Antidepressant Ineffective for Repetitive Behaviors in Autism—(Medpage today)

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By Kristina Fiore, Staff Writer, MedPage Today
Published: June 01, 2009
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine. 

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LITTLE FALLS, N.J., June 1 — Despite common off-label use, the antidepressant citalopram (Celexa) has no effect on repetitive behavior in young patients with autism spectrum disorders, researchers said.

There was no significant difference in positive response rates between children taking citalopram or those taking placebo (32.9% versus 34.2%), Bryan H. King, M.D., of the University of Washington, and colleagues reported in the June issue of Archives of Psychiatry.

“There is a robust literature that supports the use of selective serotonin reuptake inhibitors for obsessive-compulsive disorder, so we assumed that we’d see a very positive response,” Dr. King said.

Instead, he said, the results further illustrate that there is “a fairly significant placebo response rate in kids with autism who are treated with medication.”
Action Points

  • Explain that there was no significant difference in positive response rates between children taking citalopram and those taking placebo for repetitive behaviors in autism spectrum disorders.
  • Point out that in addition to the lack of therapeutic effect, citalopram exhibited significant adverse effects.
  • Note that the results further illustrate a significant placebo effect in children with autism who are treated with medication.

“It might be very sobering to recognize that treatments that we thought were very helpful like citalopram for repetitive behaviors in fact may not be,” Dr. King said, “and at the very least we need to revisit what the risks and benefits of some of these treatments are.”

No medications are currently FDA approved for the “core symptoms” of autism spectrum disorders, but selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for these patients, the researchers noted.

Antiobsessional agents such as SSRIs have been of interest because of similarities between repetitive behavior in patients with autism and those with obsessive-compulsive disorders, as well as other findings regarding serotonin abnormalities in autism.

In fact, at 59%, SSRIs account for the greatest global market share of autism therapeutics — estimated at $2.2 to $3.5 billion overall.

So to determine the safety and efficacy of citalopram for repetitive behavior in children with autism spectrum disorders, the researchers conducted a randomized controlled trial of 149 patients ages 5 to 17 at six U.S. centers.

Patients received either citalopram or placebo for 12 weeks. Dosing began at 2.5 mg/dL for all children and increased over the study period depending on weight.

Participants had autism spectrum disorders, Asperger disorder, or pervasive developmental disorder not otherwise specified, and all illnesses were at least moderate.

The researchers found no significant difference in the rate of positive response on the Clinical Global Impressions Improvement subscale between citalopram and placebo.

Nor was there any difference in score reduction on the Children’s Yale-Brown Obsessive-Compulsive scales.

Citalopram use was significantly more likely to be associated with adverse events, particularly increased energy level, impulsiveness, decreased concentration, hyperactivity, stereotype, diarrhea, insomnia, and dry skin or pruritus.

The researchers said it was notable that the placebo response was very high, although their placebo response rate of 34.2% is “consistent with some other studies involving children with autism and reinforces the value of placebo control in pediatric psychopharmacologic research.”

“Ours is not the first to demonstrate this placebo effect,” Dr. King said. “It may help to explain how it is that there are so many treatments being offered up as potentially useful in kids with autism.”

Evidence is lacking when it comes to treatment of children with autism with other therapies, he said. Using SSRIs to treat anxiety and mood disturbances, for example, has not been formally studied.

“Those studies need to be done and I think that the fact that we did not see a signal for citalopram in this case really increases the urgency with which we should approach doing those studies,” Dr. King said.

In an accompanying editorial, Fred R. Volkmar, M.D., of Yale, said that “unfortunately, pharmacological intervention studies have often been hampered by small sample sizes and ambiguous results.”

He said the study done by Dr. King and colleagues is “an important step that addresses this major gap in the literature.”

“The medication does not appear to be useful for repetitive behaviors in children with autism and related conditions,” Dr. Volkmar said. “We need more studies of this kind to advance research and guide clinical practice.”

The study was supported by the National Institutes of Health.

Dr. King reported relationships with BioMarin Pharmaceuticals, Neuropharm Ltd, Forest Laboratories, Nastech Pharmaceutical, and Seaside Therapeutics.

Dr. Volkmar reported book royalty income and grant support from the National Institute of Mental Health, the Eunice Kennedy Shriver National Institute of Childe Health and Human Development, and Autism Speaks. He also is editor of the Journal of Autism and Developmental Disorders and receives compensation in that role.

Primary source: Archives of General Psychiatry
Source reference:
King BH, et al “Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior” Arch Gen Psychiatry 2009; 66(6): 583-590.

Additional source: Archives of General Psychiatry
Source reference:
Volkmar FR “Citalopram treatment in children with autism spectrum disorders and high levels of repetitive behavior” Arch Gen Psychiatry 2009; 66(6): 581-82.

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