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Few Effective Treatment Options for Autism

Posted Apr 06 2011 10:20pm
From Medscape Medical News > Psychiatry
'Critical Need' for Additional Research Into Behavioral Interventions

Deborah Brauser

April 6, 2011 — Few medical, behavioral, or developmental treatments show strong evidence of substantial benefit for children with autism spectrum disorders (ASDs), conclude 3 new review studies published online April 4 in Pediatrics.

In the first review, which looked specifically at medication trials in ASDs, investigators found that most were lacking. However, the antipsychotics risperidone and aripiprazole had "the strongest evidence to support their use" specifically for challenging and repetitive behaviors, although each of these drugs was also associated with significant adverse effects.

In a second review, investigators found clear evidence that the gastrointestinal polypeptide secretin is not at all effective for treating ASDs.

Improvements in several areas, including cognitive performance and language skills, were found for some children with ASDs after undergoing intensive behavioral and developmental interventions, according to the third review.

However, the researchers note that "few research studies were rated of good quality and the existing evidence did not provide strong evidence in favor of any single early intervention approach."

"I think what surprised us most was the paucity of research that we found. Additional work is critically needed," the report's senior author Melissa L. McPheeters, PhD, MPH, codirector at the Vanderbilt Evidence-Based Practice Center at the Vanderbilt University Medical Center in Nashville, Tennessee, told Medscape Medical News.

'Strikingly Little Evidence'

Although as many as 1 in every 110 children in the United States has an ASD, "there is currently no consensus regarding which interventions are most effective," write the researchers.
Dr. Melissa L. McPheeters

"When looking across the different studies, certain children showed very positive improvements, especially with behavioral treatment, but others did not and remained very impaired. And there's a real lack of information about how we might go about identifying the children who are most likely to have a positive response," said Dr. McPheeters.

"If we could get more research in that area, that might lead to better targeting of these many possible interventions so we could get the right treatment to the right child."

When looking across the different studies, certain children showed very positive improvements, especially with behavioral treatment, but others did not and remained very impaired.

For the Agency for Healthcare Research and Quality (AHRQ) report, the investigators examined ASD intervention trials from MEDLINE, PsychInfo, and Education Resources Information Center databases that were published between 2000 and 2010 and included children 12 years and younger.

In the medication-specific review, "strikingly little evidence" of significant benefit was found for most ASD-treating medications, report the researchers.

However, at least 2 randomized controlled trials found parent-reported improvements in repetitive and challenging behavior for either risperidone or aripiprazole. Still, significant adverse effects associated with both drug treatments included weight gain, sedation, and risk for extrapyramidal symptoms.

"These 2 medications had the most research and are the only ones actually indicated by the FDA [US Food and Drug Administration] for autism treatment. And they are specifically indicated for the treatment of irritability," said Dr. McPheeters.

Some of the strongest study results to support [medication or device] use have been funded by pharmaceutical companies or device manufacturers that profit from the treatment.

"They did have positive results, but the flip side is that both come with potentially substantial side effects. This means we should probably limit their use to patients who are severely impaired or who are at risk of injury," she added.

The potential benefits and adverse effects of other medications, including selective serotonin reuptake inhibitors and stimulants, could not be judged due to "insufficient strength of evidence."

The investigators note that although the National Institutes of Health has funded 2 large studies assessing medical interventions for ASDs, "some of the strongest study results to support [medication or device] use have been funded by pharmaceutical companies or device manufacturers that profit from the treatment."

Final Word on Secretin

Used to treat peptic ulcers, secretin's additional possible use as a treatment for ASDs appears to stem from some animal studies and a small nonblinded case series of 3 children that reported some symptom improvements.

However, after evaluating 7 randomized controlled trials, the investigative team found no significant efficacy for secretin in treating language and communication impairment and cognitive and social skill deficits compared with placebo.

Because these studies "uniformly point to a lack of significant impact" from secretin, the investigators write that this ASD treatment approach "warrants no further study."

Dr. McPheeters added that she hopes "this is the final word" on the possibility of any useful benefits coming from this medication.

After reviewing 34 trials assessing early intensive interventions, the investigators found significant improvements in cognitive, language, and adaptive behavior skills in some of the children included.

The successful interventions emphasized specific behaviors, such as those found with the University of California, Los Angeles/Lovaas approach, or developmental principles, such as those found in the Early Start Denver Model. However,there were too few studies to be able to find strong evidence for 1 specific approach.

"We judged the literature to be low to insufficient in really establishing effectiveness at this time. Although there were individual studies with positive outcomes, we have a real need for replication because we don't have enough information to say for sure that we know that these are effective," said Dr. McPheeters.

In addition, only one of the studies evaluated was judged to be of good quality, 10 were of fair quality, and 23 were of poor quality.

Overall, the researchers write that several early intervention approaches "have significant potential," but more research is needed to determine which ones may be of most benefit to specific subgroups of children with ASDs.

Part of a Larger Report

It is important to note, said Dr. McPheeters, that the 3 reviews are part of a larger report initiated by the AHRQ, which is available on the AHRQ's Effective Healthcare Web site.

The overall report includes the 3 review studies published in Pediatrics, as well as findings about additional interventions and details of the methods.

"It's very important that clinicians, parents, educators, and caregivers of children with autism have the opportunity to look at all the evidence, which is why we tried to pull as much information together as we possibly could in the full report. We wanted to make sure it was all available so that important decisions could be made on a child-by-child basis."

In addition, recommendation guides for clinicians and for families of children with autism are currently in development by AHRQ and will be posted on the agency's Web site soon.

Although it's not new news to the professionals who serve people with autism, it is a nice compilation of existing studies in a journal that's easily assessable.

"The 3 papers are methodologically sound and were commissioned by the government to bring together what is already known," Susan L. Hyman, MD, associate professor of pediatrics at the University of Rochester Medical Center in New York and the division chief of the Neurodevelopmental and Behavioral Pediatrics Department at Golisano Children's Hospital, told Medscape Medical News.

"Although it's not new news to the professionals who serve people with autism, it is a nice compilation of existing studies in a journal that's easily assessable to pediatricians. It's important to let people know why they know things and that's what AHRQ does," she added.

Dr. Hyman, who is also chair of the autism subcommittee for the American Academy of Pediatrics, noted that the reviews are not telling clinicians to not use specific medications. Instead, the reviews are pointing out "in nonjudgmental ways" the strengths of evidence that guide practice.

The Art of Medicine

"When you're prescribing medicine without evidence, what you're calling upon is the art of medicine rather than the science. And you just need to know that."

She added that the review on secretin, especially, was not surprising. "The secretin summary basically closes the door on this treatment, that there is no indication for it for autism."

Regarding the interventions review, Dr. Hyman said that "there certainly are" other summary documents that have reached different conclusions.

"In the National Standards Project, [investigators] reviewed the literature and said that the evidence strongly supports applied behavior analysis and intervention for autism," she reported.

"I would also reach a slightly different conclusion than the authors of this new paper. They were very careful with their review of the literature, but there are a lot of intangibles when it comes to early intervention.

"And there are outcome variables beyond the core symptoms of autism that these studies measured. So they reported on what the studies reported and not on literature that looked at qualitative improvement and what families get from early intervention."

She noted that the investigators did not include studies of interventions that target isolated features of autism.

"When you look at the big picture analysis, the data is not that strong...You can lose the benefits that are measurable in other types of studies."

That said, Dr. Hyman believes the reviews are helpful and that "they're very important for clinicians to read and discuss with others."

Pediatrics. Published online April 4, 2011. First Abstract, Second Abstract, Third Abstract
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