Propranolol and autism?

"This review indicates that propranolol holds promise for EBAD [emotional, behavioural and autonomic dysregulation] and cognitive performance in ASD [autism spectrum disorder]."

So said the findings reported by Ilyas Sagar-Ouriaghli and colleagues [1] looking at the existing peer-reviewed (and conference) literature mentioning the use of the beta-blocker called propranolol in the context of autism. Beta-blockers, as I mentioned in a post some years back (see here), seem to have found quite an off-label following for a variety of diagnoses/conditions/states outside of their intended indications. Autism or autism spectrum disorder (ASD) seems to rank as one such following.

Analysing some 16 reports including "single-dose clinical trials" and more "case series and single case reports" with mention of autism, authors concluded that - so far - the research and clinical future for propranolol looks quite bright. Certainly bright enough for them to recommend further "good quality clinical trials, randomised controlled trials" to look at effectiveness and also important issues such as side-effects. I might add that included in the long list of potential drug interactions mentioned alongside propranolol, several medicines that tend to turn up with some regularity with 'some' autism in mind - the antipsychotics - need to be kept in mind and particularly the risk of hypotension from combined use.

I want to bring to your attention a few of the studies that currently populate the 'propranolol and autism' literature. The name Rachel Zamzow appears quite a bit in light of studies such as this one [2] and this one [3]. These and other results suggest that 'effects' might be quite widespread and the focus should perhaps be wide when it comes to further investigations of this particular medicine or possibly, some of its relations.

'Promising' is a word to springs to mind at the moment. We'll have to see if it endures. Oh, and then there is the questions of 'how and why' propranolol 'works' for some autism...

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[1] Sagar-Ouriaghli I. et al. Propranolol for treating emotional, behavioural, autonomic dysregulation in children and adolescents with autism spectrum disorders. J Psychopharmacol. 2018 Feb 1:269881118756245.

[2] Zamzow RM. et al. Effects of propranolol on conversational reciprocity in autism spectrum disorder: a pilot, double-blind, single-dose psychopharmacological challenge study. Psychopharmacology (Berl). 2016 Apr;233(7):1171-8.

[3] Zamzow RM. et al. Effects of acute beta-adrenergic antagonism on verbal problem solving in autism spectrum disorder and exploration of treatment response markers. J Clin Exp Neuropsychol. 2017 Aug;39(6):596-606.

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New life for beta-blockers

I approach this post with slight trepidation. A touch of anxiety because I do not want it to become some kind of advert for beta-blockers (or any approach for that matter, pharmaceutical or otherwise) for autism or anything else. This despite some interesting news on potential benefits outside of their primary purposes. I will also at this point reiterate my mantra: 'I am not a medical doctor and do not offer anything like medical advice or recommendation'. OK, got your pinch of salt ready?

I am sure that the board rooms of a few pharmaceutical companies were of a slightly more jubilant mood when they heard about this report picked up the BBC recently on the embarkation of a study to examine the potentially positive effect from the use of beta-blockers in stopping breast cancer from spreading (metastasis), based on some earlier research (full-text) findings. I can also imagine that quite a few people whose lives may have been touched by breast cancer also found the news to be important for a slightly different and perhaps more important set of reasons.

The exact process for the effect of beta-blockers on inhibiting the formation of secondary cancers is still the source of some speculation but attention seems to be focusing on the primary activity of such pharmaceutics acting on stress hormones and in particular how beta-blockers block adrenergic receptors so diminishing the effects of catecholamines. It must be added that this is not the first time that beta-blockers have shown activity against cancers either peripherally or directly.

The good news for beta-blockers did not stop there with another feel-good story in this study by Beversdorf and colleagues* on a potential role for propranolol on word fluency in autism. The main effects were that alongside what one would expect (lower blood pressure, stabilising heart rate) there were also some cognitive 'enhancing' effects to be had for the high-functioning participants with autism similar to other research undertaken by the authors. Improved functional connectivity between brain areas has been suggested as a primary effect from propranolol.

There are some potentially very interesting facets to both these stories on beta-blockers. The biochemistry of effect in both cases is bound to be complicated and indeed might (probably) not even be showing the same effect across the different findings. Beta-blockers are primarily used to address cardiac function and hypertension. Outside of what has already been detailed there is some evidence of other effects; for example including a potential anti-parasitic effect as detailed by this review of treatments for Giardia lamblia. Like many pharmaceutics (and nutraceutics), the effects are likely to be numerous.

Before both these reports of a potential effect of beta-blockers on autism and halting metastatic breast cancer came out, I had intended to cover the very delicate subject of any relationship between autism and cancer on this blog. Those that follow Donna Williams will know about her on-going treatment following her diagnosis with breast cancer. Many people will know Donna through her books, speaking engagements and her website (including her blog) about her experiences of autism. She has been very open about her cancer and continues to plot her treatment course and the associated emotions which accompany it. I wish her well. There was also the publication of this paper (open-access)** in the journal Autism Research by Crespi on autism and cancer risk following on from other reports of possible correlations between autism and specifically with breast cancer. I'm not even going to approach the PTEN findings and any onward suggestions from there.

I don't however want to make too much of any commonalities between autism and cancer with the beta-blocker connection because there might not be any. Beta-blockers are not for everyone with autism; that is for sure. One need only look at my post on the medicine cabinet and autism, and specifically the ARI parent survey of interventions to see that. For autism, if it is possible to identify best-responders to the reported cognitive effects however, there are potential openings which perhaps need further exploration bearing in mind the issues of side-effects and contra-indications. As to effect, if it is tied into the adrenergic receptors or functional connectivity, so be it. If it might be due to a more generalised 'anti-hypertensive' effect being witnessed, questions need to be asked about other classes of medication with similar functions such as the ACE inhibitors (e.g. enalapril) alongside their suggested neuroprotective effects are worthy of some autism research consideration also. The accompanying development of mice models of autism offer an ideal platform for examination.

The last words of this post should be given over to beta-blockers, as an example of the realisation that the quite startling array of pharmaceutics currently on the market seemingly offer wide and diverse effects outside of their original design. Some of these potentially therapeutic effects are only now beginning to be revealed.

* Beversdorf DQ. et al. Effect of propranolol on word fluency in autism. Cognitive & Behavioral Neurology 2011. 24: 11-17
** Crespi B. Autism and cancer risk. Autism Research. August 2011.