A Randomized, Placebo-Controlled, Blinded, Crossover, Single-Center Study of the Effects of Nuedexta in the Treatment of Neurobehavioral Symptoms of Adults with Autism Spectrum Disorder (P6.213)

Objective: To determine if Nuedexta(20mg dextromethorphan/10mg quinidine; Avanir Corporation) can improve frontal lobe pseudobulbar irritability in adult autistic patients. A double blind, placebo controlled crossover study was designed to see if there would be statistically significant difference from placebo.

Background: Autism is occurring in 1:68 children, is a lifelong condition, and has no cure. Comorbid irritability is a major problem. Theoretical excessive glutaminergic activation receptor activity in frontal cortex in autistic brain has been described. Nuedexta acts as an NMDA antagonist blocking excessive glutaminergic effect. It is approved for adults with frontal lobe irritability of pseudobulbar type, and many autistic adults may have similar irritability.

Design/Methods: Thirteen autistic adults (ADOS confirmed diagnossi, 11 male, 2 female, average age 21 years) completed a double blinded, placebo-controlled crossover study with interim washout period of 4 weeks separating each treatment vs. placebo arm. Primary outcome measure was the Aberrabt Behavioral Checklist-Irritability (ABC-I), and secondary outocome measures were Overt Aggression Scale (OAS) and total ABC. Clinical Global Impression Scales were also used assessing speech and social behaviors and irritability. Statistical analysis of mean values using a paired-t test was done.

Results: All primary and secondary standardized scales were statistically significant for improvement of irritability and function with Nuedexta over placebo. ABC-I (p=0.021), total ABC (p=0.043) and OAS (p=0.023), and CGI social was significant (p=0.022) and receptive and expressive language CGI showed strong trends (p=0.057 and 0.47 respectively). Washout baseline and initial baseline showed no statistically significant difference in scores, adding to the significance of the above outcomes. Only 1 patient dropped out for side effects in worsened behaviors possibly do to interaction with comedicat, and 1 con-compliant patient dropped out leaving 13/15 completing the 21 week study.

Conclusions: This study shows significant improvement if irritability and improved social function in adult autistic patients in treatment with Nuedexta over placebo. Further studies are warranted with Nuedexta or similar agents in this population.

Study Supported by:

This study was supported by an investigator initiated grant from Avanir Corporation that manufactures Nuedexta. The sponsor provided medication and placebo for the study and patients received this free of charge. Informed consent was obtained from the Sutter Sacramento Institutional Review Board.

Disclosure: Dr. Chez has received research support for activities with UCB, Eisai, and Lundbeck. Dr. Chez has received research support from GW and Marinus. Dr. Kile has received research support from Octapharma.