PHILADELPHIA — An old, generic drug shows it may still have legs in a new indication. A recent study shows a single dose of propranolol improves social functioning and some aspects of cognition in high-functioning individuals with autism spectrum disorder (ASD).
"It's pretty low risk. That's the handy thing. It's been used for pediatric migraine for decades," senior author David Beversdorf, MD, associate professor of radiology, neurology, and psychological sciences at the University of Missouri in Columbia, told Medscape Medical News.
Results were presented here during the 66th American Academy of Neurology (AAN) Annual Meeting.
General Social Outcomes
Propranolol is a nonselective β-adrenergic antagonist with anxiolytic properties that blocks the noradrenergically mediated sympathetic response system. It has been reported to improve verbal fluency and working memory in ASD.
To see whether it could improve performance on social and cognitive tasks in ASD, Rachel Zamzow and colleagues performed a study using a single-dose challenge of propranolol, 40 mg, or placebo given to 20 high-functioning individuals with ASD (mean age, 21.39 ± 4.55 years; all IQ >85) over 2 study sessions.
Drug or placebo was administered in a counterbalanced, double-blind manner. Half received propranolol first, half placebo first. Before the challenge, electrocardiography and galvanic skin responses were measured after an acclimatization period.
Sixty minutes after the challenge, to allow peak drug effects to occur, participants performed several tasks. As a test of sociability, 6 domains of the General Social Outcomes Measure (GSOM) were scored on a 0 to 2 scale each, for a total potential score of 12.
On the basis of a conversation of the patient with the researcher about a chosen topic, the domains were staying on topic, sharing information, reciprocity, transitions/interruptions, nonverbal communication, and eye contact. Cognitive tasks involved solving anagrams and aspects of verbal memory.
"We did get a significant improvement in...general social outcomes measures, which actually was a bit of a surprise to us because this is a single-dose study," Dr. Beversdorf said.
Participants performed significantly better on the overall sociability (GSOM) score when administered propranolol compared with placebo.
The only individual domain showing a significant difference was the nonverbal communication score (P = .04), with a trend for better performance on the sharing information score (P = .09).
Participants also had less latency on the anagram-solving task when they received the drug.
Table. Task Performance
|GSOM total score||9.4||8.6||.03|
|Anagram solving—mean latency (s)||17||21||.045|
|Anagram solving— mean discrimination indexa||11.75||11.35||.09|
aHopkins Verbal Learning Test.
The researchers also observed a positive relationship between heart rate variability and response to propranolol for the GSOM total score (P = .03).
Dr. Beversdorf said he has also done studies with nadolol, a β-blocker that acts only peripherally, not centrally, to lower heart rate and blood pressure, "and it had a similar effect."
Sana Bloch, MD, assistant clinical professor of neurology at Albert Einstein College of Medicine, Bronx, New York, pointed out to Medscape Medical News that the study used a single dose of propranolol, and what really matters is whether it can produce long-term benefit with continued dosing.
He noted that it may be hard to get commercial funding for longer-term studies of an off-patent drug, so funding may have to come from the government.
"But it's a very important factor because when you have high-functioning Asperger patients, the 1 thing they're missing is their sociability," he said. "If this takes care of the sociability, they become much more functional individuals."
He said there is definitely need for a medication that can improve sociability in high-functioning patients with Asperger's, "which is a good percentage" of them.
He said up to now, people have tried to improve social interaction in patients with ASD using antidepressants, "and we see that may make things worse." Neuroleptics have also been tried but can cause major problems.
There was no commercial funding for the study. Dr. Beversdorf and Dr. Bloch have disclosed no relevant financial relationships.
American Academy of Neurology (AAN) 66th Annual Meeting. Abstract I4-1.002. Presented April 28, 2013.
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Cite this: Cheap Drug Improves Social Function and More in Autism - Medscape - May 01, 2014.