding "really does suggest that this drug is not going to be helpful for repetitive behaviors," she says.

Earlier this year, Autism Speaks released initial results of its study of another SSRI, Prozac, finding it also not effective in reducing repetitive behaviors compared to placebo. However, the study is continuing.

Implications for Treatment & Advice for Parents

Although other SSRIs may result in a different effect, King says, there is not enough research right now to make a clear recommendation about SSRIs as a class of drugs to treat repetitive behaviors associated with autism.

And what should parents do if their child is doing well on an SSRI prescribed to reduce repetitive behaviors? "It's very hard to argue with improvement," King tells WebMD. "If a child is taking an antidepressant and seems to be doing very well, you do not want to summarily discontinue treatment for that child."

But he does suggest that parents talk to their child's health care provider and consider the possibility of taking the child off the drug to see if the benefit remains. The improved behavior may not be tied to the medication, King says.

Repetitive behaviors related to autism can have an "ebb and flow," Insel says. Children may have been enrolled in the trial when their symptoms are somewhat worse and their symptoms may have improved over time even without the medication.

SOURCES:
Bryan H. King, MD, director of child and adolescent psychiatry, Seattle Children's Hospital and professor and vice chair of psychiatry, University of Washington School of Medicine.
Fred R. Volkmar, MD, of the Yale Child Study Center and the Irving B. Harris Professor, Yale University.
King, B. Archives of General Psychiatry, June 2009; vol 66: pp 583-590.
Volkmar, F. Archives of General Psychiatry, June 2009; vol 66: pp 581-582.
Thomas R. Insel, MD, director, National Institute of Mental Health, Bethesda, Md.
Geraldine Dawson, chief science officer, Autism Speaks, New York, N.Y.
Patricia Li, spokeswoman, Forest Laboratories.
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