Researchers have conducted a placebo-controlled, randomized phase 2 study to analyze the effects of the drug arbaclofen on ASD patients.
Although arbaclofen seemed not to improve the main outcome of the parent-classified Aberrant Behavior Checklist Social Withdrawal/Lethergy subscale, post-secondary analyses did reveal enhancements in the clinician-rated Clinical Global Impressions of severity and in the Vineland Adaptive Behavior Scales 11 Socialization area, all suggesting that arbaclofen might have real potential in improving symptoms in a subset of autistic children; but more studies are required.
“Several lines of emerging data point to an imbalance between neuronal excitation and inhibition in at least a subgroup of individuals with autism spectrum disorder (ASD), including in those with fragile X syndrome (FXS), one of the most common genetic syndromes within ASD,” writes Jeremy Veenstrat-VanderWeele, MD, from Columbia University.
Earlier studies have demonstrated these potential benefits of arbaclofen in autism:
GABA-B agonists improving behavioral and brain phenotypes, including social behavior in animal models of ASD and FXS.
The GABA-B agonist arbaclofen improving social avoidance in FXS in a phase 2 placebo-controlled, randomized crossover trial.
Comparable benefits of arbaclofen on ASD indicated from a pilot open label trial.
The experimental, phase 2 trial with placebo-controlled, double-blind, randomized, multi-site design was done at 25 sites in the USA between 2011 and 2012. The researchers enrolled participants 5 to 21 years old meeting DSM-IV-TR criteria for Asperger’s Disorder, PDD-NOS, or ASD, based on interviews with caregivers and evaluation of autistic symptoms on the Autism Diagnostic Observation Schedule.
Patients who received arbaclofen began with 5 mg twice daily, the dose being increased each 7 days to either 10 mg twice-daily, 10 mg 3 times-daily, and 15 mg 3 times-daily. For patients 12 years and younger the dosage was capped at 10 mg 3 times-daily, and can be decreased in all subjects depending on severity of side effects. Researchers evaluated subjects at 2, 4, 8, and 12 weeks.
“Improvement in ABC-SW/L Scores were observed in both the arbaclofen and the placebo groups, similar to previous studies that found substantial placebo effects in ASD,” wrote the authors. They also added that in account of the negative events in the experimental group, newer, future studies would benefit from a scale that assesses lethargy and socially-related symptoms to evaluate the potential benefits of arbaclofen.