Wednesday 5 March 2014

Drug-refractory aggression and SIB

At the time of writing this post, the media is awash with two stories with an autism research slant to them. So we have the paper by Brian D’Onofrio and colleagues [1] talking about older, sorry, advancing paternal age and the risk of various conditions for offspring, including autism, and the paper by Sébastien Jacquemont and colleagues [2] on a female protective model for autism. Y'know these are serious pieces of research when the good old BBC (Auntie) puts its 10p worth into the media pot as per its headlines: "Child health problems 'linked to father's age'" and "Girls' growing brains 'more resilient', study suggests" respectively.

El coloso @ Wikipedia 
Personally, I have little more to add to the myriad of comments made about these studies, aside from saying 'yes', both represent very detailed and potentially important areas of work. For people with autism and their families or caregivers however, I am inclined to suggest that such news from these studies is not going to be particularly useful in the day-to-day context.

Hence then why I've decided to focus instead on the paper by Adler and colleagues [3] in this post, and their rather less publicised work on "drug-refractory aggression, self-injurious behavior, and severe tantrums" in the context of autism.

To talk about aggression and autism has the ability to invoke emotion. On the one hand is the realisation that aggression can be part and parcel of the presentation of some autism, and both for the person themselves and their families, can have a profound effect on quality of life. As one example, I'll take you back to a post I did a while back on self-aggression, otherwise known as self-injurious behaviour (SIB), and autism and the extreme consequences it can sometimes have (see here).

On the other hand, there is the risk that talking about aggression with autism in mind may unfairly stereotype such behaviours to autism, all autism. In much the same way that the label schizophrenia carries with it some often over-emphasised links (see here) so one has to be mindful of the possible effects of talking about such behaviours and in particular, the over-generalisation that can accompany discussions. Just for the record, I'll bring the paper by Farmer and colleagues [4] to your attention and their conclusion: "children with autism spectrum disorder were reported to have less aggression and were more likely to be rated as reactive rather than proactive". Indeed, reactive or spontaneous aggression is also a theme when it comes to autism and the CJS too (see here).

That all being said, the Adler paper is an interesting one in terms of their assertion that from a total of 250 cases, 135 participants were diagnosed with an autism spectrum condition, and "53 of these individuals met drug-refractory symptom criteria" when it came to definitions of aggression and its relations. I should also add that drug refractory means resistant to change following the use of pharmacotherapy. Not wishing to dwell too much on the methodology employed by Adler et al - based on medical records and medication history charts - the authors set about looking for what characteristics may be correlated with drug-refractory aggression among their cohort. In the end, they determined a few important factors to be related: (a) a diagnosis of autism, (b) being over the age of 12 years, and (c) the presence of intellectual disability (or learning disability).

I hope you don't feel cheated by my highlighting what are three very general factors when it comes to aggression. Personally I feel that these represent important factors not least because the issue of intellectual disability in particular, does show more than a passing connection to challenging behaviours including those with an aggression element to them (see here). Indeed within that Moss paper [5] there are also a few other important points which may well be important; not least the association between things like depression and anxiety when it comes to the presentation of aggression and self-injury. One might even assume that this could be evidence for the presence of anxiety symptoms / disorders as being present where SIB is a feature of autism? Just sayin'.

The fact also that Adler and colleagues were looking at medication resistant aggressive behaviours in the first place is important. As they note: "We define drug-refractory aggression, self-injurious behavior, and severe tantrums in people with autism spectrum disorders as behavioral symptoms requiring medication adjustment despite previous trials of risperidone and aripiprazole or previous trials of three psychotropic drugs targeting the symptom cluster, one of which was risperidone or aripiprazole". In other words, such behaviours were not managed by something like risperidone or aripiprazole (which itself is having a bit of a hard time at the moment). This point in particular brings me back to some interesting work looking at the use of antipsychotics in other conditions and how one might extrapolate from other experiences to autism. In other words, before reaching for the antipsychotics, make reasonable efforts to see if there may be other reasons / causes for challenging behaviours like aggression. Certainly take some time to look at guidance like that produced by NICE (see here) and remember the weight gain issue [6] too.

Finally, I'm not saying that pharmacotherapy may not have a place when it comes to some aggression and some autism as per other research literature on this topic [7]. Indeed, it is timely to mention something like naltrexone as one medicinal option [8] given the reported recent passing of Dr Jaquelyn McCandless (RIP). Indeed, naltrexone looks like it may very well be coming out of the research wilderness if the paper by Roy and colleagues [9] is anything to go by [watch this space for more news from our research team on this stuff...]

Not to make light of today's subject matter, I close with some music by a man who some of my brood have just discovered via the wonders of YouTube... and they are absolutely enthralled by his dancing.


[1] D’Onofrio BM. et al. Paternal Age at Childbearing and Offspring Psychiatric and Academic Morbidity. JAMA Psychiatry. 2014. February 26.

[2] Jacquemont S. et al. A Higher Mutational Burden in Females Supports a “Female Protective Model” in Neurodevelopmental Disorders. The American Journal of Human Genetics. 2014. Feburary 27.

[3] Adler BA. et al. Drug-refractory aggression, self-injurious behavior, and severe tantrums in autism spectrum disorders: A chart review study. Autism. 2014 Feb 26.

[4] Farmer C. et al. Aggression in children with autism spectrum disorders and a clinic-referred comparison group. Autism. 2014 Feb 4.

[5] Moss S. et al. Psychiatric symptoms in adults with learning disability and challenging behaviour. British Journal of Psychiatry. 2000; 177: 452-456.

[6] Wink LK. et al. Body Mass Index Change in Autism Spectrum Disorders: Comparison of Treatment with Risperidone and Aripiprazole. Journal of Child and Adolescent Psychopharmacology. 2014. February 24.

[7] Parikh MS. et al. Psychopharmacology of aggression in children and adolescents with autism: a critical review of efficacy and tolerability. J Child Adolesc Psychopharmacol. 2008 Apr;18(2):157-78.

[8] Walters AS. et al. A case report of naltrexone treatment of self-injury and social withdrawal in autism. J Autism Dev Disord. 1990 Jun;20(2):169-76.

[9] Roy A. et al. Are opioid antagonists effective in attenuating the core symptoms of autism spectrum conditions in children: a systematic review. J Intellect Disabil Res. 2014 Mar 4. doi: 10.1111/jir.12122.

---------- Adler BA, Wink LK, Early M, Shaffer R, Minshawi N, McDougle CJ, & Erickson CA (2014). Drug-refractory aggression, self-injurious behavior, and severe tantrums in autism spectrum disorders: A chart review study. Autism : the international journal of research and practice PMID: 24571823

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