Chugani, D. C., Chugani, H. T., Wiznitzer, M., Parikh, S., Evans, P. A., Hansen, R. L., . . . Hirtz, D. (2016). Efficacy of low-dose buspirone for restricted and repetitive behavior in young children with autism spectrum disorder: A randomized trial. Journal of Pediatrics, 170, 45-53.e41-44. doi:10.1016/j.jpeds.2015.11.033
Reviewed by: Brittni M. Edmond, Master’s Candidate, and Frank R. Cicero, PhD, BCBA, Seton Hall University
Why research this topic?
Autism Spectrum Disorder (ASD) is behaviorally identified by impaired social communication and repetitive, restricted behaviors. It is a neurodevelopmental disorder with an unknown cause making it somewhat difficult to treat symptoms. Researchers have found that up to 50% of those with ASD have elevated serotonin levels. Serotonin is an important chemical in the human body and has a variety of functions. It is thought that manipulation of serotonin levels in the brain using a medication, Buspirone, could possibly lessen some of the core features associated with ASD, especially in children younger than six years of age. Buspirone affects serotonin levels in the brain by stimulating receptors in a way similar to serotonin itself. Previous studies, although small in sample size, have shown some support for using Buspirone to treat symptoms in older children with ASD.
What did the researchers do?
Researchers conducted a randomized controlled trial with 166 children, ages 2-6, who were diagnosed with ASD. Efficacy measures were assessed at baseline, 24 weeks, and 48 weeks. Measures included scores from the Autism Diagnostic Observation Schedule (ADOS), Vineland Adaptive Behavior Scales, Repetitive Behavior Scales, and others. Prior to treatment, the participants underwent blood tests and positron emission tomography (PET) imaging to evaluate the effects of Buspirone on serotonin and brain tryptophan metabolism levels. Serotonin is produced from tryptophan, another important chemical in the body. The first phase of the trial continued for 24 weeks. Two of the groups received treatment of either 2.5 mg or 5.0 mg of Buspirone. The third group received a placebo treatment. After the 24-week treatment phase, efficacy measures were reassessed. Measures of serotonin and tryptophan metabolism were retested. Presence of side effects was also recorded. At the 25th week, the placebo group was re-randomized among the treatment groups receiving either 2.5 or 5.0 mg of Buspirone. The trial concluded at 48 weeks, at which time efficacy measures were once again assessed.
What did the researchers find?
As measured by the ADOS, no difference was found between groups with regard to overall symptoms of autism. Looking only at the restricted and repetitive behavior (RRB) scale of the ADOS, however, significant improvement in behavior was noted at the 2.5 mg dosage level. The RRB scale measures characteristics such as preoccupations with objects, movements like hand flapping, and echolalic speech. No improvement was found at the higher (5 mg) dosage level. This beneficial effect of Buspirone at the lower versus higher dosage is consistent with previously conducted animal models where improvements in motor behavior as well as in social behavior were shown with low-dose Buspirone. In the current study, there was no significant difference shown between groups with regard to adverse side effects.
What are the strengths and limitations of the study?
Strengths include the relatively large sample size and the ability of the results to differentiate between the effects of large and small dosages of Buspirone on behavior. The study’s use of PET scans to assess asymmetries in parts of the brain, supporting future studies on ASD and brain differences, was also important. Also, the results add support to the existing body of literature on ASD and high blood serotonin levels.
Limitations include the use of the ADOS to measure the main outcome of the study. The ADOS was designed to diagnose ASD, not to detect changes in the severity of the disorder over time. Also, the detection of drug effects on the ADOS-Social Affect Scale might be confounded by the tendency for this measure to improve, regardless of treatment, in young children. Another limitation was the lack of genetic measures to compare outcome with genetic risk or drug metabolism.
What do the results mean?
Overall, the results of the study suggest that low dose Buspirone may be a viable adjunct treatment for restricted and repetitive behaviors in young children with ASD. Specifically, a low dose of 2.5 mg appeared to have an effect on these behaviors compared to a higher dose of 5.0 mg or no medication. The researchers suggest that Buspirone may be most useful in combination with early behavioral intervention.
Citation for this article:
Edmond, B. M., & Cicero, F. R. (2019). Research synopsis: Efficacy of low-dose buspirone for restricted and repetitive behavior in young children with autism spectrum disorder: A randomized trial. Science in Autism Treatment, 16(11).
