A review of: Benjamin L. Handen, Raun D. Melmed, Robin L. Hansen, Michael G. Aman, David L. Burnham, Jon B. Bruss, Christopher J. McDougle (2009). A Double-Blind, Placebo-Controlled Trial of Oral Human Immunoglobulin for Gastrointestinal Dysfunction in Children with Autistic Disorder Journal of Autism and Developmental Disorders DOI: 10.1007/s10803-008-0687-y
I have previously reviewed studies testing the basic premises of the leaky gut theory of autism. This theory suggests that children with autism have increased permeability of their intestinal track leading to faster absorption of peptides which could disrupt neural development during the early stages of life. This theory has also contributed to the use of nutritional interventions in autism (e.g., gluten free diets). Responding to the popularity of interventions that target the GI symptoms (and underlying presumed pathophysiology) in children with autism, the authors of this study conducted a double-blind placebo examination of the effects oral immunoglobulin in the treatment of autism, with an especial focus on GI symptoms and adaptive functioning. There was a previous study of oral immunoglobulin in autism (Journal of Autism and Developmental Disorders, Volume 36, Issue 8, p.1053-1064, 2006) that suggested that the use of this medication could improve symptoms of autism. However this previous study had some major methodological limitations (no control group, no placebo, extremely small sample), which limited the validity and generalizability of their findings.
The current study was a major improvement over the previous study. It was conducted across 12 centers in the US and it included a total of 125 participants with ASDs. The diagnoses were based on DSM-IV criteria and obtained via the ADI. The participants ranged in age from 2 to 17. They were randomly assigned into 1 of 4 conditions: 1) placebo, 2) 140mg/day treatment, 3) 420mg/day treatment, 4) 840mg/day treatment. The participants did not know if they were taking the placebo drug (sugar pill) or one of the actual treatment dosages. The treatment lasted for 12 weeks. The following behavioral outcomes were collected (from the study):
Behavioral Measures: The presence of and change in the level of maladaptive behaviors was assessed using two measures. The Aberrant Behavior Checklist (ABC; Aman et al. 1985a) was completed at each study visit (monthly) and is a standardized instrument comprising five subscales designated as (a) Irritability (15 items); (b) Lethargy/Social Withdrawal (16 items); (c) Stereotypic Behavior (7 items); (d) Hyperactivity, Noncompliance (16 items); and (e) Inappropriate Speech (4 items).
The researchers failed to find any benefit of the use of oral immunoglobulin when compared to placebo on any of the outcomes examined. That is, the participants who took the placebo had the same rate of behavioral symptoms after 12 weeks of treatment than the participants that took the actual medication. Furthermore, the authors failed to find any subgroup of participants for whom the medication was particularly effective. The medication simply did not result in improvement of symptoms. Given the rigorous methodology used in this study, the data provide compelling evidence against the effectiveness of the use of oral immunoglobulin for the treatment of behavioral symptoms of autism.
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