Vol. 1, No. 12 / December 2002

Atypical antipsychotics and autism

I have questions concerning the article, “Antipsychotics in children and adolescents, part 2: Using atypicals for patients without psychosis” (October).

At the top of page 57, the authors write: “Recently, attention has turned to atypical antipsychotics, with their lower risk of extrapyramidal symptoms (EPS). Double-blind, placebo-controlled studies have demonstrated the efficacy of these agents in treating autistic and developmental disorders; risperidone and olanzapine have been studied most extensively.”

In the summary on page 58, the authors write: “Double-blind, placebo-controlled studies confirm the benefit of risperidone” in autistic and developmental disorders.

I read and reread the article, but could not find the data to support this position. The literature cited in the article represents open-label, semi-naturalistic case reports, not double-blind, placebo-controlled studies.

Double-blind studies often are the gold standard for developing treatment algorithms in evidence-based medicine. Less rigorous methods lead to scientific intrigue but rarely to overt immediate change in clinical practice.

Bradford Mark Tepper, MD
Garden City, NY

Drs. Londino and Buckley respond
Dr. Tepper raises valid concerns about the clarity of reported studies addressing the benefit of atypical antipsychotics in treating autistic disorders. The need for more established double-blind studies is clear, especially when considering treatment recommendations.

Early studies referenced in our article and in other publications—including double-blind, placebo-controlled trials—have proven the benefit of older neuroleptics, predominantly haloperidol, for treating disruptive behavior, including self-stimulatory behavior and aggression. These findings have been replicated, thus adding to their credibility. Of significance is that the American Academy of Child and Adolescent Psychiatry, in its child and adolescent practice parameters, recommends these agents for treating autism and pervasive developmental disorders.

It has followed logically that the atypical antipsychotics, which are associated with reduced risk of EPS and tardive dyskinesia, would be preferred over haloperidol. Currently, however, double-blind, placebo-controlled studies only exist for risperidone.

The Research Units of Pediatric Psychopharmacology Autism Network recently published the most conclusive study to date.1 This group of highly renowned researchers—including Christopher McDougle, MD, James McCracken, MD, and others—has spent years hypothesizing about the potential benefit of the newer antipsychotics and performing case reports and open-label trial results before publishing this double-blind, placebo-controlled study of more than 100 autistic children. We referenced the study on page 57 and in the bibliography (reference no. 11).

The study found that at a mean dosage of 2.1 mg/d, irritability was significantly reduced and overall functioning, as assessed by the Clinical Global Impressions scale, was improved or very much improved at 8 weeks. We regret
that the methods and results of this impressive study by a large cohort of investigators were not as clear as they could have been.

Interestingly, McDougle had published a 12-week, double-blind study in 31 autistic adults (mean age 28.1 +/- 7.3 years) demonstrating the effectiveness of risperidone against repetitive behavior, aggression, and anxiety.2

Dr. Tepper has reminded researchers and clinicians alike of the need for replicated, double-blind, placebo-controlled studies when determining treatment recommendations for children, adolescents, and adults. We hope that our review of the material and the responses from readers will stimulate others to pursue this vital research.

Donna Londino, MD
Peter Buckley, MD
Department of psychiatry and health behavior
Medical College of Georgia, Augusta

References
1. McCracken JT, McGough J, Shah B, et al. Risperidone in children with autism and serious behavioral problems. N Engl J Med 2002;347:314-21.
2. McDougle CJ, Holmes JP, et al. A double-blind, placebo-controlled study of risperidone in adults with autistic disorder and other pervasive developmental disorders. Arch Gen Psychiatry 1998;55(7):633-41.