More Research Needed on SSRIs for Treating Autism Disorders

Meta-analysis of the published literature suggests a small but significant effect of SSRIs in the treatment of repetitive behaviors in autism spectrum disorders (ASDs), but this effect appears to be attributable to selective publication of trial results, according to a report published online April 23 in Pediatrics.

The report concludes that without timely, transparent, and complete disclosure of trial results, it is difficult to determine the efficacy of available medications. And child psychiatrists and autism experts who reviewed the report told Psychiatric News that SSRIs are not as beneficial for repetitive behaviors in autism as they were once thought to be and should be used with caution.

The study was conducted by Melisa Carrasco, Ph.D., Fred Volkmar, M.D., and Michael Bloch, M.D., M.S., of the University of Michigan and of the Child Study Center and Department of Psychiatry at Yale University.

“This research made it clear that the effects of SSRI treatment in ASD are considerably overrated because of publication bias,” they wrote. “In addition, our search strategy uncovered as many completed SSRI trials in ASD with unpublished results as have been published, further supporting the influence of potential publication bias on effect estimates.”

For the study, the researchers searched PubMed and Clinicaltrials.gov for randomized, double-blind, placebo-controlled trials evaluating the efficacy of SSRIs for repetitive behaviors in ASD; the primary outcome was mean improvement in ratings scales of repetitive behavior. They identified five published and five unpublished but completed trials eligible for meta-analysis.

They used standard statistical methods for computing effect sizes from available data, then applied special statistical methods to adjust effect sizes for unpublished results or missing data.

The meta-analysis of five published and one unpublished trial with available data demonstrated a small but significant effect of SSRIs for the treatment of repetitive behaviors in ASDs. But when analysis was adjusted for the effect of publication bias, there was no longer a significant benefit of SSRIs for the treatment of repetitive behaviors in ASDs. Secondary analyses demonstrated no significant effect of type of medication, patient age, method of analysis, trial design, or trial duration on SSRI efficacy.

“This paper provides a helpful reminder of the ongoing problems posed by publication bias,” said child psychiatrist David Fassler, M.D., a clinical professor of psychiatry at the University of Vermont and APA treasurer. “Utilizing a meta-analysis, the authors demonstrate that the published literature overstates the efficacy of SSRIs in the treatment of repetitive behaviors in children, adolescents, and adults with autism spectrum disorders. Physicians, patients, and family members need and deserve as much information as possible, including accurate and complete research data, to make fully informed decisions about treatment options. Selective publication of trial results can influence clinical practice, potentially placing patients at increased risk and/or postponing access to more appropriate and effective intervention.”

Louis Kraus, M.D., an expert in autism, told Psychiatric News that there is a dearth of research evidence for effective treatments of the repetitive behaviors commonly seen in autism.

Kraus said treatments for children are often extrapolated from research on adults, which may not be appropriate. And in the case of autism, the clinical logic behind using SSRIs rests on their efficacy for obsessive-compulsive disorder.

“But the reality is that the data regarding effectiveness for stereotypic behaviors in autism is limited,” he said in an interview. “There is a concern that SSRIs are not as helpful as we once thought.”

He cited a June 2009 article in the Archives of General Psychiatry that found no significant benefit for citalopram over placebo for repetitive behaviors. The article is titled “Lack of Efficacy of Citalopram in Children With Autism Spectrum Disorders and High Levels of Repetitive Behavior.”

Kraus added that children with autism are unusually sensitive to medication, and even a theoretical benefit from SSRIs is likely to be accompanied by an increase in agitation. “SSRIs may offer some benefit to some children, but in a general way clinicians should not use SSRIs for stereotypic behaviors without the understanding when getting informed consent from parents that the research is not definitive in this area,” Kraus said.

Funding for the study was provided by the National Institute of Mental Health and the National Institutes of Health.

“Pharmacologic Treatment of Repetitive Behaviors in Autism Spectrum Disorders: Evidence of Publication Bias” is posted at http://pediatrics.aappublications.org/content/early/2012/04/17/peds.2011-3285.full.pdf+html. “Lack of Efficacy of Citalopram in Children With Autism Spectrum Disorders and High Levels of Repetitive Behavior” is posted at http://archpsyc.jamanetwork.com/article.aspx?articleid=210271.