Arbaclofen Shows Limited Efficacy for Social Difficulties in Children with Autism

Trials of arbaclofen for autism have produced mixed results. Although autistic children and teenagers who took the investigational drug fared no better than controls on a rating of social skills, they did show significant improvements in atypical behavior and other measures. Two clinical trials were presented at the 2023 International Society for Autism Research annual meeting in Stockholm, Sweden.

Mouse studies from the past decade have suggested that arbaclofen eases traits related to autism and other conditions, but results in people have been mixed. One of the new trials included 82 autistic children and teenagers in Canada aged 5 to 17, and the other included 122 autistic people across Europe of the same age range. At the start of both trials, participants were randomly assigned to take increasing doses (up to 20 milligrams) of arbaclofen or a placebo three times per day for 16 weeks.

Parent reports of the children’s communication in social settings, captured via the Vineland Adaptive Behavior Scales (VABS), served as the studies’ primary outcome measure. Secondary outcome measures included other parent questionnaires that assess behavioral changes as well as traits such as repetitive and atypical behaviors.

Compared with children and teenagers on a placebo, those taking arbaclofen showed significant improvements in motor skills, interactions with their peers, and atypical and repetitive behaviors, according to parent ratings. They also improved in their social and communication abilities, based on the VABS, but the results missed statistical significance.

Overall, arbaclofen was safe and well tolerated, with most common side effects being mild. In one of the trials, two 5-year-olds experienced a serious adverse event related to a loss of consciousness after taking the highest dose of arbaclofen.

Although both studies are underpowered, the researchers plan to combine data from the two studies to have a sufficiently large sample size. Arbaclofen dampens excitatory signals in the brain, which are thought to be overabundant in many forms of autism. The drug decreases autism-like behaviors in a mouse model of fragile X syndrome.

A 2016 reanalysis of Seaside’s trial data suggested that a subgroup of people with autism may benefit from arbaclofen. Responders were more likely to be verbal and have an IQ above 70. The new studies have collected additional data about the participants’ brain activity and sensory processing. Analyzing those data may provide a biomarker that predicts who is more likely to respond to arbaclofen.

From the studies’ findings, “we should conclude that we do not yet know whether arbaclofen is efficacious for social difficulties in children and adolescents with [autism],” says Jeremy Veenstra-VanderWeele, professor of developmental neuropsychiatry at Columbia University. The findings also suggest that the VABS questionnaire to evaluate social behavior was not the most sensitive measure in this trial.