Thursday, 9 November 2017

On antipsychotic treatment failure when both psychosis and autism present together

"Children with first-episode psychosis and comorbid autism spectrum disorders at first presentation are less likely to have a beneficial response to antipsychotics."

So said the results reported by Johnny Downs and colleagues [1] based on their analysis of historical health records for over 630 children and young adults "referred to mental health services in South London, United Kingdom" between 2008 and 2014. Researchers looked for evidence of "multiple treatment failure" (MTF) - defined as "the initiation of a third trial of a novel antipsychotic due to insufficient response, intolerable adverse effects, or nonadherence to prior antipsychotic treatment" - among their cohort as a function of a diagnosis of an autism spectrum disorder (ASD) and other neurodevelopmental labels such as "hyperkinetic disorders (ICD-10 F90) and intellectual disability (ICD-10 F70–9)." The hypothesis being that those with at least one mention of psychosis in their health records alongside comorbid ASD "would be more likely to experience treatment failure" as a consequence of other findings talking about "psychopharmacologic effectiveness [being] lower in populations with coexisting ASD." The reasoning for that hypothesis seemingly comes from other research such as that from Politte and colleagues [2] and is set in the context of the NICE guidance here in Blighty on the subject of antipsychotics and 'core' autism (see here).

Results: 114 of the 638 participants (~18%) studied also had a diagnosis of ASD. This kinda reiterates that psychosis and other conditions characterised by psychosis are probably not strangers when it comes to the clinical profile of [some] autism (see here and see here). Some 20% of their total cohort developed MTF during the study follow-up period. After adjusting for various potentially confounding variables researchers observed that: "ASD comorbidity was associated with a 2-fold increased risk of MTF" and further: "28% of those with comorbid ASD compared to 11% of non-ASD children had a persistently insufficient response to antipsychotics." Autism or possibly something about autism or linked to autism, seemed to potentially affect response to antipsychotics where psychosis was present.

There are a couple of other observations to make about the Downs data. When comparing the ASD - first episode psychosis (FEP) group with the not ASD - FEP group, the former showed an increased frequency of both hyperkinetic disorders a.k.a attention-deficit hyperactivity disorder (ADHD) and intellectual (learning) disability. This tallies with quite a bit of other research looking at other over-represented labels in the context of autism (see here and see here respectively). Also: "Children with ASD showed higher rates of the “persistent insufficient response” or the “insufficient response–adverse effect” trajectory but lower rates of adherence-related reasons relative to those without ASD." The adherence bit kinda suggests that for example, not taking the antipsychotic medicine when required to, was not a core reason for MTF where ASD is mentioned.

Insofar as the important questions of 'how and why' in relation to the Downs results, the authors pop into 'speculating mode'. They talk for example, about how findings "may be explained by specific neurobiological profiles related to psychosis-ASD comorbidity" mentioning things like dopamine as being important. Equally as speculative, I might add in a few ideas that could also be pertinent. The first is that some effect on immune function could be a complementary pathway in relation to the action of specific antipsychotics (see here). The second is another 'sexy' area of research with a proposed 'epigenetic' action (see here); antipsychotics potentially acting on targets linked to gene expression for example. Both areas - immune function and/or epigenetics - have some 'research form' in both psychosis and autism investigations (see here for example). Both areas require a lot more investigation in this context.

I'm going to finish with another important quote from the Downs paper: "Our results are consistent with the evidence that shows psychotic illness experienced by children and adults with ASD may be different from non-ASD samples." I think the authors might be on to something here as per other observations on important psychiatric comorbidity in relation to autism such as the presentation of bipolar disorder (see here) for example. The idea being that such 'atypical' psychosis presentation and seemingly poor(er) response to recognised treatments for such psychiatric issues could denote that either a novel phenotype may be at work or indeed, that alongside anxiety and depression (see here and see here) being present in cases of autism, psychotic and other symptoms might be seen as more 'core' features of some autism? Once again, I hark back to the [sadly forgotten] writings of Mildred Creak and colleagues [3] as a possible framework for further study...

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[1] Downs JM. et al. The Association Between Comorbid Autism Spectrum Disorders and Antipsychotic Treatment Failure in Early-Onset Psychosis. Journal of Clinical Psychiatry. 2017.

[2] Politte LC. et al. Psychopharmacological interventions in autism spectrum disorder. Harv Rev Psychiatry. 2014 Mar-Apr;22(2):76-92.

[3] Evans B. How autism became autism: The radical transformation of a central concept of child development in Britain. Hist Human Sci. 2013 Jul;26(3):3-31.

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