Beta Blocker May Ease Social Problems in Autism

April 15, 2014

The beta blocker propranolol may help teenagers and young adults with autism spectrum disorder (ASD) improve their social interaction and problem-solving skills, new research suggests.

The double-blinded, placebo-controlled study showed that 20 patients scored significantly higher (P = .03) on a performance-based measure of social competence after a single 40-mg dose of propranolol than after placebo in a separate test session.

This result is important because it suggests that a widely available, inexpensive generic medication used to treat hypertension and anxiety can alleviate at least 1 of the core symptoms of ASD, David Beversdorf, MD, the principal investigator and a neurologist at the University of Missouri, Columbia, told Medscape Medical News.

"We have drugs to treat anxiety and irritability in individuals with ASD, but not for the core symptom of impaired social communication," Dr. Beversdorf said.

The findings will be reported in May at the International Meeting for Autism Research (IMFAR) Annual Meeting in Atlanta, Georgia, but have not yet been published.

Improved Communication

The investigators studied 1 female and 19 male patients with high-functioning ASD (IQ above 85) who ranged in age from 15 to 31 years. Ten of the patients received propranolol first and placebo the next day, and the other half received the agents in reverse order. The patients underwent sociability and cognitive testing 1 hour after drug administration.

The sociability task, the General Social Outcome Measure, involved a conversation between a researcher and a patient about a topic the patient selected. (The topic changed at the second study session.) This previously validated measure tests for 6 domains:

• staying on topic
• sharing information
• reciprocity-providing or eliciting information beyond simple or vague comments
• transitions/interruptions
• nonverbal communication
• eye contact

For assessment of verbal problem-solving ability and word memorization, the patients performed anagrams and the Hopkins Verbal Learning Test.

When participants received propranolol, they solved the anagrams significantly faster and had a mean sociability score that was nearly 1 point higher compared with placebo, according to data the authors supplied:

Table. Effect of Propranolol on Social and Cognitive Abilities in Patients With Autism Spectrum Disorder (N = 20; mean ± SEM)

Outcome	Propranolol	Placebo	P -valuea
Sociability (General Social Outcome Measure, total score)	9.40 ± 0.35	8.65 ± 0.47	.03
Verbal problem solving (anagrams test latency, number of seconds to correct response)b	17.33 ± 2.21	21.52 ± 2.50	.045
Verbal memory (Hopkins Verbal Learning Test discrimination index)	11.75 ± 0.09	11.35 ± 0.20	.09 (NS)
aPaired-samples t test (P < .05). b N = 18 owing to missing data. Abbreviations: NS, not significant; SEM, standard error of the mean (rounded).

 Additionally, patients receiving propranolol showed a significant improvement in score for 1 of the sociability test domains, specifically, appropriate nonverbal communication, such as body posture and nodding. The mean (± SEM) score in propranolol recipients was 1.7 ± 0.47 vs 1.5 ± 0.69 for placebo (P = .04).

Predicting Response

The researchers had predicted that patients with high levels of stress and anxiety would respond to propranolol better than other patients would because of the drug's known anxiolytic effects, Dr. Beversdorf said. Yet he noted that they found no relationship between self-reported anxiety and the drug's effects on cognitive and social function.

They did, however, report a significant positive linear relationship (P = .03; R ² = 0.23) between drug response and baseline heart rate variability, measured with electrocardiography.

Participants with greater heart rate variability before receiving propranolol demonstrated greater response to this drug related to the total score on the General Social Outcome Measure, according to the study data.

Dr. Beversdorf said there was not enough data to determine a minimum cutoff at which heart rate variability would predict treatment response.

"Propranolol is worth further exploration in individuals with ASD," he stated. "Perhaps at a sustained, serial dosage, we'd see a more robust effect of the drug. We also don't know if it works for lower-functioning individuals or younger children [with ASD]."

Patients with asthma or depression would not be good candidates for propranolol treatment because the medication can worsen these conditions, he said.

Possible Adjunctive Treatment?

Asked by Medscape Medical News to comment on the research, Daniel Coury, MD, medical director of the Autism Speaks Autism Treatment Network in New York City, said the study raises all sorts of questions and opportunities.

"With such small numbers of patients, it's hard to say how big an impact this drug will have, but it's exciting anytime we see a benefit for children with ASD."

Dr. Coury, a developmental and behavioral pediatrician from Nationwide Children's Hospital, Columbus, Ohio, was not involved with the study. He added that this research is one of the few studies showing changes in sociability resulting from pharmacologic intervention in autistic individuals.

Should future research find that propranolol has similar or better effects in greater numbers of patients and in younger children, he speculated that the drug could be useful as an adjunct to first-line behavioral therapy.

"If propranolol can help the child focus and be more attentive, it has the potential to make behavioral treatment more effective," Dr. Coury said.

The study received grant funding from the Health Resources and Services Administration, Rockville, Maryland. The University of Missouri Center for Autism Spectrum Disorders is one of the sites in the Autism Speaks Autism Treatment Network, but Autism Speaks did not fund this study, according to the organization. Dr. Beversdorf and Dr. Coury have disclosed no relevant financial relationships.

 

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